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  <xsd:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd" />
  <xsd:import namespace="http://fasb.org/us-roles/2025" schemaLocation="https://xbrl.fasb.org/us-gaap/2025/elts/us-roles-2025.xsd" />
  <xsd:import namespace="http://fasb.org/us-gaap/2025" schemaLocation="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd" />
  <xsd:import namespace="http://fasb.org/srt/2025" schemaLocation="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd" />
  <xsd:import namespace="http://xbrl.sec.gov/ecd-sub/2025" schemaLocation="https://xbrl.sec.gov/ecd/2025/ecd-sub-2025.xsd" />
  <xsd:element name="SecuritiesPurchaseAgreementNovember2025Member" id="kala_SecuritiesPurchaseAgreementNovember2025Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="SeriesAaNonRedeemableNonControllingPreferredStockMember" id="kala_SeriesAaNonRedeemableNonControllingPreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element id="kala_DevelopmentCostsCurrent" name="DevelopmentCostsCurrent" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <xsd:element id="kala_ClassOfWarrantOrRightExercisable" name="ClassOfWarrantOrRightExercisable" nillable="true" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <xsd:element id="kala_Warrants2016Member" name="Warrants2016Member" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <xsd:element id="kala_IncreaseDecreaseInLeaseAndOtherLiabilitiesNoncurrent" name="IncreaseDecreaseInLeaseAndOtherLiabilitiesNoncurrent" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit" />
  <xsd:element id="kala_AccruedRevenueReserves" name="AccruedRevenueReserves" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <xsd:element id="kala_EmployeeStockPurchasePlanMember" name="EmployeeStockPurchasePlanMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <xsd:element id="kala_NonCashOperatingLease" name="NonCashOperatingLease" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit" />
  <xsd:element id="kala_RestrictedCashAndOtherAssetsNoncurrent" name="RestrictedCashAndOtherAssetsNoncurrent" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="kala_PrepaidLicenses" name="PrepaidLicenses" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="kala_StockWarrantsTextBlock" name="StockWarrantsTextBlock" nillable="true" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <xsd:element name="CombangioIncMember" id="kala_CombangioIncMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="FirstPatientDosedWithAnyProductInPhase2ClinicalTrialDosingMilestoneMember" id="kala_FirstPatientDosedWithAnyProductInPhase2ClinicalTrialDosingMilestoneMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="PotentialMaximumPayoutForContingentConsideration" id="kala_PotentialMaximumPayoutForContingentConsideration" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="PotentialPayoutForContingentConsiderationUponAchievementOfSpecifiedDevelopmentRegulatoryAndCommercialMilestones" id="kala_PotentialPayoutForContingentConsiderationUponAchievementOfSpecifiedDevelopmentRegulatoryAndCommercialMilestones" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="AssetAcquisitionContingentMilestoneConsiderationPayable" id="kala_AssetAcquisitionContingentMilestoneConsiderationPayable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="ScenarioAchievementOfSalesBasedMilestoneRelatingToKpi012ProductMember" id="kala_ScenarioAchievementOfSalesBasedMilestoneRelatingToKpi012ProductMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="GainLossOnFairValueReMeasurementOfContingentConsideration" id="kala_GainLossOnFairValueReMeasurementOfContingentConsideration" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="SeriesENonRedeemableNonControllingPreferredStockMember" id="kala_SeriesENonRedeemableNonControllingPreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="AssetAcquisitionContingentMilestoneConsiderationCashPaid" id="kala_AssetAcquisitionContingentMilestoneConsiderationCashPaid" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="AssetAcquisitionContingentMilestoneConsiderationEquityInterestIssuedOrIssuable" id="kala_AssetAcquisitionContingentMilestoneConsiderationEquityInterestIssuedOrIssuable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="AssetAcquisitionContingentMilestoneConsiderationNumberOfEquityInterestIssuedOrIssuable" id="kala_AssetAcquisitionContingentMilestoneConsiderationNumberOfEquityInterestIssuedOrIssuable" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="TaxCreditCarryforwardAmountAnnualLimitation" id="kala_TaxCreditCarryforwardAmountAnnualLimitation" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="debit" />
  <xsd:element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorizedAnnuallyPercent" id="kala_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorizedAnnuallyPercent" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="AwardAgreementMember" id="kala_AwardAgreementMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="CaliforniaInstituteForRegenerativeMedicineMember" id="kala_CaliforniaInstituteForRegenerativeMedicineMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="AnnualLimitOnNonEmployeeDirectorCompensationForIncumbentDirectors" id="kala_AnnualLimitOnNonEmployeeDirectorCompensationForIncumbentDirectors" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="AnnualLimitOnNonEmployeeDirectorCompensationForDirectorsFirstYearOfService" id="kala_AnnualLimitOnNonEmployeeDirectorCompensationForDirectorsFirstYearOfService" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="GrantIncomeAbstract" id="kala_GrantIncomeAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="GrantIncomeTextBlock" id="kala_GrantIncomeTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="GrantIncomeTable" id="kala_GrantIncomeTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="GrantIncomeLineItems" id="kala_GrantIncomeLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="IncomeFromGrants" id="kala_IncomeFromGrants" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="SeriesFNonRedeemableNonControllingPreferredStockMember" id="kala_SeriesFNonRedeemableNonControllingPreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="SeriesGNonRedeemableNonControllingPreferredStockMember" id="kala_SeriesGNonRedeemableNonControllingPreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="StockIssuedDuringPeriodSharesNewIssuesConversionOfPreferredStock" id="kala_StockIssuedDuringPeriodSharesNewIssuesConversionOfPreferredStock" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="StockIssuedDuringPeriodSharesNewIssuesSharesConversionOfPreferredStock" id="kala_StockIssuedDuringPeriodSharesNewIssuesSharesConversionOfPreferredStock" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="SeriesHNonRedeemableNonControllingPreferredStockMember" id="kala_SeriesHNonRedeemableNonControllingPreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="ScenarioAchievementOfSpecifiedDevelopmentAndRegulatoryMilestonesRelatingToKPI012ProductMember" id="kala_ScenarioAchievementOfSpecifiedDevelopmentAndRegulatoryMilestonesRelatingToKPI012ProductMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="AnnualLicenseMaintenanceFeesUponAchievementOfSpecificMilestones" id="kala_AnnualLicenseMaintenanceFeesUponAchievementOfSpecificMilestones" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="SeriesINonRedeemableNonControllingPreferredStockMember" id="kala_SeriesINonRedeemableNonControllingPreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="SingleReportingSegmentMember" id="kala_SingleReportingSegmentMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="ResearchAndDevelopmentExpenseProductDevelopmentCosts" id="kala_ResearchAndDevelopmentExpenseProductDevelopmentCosts" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="debit" />
  <xsd:element name="ResearchAndDevelopmentExpenseEmployeeRelatedCosts" id="kala_ResearchAndDevelopmentExpenseEmployeeRelatedCosts" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="debit" />
  <xsd:element name="AmendedAndRestatedEquityIncentivePlan2017Member" id="kala_AmendedAndRestatedEquityIncentivePlan2017Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="PaymentsOfCommonStockAndPreferredIssuanceCosts" id="kala_PaymentsOfCommonStockAndPreferredIssuanceCosts" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="UnvestedRestrictedStockUnitsMember" id="kala_UnvestedRestrictedStockUnitsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="NumberOfClosings" id="kala_NumberOfClosings" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="SeriesAaConvertibleNonRedeemablePreferredStockMember" id="kala_SeriesAaConvertibleNonRedeemablePreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="SeriesAaaConvertibleNonRedeemablePreferredStockMember" id="kala_SeriesAaaConvertibleNonRedeemablePreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="SecuritiesPurchaseAgreementJanuary2026Member" id="kala_SecuritiesPurchaseAgreementJanuary2026Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="YounetMember" id="kala_YounetMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="PlatformDevelopmentAndExclusiveLicenseAgreementMember" id="kala_PlatformDevelopmentAndExclusiveLicenseAgreementMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="LicenseAgreementInitialTerm" id="kala_LicenseAgreementInitialTerm" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="LicenseAgreementRenewalTerm" id="kala_LicenseAgreementRenewalTerm" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="LicenseAgreementMaximumCashFees" id="kala_LicenseAgreementMaximumCashFees" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="LicenseAgreementPaymentOfCashFees" id="kala_LicenseAgreementPaymentOfCashFees" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="LicenseAgreementCashFeesAmountPayable" id="kala_LicenseAgreementCashFeesAmountPayable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="LicenseAgreementCashFeesNumberOfPaymentInstallments" id="kala_LicenseAgreementCashFeesNumberOfPaymentInstallments" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" />
  <xsd:element name="LicenseAgreementCashFeesAmountOfPaymentInstallments" id="kala_LicenseAgreementCashFeesAmountOfPaymentInstallments" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="LicenseAgreementTerminationNoticePeriod" id="kala_LicenseAgreementTerminationNoticePeriod" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="LicenseAgreementSharesAgreedToIssue" id="kala_LicenseAgreementSharesAgreedToIssue" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" />
  <xsd:element name="LicenseAgreementCashPaymentAmountRenewalTerm" id="kala_LicenseAgreementCashPaymentAmountRenewalTerm" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="LicenseAgreementSharesAgreedToIssueRenewalTerm" id="kala_LicenseAgreementSharesAgreedToIssueRenewalTerm" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" />
  <xsd:element name="LicenseAgreementShareIssuancePeriodRenewalPeriod" id="kala_LicenseAgreementShareIssuancePeriodRenewalPeriod" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="LicenseAgreementMaximumDailyTradingVolumePercentage" id="kala_LicenseAgreementMaximumDailyTradingVolumePercentage" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" />
  <xsd:element name="LicenseAgreementOptionToAcquireEquityInterestsOrAllAssetsPurchasePrice" id="kala_LicenseAgreementOptionToAcquireEquityInterestsOrAllAssetsPurchasePrice" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="SeriesAaConvertibleNonRedeemablePreferredStockAndSeriesaaaConvertibleNonRedeemablePreferredStockMember" id="kala_SeriesAaConvertibleNonRedeemablePreferredStockAndSeriesaaaConvertibleNonRedeemablePreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="FinancingReceivableFaceAmount" id="kala_FinancingReceivableFaceAmount" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="debit" />
  <xsd:element name="ProceedsFromPreferredStockReservedForFutureIssuance" id="kala_ProceedsFromPreferredStockReservedForFutureIssuance" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="debit" />
  <xsd:element name="FinancingReceivableInterestRatePercentage" id="kala_FinancingReceivableInterestRatePercentage" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" />
  <xsd:element name="FinancingReceivableGracePeriodToMakePayment" id="kala_FinancingReceivableGracePeriodToMakePayment" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="FinancingReceivableDefaultInterestRatePercentage" id="kala_FinancingReceivableDefaultInterestRatePercentage" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" />
  <xsd:element name="AnnualLicenseMaintenanceFee" id="kala_AnnualLicenseMaintenanceFee" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="debit" />
  <xsd:element name="ShortTermInvestmentsTextBlock" id="kala_ShortTermInvestmentsTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="CollaborativeArrangementDisclosureAbstract" id="kala_CollaborativeArrangementDisclosureAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="PrivatePlacementAbstract" id="kala_PrivatePlacementAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="PrivatePlacementTextBlock" id="kala_PrivatePlacementTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="SeriesAaaNonRedeemableNonControllingPreferredStockMember" id="kala_SeriesAaaNonRedeemableNonControllingPreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
</xsd:schema>
