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                                                                   EXHIBIT 10.46

          CONFIDENTIAL PORTIONS HAVE BEEN OMITTED BASED UPON A REQUEST
            FOR CONFIDENTIAL TREATMENT PURSUANT TO RULE 24b-2 OF THE
         SECURITIES EXCHANGE ACT OF 1934 AND HAVE BEEN SEPARATELY FILED
                              WITH THE COMMISSION.

                         AMENDMENT TO TIMOLOL AGREEMENT

         This Amendment (the "Amendment") is made this 13th day of August, 2002,
by and between ISTA Pharmaceuticals, Inc., a Delaware corporation ("ISTA"), and
Senju Pharmaceutical Co., Ltd., a legal entity organized and existing under the
laws of Japan ("Senju").

         WHEREAS, AcSentient, Inc., a Delaware corporation ("AcSentient"), sold
and assigned to ISTA all of AcSentient's rights and certain of its obligations
and liabilities under the Agreement by and between Senju and AcSentient, dated
as of April 17, 2002 regarding timolol ophthalmic preparation (the "Agreement"),
and ISTA has therefore become a party to the Agreement and Senju has elected to
continue the Agreement with ISTA;

         WHEREAS, SENJU and ISTA hereby desire to amend the provisions of the
Agreement and desire to confirm their respective obligations under the
Agreement;

         NOW, THEREFORE, ISTA and Senju agree that:

         1.       Capitalized wordings used in this Amendment shall have the
                  meanings set forth in the Agreement. All references to
                  AcSentient in the Agreement shall hereby refer to ISTA.

         2.       Paragraph 5.04 of the Agreement shall be amended to read in
                  its entirety;

                  5.04     All of the running royalties including minimum
                  royalties in paragraph 5.01 through 5.03 shall be paid to
                  SENJU within [ * ] following the end of each semi- annual
                  period according to SENJU's fiscal year which commences April
                  1 of a year and ends March 31 of the next year. [ * ] [ * ]
                  [ * ] [ * ]

         3.       Paragraph 6.01 of the Agreement shall be amended to read in
                  its entirety;

                  6.01     Upon the remittance of royalty from ISTA to SENJU
                  under paragraph 5.04 hereof, ISTA shall furnish SENJU with an
                  accurate report stating the total quantity of the Preparation
                  in units sold by ISTA and ISTA Agent during the preceding
                  semi-annual period, the grossed invoiced sales price and the
                  Net Sales thereof and amount of the royalties accrued,
                  together with written reports regarding marketing activities
                  stipulated in paragraphs 8.01 through 8.03 herein.

*  CONFIDENTIAL PORTIONS HAVE BEEN OMITTED BASED UPON A REQUEST FOR CONFIDENTIAL
   TREATMENT PURSUANT TO RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934 AND
   HAVE BEEN SEPARATELY FILED WITH THE COMMISSION.

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         4.       Paragraph 18.07 shall be deleted in its entirety.

         5.       Article 22 of the Agreement shall be amended to read in its
                  entirety;

                  This Agreement is personal to the Parties hereto and shall not
                  be assignable, transferable or saleable to any Third Party by
                  either party without the prior express written consent of the
                  other Party, such consent not to be unreasonable withheld;
                  provided, however, that no such consent shall be required from
                  SENJU if ISTA is merged or acquired by a Third Party.

         6.       Unless stated herein, all other terms and conditions of the
                  Agreement shall remain unchanged.

         7.       This Amendment shall be effective as of the date first set
                  forth above.

         8.       This Amendment, taken together with the Agreement, represent
                  the entire agreement of the parties and shall supersede any
                  and all previous contracts, arrangements or understandings
                  between the parties with respect to the Agreement.

         9.       This Amendment may be amended at any time only by mutual
                  written agreement of the parties hereto.

         10.      This Amendment may be executed in counterparts, each of which
                  so executed will be deemed to be an original and such
                  counterparts together will constitute one and the same
                  agreement.

         IN WITNESS WHEREOF, this Amendment has been entered into as of the date
first set forth above.

ISTA PHARMACEUTICALS, INC.                       SENJU PHARMACEUTICAL CO., LTD.

By:    /s/ Vicente Anido, Jr., Ph.D.             By:    /s/ Kimio Murakami
   -----------------------------------              ----------------------------
Name:  Vicente Anido, Jr., Ph.D.                 Name:  Kimio Murakami
Title: Chief Executive Officer                   Title: Executive Vice President