<PAGE>
                                                                    Exhibit 4.21

                              AMENDED AND RESTATED
                         CONTROL DELIVERY SYSTEMS, INC.
                           CHANGE OF CONTROL AGREEMENT

     AGREEMENT made this 17th day of August, 2004, by and between Michael J.
Soja ("Executive") and Control Delivery Systems, Inc. (the "Company").

     Whereas, the Board of Directors of the Company (the "Board") recognizes
that, as is the case with many corporations, the possibility of a Change of
Control (as defined in Exhibit A) may exist and that such possibility, and the
uncertainty and questions which it may raise among management personnel, may
result in the departure or distraction of management personnel to the detriment
of the Company and its stockholders;

     Whereas, the Board has determined that appropriate steps should be taken to
reinforce and encourage the continued attention and dedication of members of the
Company's management, including Executive, to their duties, to assisting the
Board in assessing proposals with respect to a Change of Control and to advising
the Board as to the best interests of the Company and its shareholders with
respect to such potential Change of Control, without distraction and conflict
arising from the possibility of a Change of Control; and

     Whereas, the Board wishes to induce Executive and other members of
management to remain in the employ of the Company and to assure them of fair
severance should the employment of any of them terminate in specified
circumstances following a Change of Control of the Company;

     NOW, THEREFORE, in consideration of the premises and the mutual promises,
terms and conditions contained herein, the parties hereto agree as follows:

     1. Severance Benefits Following a Change of Control

          (a) Entitlement to Severance Benefits. If during that period starting
     on the date of a Change of Control and ending on the second anniversary of
     the Change of Control, the Company terminates Executive's employment
     without Cause, or if Executive terminates his employment for Good Reason,
     the Company will, subject to Section 2 below, provide severance benefits to
     Executive as set forth below in this Section 1.

          "Good Reason" means (i) failure by the Company to maintain Executive
     in the position of Vice President, Chief Financial Officer including
     holding the title of and serving as Vice President, Chief Financial Officer
     of the Company and having responsibility for performing all duties
     typically undertaken by such offices or assignment to Executive of duties
     materially inconsistent with such positions, (ii) the diminution in any
     material respect of Executive's positions or authority, excluding for this
     purpose an isolated, insubstantial and inadvertent action not taken in bad
     faith and which is remedied by the Company promptly after receipt of notice
     thereof given by Executive, (iii) failure by the Company to provide
     Executive with Base Salary as well as

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     with the compensation (including without limitation bonus and other
     incentive compensation) Executive was receiving immediately prior to the
     Change of Control and with Benefits, or (iv) relocation of Executive's
     principal place of work to a location more than 30 miles from its current
     location without Executive's consent. For purposes of this definition of
     Good Reason, "Company" means Control Delivery Systems and any successor of
     Control Delivery Systems, provided if any such successor has a parent, then
     Company shall mean the ultimate parent corporation.

          "Cause" means only (a) willful malfeasance or gross negligence in the
     performance by Executive of his or her duties, resulting in material harm
     to the Company, (b) fraud or dishonesty by Executive with respect to the
     Company, or (c) Executive's conviction of any felony involving deception,
     fraud or moral turpitude. The Company may treat a termination of
     Executive's employment as termination for Cause only after (i) giving
     Executive written notice of the intention to terminate for Cause and of his
     or her right to a hearing by the Board, (ii) at least 30 days after giving
     the notice, conducting a hearing by the Board at which Executive may be
     represented by counsel, and (iii) giving Executive 30 days' written notice
     of the results of the hearing, which shall require a vote of a majority of
     the Directors then in office other than Executive. For purposes of this
     definition of Cause, no act or omission shall be considered to have been
     "willful" unless it was not in good faith and Executive had knowledge at
     the time that the act or omission was not in the best interest of the
     Company. Any act or failure to act based on authority given pursuant to a
     resolution duly adopted by the Board or based on the advice of counsel of
     the Company shall be conclusively presumed to be done, or omitted to be
     done, by Executive in good faith and in the best interest of the Company.
     Cause shall not include willful failure due to incapacity resulting from
     physical or mental illness or any actual or anticipated failure after
     Notice of Termination for Good Reason.

          "Base Salary" means $272,497, provided that in the event the Board in
     its sole discretion increases Executive's Base Salary above $272,497, the
     Base Salary as so increased will be referred to as "Base Salary."

          "Benefits" means the following plans, policies and arrangements (or in
     any successor or supplemental plans, policies or arrangements), if and to
     the extent maintained by the Company, in each case at a level appropriate
     to Executive's position as determined by the Board and in each case in
     accordance with the terms of the pertinent plan, policy or arrangement:

          (i) the Company's 2001 Incentive Plan;

          (ii) the Company's group medical plan;

          (iii) life insurance arrangements or disability plan arrangements
     provided to executive-level employees of the Company;


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<PAGE>

          (iv) all the Company's equity plans in which executives of the Company
     participate;

          (v) the Company's normal expense reimbursement policies; and

          (vi) ordinary vacation arrangements provided to executive-level
     employees of the Company, including at least four weeks paid vacation in
     addition to Company holidays per year.

          (b) Severance Benefits Following a Change of Control. The Company will
     provide severance benefits to Executive as follows:

          (i) The Company will pay to Executive within 30 days of the
     termination a lump-sum cash amount equal to 200% of the sum of (x) Base
     Salary, plus (y) the greater of (1) 100 percent of his bonus for the
     completed year immediately preceding the Change of Control, and (2) 100
     percent of his bonus for the immediately preceding employment year.

          (ii) The Company will also pay to Executive within 30 days of the
     termination a pro-rata portion of his maximum bonus for the year of
     termination.

               (A) For purposes of this Section 1(b), the maximum bonus payable
          in such year will be calculated assuming all bonus targets or formulas
          for determining the bonus in such year had been met if Executive and
          Board had, prior to the termination of Executive's employment, agreed
          on such targets or formulas.

               (B) If no such targets or formulas have been set as of such
          termination date, then the maximum bonus shall be deemed to be the
          greater of (x) 100 percent of his bonus for the completed year
          immediately preceding the Change of Control, and (y) 100 percent of
          his bonus for the immediately preceding employment year.

          (iii) The Company will continue for a period of two years from the
     date of termination to provide Executive with medical benefits under the
     Company's group medical plan and life insurance arrangements and disability
     arrangements provided to executive level employees of the Company. To the
     extent the Company is unable to provide such benefits to Executive under
     its existing plans and arrangements, it will either arrange to provide
     Executive with substantially similar benefits upon comparable terms or pay
     Executive cash amounts equal to Executive's cost of obtaining such
     benefits.

          (iv) All options to purchase Company stock held by Executive will
     automatically and immediately vest and become exercisable upon such
     termination and remain exercisable for a period of one year following such
     termination, and all restricted stock held by Executive under restricted
     stock plans and arrangements of the Company shall automatically and
     immediately vest and no longer be subject to forfeiture upon such


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     termination. The Company agrees that it will not exercise any right that
     the Company has to purchase, repurchase or reacquire all or any part of
     such vested stock.

     2. Taxes on Severance Benefits.

     2.1 Withholding. All payments required to be made by the Company hereunder
to Executive or his dependents, beneficiaries, or estate will be subject to the
withholding of such amounts relating to tax and/or other payroll deductions as
may be required by law.

     2.2 Section 4999 Excise Taxes. In the event that it is determined that any
payment or benefit provided by the Company to or for the benefit of Executive,
either under this Agreement or otherwise, will be subject to the excise tax
imposed by Section 4999 of the Internal Revenue Code or any successor
provision(s) ("Section 4999"), the Company will, prior to the date on which any
amount of the excise tax must be paid or withheld, make an additional lump-sum
payment (the "Gross-up Payment") to Executive in an amount sufficient, after
giving effect to all federal, state and other taxes and charges (including
interest and penalties, if any) with respect to the gross-up payment, to make
Executive whole for all taxes (including withholding taxes) and any associated
interest and penalties, imposed under or as a result of Section 4999.

     2.3 Selection of Accounting Firm. Determinations under this Section 2 will
be made by PricewaterhouseCoopers, LLP or if PricewaterhouseCoopers, LLP is
unable or unwilling to serve or if the Company and Executive otherwise
determine, by another firm mutually agreed to by the Company and Executive (the
"Firm"). The determinations of the Firm will be binding upon the Company and
Executive except as the determinations are established in resolution (including
by settlement) of a controversy with the Internal Revenue Service to have been
incorrect. All fees and expenses of the Firm will be paid by the Company.

     2.4 IRS Claims. If the Internal Revenue Service asserts a claim that, if
successful, would require the Company to make a Gross-up Payment or an
additional Gross-up Payment, the Company and Executive will cooperate fully in
resolving the controversy with the Internal Revenue Service. The Company will
make or advance such Gross-up Payments as are necessary to prevent Executive
from having to bear the cost of payments made to the Internal Revenue Service in
the course of, or as a result of, the controversy. The Firm will determine the
amount of such Gross-up Payments or advances and will determine after final
resolution of the controversy whether any advances must be returned by Executive
to the Company. The Company will bear all expenses of the controversy and will
gross Executive up for any additional taxes that may be imposed upon Executive
as a result of its payment of such expenses.

     3. Withholding. All payments required to be made by the Company to
Executive under this Agreement will be subject to the withholding of such
amounts, if any, relating to tax and other payroll deductions as may be required
by law.

     4. Fees and Expenses. In the event of Executive's termination of employment
during that period starting on the date of a Change of Control and ending on the
second anniversary of


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the Change of Control, the Company will pay any and all fees and expenses
(including legal fees and other costs of arbitration or litigation) that may be
incurred by Executive in enforcing his rights under this Agreement.

     5. No Duty to Mitigate. Benefits payable under this Agreement as a result
of termination of Executive's employment will be considered severance pay in
consideration of his past service and his continued service from the Effective
Date, and his entitlement thereto will neither be governed by any duty to
mitigate his damages by seeking further employment nor offset by any
compensation that he may receive from other employment.

     6. Confidentiality. Executive agrees to maintain the confidentiality of the
Company's (and its related entities and projects) books, records, financial
information, technical information, business plans and/or strategies, and other
confidential matters unless required to make disclosure in the performance of
his duties for the Company or as a result of a legal proceeding or other legally
mandated cause. Executive further agrees to abide by all of the terms of the
Confidentiality and Inventions Agreement dated as of __________.

     The parties recognize and agree that should the Company be required to
pursue a claim against Executive under this Section 6, the Company will likely
be required to seek injunctive relief as well as damages at law. Accordingly,
Section 8, Arbitration, will not apply to any action by the Company against
Executive for violation of this Section 6.

     7. Indemnification. To the extent permitted by law, the Company will
defend, indemnify and hold Executive harmless from and against any and all
losses, liabilities, damages, expenses (including attorneys' fees and costs),
actions, causes of action or proceedings arising directly or indirectly from
Executive's performance of this Agreement or services as an employee of the
Company. Executive may retain his own counsel to defend himself in such actions,
and the Company will pay for the reasonable costs and expense of such counsel.
This indemnification is in addition to any right of indemnification to which
Executive may be entitled under the Company's Articles of Incorporation and
By-laws, any separate indemnification agreements between the Company and
Executive, and any insurance policies that may be maintained by the Company.

     8. Arbitration. Except as otherwise provided in Section 6, any dispute or
controversy between the parties involving the construction or application of any
terms, covenants or conditions of this Agreement, or any claim arising out of or
relating to this Agreement, or any claim arising out of or relating to
Executive's employment by the Company that is not resolved within ten days by
the parties will be settled by arbitration in Boston, Massachusetts, in
accordance with the rules of the American Arbitration Association then in
effect, and judgment upon the award rendered by the arbitrator(s) may be entered
in any court having jurisdiction thereof. The Company and Executive agree that
the arbitrator(s) will have no authority to award punitive or exemplary damages
or so-called consequential or remote damages such as damages for emotional
distress. Any decision of the arbitrator(s) will be final and binding upon the
parties. Either party may request that the arbitrator(s) submit written findings
of fact and


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<PAGE>

conclusions of law. The parties agree and understand that they hereby waive
their rights to a jury trial of any dispute or controversy relating to the
matters specified above in this Section 8.

     9. Rights of Survivors If Executive dies after becoming entitled to
benefits under Section 1 following termination of employment but before all such
benefits have been provided, (a) all unpaid cash amounts will be paid to the
beneficiary that has been designated by Executive in writing (the
"beneficiary"), or if none, to Executive's estate, (b) all applicable insurance
coverage will be provided to Executive's family as though Executive had
continued to live, and (c) any stock options that become exercisable under
Section 1 will be exercisable by the beneficiary, or if none, the estate.

     10. Successors. This Agreement will inure to and be binding upon the
Company's successors. The Company will require any successor to all or
substantially all of the business and/or assets of the Company by sale, merger
or consolidation (where the Company is not the surviving corporation), lease or
otherwise, by agreement in form and substance satisfactory to Executive, to
assume this Agreement expressly. This Agreement is not otherwise assignable by
the Company or the Executive.

     11. Amendment or Modification; Waiver. This Agreement may not be amended
unless agreed to in writing by Executive and the Company. No waiver by either
party of any breach of this Agreement will be deemed a waiver of a subsequent
breach.

     12. Severability. In the event that any provision of this Agreement is
determined to be invalid or unenforceable, the remaining provisions shall remain
in full force and effect to the fullest extent permitted by law.

     13. Controlling Law. This Agreement will be controlled and interpreted
pursuant to Massachusetts law, other than its choice of law principles.

     14. Entire Agreement. This Agreement (including without limitation the
Exhibits hereto) constitutes the entire agreement and supersedes conflicting
terms in all prior agreements and undertakings, both written and oral, between
Executive and the Company with respect to the subject matter hereof. Except as
otherwise set forth herein, the terms and conditions of all other agreements
with Executive, including without limitation all Restricted Stock Award
Agreements and a Confidentiality and Inventions Agreement, shall continue in
full force and effect.

     15. Notices. Any notices required or permitted to be sent under this
Agreement are to be delivered by hand or mailed by registered or certified mail,
return receipt requested, and addressed as follows:

If to the Company:

     Control Delivery Systems, Inc.
     400 Pleasant Street
     Watertown, MA 02472


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If to Executive:

     Michael J. Soja
     34 Musket Lane
     Sudbury, MA 01776

Either party may change its address for receiving notices by giving notice to
the other party.

     16. Release. Notwithstanding anything to the contrary contained in this
Agreement, in order for Executive to be eligible for the severance benefits to
be provided in accordance with this Agreement, Executive must sign (and not
revoke within seven days of signing) a release of claims in the form attached
hereto and marked Exhibit B.

            [THE REMAINDER OF THIS PAGE IS INTENTIONALLY LEFT BLANK.]


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<PAGE>

     In witness whereof, the parties hereto have executed this Agreement as of
the date first set forth above.


                                        By: /s/ Michael J. Soja
                                            ------------------------------------
                                        Name: Michael J. Soja


                                        CONTROL DELIVERY SYSTEMS, INC.


                                        By: /s/ Paul Ashton
                                            ------------------------------------
                                        Name: Paul Ashton
                                        Title: Chief Executive Officer &
                                               President


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<PAGE>

                                    Exhibit A

     "Change of Control" means the occurrence of any of the following events:

          (a) The acquisition by any Person or group of the ultimate beneficial
     ownership (within the meaning of Rule 13d-3 promulgated under the
     Securities Exchange Act of 1934, as amended (the "Exchange Act")) of more
     than 50% of the then outstanding securities of the Company entitled to vote
     generally in the election of directors; excluding, however, the following:
     (i) any acquisition directly from the Company (other than any acquisition
     by virtue of the exercise of an exercise, conversion or exchange privilege
     unless the security being so exercised, converted or exchanged was itself
     acquired directly from the Company); (ii) any acquisition by the Company;
     (iii) any acquisition by an employee benefit plan (or related trust)
     sponsored or maintained by the Company or by any corporation controlled by
     the Company; (iv) any acquisition by the Executive, by an Executive Related
     Party (as defined in Exhibit A) or by a group of which the Executive is a
     member; or (v) any acquisition by any corporation pursuant to a transaction
     which complies with clauses (i), (ii) and (iii) of subsection (c) of this
     Exhibit A; or

          (b) Individuals who, as of the date hereof, constitute the Board (the
     "Incumbent Board") cease for any reason to constitute at least a majority
     of the Board; provided, however, that any individual becoming a director
     subsequent to the date hereof whose election, or nomination for election,
     by the Company's shareholders, was approved by a vote of at least a
     majority of the directors then comprising the Incumbent Board shall be
     considered as though such individual were a member of the Incumbent Board,
     but excluding, for this purpose, any such individual whose initial
     assumption of office occurs as a result of an actual or threatened election
     contest with respect to the election or removal of directors or other
     actual or threatened solicitation of proxies or consents by or on behalf of
     a Person other than the Board; or

          (v) A reorganization, recapitalization, merger or consolidation (a
     "Corporate Transaction") of the Company, unless (i) securities representing
     more than 50% of the then outstanding securities entitled to vote generally
     in the election of directors of the Company or the corporation resulting
     from or surviving such Corporate Transaction (or the ultimate parent of the
     Company or such corporation after such Corporate Transaction) are
     beneficially owned subsequent to such Corporate Transaction by the Person
     or Persons who were the beneficial owners of the outstanding securities of
     the Company entitled to vote generally in the election of directors
     immediately prior to such Corporate Transaction, in substantially the same
     proportions as their ownership immediately prior to such Corporate
     Transaction; (ii) no Person (excluding any corporation resulting from such
     Corporate Transaction or any employee benefit plan (or related trust) of
     the Company or such corporation resulting from such Corporate Transaction)
     ultimately beneficially owns, directly or indirectly, more than 50% of the
     then outstanding securities entitled to vote generally in the election of
     directors of the Company or the corporation resulting from or surviving
     such Corporate Transaction (or the ultimate parent of the
<PAGE>

     Company or such corporation after such Corporate Transaction) except to the
     extent that such ownership existed prior to the Corporate Transaction; and
     (iii) at least a majority of the members of the board of directors of the
     corporation resulting from such Corporate Transaction were members of the
     Incumbent Board at the time of the execution of the initial agreement, or
     of the action of the Board, providing for such Corporate Transaction; or

          (c) The sale, transfer or other disposition of all or substantially
     all of the assets of the Company; or

          (vi) Approval by the shareholders of the Company of a complete
     liquidation or dissolution of the Company.

     For purposes of this definition, securities entitled to vote generally in
the election of directors that are issuable upon exercise of an exercise,
conversion or exchange privilege shall be deemed to be outstanding. In addition,
for purposes of this definition the following terms have the meanings set forth
below:

     A Person will be deemed to be the "owner" of any securities of which such
Person would be the "beneficial owner," as such term is defined in Rule 13d-3
promulgated by the Securities and Exchange Commission under the Exchange Act.

     "Person" has the meaning used in Section 13(d) of the Exchange Act, except
that "Person" does not include (i) the Executive, an Executive Related Party, or
any group of which the Executive or Executive Related Party is a member, or (ii)
the Company or a wholly owned subsidiary of the Company or an employee benefit
plan (or related trust) of the Company or of a wholly owned subsidiary.

     An "Executive Related Party" means any affiliate or associate of the
Executive other than the Company or a subsidiary of the Company. The terms
"affiliate" and "associate" have the meanings given in Rule 12b-2 under the
Exchange Act; the term "registrant" in the definition of "associate" means, in
this case, the Company.


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                                    EXHIBIT B

                                RELEASE OF CLAIMS

     FOR AND IN CONSIDERATION OF the benefits to be provided me in connection
with the termination of my employment, as set forth in the Amended and Restated
Change of Control Agreement between me and Control Delivery Systems, Inc. (the
"Company") dated as of August 17, 2004 (the "Agreement"), which benefits are
subject to my signing of this Release of Claims and to which I am not otherwise
entitled, and for other good and valuable consideration, the receipt and
sufficiency of which is hereby acknowledged, I, on my own behalf and on behalf
of my heirs, executives, administrators, beneficiaries, representatives and
assigns, and all others connected with me, hereby release and forever discharge
the Company, its subsidiaries and other affiliates and all of their respective
past, present and future officers, directors, trustees, shareholders, employees,
agents, general and limited partners, members, managers, joint venturers,
representatives, successors and assigns, and all others connected with any of
them, both individually and in their official capacities, from any and all
causes of action, rights and claims of any type or description, known or
unknown, which I have had in the past, now have, or might now have, through the
date of my signing of this Release of Claims, in any way resulting from, arising
out of or connected with my employment by the Company or any of its subsidiaries
or other affiliates or the termination of that employment or pursuant to any
federal, state or local law, regulation or other requirement (including without
limitation Title VII of the Civil Rights Act of 1964, the Age Discrimination in
Employment Act, the Americans with Disabilities Act, and the fair employment
practices laws of the state or states in which I have been employed by the
Company or any of the subsidiaries or other affiliates, each as amended from
time to time).

     Excluded from the scope of this Release of Claims is (i) any claim arising
under the terms of the Agreement and (ii) any right of indemnification or
contribution that I have pursuant to the Articles of Incorporation or By-Laws of
the Company or any of its subsidiaries or other affiliates.

     In signing this Release of Claims, I acknowledge my understanding that I
may not sign it prior to the termination of my employment, but that I may
consider the terms of this Release of Claims for up to twenty-one (21) days (or
such longer period as the Company may specify) from the later of the date my
employment with the Company terminates or the date I receive this Release of
Claims. I also acknowledge that I am advised by the Company and its Affiliates
to seek the advice of an attorney prior to signing this Release of Claims; that
I have had sufficient time to consider this Release of Claims and to consult
with an attorney, if I wished to do so, or to consult with any other person of
my choosing before signing; and that I am signing this Release of Claims
voluntarily and with a full understanding of its terms.

     I further acknowledge that, in signing this Release of Claims, I have not
relied on any promises or representations, express or implied, that are not set
forth expressly in the Agreement. I understand that I may revoke this Release of
Claims at any time within seven (7) days of the date of my signing by written
notice to the General Counsel of the Company and that this


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<PAGE>

Release of Claims will take effect only upon the expiration of such seven-day
revocation period and only if I have not timely revoked it.

Intending to be legally bound, I have signed this Release of Claims under seal
as of the date written below.


Signature:
           --------------------------
Name (please print):
                     ----------------
Date Signed:
             ------------------------


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