Document:

Form of Warrant to purchase shares of common stock

 Exhibit 4.1 
 NEITHER THIS WARRANT NOR ANY OF THE SECURITIES ISSUABLE HEREUNDER HAVE BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE “SECURITIES ACT”), OR ANY STATE SECURITIES LAW, AND MAY NOT BE SOLD, TRANSFERRED, ASSIGNED,
PLEDGED, HYPOTHECATED OR OTHERWISE DISPOSED OF OR EXERCISED UNLESS (I) A REGISTRATION STATEMENT UNDER THE SECURITIES ACT AND APPLICABLE STATE SECURITIES LAWS SHALL HAVE BECOME EFFECTIVE WITH REGARD THERETO, OR (II) AN EXEMPTION FROM
REGISTRATION UNDER THE SECURITIES ACT AND APPLICABLE STATE SECURITIES LAWS IS AVAILABLE IN CONNECTION WITH SUCH OFFER, SALE OR TRANSFER. 
 AN INVESTMENT IN
THESE SECURITIES INVOLVES A HIGH DEGREE OF RISK. HOLDERS MUST RELY ON THEIR OWN ANALYSIS OF THE INVESTMENT AND ASSESSMENT OF THE RISKS INVOLVED. 
  

			
	Warrant to Purchase	  	
	                     shares	  	Warrant Number

 Warrant to Purchase Common Stock 
 of 
 ISTA PHARMACEUTICALS, INC. 
 THIS CERTIFIES that                      or any subsequent
holder hereof (“Holder”) has the right to purchase from ISTA PHARMACEUTICALS, INC., a Delaware corporation, (the “Company”),                 
(            ) fully paid and nonassessable shares of the Company’s common stock, $0.001 par value per share (“Common Stock”), subject to adjustment as provided
herein, at a price equal to the Exercise Price as defined in Section 3 below, at any time during the Term (as defined below). 
 Holder agrees with the
Company that this Warrant to Purchase Common Stock of the Company (this “Warrant” or this “Agreement”) is issued and all rights hereunder shall be held subject to all of the conditions, limitations and provisions set forth
herein. 
 1. Date of Issuance and Term. 
 This Warrant
shall be deemed to be issued on September 26, 2008 (“Date of Issuance”). The term of this Warrant begins on the Date of Issuance and ends at 5:00 p.m., New York City time, on the date that is six (6) years after the Date of
Issuance (the “Term”). This Warrant was issued in conjunction with that certain Facility Agreement (the “Facility Agreement”) and the Registration Rights Agreement (“Registration Rights Agreement”) by and between the
Company and the initial Holder and certain other parties, each dated September 26, 2008, entered into in conjunction herewith. 
 Notwithstanding
anything herein to the contrary, the Company shall not issue to the Holder, and the Holder may not acquire, a number of shares of Common Stock upon exercise of this Warrant to the extent that, upon such exercise, the number of shares of Common Stock
then beneficially owned by the Holder and its Affiliates and any other persons or entities whose beneficial ownership of Common Stock would be aggregated with the Holder’s for purposes of Section 13(d) of the Securities Exchange Act of
1934, as amended (the “Exchange Act”) (including shares held by any “group” of which the Holder is a member, but excluding shares beneficially owned by virtue of the ownership of securities or rights to acquire securities that
have limitations on the right to convert, exercise or purchase similar to the limitation set forth herein) would exceed 9.98% of the total number of shares of Common Stock then issued and outstanding (the “9.98% Cap”). For purposes hereof,
“group” has the meaning set forth in Section 13(d) of the Exchange Act and applicable regulations of the Securities and Exchange Commission (the “SEC”), and the percentage held by the Holder shall be determined in a manner
consistent with the provisions of Section 13(d) of the Exchange Act. Upon the written request of the Holder, the Company shall, within two (2) Trading Days, confirm orally and in writing to the Holder the number of shares of Common Stock
then outstanding. 
  

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 “Affiliate” means any person or entity that, directly or indirectly through one or more intermediaries,
controls or is controlled by or is under common control with a person or entity, as such terms are used in and construed under Rule 144 under the Securities Act of 1933, as amended (the “Securities Act”). With respect to a Holder of
Warrants, any investment fund or managed account that is managed on a discretionary basis by the same investment manager as such Holder will be deemed to be an Affiliate of such Holder. 
 “Business Day” means a day on which banks are open for business in the city of New York. 
 “Trading Day”
shall mean any day on which the Common Sock is traded for any period on NASDAQ, or on the principal securities exchange or other securities market on which the Common Stock is then being traded. 
 2. Exercise. 
 (a) Manner of Exercise. During the Term,
this Warrant may be Exercised as to all or any lesser number of whole shares of Common Stock covered hereby (the “Warrant Shares” or the “Shares”) upon surrender of this Warrant, with the Exercise Form attached hereto as
Exhibit A (the “Exercise Form”) duly completed and executed, together with the full Exercise Price (as defined below, which may be satisfied by a Cash Exercise or a Cashless Exercise, as each is defined below) for each share of
Common Stock as to which this Warrant is Exercised, at the office of the Company, ISTA Pharmaceuticals, Inc., 15295 Alton Parkway, Irvine, CA 92618; Phone: (949) 788-6000, Fax: (949) 789-7744, or at such other office or agency as the
Company may designate in writing, by overnight mail, with an advance copy of the Exercise Form sent to the Company and its transfer agent (“Transfer Agent”) by facsimile (such surrender and payment of the Exercise Price hereinafter called
the “Exercise” of this Warrant). 
 (b) Date of Exercise. The “Date of Exercise” of the Warrant shall be defined as the
date that the Exercise Form attached hereto as Exhibit A, completed and executed, is sent by facsimile to the Company, and the Exercise Price is satisfied pursuant to the terms set forth in Section 3 below, provided that the
original Warrant is received by the Company within two Business Days after the Company receives a facsimile copy of the Exercise Form. Alternatively, the Date of Exercise shall be defined as the date the original Exercise Form is received by the
Company, if Holder has not sent advance notice by facsimile. Upon receipt of the properly completed and executed Exercise Form and the Exercise Price by the Company, the Holder shall be deemed for all corporate purposes to have become the holder of
record of the Warrant Shares with respect to which this Warrant has been Exercised, irrespective of the date such Warrant Shares are credited to the Holder’s Depository Trust Company (“DTC”) account or the date of delivery of the
certificates evidencing such Warrant Shares, as the case may be. 
 (c) Delivery of Common Stock Upon Exercise. Within three (3) Business
Days after any Date of Exercise, or in the case of a Cashless Major Exercise or a Cashless Default Exercise (each as defined in Section 5(c) below), within the period provided in Section 5(c)(iv) or Section 3(a)(iv), as applicable
(the “Delivery Period”), the Company shall issue and deliver (or cause its Transfer Agent to issue and deliver) in accordance with the terms hereof to or upon the order of the Holder that number of shares of Common Stock (“Exercise
Shares”) for the portion of this Warrant converted as shall be determined in accordance herewith. Upon the Exercise of this Warrant or any part hereof, the Company shall, at its own cost and expense, take all necessary action, including
obtaining and delivering an opinion of counsel, to assure that the Transfer Agent shall issue stock certificates in the name of Holder (or its nominee) or such other persons as designated by Holder and in such denominations to be specified at
Exercise representing the number of shares of Common Stock issuable upon such Exercise. The Company warrants that no instructions contrary to these instructions have been or will be given to the Transfer Agent and that, unless waived by the Holder,
this Warrant and the Exercise Shares will be free-trading, and freely transferable, and will not contain a legend restricting the resale or transferability of the Exercise Shares if the Unrestricted Conditions (as defined below) are met. 

(d) Delivery Failure. In addition to any other remedies which may be available to the Holder, in the event that the Company fails for any reason to
effect delivery of the Exercise Shares by the end of the Delivery Period (a “Delivery Failure”), the Holder will be entitled prior to the receipt by the Holder of the Exercise Shares to revoke all or part of the relevant Exercise Form by
delivery of a notice to such effect to the Company whereupon the Company and the Holder shall each be restored to their respective positions immediately prior to the delivery of such notice, except that the liquidated damages described herein shall
be payable through the date notice of revocation or rescission is given to the Company. 
  

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 (e) Legends. 
 (i) Restrictive Legend. The Holder understands that until such time as this Warrant, the Exercise Shares and the Failure Payment Shares have been registered under the Securities Act as contemplated by the Registration Rights
Agreement or otherwise may be sold pursuant to Rule 144 under the Securities Act or an exemption from registration under the Securities Act without any restriction as to the number of securities as of a particular date that can then be immediately
sold, this Warrant, the Exercise Shares and the Failure Payment Shares, as applicable, may bear a restrictive legend in substantially the following form (and a stop-transfer order may be placed against transfer of the certificates for such
securities): 
 “THE SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED, OR
APPLICABLE STATE SECURITIES LAWS. THE SECURITIES MAY NOT BE SOLD, TRANSFERRED OR ASSIGNED IN THE ABSENCE OF AN EFFECTIVE REGISTRATION STATEMENT FOR THE SECURITIES UNDER SAID ACT, OR PURSUANT TO AN EXEMPTION FROM REGISTRATION UNDER SAID ACT
INCLUDING, WITHOUT LIMITATION, PURSUANT TO RULES 144 OR 144A UNDER SAID ACT OR PURSUANT TO A PRIVATE SALE EFFECTED UNDER APPLICABLE FORMAL OR INFORMAL SEC INTERPRETATION OR GUIDANCE, SUCH AS A SO-CALLED “4(1) AND A HALF” SALE.”

 “THE SALE, TRANSFER OR ASSIGNMENT OF THE SECURITIES REPRESENTED BY THIS CERTIFICATE ARE SUBJECT TO THE TERMS AND CONDITIONS OF A
CERTAIN REGISTRATION RIGHTS AGREEMENT DATED AS OF SEPTEMBER 26, 2008, AS AMENDED FROM TIME TO TIME, AMONG THE COMPANY AND A CERTAIN HOLDERS OF ITS OUTSTANDING SECURITIES. COPIES OF SUCH AGREEMENT MAY BE OBTAINED AT NO COST BY WRITTEN REQUEST MADE BY
THE HOLDER OF RECORD OF THIS CERTIFICATE TO THE SECRETARY OF THE COMPANY.” 
 (ii) Removal of Restrictive Legends. This Warrant and the
certificates evidencing the Exercise Shares and the Failure Payment Shares, as applicable, shall not contain any legend restricting the transfer thereof (including the legend set forth above in subsection 2(e)(i)): (A) while a registration
statement (including a Registration Statement, as defined in the Registration Rights Agreement) covering the sale or resale of such security is effective under the Securities Act, or (B) following any sale of such Warrant, Exercise Shares
and/or Failure Payment Shares pursuant to Rule 144, or (C) if such Warrant, Exercise Shares and/or Failure Payment Shares are eligible for sale under Rule 144(b)(1), or (D) if such legend is not required under applicable requirements of
the Securities Act (including judicial interpretations and pronouncements issued by the staff of the SEC) and the Company shall have received an opinion of counsel to the Holder in form reasonably acceptable to the Company to such effect which, in
the case of a so-called “4(1) and a half transaction” shall be in the form attached hereto as Exhibit C (collectively, the “Unrestricted Conditions”). The Company shall cause its counsel to issue a legal opinion to the Transfer
Agent if required by the Transfer Agent to effect the issuance of this Warrant, the Exercise Shares or the Failure Payment Shares, as applicable, without a restrictive legend or removal of the legend hereunder. If the Unrestricted Conditions are met
at the time of issuance of this Warrant, the Exercise Shares or the Failure Payment Shares, then such Warrant, Exercise Shares or Failure Payment Shares, as applicable, shall be issued free of all legends. The Company agrees that at such time as the
Unrestricted Conditions are met or such legend is otherwise no longer required under this Section 2(e), it will, no later than three (3) Trading Days following the delivery (the “Unlegended Shares Delivery Deadline”) by the
Holder to the Company or the Transfer Agent of this Warrant and a certificate representing Exercise Shares and/or Failure Payment Shares, as applicable, issued with a restrictive legend (such third Trading Day, the “Legend Removal Date”),
deliver or cause to be delivered to such Holder this Warrant and/or a certificate (or electronic transfer) representing such shares that is free from all restrictive and other legends. 
 (iii) Sale of Unlegended Shares. Holder agrees that the removal of the restrictive legend from this Warrant and any certificates representing securities as set forth in Section 2(e) above is predicated
upon the Company’s reliance that the Holder would only sell, transfer, assign, pledge, hypothecate or otherwise dispose of this Warrant or any Exercise Shares and/or any Failure Payment Shares, as applicable, pursuant to either the registration
requirements of the Securities Act, including any applicable prospectus delivery requirements, or an exemption therefrom, and that if such securities are sold pursuant to a Registration Statement, they will be sold in compliance with the plan of
distribution set forth therein. 
  

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 (f) Cancellation of Warrant. This Warrant shall be canceled upon the full Exercise of this Warrant, and, as
soon as practical after the Date of Exercise, Holder shall be entitled to receive Common Stock for the number of shares purchased upon such Exercise of this Warrant, and if this Warrant is not Exercised in full, Holder shall be entitled to receive a
new Warrant (containing terms identical to this Warrant) representing any unexercised portion of this Warrant in addition to such Common Stock. 
 (g)
Holder of Record. Each person in whose name any Warrant for shares of Common Stock is issued shall, for all purposes, be deemed to be the Holder of record of such shares on the Date of Exercise of this Warrant, irrespective of the date of
delivery of the Common Stock purchased upon the Exercise of this Warrant. Nothing in this Warrant shall be construed as conferring upon Holder any rights as a stockholder of the Company. 
 (h) Delivery of Electronic Shares. In lieu of delivering physical certificates representing the Common Stock issuable upon Exercise or legend removal, or representing Failure Payment Shares, provided the
Transfer Agent is participating in the DTC Fast Automated Securities Transfer (“FAST”) program and provided further that the Holder provides the Transfer Agent with information required in order to issue shares of Common Stock to the
Holder electronically, upon written request of the Holder, the Company shall use its best efforts to cause its Transfer Agent to electronically transmit the Common Stock issuable upon Exercise to the Holder by crediting the account of the
Holder’s prime broker with DTC through its Deposit Withdrawal Agent Commission (DWAC) system. The time periods for delivery and penalties described herein shall apply to the electronic transmittals described herein. Any delivery not effected by
electronic transmission shall be effected by delivery of physical certificates. 
 (i) Buy-In. In addition to any other rights available to the
Holder, if the Company fails to cause its Transfer Agent to transmit to the Holder a certificate or certificates, or electronic shares through DWAC, representing the Exercise Shares pursuant to an Exercise on or before the Delivery Period (other
than a failure caused by any incorrect or incomplete information provided by Holder to the Company hereunder, and if after such date the Holder is required by its broker to purchase (in an open market transaction or otherwise) or the Holder’s
brokerage firm otherwise purchases shares of Common Stock to deliver in satisfaction of a sale by the Holder of the Exercise Shares which the Holder was entitled to receive upon such Exercise (a “Buy-In”), then the Company shall
(1) pay in cash to the Holder the amount by which (x) the Holder’s total purchase price (including brokerage commissions, if any) for the shares of Common Stock so purchased exceeds (y) the amount obtained by multiplying
(A) the number of Exercise Shares that the Company was required to deliver to the Holder in connection with the Exercise at issue times and (B) the price at which the sell order giving rise to such purchase obligation was executed, and
(2) at the option of the Holder, either reinstate the portion of the Warrant and equivalent number of Exercise Shares for which such Exercise was not honored or deliver to the Holder the number of shares of Common Stock that would have been
issued had the Company timely complied with its Exercise and delivery obligations hereunder. For example, if the Holder purchases Common Stock having a total purchase price of $11,000 to cover a Buy-In with respect to an attempted Exercise to cover
the sale of Common Stock with an aggregate sale price giving rise to such purchase obligation of $10,000, under clause (1) of the immediately preceding sentence the Company shall be required to pay the Holder $1,000. The Holder shall provide
the Company written notice indicating the amounts payable to the Holder in respect of the Buy-In, together with applicable confirmations and other evidence reasonably requested by the Company. Nothing herein shall limit a Holder’s right to
pursue any other remedies available to it hereunder, at law or in equity including, without limitation, a decree of specific performance and/or injunctive relief with respect to the Company’s failure to timely deliver certificates representing
shares of Common Stock upon Exercise of the Warrant as required pursuant to the terms hereof. 
 3. Payment of Warrant Exercise Price. 
 (a) Exercise Price. The Exercise Price (“Exercise Price”) shall initially equal $1.41 per share, subject to adjustment pursuant to the terms
hereof, including but not limited to Section 5 below. 
 Payment of the Exercise Price may be made by either of the following, or a combination thereof,
at the election of Holder: 
 (i) Cash Exercise: The Holder may exercise this Warrant in cash, bank or cashier’s check or wire transfer (a
“Cash Exercise”); or 
  

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 (ii) Cashless Exercise: The Holder, at its option, may exercise this Warrant in a cashless exercise transaction.
In order to effect a cashless exercise, the Holder shall surrender this Warrant at the principal office of the Company together with notice of cashless election, in which event the Company shall issue Holder a number of shares of Common Stock
computed using the following formula (a “Cashless Exercise”): 
 X = Y (A-B)/A 
 where:        X = the number of shares of Common Stock to be issued to Holder. 
 Y = the number of shares of Common Stock for which this Warrant is being Exercised. 
 A = the Market Price of one (1) share of Common Stock (for purposes of this Section 3(a)(ii), where “Market Price,” as of any date,
means the Volume Weighted Average Price (as defined herein) of the Company’s Common Stock during the ten (10) consecutive Trading Day period immediately preceding the date in question. 
 B = the Exercise Price. 
 As
used herein, the “Volume Weighted Average Price” for any security as of any date means the volume weighted average sale price on The NASDAQ Global Market (“NASDAQ”) as reported by, or based upon data reported by, Bloomberg
Financial Markets or an equivalent, reliable reporting service mutually acceptable to and hereafter designated by holders of a majority in interest of the Warrants and the Company (“Bloomberg”) or, if NASDAQ is not the principal trading
market for such security, the volume weighted average sale price of such security on the principal securities exchange or trading market where such security is listed or traded as reported by Bloomberg, or, if no volume weighted average sale price
is reported for such security, then the last closing trade price of such security as reported by Bloomberg, or, if no last closing trade price is reported for such security by Bloomberg, the average of the bid prices of any market makers for such
security that are listed in the over the counter market by the Financial Industry Regulatory Authority, Inc. or in the “pink sheets” by the Pink OTC Market, Inc. If the Volume Weighted Average Price cannot be calculated for such security
on such date in the manner provided above, the volume weighted average price shall be the fair market value as mutually determined by the Company and the Holders of a majority in interest of the Warrants being Exercised for which the calculation of
the volume weighted average price is required in order to determine the Exercise Price of such Warrants. 
 For purposes of Rule 144 and sub-section
(d)(3)(ii) thereof, it is intended, understood and acknowledged that the Common Stock issuable upon Exercise of this Warrant in a Cashless Exercise transaction shall be deemed to have been acquired at the time this Warrant was issued. Moreover, it
is intended, understood and acknowledged that the holding period for the Common Stock issuable upon Exercise of this Warrant in a Cashless Exercise transaction shall be deemed to have commenced on the date this Warrant was issued. 
 (iii) Cashless Major Exercise. The Holder may exercise this Warrant in a Cashless Major Exercise pursuant to Section 5(c)(i) below. In order to effect a
Cashless Major Exercise, the Holder shall surrender this Warrant at the principal office of the Company together with the Exercise Form indicating that the Holder is exercising this Warrant (or such portion thereof) pursuant to a Cashless Major
Exercise, in which event the Company shall issue a number of shares of Common Stock equal to the Black-Scholes Value (as defined in Section 5(c)(iii) below) of the Warrant (or such applicable portion being exercised) divided by 95% of the
closing price of the Common Stock on the principal securities exchange or other securities market on which the Common Stock is then traded on the Trading Day immediately preceding the date on which the applicable Major Transaction is consummated.

 (iv) Cashless Default Exercise. The Holder may exercise this Warrant in a Cashless Default Exercise pursuant to Section 11(b)(i) below. In
order to effect a Cashless Default Exercise, the Holder shall surrender this Warrant to the principal office of the Company together with the Exercise Form indicating that the Holder is exercising this Warrant pursuant to a Cashless Default
Exercise, in 

  

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which event the Company shall issue to the Holder, within five (5) Trading Days of the applicable Default Notice, a number of shares of Common Stock
(which shares shall be valued at 95% of the Volume Weighted Average Price for the five (5) Trading Days prior to the applicable Default Notice) equal to the greater of (A) the Black-Scholes value (determined by use of the Black-Scholes
Option Pricing Model using the criteria set forth on Schedule I hereto) of the remaining unexercised portion of this Warrant on the date of such Default Notice and (B) the Black-Scholes value (determined by use of the Black-Scholes Option
Pricing Model using the criteria set forth on Schedule I hereto) of the remaining unexercised portion of this Warrant on the Trading Day immediately preceding the date that the Mandatory Redemption Amount is paid to the Holder. 
 (b) Dispute Resolution. In the case of a dispute as to the determination of the closing price or the Volume Weighted Average Price of the Company’s
Common Stock or the arithmetic calculation of the Exercise Price, Market Price or any Major Transaction Warrant Early Termination Price, the Company shall submit the disputed determinations or arithmetic calculations via facsimile within two
(2) Business Days of receipt, or deemed receipt, of the Exercise Notice or Major Transaction Early Termination Notice, or other event giving rise to such dispute, as the case may be, to the Holder. If the Holder and the Company are unable to
agree upon such determination or calculation within two (2) Business Days of such disputed determination or arithmetic calculation being submitted to the Holder, then the Company shall, within two (2) Business Days submit via facsimile
(i) the disputed determination of the closing price or the Volume Weighted Average Price of the Company’s Common Stock to an independent, reputable investment bank selected by the Company and approved by the Holder, which approval shall
not be unreasonably withheld or (ii) the disputed arithmetic calculation of the Exercise Price, Market Price or any Major Transaction Warrant Early Termination Price to the Company’s independent, outside accountant. The Company shall cause
the investment bank or the accountant, as the case may be, to perform the determinations or calculations and notify the Company and the Holder of the results no later than five (5) Business Days from the time it receives the disputed
determinations or calculations. If the determination or calculation of such investment bank or accountant is equal to the determination or calculation of the Company, then the expenses of the investment bank or accountant shall be borne by the
Holder. Otherwise such expenses shall be borne by the Company. Such investment bank’s or accountant’s determination or calculation, as the case may be, shall be binding upon all parties absent demonstrable error. 
 4. Transfer and Registration. 
 (a) Transfer Rights.
Subject to the provisions of Section 8 of this Warrant, this Warrant may be transferred on the books of the Company, in whole or in part, in person or by attorney, upon surrender of this Warrant properly completed and endorsed. This Warrant
shall be canceled upon such surrender and, as soon as practicable thereafter, the person to whom such transfer is made shall be entitled to receive a new Warrant or Warrants as to the portion of this Warrant transferred, and Holder shall be entitled
to receive a new Warrant as to the portion hereof retained. 
 (b) Registrable Securities. The Common Stock issuable upon the Exercise of this
Warrant has registration rights pursuant to the Registration Rights Agreement. 
 5. Adjustments Upon Certain Events. 
 (a) Participation. The Holder, as the holder of this Warrant, shall be entitled to receive such dividends paid and distributions of any kind made to the
holders of Common Stock of the Company to the same extent as if the Holder had Exercised this Warrant into Common Stock (without regard to any limitations on exercise herein or elsewhere and without regard to whether or not a sufficient number of
shares are authorized and reserved to effect any such exercise and issuance) and had held such shares of Common Stock on the record date for such dividends and distributions. Payments under the preceding sentence shall be made concurrently with the
dividend or distribution to the holders of Common Stock. 
 (b) Recapitalization or Reclassification. If the Company shall at any time effect a
stock split, payment of stock dividend, recapitalization, reclassification or other similar transaction of such character that the shares of Common Stock shall be changed into or become exchangeable for a larger or smaller number of shares, then
upon the effective date thereof, the number of shares of Common Stock which Holder shall be entitled to purchase upon Exercise of this Warrant shall be increased or decreased, as the case may be, in direct proportion to the increase or decrease in
the number of shares of Common Stock by reason of such stock split, payment of stock dividend, recapitalization, reclassification or similar transaction, and the Exercise Price shall be, in the case of an 

  

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increase in the number of shares, proportionally decreased and, in the case of decrease in the number of shares, proportionally increased. The Company shall
give Holder the same notice it provides to holders of Common Stock of any transaction described in this Section 5(b). 
 (c) Rights Upon Major
Transaction. 
 (i) Major Transaction. In the event that a Major Transaction (as defined below) occurs, then (1) in the case of a Cash-Out
Major Transaction and in the case of a Mixed Major Transaction to the extent of the percentage of the cash consideration in the Mixed Major Transaction (determined in accordance with the definition of a Mixed Major Transaction below), the Holder may
require early termination of the Holder’s outstanding Warrants in accordance with Section 5(c)(iii) below and (2) in the case of all other Major Transactions and in the case of a Mixed Major Transaction to the extent of the percentage
of the consideration represented by securities of a Successor Entity in the Mixed Major Transaction, the Holder shall have the right to exercise this Warrant as a Cashless Major Exercise. The Holder may waive its rights under this Section 5(c)
with respect to any Major Transaction. 
 Consummation of each of the following events shall constitute a “Major Transaction”: 
 (A) any (i) merger, reverse merger, reorganization, consolidation, exchange of shares, recapitalization, business combination, or other similar transaction
involving the Company, other than any such transaction in which (1) the holders of the outstanding Common Stock immediately prior to such transaction continue (i) to hold, in the aggregate, shares of Common Stock possessing more than fifty
percent (50%) of the total combined voting power of all outstanding voting securities of the Company or of the surviving entity (or the parent of the surviving entity) immediately after such transaction and (ii) to have the ability to
elect a majority of the Board of Directors of the Company and (2) as a result of which the shares of Common Stock are not exchanged for or changed into the same or a different number of shares of the same or another class or classes of stock or
securities of the Company or another entity; or (ii) sale, transfer, issuance or other disposition of, or the acquisition by any person or group (within the meaning of Section 13(d)(3) of the Exchange Act) of, the beneficial ownership of
fifty percent (50%) or more of the total combined voting power of all outstanding equity securities of the Company or any of its subsidiaries, in a single transaction or series of related transactions (collectively, a “Change of Control
Transaction”); 
 (B) the sale or transfer of assets of the Company, in a single transaction or series of related transactions, to another Person for a
purchase price of more than 50% of the value of the Company’s assets as shown on the most recent financial statements of the Company filed with the SEC; 
 (C) an issuance or series of related issuances by the Company after the date of this Warrant to any person or group of persons acting in concert (regardless of whether such persons constitute a group within the meaning of
Section 13(d)(3) of the Exchange Act), of an aggregate number of shares of Common Stock in excess of 35% of the Company’s outstanding Common Stock immediately prior to the date of such issuance; 
 (D) the liquidation, bankruptcy, insolvency, dissolution or winding-up (or the occurrence of any analogous proceeding) affecting the Company; or 
 (E) the shares of Common Stock cease to be listed, traded or publicly quoted on NASDAQ and are not promptly re-listed or requoted on either the New York Stock Exchange,
the American Stock Exchange, the NASDAQ Global Select Market or the NASDAQ Capital Market. 
 (ii) [Intentionally deleted] 
 (iii) Notice; Major Transaction Early Termination Right; Notice of Cashless Major Exercise. At least thirty (30) days prior to the consummation of any Major
Transaction, but, in any event, within five Business Days following the first to occur of (x) the date of the public announcement of such Major Transaction if such announcement is made before 4:00 p.m., New York City time, or (y) the day
following the public announcement of such Major Transaction if such announcement is made on and after 4:00 p.m., New York City time, the Company shall deliver written notice thereof via facsimile and overnight courier to the Holder (a “Major
Transaction 

  

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Notice”). At any time during the period beginning after the Holder’s receipt of a Major Transaction Notice and ending five (5) Trading Days
prior to the consummation of such Major Transaction (the “Early Termination Period”), the Holder may require an early termination (an “Early Termination Upon Major Transaction”) of all or any portion of this Warrant not eligible
to be treated as a Cashless Major Exercise (without taking into consideration the 9.98% Cap) by delivering written notice thereof (“Major Transaction Early Termination Notice”) to the Company, which Major Transaction Early Termination
Notice shall indicate the portion of the Warrant that the Holder is electing to be subject to an Early Termination Upon Major Transaction. The portion of this Warrant subject to early termination pursuant to this Section 5(c)(iii) (the
“Terminated Portion”), shall be terminated by the Company at a price (the “Major Transaction Warrant Early Termination Price”) payable to the Holder in cash equal to the “Black Scholes Value” of the Terminated Portion
determined by use of the Black Scholes Option Pricing Model using the criteria set forth in Schedule 1 hereto (the “Black Scholes Value”). 
 To the extent the Holder shall elect to effect a Cashless Major Exercise in respect of a Major Transaction, the Holder shall deliver its exercise notice in accordance with Section 3(a)(iii), within the Early Termination Period.

 (iv) Escrow; Payment of Major Transaction Warrant Early Termination Price. Following the receipt of a Major Transaction Early Termination Notice or
a Cashless Major Exercise from the Holder, the Company shall not effect a Major Transaction that is being treated as an early termination or is eligible to be treated as a Cashless Major Exercise unless it either obtains the written agreement of the
Successor Entity that payment of the Major Transaction Warrant Early Termination Price and/or applicable Exercise Shares shall be made to the Holder prior to consummation of such Major Transaction or it shall first place into an escrow account with
an independent escrow agent, at least three (3) Business Days prior to the closing date of the Major Transaction (the “Major Transaction Escrow Deadline”), an amount in shares of Common Stock or cash, as applicable, equal to the Major
Transaction Warrant Early Termination Price and/or applicable Exercise Shares. Concurrently upon closing of such Major Transaction, the Company shall pay or shall instruct the escrow agent to pay the Major Transaction Warrant Early Termination Price
and/or applicable Exercise Shares to the Holder. For purposes of determining the amount required to be placed in escrow pursuant to the provisions of this subsection (iv) and without affecting the amount of the actual Major Transaction Warrant
Early Termination Price and/or applicable Exercise Shares, the calculation of the price referred to in clause (1) of the first column of Schedule 1 hereto with respect to Stock Price shall be determined based on the Closing Market Price
(as defined on Schedule I) of the Common Stock on the Trading Day immediately preceding the date that the funds and/or applicable Exercise Shares, as applicable, are deposited with the escrow agent. 
 (v) Injunction. Following the receipt of a Major Transaction Early Termination Notice or notice of a Cashless Major Exercise from the Holder, in the event that
the Company attempts to consummate a Major Transaction without either placing the Major Transaction Warrant Early Termination Price or applicable Exercise Shares, as applicable, in escrow in accordance with subsection (iv) above or obtaining
the written agreement of the Successor Entity that payment of the Major Transaction Warrant Early Termination Price or issuance of the applicable Exercise Shares, as applicable, will be made to the Holder prior to consummation of such Major
Transaction, the Holder shall have the right to apply for an injunction in any state or federal courts sitting in the City of New York, borough of Manhattan to prevent the closing of such Major Transaction until the Major Transaction Warrant Early
Termination Price is paid to the Holder, in full or the applicable Exercise Shares are delivered, as applicable. 
 An early termination required by this
Section 5(c) shall be made in accordance with the provisions of Section 12 and shall have priority to payments to holders of Common Stock in connection with a Major Transaction except to the extent that a court of competent jurisdiction
determines that the Holder would be deemed to be a creditor of the Company, in which case the Holder shall be treated on a pari passu basis with the holders of Common Stock. Further, for the avoidance of doubt, the Holder shall not have rights
senior to the Company’s common shareholders in any U.S. bankruptcy proceedings of the Company, provided that nothing herein shall limit or shall be deemed to limit Holder’s right to pursue remedies in the event of a breach by Company of
its obligations and agreements with respect to the Warrant; provided, further, that nothing herein shall limit or shall be deemed to limit Holder’s rights in respect of any transactions other than the Warrant. To the extent an early termination
required by this Section 5(c)(iii) are deemed or determined by a court of competent jurisdiction to be prepayments of the Warrant by the Company, such early termination shall be deemed to be voluntary prepayments. Notwithstanding anything to
the contrary in this Section 5, until the Major Transaction Warrant Early Termination Price is paid in full, this Warrant may be exercised, in whole or in part, by the Holder into shares of 

  

 8 

 
Common Stock, or in the event the Exercise Date is after the consummation of the Major Transaction, shares of publicly traded common stock (or their
equivalent) of the Successor Entity pursuant to Section 5(c). The parties hereto agree that in the event of the Company’s early termination of any portion of the Warrant under this Section 5(c), the Holder’s damages would be
uncertain and difficult to estimate because of the parties’ inability to predict future interest rates and the uncertainty of the availability of a suitable substitute investment opportunity for the Holder. Accordingly, any premium due under
this Section 5(c) is intended by the parties to be, and shall be deemed, a reasonable estimate of the Holder’s actual loss of its investment opportunity and not as a penalty. 
 For purposes hereof: 
 “Cash-Out Major Transaction” means a Major Transaction in which the consideration payable
to holders of Common Stock in connection with the Major Transaction consists solely of cash. 
 “Cashless Default Exercise” shall mean an exercise
of this Warrant as a “Cashless Default Exercise” in accordance with Section 3(a)(iv) and 11(b) hereof. “Cashless Major Exercise” shall mean an exercise of this Warrant or portion thereof as a “Cashless Major
Exercise” in accordance with Section 3(a)(iii) and 5(c)(i) hereof. 
 “Eligible Market” means the over the counter Bulletin Board, the
New York Stock Exchange, Inc., the NYSE Arca, the NASDAQ Capital Market, the NASDAQ Global Market, the NASDAQ Global Select Market or the American Stock Exchange. 
 “Mixed Major Transaction” means a Major Transaction in which the consideration payable to holders of Common Stock consists partially of cash and partially of securities of a Successor Entity. If the Successor Entity is a Publicly
Traded Successor Entity, the percentage of consideration represented by securities of such Successor Entity shall be equal to the percentage that the value of the aggregate anticipated number of shares of the Publicly Traded Successor Entity to be
issued to holders of Common Stock of the Company represents in comparison to the aggregate value of all consideration, including cash consideration, in such Mixed Major Transaction, as such values are set forth in any definitive agreement for the
Mixed Major Transaction that has been executed at the time of the first public announcement of the Major Transaction or, if no such value is determinable from such definitive agreement, based on the closing market price for shares of the Publicly
Traded Successor Entity on its principal securities exchange on the Trading Day preceding the first public announcement of the Mixed Major Transaction. If the Successor Entity is a Private Successor Entity, the percentage of consideration
represented by securities of such Successor Entity shall be determined in good-faith by the Company’s Board of Directors 
 “Parent Entity” of
a Person means an entity that, directly or indirectly, controls the applicable Person and whose common stock or equivalent equity security is quoted or listed on an Eligible Market, or, if there is more than one such Person or Parent Entity, the
Person or Parent Entity with the largest public market capitalization as of the date of consummation of a Major Transaction. 
 “Person” means an
individual, a limited liability company, a partnership, a joint venture, a corporation, a trust, an unincorporated organization, any other entity and a government or any department or agency thereof. 
 “Private Successor Entity” means a Successor Entity that is not a Publicly Traded Successor Entity. 
 “Publicly Traded Successor Entity” means a Successor Entity that is a publicly traded corporation whose common stock is quoted on or listed for trading on an
Eligible Market (as defined above). 
 “Successor Entity” means any Person purchasing the Company’s assets or Common Stock, or any successor
entity resulting from such Major Transaction, or if the Warrant is to be exercisable for shares of capital stock of its Parent Entity (as defined above), its Parent Entity. 
  

 9 

 (d) Exercise Price Adjusted. As used in this Warrant, the term “Exercise Price” shall mean the
purchase price per share specified in Section 3(a) of this Warrant, until the occurrence of an event stated in this Section 5 or otherwise set forth in this Warrant, and thereafter shall mean said price as adjusted from time to time in
accordance with the provisions of said subsection. No adjustment made pursuant to any provision of this Section 5 shall have the net effect of increasing or decreasing the Exercise Price in relation to the split adjusted and distribution
adjusted price of the Common Stock. 
 (e) Adjustments: Additional Shares, Securities or Assets. In the event that at any time, as a result of
an adjustment made pursuant to this Section 5 or otherwise, Holder shall, upon Exercise of this Warrant, become entitled to receive shares and/or other securities or assets (other than Common Stock) then, wherever appropriate, all references
herein to shares of Common Stock shall be deemed to refer to and include such shares and/or other securities or assets; and thereafter the number of such shares and/or other securities or assets shall be subject to adjustment from time to time in a
manner and upon terms as nearly equivalent as practicable to the provisions of this Section 5. 
 (f) Notice of Adjustments. Whenever the
Exercise Price is adjusted pursuant to the terms of this Warrant, the Company shall promptly mail to the Holder a notice (an “Exercise Price Adjustment Notice”) setting forth the Exercise Price after such adjustment and setting forth a
statement of the facts requiring such adjustment. The Company shall, upon the written request at any time of the Holder, furnish to such Holder a like Warrant setting forth (i) such adjustment or readjustment, (ii) the Exercise Price at
the time in effect and (iii) the number of shares of Common Stock and the amount, if any, of other securities or property which at the time would be received upon Exercise of the Warrant. For purposes of clarification, whether or not the
Company provides an Exercise Price Adjustment Notice pursuant to this Section 5(f), upon the occurrence of any event that leads to an adjustment of the Exercise Price, the Holder would be entitled to receive a number of Exercise Shares based
upon the new Exercise Price, as adjusted, for exercises occurring on or after the date of such adjustment, regardless of whether the Holder accurately refers to the adjusted Exercise Price in the Exercise Form. 
 6. Fractional Interests. 
 No fractional shares or scrip representing
fractional shares shall be issuable upon the Exercise of this Warrant, but on Exercise of this Warrant, Holder may purchase only a whole number of shares of Common Stock. If, on Exercise of this Warrant, Holder would be entitled to a fractional
share of Common Stock or a right to acquire a fractional share of Common Stock, such fractional share shall be disregarded and the number of shares of Common Stock issuable upon Exercise shall be the next higher whole number of shares. 

7. Reservation of Shares. 
 From and after the date hereof, the
Company shall at all times reserve for issuance such number of authorized and unissued shares of Common Stock (or other securities substituted therefor as herein above provided) as shall be sufficient for the Exercise of this Warrant and payment of
the Exercise Price. If at any time the number of shares of Common Stock authorized and reserved for issuance is below the number of shares sufficient for the Exercise of this Warrant (a “Share Authorization Failure”) (based on the Exercise
Price in effect from time to time), the Company will promptly take all corporate action necessary to authorize and reserve a sufficient number of shares, including, without limitation, calling a special meeting of stockholders to authorize
additional shares to meet the Company’s obligations under this Section 7, in the case of an insufficient number of authorized shares, and using its best efforts to obtain stockholder approval of an increase in such authorized number of
shares. The Company covenants and agrees that upon the Exercise of this Warrant, all shares of Common Stock issuable upon such Exercise shall be duly and validly issued, fully paid and nonassessable and not subject to preemptive rights, rights of
first refusal or similar rights of any Person. 
 8. Restrictions on Transfer. 
 (a) Registration or Exemption Required. Assuming the accuracy of the representations and warranties of the Holder contained in the Facility Agreement, this Warrant has been issued in a transaction exempt
from the registration requirements of the Securities Act by virtue of Regulation D and exempt from state registration or qualification under applicable state laws. None of the Warrant, the Exercise Shares or Failure Payment Shares may be pledged,
transferred, sold or assigned except pursuant to an effective registration statement or an exemption to the registration requirements of the Securities Act and applicable state laws including, without limitation, a so-called “4(1) and a
half” transaction. 
  

 10 

 (b) Assignment. Subject to Section 8(a), the Holder may sell, transfer, assign, pledge, or otherwise
dispose of this Warrant, in whole or in part, provided that no such sale, transfer, assignment, pledge, or hypothecation of this Warrant shall be in an amount representing less than the lesser of (a) 250,000 shares of Common Stock and
(b) the remaining shares of Common Stock issuable under this Warrant. Holder shall deliver a written notice to Company, substantially in the form of the Assignment attached hereto as Exhibit B, indicating the Person or Persons to
whom the Warrant shall be assigned and the respective number of warrants to be assigned to each assignee. The Company shall effect the assignment within three (3) Business Days of its receipt of a properly completed and executed form of
Assignment and, if required by this Warrant, receipt by the Company of an opinion of counsel (the “Transfer Delivery Period”), and shall deliver to the assignee(s) designated by Holder a Warrant or Warrants of like tenor and terms for the
appropriate number of shares. This Warrant and the rights evidenced hereby shall inure to the benefit of and be binding upon the successors and assigns of the Holder. The provisions of this Warrant are intended to be for the benefit of all Holders
from time to time of this Warrant, and shall be enforceable by any such Holder. For avoidance of doubt, in the event Holder notifies the Company that such sale or transfer is a so called “4(1) and half” transaction, the parties hereto
agree that a legal opinion from outside counsel for the Holder delivered to counsel for the Company substantially in the form attached hereto as Exhibit C shall be the only requirement to satisfy an exemption from registration under the
Securities Act to effectuate such “4(1) and half” transaction. 
 9. Noncircumvention. 
 The Company hereby covenants and agrees that the Company will not, by amendment of its certificate of incorporation, bylaws or through any reorganization, transfer of
assets, consolidation, merger, scheme of arrangement, dissolution, issue or sale of securities, or any other voluntary action, avoid or seek to avoid the observance or performance of any of the terms of this Warrant, and will at all times in good
faith carry out all the provisions of this Warrant and take all action as may be reasonably required to protect the rights of the Holder. Without limiting the generality of the foregoing, the Company (i) shall not increase the par value of any
shares of Common Stock receivable upon the exercise of this Warrant above the Exercise Price then in effect, and (ii) shall take all such actions as may be necessary or appropriate in order that the Company may validly and legally issue fully
paid and nonassessable shares of Common Stock upon the exercise of this Warrant. 
 10. Events of Failure; Definition of Black Scholes Value.

 (a) Definition. 
 The occurrence of each of the
following shall be considered to be an “Event of Failure.” 
 (i) A Delivery Failure occurs, where a “Delivery Failure”
shall be deemed to have occurred if the Company fails to use its best efforts to deliver Exercise Shares to the Holder within any applicable Delivery Period (other than due to the limitation contained in the proviso in the second paragraph of
Section 1); 
 (ii) A Legend Removal Failure occurs, where a “Legend Removal Failure” shall be deemed to have occurred if the
Company fails to use its best efforts to issue this Warrant and/or Exercise Shares without a restrictive legend, or fails to use it best efforts to remove a restrictive legend, when and as required under Section 2(e) hereof; 
 (iii) a Transfer Delivery Failure occurs, where a “Transfer Delivery Failure” shall be deemed to have occurred if the Company fails to use its
best efforts to deliver a Warrant within any applicable Transfer Delivery Period; and 
 (iv) a Registration Failure (as defined below).

 For purpose hereof, “Registration Failure” means that (A) the Company fails to file with the SEC on or before the Filing Deadline (as
defined in the Registration Rights Agreement) any Registration Statement required to be filed pursuant to Section 2(a) of the Registration Rights Agreement, (B) the Company fails to use its reasonable best efforts to obtain effectiveness
with the SEC, prior to the Registration Deadline (as defined in the Registration Rights Agreement), and if such Registration Statement is not so filed prior to the Registration Deadline, as soon as possible thereafter, of any Registration Statement
(as defined in the Registration Rights 

  

 11 

 
Agreement) that are required to be filed pursuant to Section 2(a) of the Registration Rights Agreement, or fails to use reasonable best efforts to keep
such Registration Statement current and effective as required in Section 3 of the Registration Rights Agreement (subject to the Company’s right to delay or suspend effectiveness pursuant to Section 3(q) of the Registration Rights
Agreement), (C) the Company fails to file any additional Registration Statement required to be filed pursuant to Section 2(a)(ii) of the Registration Rights Agreement on or before the Additional Filing Deadline, or fails to use its best
efforts to cause such new Registration Statement to become effective on or before the Additional Registration Deadline, and, if such effectiveness does not occur within such period, as soon as possible thereafter, (D) any Registration Statement
required to be filed under the Registration Rights Agreement, after its initial effectiveness and during the Registration Period (as defined in the Registration Rights Agreement), lapses in effect or sales of all of the Registrable Securities (as
defined in the Registration Rights Agreement) cannot otherwise be made thereunder (whether by reason of the Company’s failure to amend or supplement the prospectus included therein in accordance with the Registration Rights Agreement, the
Company’s failure to file and, subject to Section 3(q) of the Registration Rights Agreement use reasonable best efforts to obtain effectiveness with the SEC of an additional Registration Statement or amended Registration Statement required
pursuant to Section 2(a)(ii) or Section 3(b) of the Registration Rights Agreement, as applicable, or otherwise), provided that in no case shall a Registration Failure be deemed to have occurred or be continuing after the Registration
Period (as defined in the Registration Rights Agreement) or, to the extent such Registration Failure results from a breach by the Holder of its obligations pursuant to Section 4 of the Registration Rights Agreement, and (E) the Company
fails to provide a commercially reasonable written response to any comments to any Registration Statement submitted by the SEC within twenty (20) days after the date that such SEC comments are received by the Company. 
 (b) Failure Payments; Black-Scholes Determination. The Company understands that any Event of Failure (as defined above) could result in economic loss to the
Holder. In the event that any Event of Failure occurs (other than an Event of Failure caused by the submission of any incomplete or inaccurate information required to be furnished by the Holder), as compensation to the Holder for such loss, the
Company agrees to pay (as liquidated damages and not as a penalty) to the Holder, at the Company’s option, an amount payable (i) in cash or (ii) in shares of Common Stock that are valued for these purposes at 95% of the Volume
Weighted Average Price on the date of such calculation (“Failure Payments”), in each case equal to 18% per annum (or the maximum rate permitted by applicable law, whichever is less) of the Black-Scholes value (as determined below) of
the remaining unexercised portion of this Warrant on the date of such Event of Failure (as recalculated on the first Business Day of each month thereafter for as long as Failure Payments shall continue to accrue), which shall accrue daily from the
date of such Event of Failure until the Event of Failure is cured, accruing daily and compounded monthly, provided, however, the Holder shall only receive up to such amount of shares of Common Stock in respect of Failure Payments such that Holder
and any other persons or entities whose beneficial ownership of Common Stock would be aggregated with the Holder’s for purposes of Section 13(d) of the Exchange Act (including shares held by any “group” of which the Holder is a
member, but excluding shares beneficially owned by virtue of the ownership of securities or rights to acquire securities that have limitations on the right to convert, exercise or purchase similar to the limitation set forth herein) shall not
collectively beneficially own greater than 9.98% of the total number of shares of Common Stock of the Company then issued and outstanding and provided further, that the foregoing proviso shall not be construed to require any cash payment of the
remaining Failure Payments. For purposes of clarification, it is agreed and understood that Failure Payments shall continue to accrue following any Event of Default until the applicable Default Amount is paid in full. 
 Notwithstanding the above, in the event that the Company (i) has, by the Filing Deadline (as defined the Registration Rights Agreement) filed a Registration
Statement (as defined in the Registration Rights Agreement) covering the number of shares required by the Registration Rights Agreement, and (ii) has responded in writing to any comments to the Registration Statement that the Company has
received from the SEC, within seven (7) Business Days of such receipt, and nevertheless the SEC has not declared effective a Registration Statement covering the full number of Warrant Shares issuable upon exercise of the Warrants by the
Registration Deadline (as defined in the Registration Rights Agreement) then, the Failure Payments attributable to such late Registration Effectiveness shall be reduced from 18% to 15% (calculated as set forth above). The Company shall satisfy any
Failure Payments under this Section pursuant to Section 10(c) below. Failure Payments are in addition to any Shares that the Holder is entitled to receive upon Exercise of this Warrant. 
 For purposes hereof, the “Black-Scholes” value of a Warrant shall be determined by use of the Black Scholes Option Pricing Model using the criteria set forth
on Schedule 1 hereto. 
  

 12 

 (c) Payment of Accrued Failure Payments. The Failure Payment Shares representing accrued Failure Payments for each
Event of Failure shall be issued and delivered on or before the fifth (5th) Business Day of each month following a month in which Failure Payments accrued. Nothing herein shall limit the Holder’s right to pursue actual damages (to the
extent in excess of the Failure Payments) for the Company’s Event of Failure, and the Holder shall have the right to pursue all remedies available at law or in equity (including a decree of specific performance and/or injunctive relief).
Notwithstanding the above, if a particular Event of Failure results in an Event of Default pursuant to Section 11 hereof, then the Failure Payment, for that Event of Failure only, shall be considered to have been satisfied upon payment to the
Holder of an amount equal to the greater of (i) the Failure Payment, or (ii) the Default Amount, payable in accordance with Section 11. 
 (d) Maximum Interest Rate. Nothing contained herein or in any document referred to herein or delivered in connection herewith shall be deemed to establish or require the payment of a rate of interest or other charges in excess of the
maximum permitted by applicable law. In the event that the rate of interest or dividends required to be paid or other charges hereunder exceed the maximum permitted by such law, any payments in excess of such maximum shall be credited against
amounts owed by the Company to the Holder and thus refunded to the Company. 
 11. Default. 
 (a) Events Of Default. Each of the following events shall be considered to be an “Event of Default,” unless waived by the Holder: 
 (i) Failure To Effect Registration. With respect to all Registration Failures, a Registration Failure occurs and remains uncured for a period of more than thirty
(30) days (or forty-five (45) days in the case where the Company (i) has, by the Filing Deadline (as defined the Registration Rights Agreement) filed a Registration Statement (as defined in the Registration Rights Agreement) covering
this Warrant and the number of shares required by the Registration Rights Agreement, and (ii) has responded in writing to any comments to the Registration Statement that the Company has received from the SEC, within seven (7) Business Days
of such receipt, and nevertheless the SEC has not declared effective a Registration Statement covering the this Warrant and the Shares by the Registration Deadline (as defined in the Registration Rights Agreement)), and such Registration
Failure relates solely to the Company’s failure to have the Registration Statement declared effective by the Registration Deadline (as defined in the Registration Rights Agreement) and with respect to a Registration Failure provided in clause
(E) of the definition of “Registration Failure”, such Registration Failure occurs and remains uncured for a period of more than thirty (30) days; provided, however, that in no event shall a Registration Failure be deemed to have
occurred or be continuing after the expiration of the Registration Period (as defined in the Registration Rights Agreement) or to the extent such failure results from a breach by Holder of its obligations to Section 4 of the Registration Rights
Agreement. 
 (ii) Failure To Deliver Common Stock. Other than as provided in Section 11(a)(iv)(C) below, a Delivery Failure (as defined above)
occurs and remains uncured for a period of more than twenty (20) days; or at any time, the Company announces or states in writing that it will not honor its obligations to issue shares of Common Stock to the Holder upon Exercise by the Holder
of the Exercise rights of the Holder in accordance with the terms of this Warrant. 
 (iii) Legend Removal Failure. A Legend Removal Failure (as
defined above) occurs and remains uncured for a period of twenty (20) days; and 
 (iv) Corporate Existence; Major Transaction. (A) The
Company has effected a Major Transaction without paying the Major Transaction Warrant Early Termination Price, if applicable, to the Holder pursuant to Section 5(c)(iii), or (B) a Delivery Failure has occurred with respect to the Exercise
Shares issuable upon exercise by the Holder of a Cashless Major Exercise. 
 (b) Mandatory Early Termination. 
 (i) Mandatory Early Termination Amount; Cashless Default Exercise. If any Events of Default shall occur then, unless waived by the Holder, upon the occurrence and
during the continuation of any Event of Default, at the option of the Holder, such option exercisable through the delivery of written notice to the Company by such Holder (the “Default Notice”), the Company shall have the right to
terminate the outstanding amount of this Warrant and pay to the Holder (a “Mandatory Early Termination”), in full satisfaction of its obligations hereunder by delivery of a notice to such effect to the Holder within two (2) Business
Days following receipt of the 

  

 13 

 
Default Notice, an amount payable in cash (the “Mandatory Early Termination Amount” or the “Default Amount”) equal to the greater of
(i) the Black-Scholes value (as determined in accordance with Section 10(b)) of the remaining unexercised portion of this Warrant on the date of such Default Notice and (2) the Black-Scholes value (also as determined in accordance
with Section 10(b)) of the remaining unexercised portion of this Warrant on the Trading Day immediately preceding the date that the Mandatory Early Termination Amount is paid to the Holder. In the event the Company does not exercise its right
to consummate a Mandatory Early Termination, then the Holder shall have the right to exercise this Warrant pursuant to a Cashless Default Exercise in accordance with Section 3(a)(iv) above. 
 The Mandatory Early Termination Amount shall be payable within five (5) Business Days following the date of the applicable Default Notice. 
 (ii) Liquidated Damages. The parties hereto acknowledge and agree that the sums payable as Failure Payments or pursuant to a Mandatory Early Termination shall
give rise to liquidated damages and not penalties. The parties further acknowledge that (i) the amount of loss or damages likely to be incurred by the Holder is incapable or is difficult to precisely estimate, (ii) the amounts specified
bear a reasonable proportion and are not plainly or grossly disproportionate to the probable loss likely to be incurred by the Holder, and (iii) the parties are sophisticated business parties and have been represented by sophisticated and able
legal and financial counsel and negotiated this Agreement at arm’s length. 
 The Default Amount, together with all other amounts payable hereunder,
shall immediately become due and payable, all without demand, presentment or notice, all of which hereby are expressly waived, together with all costs, including, without limitation, legal fees and expenses, of collection, and the Holder shall be
entitled to exercise all other rights and remedies available at law or in equity. 
 (c) Posting Of Bond. In the event that any Event of
Default occurs hereunder, the Company may not raise as a legal defense (in any Lawsuit, as defined below, or otherwise) or justification to such Event of Default any claim that such Holder or any one associated or affiliated with such Holder has
been engaged in any violation of law, unless the Company has posted a surety bond (a “Surety Bond”) for the benefit of such Holder in the amount of 130% of the aggregate Surety Bond Value (as defined below) of all of the Holder’s
Warrants (the “Bond Amount”), which Surety Bond shall remain in effect until the completion of litigation of the dispute and the proceeds of which shall be payable to such Holder to the extent Holder obtains judgment. For clarity, it is
acknowledged by the Holder and the Company that the Surety Bond shall not be deemed to collateralize the Company’s obligations under this Warrant. 
 For purposes hereof, a “Lawsuit” shall mean any lawsuit, arbitration or other dispute resolution filed by either party herein pertaining to any of this Warrant, the Facility Agreement and the Registration Rights Agreement.

 “Surety Bond Value,” for the Warrants shall mean 130% of the of the Black-Scholes value of the remaining unexercised portion of this Warrant on
the Trading Day immediately preceding the date that such bond goes into effect). 
 (d) Injunction And Posting Of Bond. In the event that the
Event of Default referred to in subsection (c) above pertains to the Company’s failure to deliver unlegended shares of Common Stock to the Holder pursuant to a Warrant Exercise, legend removal request, or otherwise, the Company may not
refuse such unlegended share delivery based on any claim that such Holder or any one associated or affiliated with such Holder has been engaged in any violation of law, unless an injunction from a court, on prior notice to Holder, restraining and or
enjoining Exercise of all or part of said Warrant shall have been sought and obtained by the Company and the Company has posted a Surety Bond for the benefit of such Holder in the amount of the Bond Amount, which Surety Bond shall remain in effect
until the completion of litigation of the dispute and the proceeds of which shall be payable to such Holder to the extent Holder obtains judgment. 
 (e) Remedies, Other Obligations, Breaches And Injunctive Relief. The remedies provided in this Warrant shall be cumulative and in addition to all other remedies available under this Warrant, the Facility Agreement and the
Registration Rights Agreement, at law or in equity (including a decree of specific performance and/or other injunctive relief), and nothing herein shall limit the right of the Holder to pursue actual damages for any failure by the Company to comply
with the terms of this Warrant. The Company acknowledges that a breach by it of its obligations hereunder will cause irreparable harm to the Holder and that the remedy at law for 

  

 14 

 
any such breach may be inadequate. The Company therefore agrees that, in the event of any such breach or threatened breach, the holder of this Warrant shall
be entitled, in addition to all other available remedies, to an injunction restraining any breach, without the necessity of showing economic loss and without any bond or other security being required. 
 12. Holder’s Early Terminations. 
 (a) Mechanics of
Holder’s Early Terminations. In the event that the Holder has sent a Default Notice or a Major Transaction Early Termination Notice to the Company pursuant to Section 5(c) or a Default Notice pursuant to Section 11(b)(i),
respectively (each, an “Early Termination Notice”), the Holder shall promptly submit this Warrant to the Company. If the Holder has submitted a Major Transaction Early Termination Notice in accordance with Section 5(c)(iii), the
Company shall deliver the applicable Major Transaction Warrant Early Termination Price to the Holder concurrently with the consummation of such Major Transaction. In the event that the Company does not pay the applicable Major Transaction Warrant
Early Termination Price to the Holder within the time period required, at any time thereafter and until the Company pays such unpaid Major Transaction Warrant Early Termination Price in full, the Holder shall have the option, in lieu of early
termination, to require the Company to promptly return to the Holder all or any portion of this Warrant that was submitted for early termination and for which the applicable Major Transaction Warrant Early Termination Price (together with any late
charges thereon) has not been paid. Upon the Company’s receipt of such notice, (x) the applicable Early Termination Notice shall be null and void with respect to such applicable portion of this Warrant, (y) the Company shall
immediately return this Warrant, or issue a new Warrant to the Holder representing the portion of this Warrant that was submitted for early termination and (z) the Exercise Price of this Warrant or such new Warrant shall be adjusted to the
lesser of (A) the Exercise Price as in effect on the date on which the applicable Early Termination Notice is voided and (B) the lowest closing price for the Common Stock on NASDAQ, or, if NASDAQ is not the principal trading market for the
Common Stock, the principal securities exchange or other securities market on which the Common Stock is then being traded, during the period beginning on and including the date on which the applicable Early Termination Notice is delivered to the
Company and ending on and including the date on which the applicable Early Termination Notice is voided. The Holder’s delivery of a notice voiding a Early Termination Notice and exercise of its rights following such notice shall not affect the
Company’s obligations to make any payments of Failure Payments which have accrued prior to the date of such notice with respect to the Warrant subject to such notice. 
 13. Benefits of this Warrant. 
 Nothing in this Warrant shall be construed to confer upon any person other than the
Company and Holder any legal or equitable right, remedy or claim under this Warrant and this Warrant shall be for the sole and exclusive benefit of the Company and Holder. 
 14. Governing Law. 
 All questions concerning the construction, validity, enforcement and interpretation of this
Agreement shall be governed by and construed and enforced in accordance with the internal laws of the State of New York, without regard to the principles of conflicts of law thereof. Each party agrees that all legal proceedings concerning the
interpretations, enforcement and defense of the transactions contemplated by this Agreement (whether brought against a party hereto or its respective affiliates, directors, officers, shareholders, employees or agents) shall be commenced exclusively
in the state and federal courts sitting in the City of New York. Each party hereby irrevocably submits to the exclusive jurisdiction of the state and federal courts sitting in the City of New York, borough of Manhattan for the adjudication of any
dispute hereunder or in connection herewith or with any transaction contemplated hereby or discussed herein, and hereby irrevocably waives, and agrees not to assert in any suit, action or proceeding, any claim that it is not personally subject to
the jurisdiction of any such court, that such suit, action or proceeding is improper or is an inconvenient venue for such proceeding. Each party hereby irrevocably waives personal service of process and consents to process being served in any such
suit, action or proceeding by mailing a copy thereof via registered or certified mail or overnight delivery (with evidence of delivery) to such party at the address in effect for notices to it under this Agreement and agrees that such service shall
constitute good and sufficient service of process and notice thereof. Nothing contained herein shall be deemed to limit in any way any right to serve process in any other manner permitted by law. The parties hereby waive all rights to a trial by
jury. If either party shall commence an action or proceeding to enforce any provisions of this Agreement, then the prevailing party in such action or proceeding shall be reimbursed by the other party for its reasonable attorneys’ fees and other
costs and expenses incurred with the investigation, preparation and prosecution of such action or proceeding. 
  

 15 

 15. Loss of Warrant. 
 Upon receipt by the Company of evidence of the loss, theft, destruction or mutilation of this Warrant, and (in the case of loss, theft or destruction) of indemnity or security reasonably satisfactory to the Company, and upon surrender and
cancellation of this Warrant, if mutilated, the Company shall execute and deliver a new Warrant of like tenor and date. 
 16. Notice or Demands.

 Notices or demands pursuant to this Warrant to be given or made by Holder to or on the Company shall be sufficiently given or made if sent by certified or
registered mail, return receipt requested, postage prepaid, and addressed, until another address is designated in writing by the Company, to the address set forth in Section 2(a) above. Notices or demands pursuant to this Warrant to be given or
made by the Company to or on Holder shall be sufficiently given or made if sent by certified or registered mail, return receipt requested, postage prepaid, and addressed, to the address of Holder set forth in the Company’s records, until
another address is designated in writing by Holder. 
  

 16 

 IN WITNESS WHEREOF, the undersigned has executed this Warrant as of the date first written above. 
  

			
	ISTA PHARMACEUTICALS, INC.
		
	By:	 	 
		 	Name: Vicente Anido, Jr., Ph.D.
		 	Title:    President and Chief Executive Officer

 A 
 EXERCISE FORM FOR WARRANT 
 TO: ISTA PHARMACEUTICALS, INC. 
 CHECK THE APPLICABLE BOX: 
  

	 ̈	Cash Exercise or Cashless Exercise 

 The
undersigned hereby irrevocably exercises the attached warrant (the “Warrant”) with respect to shares of Common Stock (the “Common Stock”) of ISTA PHARMACEUTICALS, INC., a Delaware corporation (the “Company”), and, if
pursuant to a Cashless Exercise, herewith makes payment of the Exercise Price with respect to such shares in full, all in accordance with the conditions and provisions of said Warrant. 
  

	 ̈	Cashless Major Exercise 

 The undersigned
hereby irrevocably exercises the Warrant with respect to         % of the Warrant currently outstanding pursuant to a Cashless Major Exercise in accordance with the terms of the Warrant. 
  

	 ̈	Cashless Default Exercise 

 The undersigned
hereby irrevocably exercises the Warrant pursuant to a Cashless Default Exercise, in accordance with the terms of the Warrant. 
 1. The undersigned agrees
not to offer, sell, transfer, assign, pledge, hypothecate or otherwise dispose of any of the Common Stock obtained on Exercise of the Warrant, except in accordance with the provisions of Section 8(a) of the Warrant. 
 2. The number of shares of Common Stock beneficially owned by the Holder and its Affiliates (as defined in the Warrant) and any other persons or entities whose
beneficial ownership of Common Stock would be aggregated with the Holder’s for purposes of Section 13(d) of the Securities Exchange Act of 1934 (the “Exchange Act”) (including shares held by any “group” of which the
Holder is a member, but excluding shares beneficially owned by virtue of the ownership of securities or rights to acquire securities that have limitations on the right to convert, exercise or purchase similar to the limitation set forth herein) is
                    . For purposes hereof, “group” has the meaning set forth in Section 13(d) of the Exchange Act and
applicable regulations of the Securities and Exchange Commission, and the number of shares beneficially owned has been determined in a manner consistent with Section 13(d) of the Exchange Act and the rules and regulations promulgated
thereunder. 
 3. The undersigned requests that any stock certificates for such shares be issued free of any restrictive legend, if appropriate, and a
warrant representing any unexercised portion hereof be issued, pursuant to the Warrant in the name of the undersigned and delivered to the undersigned at the address set forth below. 
 4. Capitalized terms used but not otherwise defined in this Exercise Form shall have the meaning ascribed thereto in the Warrant. 
 Dated:                      
   
  
 Signature 
   
  
 Print Name 
   
  
 Address 
 NOTICE 
 The signature to the foregoing Exercise Form must correspond to the name as written upon the face of the attached Warrant in every particular, without alteration or
enlargement or any change whatsoever. 

 B 
 ASSIGNMENT 
 (To be executed by the registered holder 
 desiring to transfer the Warrant) 
 FOR VALUE RECEIVED, the undersigned holder of the attached warrant
(the “Warrant”) hereby sells, assigns and transfers unto the person or persons below named the right to purchase
                     shares of the Common Stock of ISTA PHARMACEUTICALS, INC., a Delaware corporation, evidenced by the attached
Warrant and does hereby irrevocably constitute and appoint                      attorney to transfer the said Warrant on the books of the
Company, with full power of substitution in the premises. 
  

					
			
	Dated:                     	 		 	  
		 		 	Signature

 Fill in for new registration of Warrant: 
  

	
	
	  
	Name
	
	  
	Address
	
	  
	Please print name and address of assignee
	(including zip code number)

 NOTICE 
 The signature
to the foregoing Assignment must correspond to the name as written upon the face of the attached Warrant in every particular, without alteration or enlargement or any change whatsoever. 

 C 
 FORM OF OPINION 
                     , 20__ 
 [                        ] 
  

	Re:	ISTA Pharmaceuticals, Inc. (the “Company”) 

 Dear Sir:

 [                    ]
(“[                    ]”) intends to transfer
                 Warrants (the “Warrants”) of the Company to
                     (“                ”)
without registration under the Securities Act of 1933, as amended (the “Securities Act”). In connection therewith, we have examined and relied upon the truth of representations contained in an Investor Representation Letter attached hereto
and have examined such other documents and issues of law as we have deemed relevant. 
 Based on and subject to the foregoing, we are of the opinion that the
transfer of the Warrants by                      to
                     may be effected without registration under the Securities Act, provided, however, that the Warrants to be transferred to
                     contain a legend restricting its transferability pursuant to the Securities Act and that transfer of the Warrants is
subject to a stop order. 
 The foregoing opinion is furnished only to
                     and may not be used, circulated, quoted or otherwise referred to or relied upon by you for any purposes other than the
purpose for which furnished or by any other person for any purpose, without our prior written consent. 
 Very truly yours, 

 [FORM OF INVESTOR REPRESENTATION LETTER] 
                     , 20__ 
 [                        ] 
 Gentlemen: 
                      (“            ”) has agreed to
purchase                      Warrants (the “Warrants”) of ISTA Pharmaceuticals, Inc. (the “Company”) from
[                    ]
(“[                    ]”). We understand that the Warrants are “restricted securities.” We represent and warrant that
             is a sophisticated institutional investor that would qualify as an “Accredited Investor” as defined in Rule 501 of Regulation D under the Securities Act of
1933, as amended (the “Securities Act”). 
                      represents and warrants as of the date hereof as follows: 
 1. That it is acquiring the Warrants and the shares of common stock, $0.001 par value per share underlying such Warrants (the “Exercise Shares”)
solely for its account for investment and not with a view to or for sale or distribution of said Warrants or Exercise Shares or any part thereof.                 
also represents that the entire legal and beneficial interests of the Warrants and Exercise Shares                  is acquiring is being acquired for, and will
be held for, its account only; 
 2. That the Warrants and the Exercise Shares have not been registered under the Securities Act on the basis
that no distribution or public offering of the stock of the Company is to be effected.                  realizes that the basis for the exemption may not be
present if, notwithstanding its representations,                  has a present intention of acquiring the securities for a fixed or determinable period in the
future, selling (in connection with a distribution or otherwise), granting any participation in, or otherwise distributing the securities.                  has no
such present intention; 
 3. That the Warrants and the Exercise Shares must be held indefinitely unless they are subsequently registered
under the Securities Act or an exemption from such registration is available.                  recognizes that the Company has no obligation to register the
Warrants, or to comply with any exemption from such registration; 
 4. That neither the Warrants nor the Exercise Shares may be sold pursuant
to Rule 144 adopted under the Securities Act unless certain conditions are met, including, among other things, the existence of a public market for the shares, the availability of certain current public information about Company, the resale
following the required holding period under Rule 144 and the number of shares being sold during any three month period not exceeding specified limitations; 
 5. That it will not make any disposition of all or any part of the Warrants or Exercise Shares in any event unless and until: 
 (i) The Company shall have received a letter secured by                  from the Securities and Exchange Commission stating that
no action will be recommended to the Securities and Exchange Commission with respect to the proposed disposition; 
 (ii) There is then in
effect a registration statement under the Securities Act covering such proposed disposition and such disposition is made in accordance with said registration statement; or 
 (iii)                  shall have notified the Company of the proposed disposition and, in the case of a sale or transfer in a so
called “4(1) and a half” transaction, shall have furnished counsel to the Company with an opinion of counsel, reasonably satisfactory to counsel to the Company. 

 We acknowledge that the Company will place stop orders with respect to the Warrants and the Exercise Shares, and if a
registration statement is not effective, the Exercise Shares shall bear the following restrictive legend: 
 “THE SECURITIES REPRESENTED
BY THIS CERTIFICATE HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED, OR APPLICABLE STATE SECURITIES LAWS. THE SECURITIES MAY NOT BE SOLD, TRANSFERRED OR ASSIGNED IN THE ABSENCE OF AN EFFECTIVE REGISTRATION STATEMENT FOR THE
SECURITIES UNDER SAID ACT, OR PURSUANT TO AN EXEMPTION FROM REGISTRATION UNDER SAID ACT INCLUDING, WITHOUT LIMITATION, PURSUANT TO RULES 144 OR 144A UNDER SAID ACT OR PURSUANT TO A PRIVATE SALE EFFECTED UNDER APPLICABLE FORMAL OR INFORMAL SEC
INTERPRETATION OR GUIDANCE, SUCH AS A SO-CALLED “4(1) AND A HALF” SALE.” 
 “THE SALE, TRANSFER OR ASSIGNMENT OF THE
SECURITIES REPRESENTED BY THIS CERTIFICATE ARE SUBJECT TO THE TERMS AND CONDITIONS OF A CERTAIN REGISTRATION RIGHTS AGREEMENT DATED AS OF SEPTEMBER 26, 2008, AS AMENDED FROM TIME TO TIME, AMONG THE COMPANY AND A CERTAIN HOLDERS OF ITS OUTSTANDING
SECURITIES. COPIES OF SUCH AGREEMENT MAY BE OBTAINED AT NO COST BY WRITTEN REQUEST MADE BY THE HOLDER OF RECORD OF THIS CERTIFICATE TO THE SECRETARY OF THE COMPANY.” 
 At any time and from time to time after the date hereof,                      shall, without further
consideration, execute and deliver to [                    ] or the Company such other instruments or documents and shall take such other
actions as they may reasonably request to carry out the transactions contemplated hereby. 
 Very truly yours, 

 Schedule 1 
 Black-Scholes Value 
  

					
	 	  	 Calculation Under Section 3(a)(iii) or 5(c)(iii)
	  	 Calculation Under Section 10(b) or 11(b)

			
	 Remaining Term
	  	Number of calendar days from date of public announcement of the Major Transaction until the last date on which the Warrant may be exercised.	  	Number of calendar days from date of the Event of Failure until the last date on which the Warrant may be exercised.
			
	 Interest Rate
	  	A risk-free interest rate corresponding to the US$ LIBOR/Swap rate for a period equal to the Remaining Term.	  	A risk-free interest rate corresponding to the US$ LIBOR/Swap rate for a period equal to the Remaining Term.
			
	 Volatility
	  	 If the first public announcement of the Major Transaction is made at or prior to 4:00 p.m., New York City time, the arithmetic mean of historic
volatility for the 10, 30 and 50 Trading Day periods ending on the date of such first public announcement, obtained from the HVT or similar function on Bloomberg.
  
 If the first public announcement of the Major Transaction is made after 4:00 p.m., New York City time, the arithmetic mean of historic volatility for the 10, 30 and 50
Trading Day periods ending on the next succeeding Trading Day following the date of such first public announcement, obtained from the HVT or similar function on Bloomberg.
	  	The arithmetic mean of historic volatility for the 10, 30 and 50 Trading Day periods made immediately preceding the date of such calculation, obtained from the HVT or similar function on
Bloomberg.
			
	 Stock Price
	  	The greater of (1) the closing price of the Common Stock on NASDAQ, or, if that is not the principal trading market for the Common Stock, such principal market on which the Common Stock is
traded or listed (the “Closing Market Price”) on the trading day immediately preceding the date on which a Major Transaction is consummated, (2) the first Closing Market Price following the first public announcement of a Major
Transaction, or (3) the Volume Weighted Average Price as of the date immediately preceding the first public announcement of the Major Transaction.	  	The volume Weighted Average Price on the date of such calculation.
			
	 Dividends
	  	Zero.	  	Zero.
			
	 Strike Price
	  	Exercise Price as defined in section 3(a).	  	Exercise Price as defined in section 3(a).Facility Agreement, dated September 26, 2008

 Exhibit 10.1 
 FACILITY AGREEMENT 
 FACILITY AGREEMENT (this “Agreement”), dated as of
September 26, 2008 (the “Agreement Date”), between ISTA Pharmaceuticals, Inc., a Delaware corporation (the “Borrower”), and those lenders set forth on Schedule 1 attached hereto (individually, a
“Lender” and together, the “Lenders” and, together with the Borrower, the “Parties”). 
 W I T N E S S E T H: 
 WHEREAS, the Borrower wishes to borrow from the Lenders up to sixty-five million Dollars
($65,000,000) for the purpose described in Section 2.1; and 
 WHEREAS, the Lenders desire to make loans to the Borrower from time to
time for such purpose. 
 NOW, THEREFORE, in consideration of the mutual agreements set forth herein, the Lenders and the Borrower agree as
follows: 
 ARTICLE 1 
 DEFINITIONS 
 Section 1.1 General Definitions. Wherever used in this Agreement, the Exhibits or the Schedules
attached hereto, unless the context otherwise requires, the following terms have the following meanings: 
 “Additional
Amounts” has the meaning given to it in Section 2.6(b). 
 “Affiliate” means, with respect to any Person, any
other Person: 
 (a) that owns, directly or indirectly, in the aggregate of more than fifty percent (50%) of the
beneficial ownership interest of such Person; or 
 (b) that directly or indirectly through one or more intermediaries
controls, or is controlled by, or is under common control with, such Person; or 
 (c) that directly or indirectly is a
general partner, controlling shareholder, or managing member of such Person. 
 “Business Day” means a day on which banks
are open for business in The City of New York. 
 “Cash and Cash Equivalents” means with respect to any date of
determination, the amount shown as such on the consolidated balance sheet of the Borrower and its Subsidiaries at the time such balance sheet is filed with the SEC on Form 10–Q or Form 10–K under the Exchange Act or otherwise made
available to the Borrower’s stockholders. 
 “Code” means the Internal Revenue Code of 1986, as amended, and any
Treasury Regulations promulgated thereunder. 

 “Common Stock” means the common stock, par value $0.001 per share, of the Borrower.

 “Convertible Notes” means those certain Senior Subordinated Convertible Notes issued by the Borrower on June 22,
2006 in the aggregate principal amount of $40,000,000. 
 “Indebtedness” means the following, whether direct or contingent:

 (a) all indebtedness for borrowed money; 
 (b) the deferred purchase price of assets or services which in accordance with GAAP would be shown to be a liability (or on the liability
side of a balance sheet); 
 (c) all guaranty obligations; 
 (d) the maximum amount of all letters of credit issued or acceptance facilities established for the account of the Borrower and, without
duplication, all drafts drawn thereunder (other than letters of credit supporting other indebtedness of Borrower and which are otherwise permitted hereunder); 
 (e) all capitalized lease obligations; 
 (f) all indebtedness of another Person secured by any Lien on any property of the Borrower, whether or not such indebtedness has been assumed or is recourse; 
 (g) all obligations under take-or-pay or similar arrangements or under any interest rate swaps, caps, floors, collars and other interest
hedge or protection agreements, treasury locks, equity forward contracts, currency agreements or commodity purchase or option agreements or other interest or exchange rate or commodity price hedging agreements and any other derivative instruments,
in each case, whether the Borrower is liable contingently or otherwise, as obligor, guarantor or otherwise, or in respect of which obligations the Borrower otherwise assures a creditor against loss; 
 (h) indebtedness created or arising under any conditional sale or title retention agreement; and 
 (i) obligations of the Borrower with respect to withdrawal liability to or on behalf of any “multi employer plan” as defined in
Section 4001(a) of ERISA. 
 “Default” means any event which, at the giving of notice, lapse of time or
fulfillment of any other applicable condition (or any combination of the foregoing), would constitute an Event of Default. 
 “Disbursement” has the meaning given to it in Section 2.2(a). 
 “Disbursement Date” means
the date on which a Disbursement occurs. 
 “Disbursement Request” has the meaning given to it in Section 2.2(a).

 “Dollars” and the “$” sign mean the lawful currency of the United States of America. 
  

 2 

 “Event of Default” has the meaning given to it in Section 5.5. 
 “Evidence of Disbursement” has the meaning given to it in Section 2.2. 
 “Exchange Act” means the Securities Exchange Act of 1934, as amended, including the rules and regulations promulgated thereunder.

 “Excluded Taxes” means all income taxes, minimum or alternative minimum income taxes, withholding taxes imposed on gross
amounts, any tax determined based upon income, capital gains, gross income, sales, net profits, windfall profits or similar items, franchise taxes (or any other tax measured by capital, capital stock or net worth), gross receipts taxes, branch
profits taxes, margin taxes (or any other taxes imposed on or measured by net income, or imposed in lieu of net income) payable by the Lenders in any jurisdiction to any Government Authority (or political subdivision or taxing authority thereof) in
connection with any payments received under this Agreement by the Lenders, or any such tax imposed in connection with the execution and delivery of, and the performance of its obligations under, this Agreement. 
 “Final Payment” means such amount as may be necessary to repay the Loan in full and any other amounts owing by the Borrower to the
Lenders pursuant to the Financing Documents. 
 “Final Payment Date” means the earlier of (i) the date on which the
Borrower repays the outstanding principal of the Loan (together with any other amounts accrued and unpaid under this Agreement) to the Lenders pursuant to this Agreement and (ii) the fifth anniversary of the Agreement Date. 
 “Financing Documents” means this Agreement, the Notes, the Registration Rights Agreement, the Security Agreement, the Warrants and any
other document or instrument delivered in connection with any of the foregoing whether or not specifically mentioned herein or therein. 
 “GAAP” means generally accepted accounting principles consistently applied as set forth in the opinions and pronouncements of the Accounting Principles Board and the American Institute of Certified Public Accountants and
statements and pronouncements of the Financial Accounting Standards Board (or agencies with similar functions of comparable stature and authority within the accounting profession). 
 “Government Authority” means any government, governmental department, ministry, cabinet, commission, board, bureau, agency, tribunal,
regulatory authority, instrumentality, judicial, legislative, fiscal, or administrative body or entity, whether domestic or foreign, federal, state or local, having jurisdiction over the matter or matters and Person or Persons in question,
including, without limitation, the SEC. 
 “Indemnified Person” has the meaning given to it in Section 6.11.

 “Indemnity” has the meaning given to it in Section 6.11. 
 “Interest Rate” means 6.5% simple interest per annum, payable on the outstanding principal amount of each of the Notes. 
 “Lien” means any lien, pledge, preferential arrangement, mortgage, security interest, deed of trust, charge, assignment, hypothecation,
title retention, privilege or other encumbrance on or with respect to property or interest in property having the practical effect of constituting a security interest, in each case with respect to the payment of any obligation with, or from the
proceeds of, any asset or revenue of any kind. 
  

 3 

 “Loan” means the loan to be made available by the Lenders to the Borrower pursuant to
Section 2.2 in the maximum aggregate amount of sixty five million Dollars ($65,000,000) or, as the context may require, the principal amount thereof from time to time outstanding. 
 “Loss” has the meaning given to it in Section 6.11. 
 “Major Transaction” has the meaning set forth in the Warrants. 
 “Material Adverse
Effect” means a material adverse effect on (a) the business, operations, prospects, condition (financial or otherwise) or property of the Borrower, (b) the validity or enforceability of any provision of any Financing Document,
(c) the ability of the Borrower to timely perform its Obligations or (d) the rights and remedies of the Lenders under any Financing Document. 
 “Notes” means the notes issued to the Lenders evidencing the Loan in the form attached hereto as Exhibit A 
 “Obligations” means all obligations (monetary or otherwise) of the Borrower arising under or in connection with the Financing Documents. 
 “Organizational Documents” means the Certificate of Incorporation and Bylaws, each as amended to date, of the Borrower. 
 “Permitted Indebtedness” means the principal of (and premium, if any), interest on, and all fees and other amounts (including, without
limitation, any reasonable out-of-pocket costs, enforcement expenses (including reasonable out-of-pocket legal fees and disbursements), collateral protection expenses and other reimbursement or indemnity obligations relating thereto) payable by
Borrower and/or its Subsidiaries under or in connection with: (i) Indebtedness of Borrower in favor of the Lenders arising under this Agreement or any other Financing Document, (ii) Indebtedness pursuant to that certain Loan and Security
Agreement, dated as of December 22, 2005, as amended, supplemented or otherwise modified from time to time, between the Borrower and Silicon Valley Bank, with the amount that Borrower may borrow under said agreement not to exceed the lesser of
$25,000,000 and 85% of eligible accounts receivable as of the end of the preceding fiscal quarter plus net cash, (iii) Indebtedness existing as of the date hereof (which the Borrower represents to not be in excess of $50,579,893.20,
(iv) future Indebtedness in respect of purchase money financing, capital lease obligations and equipment financing facilities in an aggregate amount not to be in excess of $5,000,000 at any given time, and letters of credit required in
connection with the purchase of equipment, (v) Indebtedness to trade creditors incurred in the ordinary course of business, (vi) Indebtedness in respect of the purchase price for, or in connection with a bona fide arm’s-length
purchase of, any assets (including Indebtedness assumed as a result of such purchase) so long as the aggregate amount of such Indebtedness outstanding at any time shall not exceed the sum of (x) 25% of the assets of the Borrower determined in
accordance with GAAP and (y) 50% of the principal amount of the Notes repaid by the Borrower to the Lenders, in each case at the time of calculation, (vii) Indebtedness secured by Borrower’s auction rate securities in an amount not to
exceed $4,700,000, and (viii) extension, refinancings and renewals of any of the foregoing items of Permitted Indebtedness, provided that the principal amount is not increased or the terms modified to impose more burdensome terms upon the
Borrower. Any Indebtedness in excess of the amount permitted pursuant to clause (vi) shall be subject to a Subordination Agreement. 
  

 4 

 “Permitted Liens” means: (i) Liens existing on the date hereof and disclosed on
Exhibit B hereof; (ii) Liens in favor of the Lenders; (iii) statutory Liens created by operation of applicable law; (iv) Liens arising in the ordinary course of business and securing obligations that are not overdue or are being
contested in good faith by appropriate proceedings; (v) Liens securing purchase money or capitalized lease equipment financing; (vi) Liens for Taxes not yet due and payable or that are being contested in good faith by appropriate
proceedings; (vii) Liens arising from judgments, decrees or attachments in circumstances not constituting an Event of Default; (viii) licenses and sub-licenses granted in the ordinary course of Borrower’s business and, with respect to
any licenses where Borrower is the licensee or sublicensee, any interest or title of a licensor or sublicensor under any such license or sublicense; (ix) Liens securing Permitted Indebtedness; (x) any option or other agreement to purchase
any asset of the Borrower or any Subsidiary the disposition of which is not otherwise prohibited hereby; and (xi) Liens in favor of financial institutions arising in connection with Borrower’s accounts maintained in the ordinary course of
Borrower’s business held at such institutions to secure standard fees for services charged by, but not financing made available by, such institutions. 
 “Person” means and includes any natural person, individual, partnership, joint venture, corporation, trust, limited liability company, limited company, joint stock company, unincorporated
organization, government entity or any political subdivision or agency thereof, or any other entity. 
 “Registration Rights
Agreement” means the Registration Rights Agreement, dated as of the date hereof, among the Borrower and the Lenders. 
 “SEC” means the United States Securities and Exchange Commission. 
 “Securities Act” means the
Securities Act of 1933, as amended, including the rules and regulations promulgated thereunder. 
 “Security Agreement”
means the Security Agreement, dated as of the date hereof, among the Borrower and the Lenders granting to the Lenders a first priority security interest in the Borrower’s intellectual property as described therein. 
 “Subordination Agreement” means the Agreement attached hereto as Exhibit C. 
 “Subsidiary or Subsidiaries” means, as to the Borrower, any entity of which securities or other ownership interests having ordinary
voting power to elect a majority of the board of directors or other persons performing similar functions are at the time directly or indirectly owned by the Borrower. 
 “Taxes” means all deductions or withholdings for any and all present and future taxes, levies, imposts, stamp or other duties, fees, assessments, deductions, withholdings, all other governmental
charges, and all liabilities with respect thereto. 
 “Warrants” means the warrants attached hereto as part of
Exhibit D issued pursuant to Section 2.10. 
  

 5 

 Section 1.2 Interpretation. In this Agreement, unless the context otherwise requires, all
words and personal pronouns relating thereto shall be read and construed as the number and gender of the party or parties requires and the verb shall be read and construed as agreeing with the required word and pronoun; the division of this
Agreement into Articles and Sections and the use of headings and captions is for convenience of reference only and shall not modify or affect the interpretation or construction of this Agreement or any of its provisions; the words
“herein,” “hereof,” “hereunder,” “hereinafter” and “hereto” and words of similar import refer to this Agreement as a whole and not to any particular Article or Section hereof; the words
“include,” “including,” and derivations thereof shall be deemed to have the phrase “without limitation” attached thereto unless otherwise expressly stated; references to a specified Article, Exhibit, Section or Schedule
shall be construed as a reference to that specified Article, Exhibit, Section or Schedule of this Agreement; and any reference to any of the Financing Documents means such document as the same shall be amended, supplemented or modified and from time
to time in effect. 
 Section 1.3 Business Day Adjustment. If the day by which a payment is due to be made is not a Business
Day, that payment shall be made by the next succeeding Business Day unless that next succeeding Business Day falls in a different calendar month, in which case that payment shall be made by the Business Day immediately preceding the day by which
such payment is due to be made. 
 ARTICLE 2 
 AGREEMENT FOR THE LOAN 
 Section 2.1 Use of Proceeds. The Borrower shall use the
proceeds from the Loan to redeem the Convertible Notes and for operating expenses and general corporate purposes. 
 Section 2.2
Disbursements. Subject to satisfaction of the conditions contained in Article IV, a disbursement of a portion of the Loan (each a “Disbursement”) in the minimum amount of $5,000,000 shall be made upon the Borrower’s
request (a “Disbursement Request”) in the form of Schedule 2, delivered to the Lenders not less than 15 Business Days prior to the date of such Disbursement. Against each Disbursement, the Borrower shall deliver to the Lenders
a completed receipt (the “Evidence of Disbursement”) in the form of Schedule 3, which receipt shall not be effective until the Disbursement is actually advanced to the Borrower. Borrower’s ability to issue Disbursement
Requests shall terminate on the one (1) year anniversary of the Agreement Date. The Lenders shall fulfill each Disbursement Request in accordance with their respective allocations set forth on Schedule 1 attached hereto. 
 Section 2.3 Payment. (a) The Borrower shall remit the Final Payment to the Lenders on the earlier to occur of (i) the Final
Payment Date and (ii) an Event of Default, after the expiration of all applicable cure or grace periods. The Borrower may prepay the Loan at any time without premium or penalty. The Borrower shall remit to the Lenders, and the Lenders shall
receive, 33% of the principal amount outstanding on the Notes on each of the third and fourth anniversaries of the Agreement Date and 34% of such principal amount outstanding on the fifth anniversary of the Agreement Date. 
 (b) If the Borrower disposes in one or more transactions less than 50% of its assets determined in accordance with GAAP, the Borrower shall remit to the
Lenders, and the Lenders shall receive, as prepayment of the Notes, 50% of the proceeds of such disposition(s) within 5 days of the Borrower’s receipt thereof. 
  

 6 

 Section 2.4 Transaction Fee. On the date hereof, the Borrower has paid to Deerfield
Management Company, L.P. a transaction fee of $1,625,000. 
 Section 2.5 Payments. Payments of any amounts due to the Lenders
under this Agreement shall be made in Dollars in immediately available funds prior to 11:00 a.m New York City time on such date that any such payment is due, at such bank or places, as the Lenders shall from time to time designate in writing at
least 5 Business Days prior to the date such payment is due. The Borrower shall pay all and any costs (administrative or otherwise) imposed by banks, clearing houses, or any other financial institution, in connection with making any payments under
any of the Financing Documents, except for any costs imposed by the Lenders’ banking institutions. 
 Section 2.6 Taxes, Duties and
Fees. 
 (a) The Borrower shall pay or cause to be paid all present and future Taxes (other than Excluded Taxes, if any),
duties, fees and other charges of whatsoever nature, if any, now or at any time hereafter levied or /imposed by any Government Authority, by any department, agency, political subdivision or taxing or other authority thereof or therein, by any
organization of which the applicable Government Authority is a member, or by any jurisdiction through which the Borrower makes payments hereunder, on or in connection with the payment of any and all amounts due under this Agreement, and all payments
of principal and other amounts due under this Agreement shall be made without deduction for or on account of any such Taxes, duties, fees and other charges, except for Excluded Taxes, which may be deducted or withheld from payments made by the
Borrower only if such deduction or withholding is required by applicable law. 
 (b) If the Borrower is required to withhold
any such amount or is prevented by operation of law or otherwise from paying or causing to be paid such Taxes, duties, fees or other charges as aforesaid except for Excluded Taxes, the principal or other amounts due under this Agreement (as
applicable) shall be increased to such amount as shall be necessary to yield and remit to the Lenders the full amount it would have received taking into account any such Taxes (except for Excluded Taxes), duties, fees or other charges payable on
amounts payable by the Borrower under this Section 2.6(b) had such payment been made without deduction of such Taxes, duties, fees or other charges (all and any of such additional amounts, herein referred to as the “Additional
Amounts”). 
 (c) If Section 2.6(b) above applies and the Lenders so require the Borrower shall deliver to the
Lenders official tax receipts evidencing payment (or certified copies of them) of the Additional Amounts within thirty (30) days of the date of payment. 
 (d) If the Lenders receive a refund from a Government Authority to which the Borrower has paid withholding Taxes pursuant to this
Section 2.6, the Lenders shall pay such refund to the Borrower. 
 Section 2.7 Costs, Expenses and Losses. If, as a result
of any failure by the Borrower to pay any sums due under this Agreement on the due date therefor (after the expiration of any applicable grace periods), or to borrow in accordance with a Disbursement Request made pursuant to Section 2.2, the
Lenders shall incur costs, expenses and/or losses, by reason of the liquidation or redeployment of deposits from third parties or in connection with obtaining funds to make or maintain any Disbursement, the Borrower shall pay to the Lenders upon
request by the Lenders, the amount of such costs, expenses and/or losses 

  

 7 

 
within fifteen (15) days after receipt by it of a certificate from the Lenders setting forth in reasonable detail such costs, expenses and/or losses,
along with supporting documentation. For the purposes of the preceding sentence, “costs, expenses and/or losses” shall include, without limitation, any interest paid or payable to carry any unpaid amount and any loss, premium, penalty or
expense which may be incurred in obtaining, liquidating or employing deposits of or borrowings from third parties in order to make, maintain or fund the Loan or any portion thereof. 
 Section 2.8 Interest Rate. The principal amount outstanding under the Loan shall bear interest at the Interest Rate (calculated on the
basis of the actual number of days elapsed in each month). Interest shall be paid quarterly in arrears commencing on December 31, 2008 and on the first Business Day following the end of each March, June, September and December thereafter.

 Section 2.9 Interest on Late Payments. Without limiting the remedies available to the Lenders under the Financing Documents
or otherwise, to the maximum extent permitted by applicable law, if the Borrower fails to make any payment of principal or interest with respect to the Loan when due (after the expiration of any applicable grace periods), the Borrower shall pay, in
respect of the outstanding principal amount and interest of the Loan, interest at the rate per annum equal to the Interest Rate plus ten percent (10%) for so long as such payment remains outstanding. Such interest shall be payable on demand.

 Section 2.10 Delivery of Warrants. (a) As of the date hereof, the Borrower shall issue to the Lenders Warrants to
purchase an aggregate of 12,500,000 shares of Common Stock at an initial Exercise Price (as defined in the Warrants) of $1.41 (the “Initial Exercise Price”). 
 (b) Concurrently with each Disbursement, the Borrower shall issue to Lenders Warrants to purchase an aggregate number of shares of Common Stock equal to the dollar amount of such Disbursement divided by ten (10). The
Warrants issued pursuant to this Section 2.10 shall be in the form annexed hereto as Exhibit D and shall be issued at an initial Exercise Price equal to the greater of the Initial Exercise Price and the Closing Price for shares of Common Stock
on the Trading Day immediately preceding the date of such Disbursement. The Term (as defined in the Warrants) for Warrants issued pursuant to this subsection (b) shall end on 5:00 p.m. New York City time on the sixth anniversary of the date of
this Agreement. 
 (c) As used herein, the Closing Price for Common Stock as of any date means the closing sale price (based on a Trading Day
from 9:30 a.m. to 4:00 p.m. (New York City time)) on The NASDAQ Global Market (“NASDAQ”) or, if NASDAQ is not the principal trading market for Common Stock, the closing sale price of Common Stock on the principal securities exchange or
trading market where Common Stock is listed. 
 (d) All Warrants issued pursuant to this Section 2.10 shall be allocated among the
Lenders as set forth on Schedule 1. 
 (e) Notwithstanding anything herein to the contrary, the number of shares of Common Stock into which a
Warrant is exercisable on any relevant issue date pursuant to subsection (b) above shall be adjusted to reflect any adjustments in the number of shares of Common Stock into which such Warrant is exercisable that would have taken effect pursuant
to the terms of the Warrant had such Warrant been issued on the date hereof and remained outstanding through the date of such issuance. 
  

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 (f) If at any time after the date of this Agreement for so long as any Warrants issuable pursuant to this
Agreement (the “Agreement Warrants”) are outstanding, the Borrower issues or sells any shares of Common Stock (a “Borrower Issuance”), the Company shall issue Warrants (“New Warrants”) to the
Lenders, concurrently with each such Borrower Issuance exercisable into a number of shares of Common Stock equal to (i) the number of shares of Common Stock issued in such Borrower Issuance, other than Excluded Shares, multiplied by
(ii) the Warrant Percentage multiplied by the Outstanding Debt Percentage. Any New Warrants issued shall be in the form of Exhibit D hereto except that the “Exercise Price” thereunder shall be equal to the greater of the Initial
Exercise Price and the Closing Price of the Common Stock on the date prior to the Borrower Issuance. The Term (as defined in the Warrants) for New Warrants issued pursuant to this subsection (f) shall end on 5:00 p.m. New York City time on the
sixth anniversary of the date of this Agreement. 
 For purposes hereof: 
 “Adjusted Total Common Stock Outstanding” shall mean at any date or time as of which such number is to be determined, all shares of Common
Stock outstanding (excluding shares then owned or held by or for the account of the Borrower or any subsidiary thereof) as of such date or time and all shares of Common Stock issuable upon exercise of any Agreement Warrants and New Warrants that are
outstanding on such date. 
 “Excluded Shares” shall mean shares of Common Stock issued pursuant to, or in connection with
(i) any equity compensation plan for officers, directors and employees, (ii) any Agreement Warrants or New Warrants, whether by exercise thereof or otherwise issuable pursuant to the terms thereof, (iii) stock splits,
reclassifications and other similar events which consist solely of the shares of Common Stock changing into or becoming exchangeable for a larger number of shares or (iv) acquisition agreements, licensing agreements, co-promotion or
co-marketing agreements, or joint venture or partnership agreements, in each case relating to the development or commercial exploitation of the pharmaceutical products of the Company or the intellectual property relating thereto and on terms that
are normal, reasonable and customary within the Company’s industry for transactions of this type; provided, that with respect to this clause (iv) in amounts not to exceed (x)(i) 1,651,831 shares of Common Stock (subject to appropriate
adjustment to reflect any stock splits, reclassifications or other similar events) for any transaction occurring at a time when the Closing Price for Common Stock on the Trading Day preceding the issuance of such shares is $2.50 or less or
(ii) 3,303,662 shares of Common Stock (subject to appropriate adjustment to reflect any stock splits, reclassifications or other similar events) for any transaction occurring at a time when the Closing Price for Common Stock on the Trading Day
immediately preceding the issuance of such shares is greater than $2.50; provided, further that with respect to this clause (iv) only up to an aggregate of 6,607,324 shares of Common Stock (subject to appropriate adjustment to reflect any stock
splits, reclassifications or other similar events) issued prior to the sixth anniversary of this Agreement shall be deemed Excluded Shares: 
 “Outstanding Debt Percentage” shall mean a fraction represented as a decimal expressed to the third decimal place equal to the total principal amount outstanding under the Loan five (5) Business Days following the receipt of
the proceeds from such Borrower Issuance by the Borrower divided by the total amount of all Disbursements made pursuant to this Agreement prior to such Borrower Issuance. 
  

 9 

 “Warrant Percentage” shall mean a fraction, represented as a decimal expressed to the third
decimal place equal to (x) the number of shares of Common Stock into which all Agreement Warrants and New Warrants issued prior to the date of such Borrower Issuance are exercisable (without regard to 9.98% restrictions contained therein)
immediately prior to the consummation of the Borrower Issuance, divided by (y) the Adjusted Total Common Stock Outstanding immediately prior to consummation of the Borrower Issuance. 
 ARTICLE 3 
 REPRESENTATIONS AND WARRANTIES 
 Section 3.1 Representations and Warranties of the Borrower. The Borrower represents and warrants as of the date hereof and as of each
Disbursement Date as follows: 
 (a) The Borrower is a corporation duly incorporated and validly existing under the laws of
the State of Delaware. 
 (b) The Borrower is conducting its business in compliance with its Organizational Documents. The
Organizational Documents of the Borrower (including all amendments thereto) as currently in effect have been made available to the Lenders and remain in full force and effect with no defaults outstanding thereunder. 
 (c) The Borrower has full power and authority to enter into each of the Financing Documents and to make the borrowings and the other
transactions contemplated thereby. 
 (d) All authorizations, consents, approvals, registrations, exemptions and licenses with
or from Government Authorities or other Persons that are necessary for the conduct of its business as currently conducted and as proposed to be conducted, for the borrowing hereunder, the execution and delivery of the Financing Documents and the
performance by the Borrower of the Obligations, have been obtained and are in full force and effect, except (i) for such registrations and filings in connection with the issuance of the Warrants and shares of Common Stock pursuant the Financing
Documents necessary to comply with federal and state securities laws, rules and regulations, and (ii) to the extent that any failure to so obtain for the conduct of the business as currently and proposed to be conducted could not reasonably be
expected to have a Material Adverse Effect; provided, however, that the failure to receive an approval from Government Authorities for the development or sale of any product shall not constitute a Material Adverse Effect or a violation of
this Section 3.1(d). 
 (e) Each Financing Document has been duly authorized, executed and delivered by the Borrower and
constitutes the valid and legally binding obligation of the Borrower, enforceable in accordance with its terms, except as such enforceability may be limited by (i) applicable insolvency, bankruptcy, reorganization, moratorium or other similar
laws affecting creditors’ rights generally, and (ii) applicable equitable principles (whether considered in a proceeding at law or in equity). 
 (f) No Default or Event of Default (or any other default or event of default, however described) has occurred under any of the Financing Documents. 
  

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 (g) Neither the entering into any of the Financing Documents nor the compliance with any
of its terms conflicts with, violates or results in a breach of any of the terms of, or constitutes a default or event of default (however described) or requires any consent under, any agreement to which the Borrower is a party or by which it is
bound, or violates any of the terms of the Organizational Documents or any judgment, decree, resolution, award or order or any statute, rule or regulation applicable to the Borrower or its assets. 
 (h) The Borrower is not engaged in or the subject of any litigation, arbitration, administrative regulatory compliance proceeding, or
investigation, nor are there any litigation, arbitration, administrative regulatory compliance proceedings or investigations pending or, to the knowledge of the Borrower, threatened before any court or arbitrator or before or by any Government
Authority against the Borrower, except for those that have been publicly disclosed in reports filed with the SEC and the Borrower is not aware of any facts reasonably likely to give rise to any such proceedings other than as may have been publicly
disclosed in such reports. 
 (i) The Borrower (i) is capable of paying its debts as they fall due, is not unable and has
not admitted its inability to pay debts as they fall due, (ii) is not bankrupt or insolvent and (iii) has not taken action, and no such action has been taken by a third party, for the Borrower’s winding up, dissolution, or liquidation
or similar executory or judicial proceeding or for the appointment of a liquidator, custodian, receiver, trustee, administrator or other similar officer for the Borrower or any or all of its assets or revenues. 
 (j) No Lien exists on Borrower’s property, except for Permitted Liens. 
 (k) The obligation of the Borrower to make any payment under this Agreement (together with all charges in connection therewith) is
absolute and unconditional, and there exists no right of setoff or recoupment, counterclaim, cross-claim or defense of any nature whatsoever to any such payment. 
 Section 3.2 Borrower Acknowledgment. The Borrower acknowledges that it has made the representations and warranties referred to in Section 3.1 with the intention of persuading the Lenders to enter
into the Financing Documents and that the Lenders have entered into the Financing Documents on the basis of, and in full reliance on, each of such representations and warranties. The Borrower represents and warrants to the Lenders that none of such
representations and warranties omits any matter the omission of which makes any of such representations and warranties misleading. 
 Section 3.3 Representations and Warranties of the Lenders. Each of the Lenders represents and warrants to the Borrower as of the date hereof and as of each date Warrants are granted pursuant to this Agreement that: 

(a) It is acquiring the Warrants and the shares of Common Stock issued upon exercise of the Warrants (the “Exercise
Shares”) solely for its account for investment and not with a view to or for sale or distribution of the Warrants or Exercise Shares or any part thereof. The entire legal and beneficial interests of the Warrants and Exercise Shares such
Lender is acquiring is being acquired for, and will be held for, its account only. 
  

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 (b) The Warrants and the Exercise Shares have not been registered under the Securities
Act on the basis that no distribution or public offering of the stock of the Borrower is to be effected. It realizes that the basis for the exemptions may not be present if, notwithstanding its representations, such Lender has a present intention of
acquiring the securities for a fixed or determinable period in the future, selling (in connection with a distribution or otherwise), granting any participation in, or otherwise distributing the securities. None of the Lenders has such present
intention. 
 (c) The Warrants and the Exercise Shares must be held indefinitely unless they are subsequently registered under
the Securities Act or an exemption for such registration is available. 
 (d) Neither the Warrants nor the Exercise Shares may
be sold pursuant to Rule 144 adopted under the Securities Act unless certain conditions are met, including, among other things, the existence of a public market for the shares, the availability of certain current public information about the
Borrower, the resale following the required holding period under Rule 144 and the number of shares being sold during any three month period not exceeding specified limitation. 
 (e) It will not make any disposition of all or any part of the Warrants or Exercise Shares until: 
 (i) The Borrower shall have received a letter secured by such Lender from the SEC stating that no action will be recommended to the SEC
with respect to the proposed disposition; 
 (ii) There is then in effect a registration statement under the Securities Act
covering such proposed disposition and such disposition is made in accordance with said registration statement; or 
 (iii)
Such Lender shall have notified the Borrower of the proposed disposition and, in the case of a sale or transfer in a so-called “4(1) and a half” transaction, shall have furnished counsel for the Borrower with an opinion of counsel,
substantially in the form annexed as Exhibit C to the Warrant. The Borrower agrees that it will not require an opinion of counsel with respect to transactions under Rule 144 of the Securities Act. 
 (f) It understands and agrees that all certificates evidencing the shares to be issued to the Lenders upon exercise of the Warrants may
bear the following legend: 
 “THE SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933,
OR APPLICABLE STATE SECURITIES LAWS. THE SECURITIES MAY NOT BE SOLD, TRANSFERRED OR ASSIGNED IN THE ABSENCE OF AN EFFECTIVE REGISTRATION STATEMENT FOR THE SECURITIES UNDER SAID ACT, OR PURSUANT TO AN EXEMPTION FROM REGISTRATION UNDER SAID ACT
INCLUDING, WITHOUT LIMITATION, PURSUANT TO RULES 144 OR 144A UNDER SAID ACT OR PURSUANT TO A PRIVATE SALE EFFECTED UNDER APPLICABLE FORMAL OR INFORMAL SEC INTERPRETATION OR GUIDANCE, SUCH AS A SO-CALLED “4(1) AND A HALF” SALE.”

  

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 “THE SALE, TRANSFER OR ASSIGNMENT OF THE SECURITIES REPRESENTED BY THIS CERTIFICATE ARE SUBJECT TO
THE TERMS OF A CERTAIN REGISTRATION RIGHTS AGREEMENT DATED AS OF SEPTEMBER 26, 2008, AS AMENDED FROM TIME TO TIME, AMONG THE COMPANY AND CERTAIN HOLDERS OF ITS OUTSTANDING SECURITIES. COPIES OF SUCH AGREEMENT MAY BE OBTAINED AT NO COST BY WRITTEN
REQUEST MADE BY THE HOLDER OF RECORD OF THIS CERTIFICATE TO THE SECRETARY OF THE COMPANY.” 
 (g) Such Lender is an
“accredited investor” as defined in Regulation D promulgated the Securities Act. 
 (h) Such Lender is a
limited partnership duly organized and validly existing under the laws of the jurisdiction of its formation. 
 (i) Each
Financing Document to which it is a party has been duly authorized, executed and delivered by such Lender and constitutes the valid and legally binding obligation of such Lender, enforceable in accordance with its terms, except as such
enforceability may be limited by (i) applicable insolvency, bankruptcy, reorganization, moratorium or other similar laws affecting creditors’ rights generally, and (ii) applicable equitable principles (whether considered in a
proceeding at law or in equity). 
 (j) Such Lender has full power and authority to make the Disbursements and to enter into
and perform its other obligations under each of the Financing Documents and carry out the other transactions contemplated thereby. Such Lender has sufficient funds, and will at all times during the first year following the Agreement Date, have
sufficient funds to make the Disbursements. 
 ARTICLE 4 
 CONDITIONS OF DISBURSEMENTS 
 Section 4.1 Conditions to Initial Disbursement of the
Loan. The obligation of the Lenders to make the initial Disbursement shall be subject to the fulfillment of the following conditions: 
 (a) The Lenders shall have received a copy of all documents authorizing the Borrower to execute, deliver and perform each of the Financing Documents and to engage in the transactions contemplated thereby and an
opinion of Borrower’s counsel satisfactory to the Lenders. 
 Unless otherwise notified by the Borrower and without prejudice to the
generality of this Section 4.1, the right of the Lenders to require compliance with any condition under this Agreement which may be waived by the Lenders in respect of any Disbursement is expressly preserved for the purpose of any subsequent
Disbursement. 
  

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 ARTICLE 5 
 PARTICULAR COVENANTS AND EVENTS OF DEFAULT 
 Section 5.1 Affirmative Covenants. Unless
the Lenders shall otherwise agree: 
 (a) The Borrower shall (i) maintain its existence and qualify and remain qualified
to do its business as currently conducted, except where the failure to so maintain such qualification would not reasonably be expected to have a Material Adverse Effect, (ii) maintain all approvals necessary for the Financing Documents to be in
effect, and (iii) operate its business with reasonable due diligence, efficiency and in conformity with sound business practices. 
 (b) The Borrower shall comply in all material respects with all applicable laws, rules, regulations and orders of any Government Authority, except where the necessity of compliance therewith is contested in good faith
by appropriate proceedings or where the failure to so comply, individually or in the aggregate, would not reasonably be expected to have a Material Adverse Effect. 
 (c) The Borrower shall obtain, make and keep in full force and effect all licenses, contracts, consents, approvals and authorizations from
and registrations with Government Authorities that may be required to conduct its business, except to the extent that the failure to do so would not reasonably be expected to have a Material Adverse Effect. 
 (d) The Borrower shall promptly notify the Lenders of the occurrence of (i) any Default or Event of Default; or (ii) any claims,
litigation, arbitration, mediation or administrative or regulatory proceedings that are instituted or threatened against the Borrower, except for matters that, individually or in the aggregate, could not reasonably be expected to have a Material
Adverse Effect; and (iii) each event which, at the giving of notice, lapse of time, determination of materiality or fulfillment of any other applicable condition (or any combination of the foregoing), would constitute an event of default
(however described) under any of the Financing Documents. 
 (e) The Borrower shall comply with the terms of each of the
Financing Documents. 
 (f) (i) If the Borrower is not required to file reports pursuant to Sections 13 or 15(d) of the
Exchange Act, the Borrower will provide quarterly financial statements for itself and its Subsidiaries within 45 days after the end of each quarter, and annual financial statements within 120 days after the end of each year; (ii) the Borrower
will timely file with the SEC (subject to appropriate extensions made under Rule 12b-25 of the Exchange Act) any annual reports, quarterly reports and other periodic reports pursuant to Section 13 or 15(d) of the Exchange Act; and
(iii) the Borrower and its Subsidiaries will provide to the Lenders copies of all documents, reports, financial data and other information as the Lenders may reasonably request, and permit the Lenders to visit and inspect any of the properties
of the Borrower and its Subsidiaries, and to discuss its and their affairs, finances and accounts with its and their officers, all at such times as the Lenders may reasonably request; and (iv) the Lenders shall have the right to consult with
and advise the management of the Borrower and its Subsidiaries on matters relating to the operation of the Borrower and it Subsidiaries. 
  

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 Section 5.2 Negative Covenants. Unless the Lenders shall otherwise agree: 
 (a) The Borrower shall not (i) liquidate or dissolve; or (ii) enter into any merger, consolidation or reorganization, unless
either (A) the Borrower is the surviving corporation, or (B) in the case where Borrower is not the surviving corporation, the Person so resulting or surviving shall expressly assume the Obligations or otherwise redeem all outstanding
Obligations. 
 (b) The Borrower shall not (i) enter into any partnership, joint venture, syndicate, pool, profit-sharing
or royalty agreement or other combination, or engage in any transaction with an Affiliate, whereby its income or profits are, or might be, shared with another Person or enter into any management contract or similar arrangement whereby a substantial
part of its business is managed by another Person, (ii) distribute, or permit the distribution of, any assets of the Borrower or its Subsidiaries, including its intangibles, to any shareholders of the Borrower or the holder of any equity
interest in any Subsidiary of the Borrower or any of its Affiliates (other than the Borrower or a Subsidiary of the Borrower); provided, however, that (A) with respect to the restrictions in clause (i), the Borrower may enter into any
collaborative arrangement, licensing agreement, joint venture or partnership providing for the research, development or commercial exploitation of compounds, products or services whereby payments received therefrom or its income or profits are, or
might be, shared in the ordinary course of business with another Person; and (B) with respect to the restrictions in clause (ii), royalties and other payments made by any partnership, joint venture, syndicate, pool, profit-sharing or royalty
agreement or other combination, to the parties thereto in the ordinary course of business shall not be deemed to be a distribution of assets. 
 (c) The Borrower shall not: (i) create, incur or suffer any Lien upon any of its assets, now owned or hereafter acquired, except Permitted Liens; or (ii) assign, sell, transfer or otherwise dispose of, any
of the Financing Documents, or the rights and obligations thereunder. 
 (d) The Borrower shall not create, incur assume,
guarantee or be remain liable with respect to any Indebtedness, other than Permitted Indebtedness, or prepay any Indebtedness (other than Permitted Indebtedness) or take any actions which impose on the Borrower an obligation to prepay any
Indebtedness, except Permitted Indebtedness. 
 Section 5.3 Reimbursement of Taxes. The Borrower shall pay all Taxes, duties,
fees or other charges payable on or in connection with the execution, issue, delivery, registration, notarization or enforcement of the Financing Documents and shall, upon notice from the Lenders, reimburse the Lenders for any such Taxes, duties,
fees or other charges paid by the Lenders thereon; provided, however, that notwithstanding the foregoing, under no circumstances shall the Borrower have any obligation to reimburse the Lenders for Excluded Taxes. 
 Section 5.4 Major Transaction. If a Major Transaction occurs, the Lenders, in the exercise of their sole discretion, may deliver a written
notice to the Borrower (the “Put Notice”) within 10 Business Days after the date of the announcement of such Major Transaction, that (a) 110% of the outstanding principal of the Notes and (b) accrued and unpaid interest on
the Notes, and with any other amounts accrued or payable under the Financing Documents ((a) and (b) together, the “Put Price”) is immediately due and payable upon consummation of the Major Transaction. If the Lenders deliver a
Put Notice, then upon such consummation, the Borrower shall pay the Put Price to the Lenders and the Obligations shall terminate. 
  

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 Section 5.5 General Acceleration Provision upon Events of Default. If one or more of the
events specified in this Section 5.5 shall have happened and be continuing beyond the applicable cure period (each, an “Event of Default”), the Lenders, by written notice to the Borrower, may cancel the Borrower’s right to
request Disbursements and declare the principal of, accrued and unpaid interest on, the Notes or any part of any of them (together with any other amounts accrued or payable under this Agreement) to be, and the same shall thereupon become,
immediately due and payable, without any further notice and without any presentment, demand, or protest of any kind, all of which are hereby expressly waived by the Borrower, and take any further action available at law or in equity, including,
without limitation, the sale of the Loan and all other rights acquired in connection with the Loan: 
 (a) A Lender shall have
failed to receive payment of (i) principal when due, or (ii) interest and any other amounts due under the Loan or the Notes within five (5) Business Days of their due date. 
 (b) The Borrower shall have failed to comply with the due observance or performance of any other covenant contained in this Agreement or
any Note and such failure shall not have been cured by Borrower within 30 days after receiving written notice of such default or failure from the Lenders. 
 (c) Any representation or warranty made by the Borrower in any Financing Document shall be have been incorrect, false or misleading as of the date it was made, deemed made, reaffirmed or confirmed. 
 (d) (i) The Borrower shall generally be unable to pay its debts as such debts become due, or shall admit in writing its inability to
pay its debts as they come due or shall make a general assignment for the benefit of creditors; (ii) the Borrower shall declare a moratorium on the payment of its debts; (iii) the commencement by the Borrower of proceedings to be
adjudicated bankrupt or insolvent, or the consent by it to the commencement of bankruptcy or insolvency proceedings against it, or the filing by it of a petition or answer or consent seeking reorganization, intervention or other similar relief under
any applicable law, or the consent by it to the filing of any such petition or to the appointment of an intervenor, receiver, liquidator, assignee, trustee, sequestrator (or other similar official) of all or substantially all of its assets;
(iv) the commencement against the Borrower of a proceeding in any court of competent jurisdiction under any bankruptcy or other applicable law (as now or hereafter in effect) seeking its liquidation, winding up, dissolution, reorganization,
arrangement, adjustment, or the appointment of an intervenor, receiver, liquidator, assignee, trustee, sequestrator (or other similar official), and any such proceeding shall continue undismissed, or any order, judgment or decree approving or
ordering any of the foregoing shall continue unstayed or otherwise in effect, for a period of ninety (90) days; (v) the making by the Borrower of an assignment for the benefit of creditors, or the admission by it in writing of its
inability to pay its debt generally as they become due; or (vi) any other event shall have occurred which under any applicable law would have an effect analogous to any of those events listed above in this subsection. 
  

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 (e) One or more judgments against the Borrower taken as a whole or attachments against
any of its property, which in the aggregate exceed $500,000, or which could have a Material Adverse Effect remain(s) unpaid, unstayed on appeal, undischarged, unbonded or undismissed for a period of thirty (30) days from the date of entry of
such judgment. 
 (f) Any license, permit or approval held by the Borrower from any Government Authority shall have been
suspended, canceled or revoked and such suspension, cancellation or revocation could reasonably be expected to have a Material Adverse Effect, and such suspension, cancellation or revocation shall not have been cured within 30 days. 
 (g) Any authorization necessary for the execution, delivery or performance of any Financing Document or for the validity or enforceability
of any of the Obligations under any Financing Document is not given or is withdrawn or ceases to remain in full force or effect. 
 (h) The validity of or any Financing Document shall be contested by any legislative, executive or judicial body of any jurisdiction, or any treaty, law, regulation, communiqué, decree, ordinance or policy of any jurisdiction shall
purport to render any material provision of any Financing Document invalid or unenforceable or shall purport to prevent or materially delay the performance or observance by the Borrower of the Obligations, and the parties are unable to negotiate a
replacement provision pursuant to Section 6.7 below. 
 (i) The Borrower has failed to comply in any material respect
with the reporting requirements of the Exchange Act, unless corrected by the Borrower promptly (if capable of such correction) through the filing of an amendment to an existing report or making an appropriate subsequent filing with the SEC.

 (j) There is a failure to perform in any agreement to which the Borrower is a party with a third party or parties resulting
in a right by such third party or parties to accelerate the maturity of any Indebtedness for borrowed money in an amount in excess of $1,000,000. 
 (k) If an Event of Default pursuant to the Warrants (as such term is defined in the Warrants) shall have occurred, but only if a Lender is a holder of any of the Warrants at the time of such Event of Default.

 (l) Cash and Cash Equivalents on the last day of each calendar quarter are less than $10,000,000. 
 Section 5.6 Automatic Acceleration on Dissolution or Bankruptcy. Notwithstanding any other provisions of this Agreement, if an Event of
Default under Section 5.5(d) shall occur, the principal of the Loan (together with any other amounts accrued or payable under this Agreement) shall thereupon become immediately due and payable without any presentment, demand, protest or notice
of any kind, all of which are hereby expressly waived by the Borrower. 
 Section 5.7 Recovery of Amounts Due. If any amount
payable hereunder is not paid as and when due, the Borrower hereby authorizes the Lender to proceed, to the fullest extent permitted by applicable law, without prior notice, by right of set-off, banker’s lien or counterclaim, against any moneys
or other assets of the Borrower to the full extent of all amounts payable to the Lenders. 
  

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 ARTICLE 6 
 MISCELLANEOUS 
 Section 6.1 Notices. Any notice, request or other communication to be
given or made under this Agreement shall be in writing. Such notice, request or other communication shall be deemed to have been duly given or made when it shall be delivered by hand, overnight mail, international courier (confirmed by facsimile),
or facsimile (with a hard copy delivered within two (2) Business Days) to the Party to which it is required or permitted to be given or made at such Party’s address specified below or at such other address as such Party shall have
designated by notice to the other Parties. 
 For the Borrower: 
 ISTA Pharmaceuticals, Inc. 
 15295 Alton Parkway 
 Irvine, CA 92618 
 Attention: Chief Executive Officer 
 Facsimile: (949) 789-7740 
 with a courtesy copy to: 
 Stradling Yocca Carlson & Rauth 
 660 Newport Center Drive, Suite 1600 
 Newport Beach, California 92660 
 Attention: Michael A. Hedge, Esq. 
 Facsimile: (949) 725-4100 
 For the Deerfield Lenders c/o: 
 Deerfield Private Design Fund, L.P. 
 780 Third Avenue, 37th Floor 
 New York, New York 10017 
 Attention: James E. Flynn 
 Facsimile: (212) 573-8111 
 with a courtesy copy to: 
 Katten Muchin Rosenman LLP 
 575 Madison Avenue 
 New York, New York 10022-2585 
 Facsimile: (212) 894-5827 
 Attention: Robert I. Fisher 
  

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 For the Sprout Lenders c/o: 
 New Leaf Venture Partners, LLC 
 Times Square Tower 
 7 Times Square - Suite 1603 
 New York, NY 10036 
 Att: Craig Slutzkin 
 Phone: 646-871-6420 
 FAX: 646-519-2773 
 For the Sanderling Lenders c/o: 
 Sanderling Ventures 
 400 S. El Camino Real, Suite 1200 
 San Mateo, CA 94402 
 P: (650) 401-2000 
 F: (650) 375-7077 
 Section 6.2 Waiver of Notice. Whenever any notice is required to be given to the Lenders or the Borrower under the any of the Financing Documents, a waiver thereof in writing signed by the person or persons entitled to such
notice, whether before or after the time stated therein, shall be deemed equivalent to the giving of such notice. 
 Section 6.3
Reimbursement of Legal and Other Expenses. If any amount owing to the Lenders under any Financing Document shall be collected through enforcement of this Agreement, any refinancing or restructuring of the Loan in the nature of a work-out,
settlement, negotiation, or any process of law, or shall be placed in the hands of third Persons for collection, the Borrower shall pay (in addition to all monies then due in respect of the Loan or otherwise payable under any Financing Document)
attorneys’ and other fees and expenses incurred in respect of such collection. 
 Section 6.4 Applicable Law and Consent to
Non-Exclusive New York Jurisdiction. This Agreement shall be governed by and construed in accordance with the laws of the State of New York, without giving effect to the conflicts of laws principles thereof other than Sections 5-1401 and 5-1402
of the General Obligations Law of such State. 
 (a) Any rights of the Lenders arising out of or relating to any Financing
Document, may, at the option of the Lenders, be enforced by the Lenders in the courts of the United States of America located in the Southern District of the State of New York or in any other courts having jurisdiction. For the benefit of the
Lenders, the Borrower hereby irrevocably agrees that any legal action, suit or other proceeding arising out of any Financing Document may be brought in the courts of the State of New York or of the United States of America for the Southern District
of New York. The Borrower irrevocably consents to the service of any and all process in any such legal action, suit or other proceeding by the mailing of copies of such process to the Borrower at its address specified in Section 6.1 by
registered mail, return receipt requested. By the execution and delivery of this Agreement, the Borrower hereby irrevocably consents and submits to the jurisdiction of any such court in any such action, suit or other proceeding. Final judgment
against the Borrower in any such action, suit or other proceeding shall be conclusive and may be enforced in any other jurisdiction by suit on the judgment. Nothing contained in any Financing Document shall affect the right of the Lenders to
commence legal proceedings in any court having jurisdiction, or concurrently in more than one jurisdiction, or to serve process, pleadings and other legal papers upon the Borrower in any manner authorized by the laws of any such jurisdiction.

  

 19 

 (b) The Borrower irrevocably waives, to the fullest extent permitted by applicable law,
any objection which it may now or hereafter have to the laying of venue of any action, suit or other proceeding arising out of or relating to any Financing Document, brought in the courts of the State of New York or in the United States District
Court for the Southern District of New York, and any claim that any such action, suit or other proceeding brought in any such court has been brought in an inconvenient forum. 
 (c) The Borrower hereby waives any and all rights to demand a trial by jury in any action, suit or other proceeding arising out of any
Financing Document or the transactions contemplated by any Financing Document. 
 (d) To the extent that the Parties may, in
any suit, action or other proceeding brought in any court arising out of or in connection with any Financing Document, be entitled to the benefit of any provision of law requiring the Borrower or the Lenders, as applicable, in such suit, action or
other proceeding to post security for the costs of the Borrower or the Lenders, as applicable, or to post a bond or to take similar action, the Parties hereby irrevocably waive such benefit, in each case to the fullest extent now or hereafter
permitted under any applicable laws. 
 Section 6.5 Successor and Assigns. This Agreement shall bind and inure to the
respective successors and assigns of the Parties, except that the Borrower may not assign or otherwise transfer all or any part of its rights under this Agreement or the Obligations without the prior written consent of the Lenders, and except as set
forth in the next sentence the Lenders may not assign or otherwise transfer all or any part of their obligations under this Agreement without the prior written consent of the Borrower. Each Lender may assign or other transfer all of any part of its
obligations under this Agreement to any Affiliate of such Lender. Notwithstanding the foregoing, nothing in this Agreement is deemed to limit or otherwise restrict a merger, reorganization or sale of substantially all of the assets of the Borrower.
Notwithstanding anything to the contrary contained herein, if any assignment or participation is to any Person that is not a “United States person” within the meaning of Section 7701(a)(30) of the Code, then such Person shall submit
to the Borrower, on or before the date of such assignment or participation an IRS Form W–8BEN (or any successor form) certifying as to such Person’s status for purposes of determining exemption from United States withholding tax,
information reporting and backup withholding with respect to all payments to be made to such Person. Any attempted assignment or participation in violation of this Section 6.5 shall be void and of no force and effect. Until there has been a
valid assignment of this Agreement and of all of the rights hereunder by a Lender in accordance with this Section 6.5, the Borrower shall deem and treat such Lender as the absolute beneficial owner and holder of this Agreement and of all of the
rights hereunder for all purposes. 
 Section 6.6 Entire Agreement. The Financing Documents contain the entire understanding of
the Parties with respect to the matters covered thereby and supersede any and all other written and oral communications, negotiations, commitments and writings with respect thereto. The provisions of this Agreement may be waived, modified,
supplemented or amended only by an instrument in writing signed by the authorized officer of each Party. 
  

 20 

 Section 6.7 Severability. If any provision contained in this Agreement shall be invalid,
illegal or unenforceable in any respect under any law, the validity, legality and enforceability of the remaining provisions shall not in any way be affected or impaired thereby. The Parties shall endeavor in good faith negotiations to replace the
invalid, illegal or unenforceable provisions with valid provisions the economic effect of which comes as close as possible to that of the invalid, illegal or unenforceable provision. 
 Section 6.8 Counterparts. This Agreement may be executed in several counterparts, and by each Party on separate counterparts, each of which
and any photocopies and facsimile copies thereof shall be deemed an original, but all of which together shall constitute one and the same agreement. 
 Section 6.9 Survival. 
 (a) This Agreement and all agreements, representations and
warranties made in the Financing Documents, and in any document, certificate or statement delivered pursuant thereto or in connection therewith shall be considered to have been relied upon by the other Parties and shall survive the execution and
delivery of this Agreement and the making of the Loan hereunder regardless of any investigation made by any such other Party or on its behalf, and shall continue in force until all amounts payable under the Financing Documents shall have been fully
paid in accordance with the provisions hereof and thereof, and the Lenders shall not be deemed to have waived, by reason of making the Loan, any Default that may arise by reason of such representation or warranty proving to have been false or
misleading, notwithstanding that the Lenders may have had notice or knowledge of any such Default or may have had notice or knowledge that such representation or warranty was false or misleading at the time any Disbursement was made hereunder.

 (b) The obligations of the Borrower under Section 2.7 and the obligations of the Borrower and the Lenders under this
Article VII hereof shall survive and remain in full force and effect regardless of the consummation of the transactions contemplated hereby, the repayment of the Loan, or the termination of this Agreement or any provision hereof. 
 Section 6.10 Waiver. Neither the failure of, nor any delay on the part of, any Party in exercising any right, power or privilege hereunder,
or under any agreement, document or instrument mentioned herein, shall operate as a waiver thereof, nor shall any single or partial exercise of any right, power or privilege hereunder, or under any agreement, document or instrument mentioned herein,
preclude other or further exercise thereof or the exercise of any other right, power or privilege; nor shall any waiver of any right, power, privilege or default hereunder, or under any agreement, document or instrument mentioned herein, constitute
a waiver of any other right, power, privilege or default or constitute a waiver of any default of the same or of any other term or provision. No course of dealing and no delay in exercising, or omission to exercise, any right, power or remedy
accruing to the Lenders upon any default under this Agreement, or any other agreement shall impair any such right, power or remedy or be construed to be a waiver thereof or an acquiescence therein; nor shall the action of the Lenders in respect of
any such default, or any acquiescence by it therein, affect or impair any right, power or remedy of the Lenders in respect of any other default. All rights and remedies herein provided are cumulative and not exclusive of any rights or remedies
otherwise provided by law. 
  

 21 

 Section 6.11 Indemnity. 
 (a) The Parties shall, at all times, indemnify and hold each other harmless (the “Indemnity”) and each of their
respective directors, partners, officers, employees, agents, counsel and advisors (each, an “Indemnified Person”) in connection with any losses, claims (including the cost of defending against such claims), damages, liabilities,
penalties, or other expenses arising out of, or relating to, the Financing Documents, the extension of credit hereunder or the Loan or the use or intended use of the Loan, which an Indemnified Person may incur or to which an Indemnified Person may
become subject (each, a “Loss”). The Indemnity shall not apply to the extent that a court or arbitral tribunal with jurisdiction over the subject matter of the Loss, and over the Lenders or the Borrower, as applicable, and such
other Indemnified Person that had an adequate opportunity to defend its interests, determines that such Loss resulted from the gross negligence or willful misconduct of the Indemnified Person, which determination results in a final, non-appealable
judgment or decision of a court or tribunal of competent jurisdiction. The Indemnity is independent of and in addition to any other agreement of any Party under any Financing Document to pay any amount to the Lenders or the Borrower, as applicable,
and any exclusion of any obligation to pay any amount under this subsection shall not affect the requirement to pay such amount under any other section hereof or under any other agreement. 
 (b) Without prejudice to the survival of any other agreement of any of the Parties hereunder, the agreements and the obligations of the
Parties contained in this Section 6.11 shall survive the termination of each other provision hereof and the payment of all amounts payable to the Lenders hereunder. 
 Section 6.12 No Usury. The Financing Documents are hereby expressly limited so that in no contingency or event whatsoever, whether by reason of acceleration or otherwise, shall the amount paid or agreed
to be paid to the Lenders for the Loan exceed the maximum amount permissible under applicable law. If from any circumstance whatsoever fulfillment of any provision hereof, at the time performance of such provision shall be due, shall involve
transcending the limit of validity prescribed by law, then, ipso facto, the obligation to be fulfilled shall be reduced to the limit of such validity, and if from any such circumstance the Lenders shall ever receive anything which might be deemed
interest under applicable law, that would exceed the highest lawful rate, such amount that would be deemed excessive interest shall be applied to the reduction of the principal amount owing on account of the Loan, or if such deemed excessive
interest exceeds the unpaid balance of principal of the Loan, such deemed excess shall be refunded to the Borrower. All sums paid or agreed to be paid to the Lenders for the Loan shall, to the extent permitted by applicable law, be deemed to be
amortized, prorated, allocated and spread throughout the full term of the Loan until payment in full so that the deemed rate of interest on account of the Loan is uniform throughout the term thereof. The terms and provisions of this paragraph shall
control and supersede every other provision of this Agreement and the Notes. 
 Section 6.13 Further Assurances. From time to
time, the Borrower shall perform any and all acts and execute and deliver to the Lenders such additional documents as may be necessary or as requested by the Lenders to carry out the purposes of any Financing Document or any or to preserve and
protect the Lenders’ rights as contemplated therein. 
  

 22 

 Section 6.14 Termination. Subject to the provisions of Section 6.9(b), upon repayment
of all outstanding principal of the Loan (together with any other amounts accrued and unpaid under this Agreement), the Borrower may terminate this Agreement upon 10 days’ notice to the Lenders. 
 Section 6.15 Amendment. This Agreement may be amended and waivers granted hereunder by Lenders that hold fifty one percent (51%) of
the aggregate principal amount of the Notes so long as such amendment or waiver treats all holders of the Notes the same. 
 [SIGNATURE
PAGE FOLLOWS] 
  

 23 

 IN WITNESS WHEREOF, the undersigned Lender and the Company have caused this Agreement to be duly executed
as of the date first written above. 
  

													
	COMPANY:	 	LENDER:
	ISTA PHARMACEUTICALS, INC.	 	DEERFIELD PRIVATE DESIGN FUND, L.P.
					
	By:	 	/s/ Vicente Anido, Jr., Ph.D.	 		 	By:	 	/s/ James Flynn
		 	Name: 	 	Vicente Anido, Jr., Ph.D.	 		 		 	Name: 	 	James Flynn
		 	Title:	 	President and Chief Executive Officer	 		 		 	Title:	 	General Partner
		
	LENDER:	 	LENDER:
	DEERFIELD PRIVATE DESIGN INTERNATIONAL, L.P.	 	DEERFIELD SPECIAL SITUATIONS FUND, L.P.
					
	By:	 	/s/ James Flynn	 		 	By:	 	/s/ James Flynn
		 	Name: 	 	James Flynn	 		 		 	Name: 	 	James Flynn
		 	Title:	 	General Partner	 		 		 	Title:	 	General Partner
		
	LENDER:	 	LENDER:
	DEERFIELD SPECIAL SITUATIONS FUND INTERNATIONAL LIMITED	 	SANDERLING VENTURE PARTNERS VI CO-INVESTMENT FUND, L.P.
		 	By: Middleton, McNeil, Mills & Associates VI, LLC
					
	By:	 	/s/ James Flynn	 		 	By:	 	/s/ Robert G. McNeil
		 	Name: 	 	James Flynn	 		 		 	Name: 	 	Robert G. McNeil
		 	Title:	 	General Partner	 		 		 	Title:	 	Managing Director
		
	LENDER:	 	LENDER:
	SANDERLING VI LIMITED PARTNERSHIP	 	SANDERLING VI BETEILIGUNGS GMBH & CO. KG
	By: Middleton, McNeil, Mills & Associates VI, LLC	 	
					
	By:	 	/s/ Robert G. McNeil	 		 	By:	 	/s/ Robert G. McNeil
		 	Name: 	 	Robert G. McNeil	 		 		 	Name: 	 	Robert G. McNeil
		 	Title:	 	Managing Director	 		 		 	Title:	 	Managing Director
		
	LENDER:	 	LENDER:
	SANDERLING VENTURES MANAGEMENT VI	 	SPROUT CAPITAL IX, L.P.
		 	By: DLJ Capital Corporation
		 	Its: Managing General Partner
					
	By:	 	/s/ Robert G. McNeil	 		 	By:	 	/s/ Craig L. Slutzkin
		 	Name: 	 	Robert G. McNeil	 		 		 	Name: 	 	Craig L. Slutzkin
		 	Title:	 	Owner	 		 		 	Title:	 	Attorney in Fact
		
	LENDER:	 	LENDER:
	SPROUT ENTREPRENEURS’ FUND, L.P.	 	SPROUT IX PLAN INVESTORS, L.P.
	By: DLJ Capital Corporation	 	By: DLJ LBO Plans Management Corporation II
	Its: General Partner	 	Its: General Partner
					
	By:	 	/s/ Craig L. Slutzkin	 		 	By:	 	/s/ Craig L. Slutzkin
		 	Name: 	 	Craig L. Slutzkin	 		 		 	Name: 	 	Craig L. Slutzkin
		 	Title:	 	Attorney in Fact	 		 		 	Title:	 	Attorney in Fact

 SCHEDULE 1 
 SCHEDULE OF LENDERS 
  

							
	 LENDER
	  	ALLOCATION OF
DISBURSEMENTS	 	 	ALLOCATION OF
WARRANTS	 
	 Deerfield Private Design Fund, L.P.,
	  	28.11	%	 	28.11	%
	 Deerfield Private Design International, L.P.,
	  	45.28	%	 	45.28	%
	 Deerfield Special Situations Fund, L.P.
	  	2.88	%	 	2.88	%
	 Deerfield Special Situations Fund International Limited
	  	5.28	%	 	5.28	%
	 Sprout Capital IX, L.P.
	  	10.23	%	 	10.23	%
	 Sprout Entrepreneurs’ Fund, L.P.
	  	0.04	%	 	0.04	%
	 Sprout IX Plan Investors, L.P.
	  	0.49	%	 	0.49	%
	 Sanderling Venture Partners VI Co-Investment Fund, L.P.
	  	7.01	%	 	7.01	%
	 Sanderling VI Limited Partnership
	  	0.16	%	 	0.16	%
	 Sanderling VI Beteiligungs GmbH & Co. KG
	  	0.14	%	 	0.14	%
	 Sanderling Ventures Management VI
	  	0.38	%	 	0.38	%

 SCHEDULE 2 
 FORM OF DISBURSEMENT REQUEST 
 [LETTERHEAD OF THE BORROWER] 
 [Date] 
 Ladies and Gentlemen: 
 Request for Disbursement of the Loan 
 1.
Please refer to the Facility Agreement (the “Facility Agreement”), dated as of September 26, 2008, between ISTA Pharmaceuticals, Inc. (the “Borrower”) and the Lenders (as defined therein). 
 2. Terms defined in the Facility Agreement shall have the same meanings herein. 
 3. The Borrower hereby requests a Disbursement, on [date], of the amount of [amount of drawdown], in accordance with the provisions of Section 2.2
of the Facility Agreement. You are requested to pay the amount to the following account [account number] at [name of bank]. 
 4. Attached
hereto is a signed but undated receipt for the amount hereby requested to be disbursed, and we hereby authorize the Lenders to date such receipt as of the date of actual disbursement by the Lenders of the funds hereby requested to be disbursed.

 5. The Borrower hereby certifies as follows: 
 (a) The representations and warranties in Article III of the Facility Agreement are true in all material respects on the date hereof with the same effect as though such representations and warranties had been
made on today’s date; and 
 (b) All of the conditions set forth in Article IV of the Facility Agreement have been
satisfied. 
 6. The above certifications are effective as of the date of this request for Disbursement and will continue to be effective as
of the Disbursement Date. If any of these certifications is no longer valid as of or prior to the Disbursement Date, the Borrower will immediately notify the Lenders and will repay the amount disbursed upon demand by the Lenders if Disbursement is
made prior to the receipt of such notice. 
  

			
	ISTA PHARMACEUTICALS, INC.
		
	By:	 	 
	Name: 	 	 
	Title:	 	 

 SCHEDULE 3 
 FORM OF EVIDENCE OF DISBURSEMENT 
 [LETTERHEAD OF THE BORROWER] 
 [Date] 
 Ladies and Gentlemen: 
  

	 	Re:	Disbursement Receipt 

 ISTA Pharmaceuticals, Inc. (the
“Borrower”) hereby acknowledge receipt of the sum of [insert amount of disbursement] disbursed to us by the Lenders (as defined therein) under the Loan provided for in the Facility Agreement, dated as of September 26, 2008,
between the Borrower and the Lenders. 
  

			
	Yours faithfully,
	
	ISTA PHARMACEUTICALS, INC.
		
	By:	 	 
	Name: 	 	 
	Title:	 	 

 EXHIBIT A 
 Form of Promissory Note 
 September __, 2008 
 FOR VALUE RECEIVED, ISTA Pharmaceuticals, Inc., a Delaware corporation (the “Maker”), by means of this Promissory Note (this
“Note”), hereby unconditionally promises to pay to              [            ] (the “Payee”), a
principal amount equal to the lesser of (a) $[            ] and (b) the aggregate amount of Disbursements allocated to the Payee pursuant to Section 2.2 of the Facility
Agreement (as defined below), as such principal amount is increased pursuant to the Facility Agreement, in lawful money of the United States of America and in immediately available funds, on the dates provided in the Facility Agreement. 

This Note is a “Note” referred to in the Facility Agreement dated as of the date hereof among the Maker, the Payee and the other parties
thereto (as modified and supplemented and in effect from time to time, the “Facility Agreement”), with respect to the Loan made by the Payee thereunder. Capitalized terms used herein and not expressly defined in this Note shall have
the respective meanings assigned to them in the Facility Agreement. 
 This Note shall bear interest on the principal amount hereof, as such
principal amount may be increased or decreased, at the rates and pursuant to the provisions set forth in the Facility Agreement. 
 The Maker
shall make all payments to the Payee of interest and principal under this Note in the manner provided in and otherwise in accordance with the Facility Agreement. The outstanding principal amount of this Note shall be due and payable in full on the
Final Payment Date. 
 If default is made in the punctual payment of principal or any other amount under this Note in accordance with the
Facility Agreement, or if any other Event of Default has occurred, this Note shall, at the Payee’s option exercised at any time upon or after the occurrence of any such payment default or other Event of Default and in accordance with the
applicable provisions of the Facility Agreement, become immediately due and payable. 
 All payments of any kind due to the Payee from the
Maker pursuant to this Note shall be made in the full face amount thereof. All such payments will be free and clear of, and without deduction or withholding for, any Taxes other than Excluded Taxes. The Maker shall pay all and any costs
(administrative or otherwise) imposed by banks, clearing houses, or any other financial institution, in connection with making any payments hereunder, except for any costs imposed by the Payee’s banking institutions. 
 The Maker shall pay all costs of collection, including, without limitation, all reasonable, documented legal expenses and attorneys’ fees, paid or
incurred by the Payee in collecting and enforcing this Note. 
 The Maker and every endorser of this Note, or the obligations represented
hereby, expressly waives presentment, protest, demand, notice of dishonor or default, and notice of any kind with respect to this Note and the Facility Agreement or the performance of the obligations under this Note and/or the Facility Agreement. No
renewal or extension of this Note or the Facility Agreement, no release of any Person primarily or secondarily liable on this Note or the Facility Agreement, including the Maker and any endorser, no delay in the enforcement of payment of this Note
or the Facility Agreement, and no delay or omission in exercising any right or power under this Note or the Facility Agreement shall affect the liability of the Maker or any endorser of this Note. 

 No delay or omission by the Payee in exercising any power or right hereunder shall impair such right or
power or be construed to be a waiver of any default, nor shall any single or partial exercise of any power or right hereunder preclude the full exercise thereof or the exercise of any other power or right. The provisions of this Note may be waived
or amended only in a writing signed by the Maker and the Payee. This Note may be prepaid in whole or in part without premium or penalty. 
 THIS NOTE, AND ANY RIGHTS OF THE PAYEE ARISING OUT OF OR RELATING TO THIS NOTE, MAY, AT THE OPTION OF THE PAYEE, BE ENFORCED BY THE PAYEE IN THE COURTS OF THE UNITED STATES OF AMERICA LOCATED IN THE SOUTHERN DISTRICT OF THE STATE OF NEW
YORK OR IN ANY OTHER COURTS HAVING JURISDICTION. FOR THE BENEFIT OF THE PAYEE, THE MAKER HEREBY IRREVOCABLY AGREES THAT ANY LEGAL ACTION, SUIT OR OTHER PROCEEDING ARISING OUT OF OR RELATING TO THIS NOTE MAY BE BROUGHT IN THE COURTS OF THE STATE OF
NEW YORK OR OF THE UNITED STATES OF AMERICA FOR THE SOUTHERN DISTRICT OF NEW YORK, AND HEREBY CONSENTS THAT PERSONAL SERVICE OF SUMMONS OR OTHER LEGAL PROCESS MAY BE MADE AS SET FORTH IN SECTION 6.4 OF THE FACILITY AGREEMENT, WHICH SERVICE THE
MAKER AGREES SHALL BE SUFFICIENT AND VALID. THE MAKER HEREBY WAIVES ANY AND ALL RIGHTS TO DEMAND A TRIAL BY JURY IN ANY ACTION, SUIT OR OTHER PROCEEDING ARISING OUT OF OR RELATING TO THIS NOTE OR THE TRANSACTIONS CONTEMPLATED BY THIS NOTE.

 This Note shall be governed by, and construed in accordance with, the laws of the State of New York applicable to contracts made and to be
performed in such State, without giving effect to the conflicts of laws principles thereof other than Sections 5-1401 and 5-1402 of the General Obligations Law of the State of New York. 
 Whenever this Note is held by a noteholder that is not a “United States person” within the meaning of Section 7701(a)(30) of the Internal
Revenue Code of 1986, as amended (the “Code”), then it is the intention of the Maker and such noteholder that (x) all interest accrued and paid on this Note will qualify for exemption from United States withholding tax as
“portfolio interest” because this Note is an obligation which is in “registered form” within the meaning of Sections 871(h)(2)(B) and 881(c)(2)(B) of the Code and the applicable Treasury Regulations promulgated thereunder, and
(y) as such, all interest accrued and paid on this Note will be exempt from United States information reporting under Sections 6041 and 6049 of the Code and United States backup withholding under Section 3406 of the Code. The Maker and the
Payee shall cooperate with one another, and execute and file such forms or other documents, or do or refrain from doing such other acts, as may be required, to secure such exemptions from United States withholding tax, information reporting, and
backup withholding. In furtherance of the foregoing, any transferee or assignee noteholder that is not a United States person shall represent, warrant and covenant to the Maker that (i) such noteholder is not, and will not be as long as any
amounts due under this Note have not been paid in full, a “United States person,” within the meaning of Section 7701(a)(30) of the Code; (ii) such noteholder is not, and will not be as long as any amounts due under this Note have
not been paid in full, a person described in Section 881(c)(3) of the Code; (iii) on or prior to the date of transfer or assignment (and on or prior 

 
to the date the form provided pursuant to this clause (iii) is no longer valid) until all amounts due under this Note have been paid in full, such
noteholder shall provide the Maker with a properly executed U.S. Internal Revenue Service (“IRS”) Form W-8BEN, Certificate of Foreign Status of Beneficial Owner for United States Tax Withholding (or any successor form prescribed by
the IRS), certifying as to such noteholder’s status for purposes of determining exemption from United States withholding tax, information reporting and backup withholding with respect to all payments to be made to such noteholder hereunder;
(iv) if an event occurs that would require a change in the exempt status of such noteholder or any of the other information provided on the most recent IRS Form W-8BEN (or successor form) previously submitted by such noteholder to the Maker,
such noteholder will so inform the Maker in writing (or by submitting to the Maker a new IRS Form W-8BEN or successor form) within 30 days after the occurrence of such event; and (v) such noteholder will not assign or otherwise transfer this
Note or any of its rights hereunder except in accordance with the provisions hereof. 
 In order to qualify as a “registered note”
for purposes of the Code, transfer of this Note may be effected only by (i) surrender of this Note to the Maker and the re-issuance of this Note to the transferee, or the Maker’s issuance to the Payee of a new note in the same form as this
Note but with the transferee denoted as the Payee, or (ii) the recording of the identity of the transferee by the Affiliate of the Payee that is maintaining a record ownership register of this Note as agent to, and on behalf of, the Maker. Such
Affiliate in its capacity as such agent shall notify the Maker in writing immediately upon any change in such identity. The terms and conditions of this Note shall be binding upon and inure to the benefit of the Maker and the Payee and their
permitted assigns; provided, however, that if any such assignment (whether by operation of law, by way of transfer or participation, or otherwise) is to any noteholder that is not a “United States person” within the meaning of
Section 7701(a)(30) of the Code, then such noteholder shall submit to the Maker on or before the date of such assignment an IRS Form W-8BEN (or any successor form) certifying as to such noteholder’s status for purposes of determining
exemption from United States withholding tax, information reporting and backup withholding with respect to all payments to be made to such noteholder under the new note (or other instrument). Any attempted transfer in violation of the relevant
provisions of this Note shall be void and of no force and effect. Until there has been a valid transfer of this Note and of all of the rights hereunder by the Payee in accordance with this Note, the Maker shall deem and treat the Payee as the
absolute beneficial owner and holder of this Note and of all of the rights hereunder for all purposes (including, without limitation, for the purpose of receiving all payments to be made under this Note). 
 It is the intention of the Maker and the Payee that this Note is to be a registered instrument and not a bearer instrument and the provisions of this
Note are to be interpreted accordingly. This Note is intended to be registered as to both principal and interest and all payments hereunder shall be made to the named Payee or, in the event of a transfer pursuant to the Facility Agreement and this
Note, to the transferee identified in the record of ownership of this Note maintained by the Payee on behalf of the Maker. Transfer of this Note may not be effected except in accordance with the provisions hereof. 

 IN WITNESS WHEREOF, an authorized representative of the Maker has executed this Note as of the date first
written above. 
 ISTA PHARMACEUTICALS, INC. 
  

			
	By:	 	 
		 	Name:
		 	Title:

 EXHIBIT B 
 Existing Liens 
 [intentionally omitted] 

 EXHIBIT C 
 Subordination Agreement 
 [intentionally omitted] 

 EXHIBIT D 
 Form of Warrant 
 [intentionally omitted]

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