Conditions: Inflammation Eye Pain Postoperative Cataract
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 241
Healthy volunteers: no

Brief summary:
This was a randomized, double-masked, vehicle-controlled, Phase 3 study evaluating the efficacy and safety of OCS-01 QD compared to vehicle in the treatment of inflammation and pain following cataract surgery.

Detailed description:

Arms:
arm 1: 1 drop of OCS-01 (Dexamethasone ophthalmic suspension 1.5% \[15 mg/mL\]) in the study eye once daily (QD) for 14 days, beginning 1-day post-surgery in the study eye. arm 2: 1 drop of vehicle in the study eye QD for 14 days, beginning 1-day post-surgery in the study eye.

Interventions: intervention 1: OCS-01 intervention 2: Vehicle
Intervention descriptions: intervention 1: Dexamethasone ophthalmic suspension, 1.5% intervention 2: Vehicle

Protocol document:
Prot_000.pdf: 




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SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN  
A Randomized, Double-masked, Vehicle-controlled Study Evaluating 
the Efficacy and Safety of OCS-01 eyedrops compared to Vehicle in the 
Treatment of Inflammation and Pain Following Cataract Surgery 
 
 
Sponsor: 
 
Oculis Operations Sàrl 
 
 
 
EPFL Innovation Park  
Building D 
 
 
 
1015 Lausanne, Switzerland 
 
 
Protocol Number: 
DX218 
 
 
Author:  
 
 
 
 
 
 
 
 
Date:    
 
13JUL2023 
Version:  
 
1.0 
 


A Randomized, Double-masked, Vehicle-controlled Study Evaluating the Efficacy and Safety of 
OCS-01 eyedrops compared to Vehicle in the Treatment of Inflammation and Pain Following 
Cataract Surgery 
Protocol Number: 
DX218 
SAP Version: 
1.0 
SAP Date: 
13JUL2023 








1. Introduction 
The purpose of this statistical analysis plan (SAP) is to describe the planned analyses and reporting for 
protocol DX218, Version 1.0 dated 10MAY2022. 
This SAP is being written with due consideration of the recommendations outlined in the most recent 
International Conference on Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials and the most recent ICH E3 Guideline, entitled Guidance for Industry: Structure 
and Content of Clinical Study Reports. 
This SAP describes the data that will be analyzed and the subject characteristics, efficacy, and safety 
assessments that will be evaluated. This SAP provides details of the specific statistical methods that will 
be used. The statistical analysis methods presented in this document will supersede the statistical analysis 
methods described in the clinical protocol. If additional analyses are required to supplement the planned 
analyses described in this SAP, they may be completed and will be identified in the clinical study report. 
2. Study Objectives 
The primary objective of this study is to evaluate the efficacy and safety of OCS-01 QD compared to placebo 
(vehicle) in the treatment of inflammation and pain following cataract surgery. 
2.1 
Primary Efficacy Measures 
The primary efficacy measures are the following, listed in hierarchical order: 
• 
Absence of anterior chamber cells (i.e., score of “0”) at Visit 6 (
 
• 
Absence of pain (i.e., score of “0”) at Visit 4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.3 
Safety Measures 
The primary safety measures include the following: 
• 
Change from baseline in pin-hole visual acuity (VA) (without any other correction) as measured on 
the ETDRS chart 
• 
Change from baseline of intraocular pressure (IOP) 
• 
Change in endothelial cell density assessed at Visit 8 


• 
Adverse event (AE) rates 
Additional safety measures described in the protocol include: 
• 
Slit lamp biomicroscopy parameters; 
• 
Dilated indirect ophthalmoscopy parameters; 
• 
Endothelial cell parameters, including density, %hexagonal, and %CV. 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 








4. Study Treatments 
Study eyes will be treated with either OCS-01 (dexamethasone Ophthalmic Suspension, 1.5% (15 mg/mL) 
QD  or placebo (vehicle) QD ophthalmic suspension  during the treatment period of the study. 
4.1 
Method of Assigning Subjects to Treatment Groups 
At Visit 2 
 each subject who signed an informed consent form at Visit 1 
 will be 
assigned a screening number. Screening numbers will be assigned in sequential order at each site 
beginning with 001 and will follow the two-digit site number (e.g., subject 077 at Site 99 will have Screening 
Number 99-077). No subjects should be rescreened except in special circumstances in which sites should 
obtain approval to re-screen. Inclusion and exclusion criteria will be reviewed, and qualifying subjects will 
be enrolled into the study. Each subject who qualifies for entry will be assigned a randomization number 
and corresponding treatment according to the randomization code. Subjects will be randomly assigned to 
either OCS-01 QD or placebo (vehicle) QD using a 1:1 assignment ratio, stratified by site, via an interactive 
response system. 
Randomization numbers will be assigned in sequential order at each site beginning with 1001 and will follow 
the two digit site number (e.g., randomized subject 1005 at Site 99 will have Randomization Number 99-
1005). Sequentially numbered study drug kits will be provided to each investigational site, in accordance 
with the site-specific randomized study drug kit list, which consists of sequential 4-digit kit ID numbers. The 
interactive response system (IRT) will be utilized to assign the randomized subject the lowest 4-digit study 
drug kit number available at their investigative site associated with randomized treatment, in a masked 
manner to the site study team. If a randomized subject is discontinued from the study for any reason, their 
randomization number and randomized study drug kit number will not be reassigned.  
The subject number will be used to identify subjects in all datasets and listings for this study.  
4.2 
Masking and Unmasking 
An independent, unmasked biostatistician who is not otherwise involved in the trial will generate the 
complete randomized study drug kit list. The subject, Sponsor, Investigators, and study staff will be masked 
during the randomization process and throughout the study. 
The randomization code should be broken only in the event of a medical emergency, or when knowing the 
treatment assignment is absolutely necessary for the medical management of the study subject. When 
possible (i.e., in non-emergency situations), the study Sponsor or representative should be notified prior to 
unmasking study drug. In emergency situations, the Investigator must notify the Sponsor within 24 hours 
after determining that it is necessary to unmask the treatment assignment. The Investigator must also 
indicate in source documents and in the eCRF that the mask was broken and provide the date, time, and 
reason for breaking the mask. Any AE or SAE associated with breaking the mask must be recorded and 
reported as specified in the protocol. More details about the emergency unmasking process can be found 
in the IRT Plan as a separate document. 


 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
6. Data Preparation 
6.1 
Input Data 
Study data from source documents will be entered into the electronic Case Report Forms (eCRF) supplied 
by Statistics & Data Corporation (SDC) using the electronic data capture (EDC) system iMedNet™ v1.221.2 
or higher. Additional details about the EDC system can be found in the Data Management Plan as a 
separate document. 


In addition, the following study data which is not captured directly within the iMedNet system but is obtained 
from external vendors will also be included for analysis. These data sources are described in detail in data 
transfer agreements developed between data management and the respective external laboratory or 
reading center: 
• 
Endothelial cell density 
After data are entered into the clinical study database, electronic edit checks and data review will be 
performed. All data validation specifications and procedures are detailed in the Data Validation Manual as 
a separate document. When the database has been declared to be complete and accurate and all 
prerequisites for database lock have been met, including availability of all external data, the database will 
be locked. Following database lock, approval will be obtained from the Sponsor to unmask the study.  
Final analysis will be carried out after the following have occurred: 
• 
Database lock has occurred, including receipt of all final versions of external vendor data, with 
written authorization provided by appropriate SDC and Sponsor personnel. 
• 
Protocol deviations have been classified (major/minor deviations). 
• 
Analysis populations have been determined. 
• 
Randomized treatment codes have been unmasked. 
Any changes to the database after data have been locked or after unmasking can only be made with the 
approval of the Sponsor in consultation with SDC and per SDC standard operating procedures (SOPs). 
Adjustments to or repeats of analyses will be conducted as appropriate and in consultation with Sponsor.   
6.2 
Output Data 
Data from iMedNet and external data will be transferred to Biostatistics and incorporated into standard 
formats following the Study Data Tabulation Model (SDTM). Data will then be mapped to analysis datasets 
using the Analysis Data Model (ADaM). Both SDTM and ADaM-formatted data will be used to create the 
subject listings, while all tables and figures will be based on the ADaM-formatted data. 
SDTM will follow the SDTM version 1.7 model and will be implemented using the SDTM Implementation 
Guide version 3.3 and the most recent version of SDTM Controlled Terminology at the time of programming 
start. ADaM data will follow the ADaM version 2.1 model and will be implemented using the ADaM 
Implementation Guide version 1.1. Both SDTM and ADaM will be validated using Pinnacle 21 version 4.02. 
Any discrepancies in the validation will be noted in reviewer’s guides accompanying the final data transfers. 
Define.xml will be created for SDTM and ADaM using the Define-XML version 2.0 model. 
7. Analysis Populations 
7.1 
Full Analysis Set 
The full analysis set (FAS) will consist of all randomized subjects, analyzing subjects under the treatment 
to which they were randomized. 


7.2 
Per Protocol 
The per protocol (PP) population is a subset of the FAS and includes subjects who remain in the study 
through Visit 6 
) with no major protocol violations that would affect the assessment of the primary 
efficacy endpoints of the study, analyzing subjects under the treatment received. Major protocol violations 
will be identified prior to unmasking treatment. 
7.3 
Safety 
The safety population includes all randomized subjects who receive at least 1 dose of study medication. 
The safety population will be analyzed as treated and will be used for the safety analyses. No data will be 
excluded for any reason. 
8. General Statistical Considerations 
8.1 
Unit of Analysis 
The unit of analysis in this study will be the study eye for all ocular efficacy and safety summaries and the 
subject for all non-ocular summaries. 
8.2 
Missing or Inconclusive Data Handling 
Partial/missing start and end dates for AEs and concomitant medications will be imputed as follows: 
Partial/missing start date:  
• 
Dates with missing day only will be imputed as the 1st of the month unless the month and year are 
same as the month and year of first dose of study medication, in which case missing day will be 
imputed as the first dose day of study medication.  
• 
Dates with both day and month missing will be imputed as 1 Jan unless the year is same as the 
year of first dose of study medication, in which case missing day and month will be imputed as the 
first dose day and month of study medication. 
• 
Completely missing dates will be imputed as the first dose date of study medication unless the end 
date is on or before the first dose date of study medication, in which case missing date will be 
imputed as 1 Jan of the same year as the end date. 
Partial/missing end date:  
• 
Dates with missing day only will be imputed as the last day of the month unless the month and year 
are the same as the month and year of the last dose of study medication, in which case missing 
day will be imputed as the last dose day of study medication.  
• 
Dates with both day and month missing will be imputed as 31 Dec unless the year is same as the 
year of the last dose of study medication, in which case missing day and month will be imputed as 
the last dose day and month of study medication.  


• 
If the ongoing flag is missing or “Yes” then the date will not be imputed unless death date is 
available, in which case the missing date will be imputed as the death date. If ongoing is “No” then 
the missing end date will be imputed as the last dose date. 
• 
If the imputed date is after the date of death, then the end date will be set equal to the date of 
death.  
The original dates will be displayed in data listings and the imputed dates will be used in derivations only 
(study day, treatment-emergence status, etc.). 
The strategy for handling intercurrent events from Section 2.5 will be utilized for imputing missing data 
during the primary analyses of the primary efficacy variables. 
8.3 
Definition of Baseline 
Baseline is defined as the last measurement prior to the first dose of study medication. Change from 
baseline will be calculated as, Follow-up Visit – Baseline Visit. 
8.4 
Data Analysis Conventions 
All data analyses will be performed by SDC after the study is completed and the database has been locked 
and released for unmasking, as described in Section 6.2. Statistical programming and analyses will be 
performed using SAS® Version 9.4 or higher. Output will be provided in rich text format (RTF) for tables and 
portable document format (PDF) for tables, listings, and figures using landscape orientation. 
Summaries for continuous and ordinal variables will include the number of observations (n), arithmetic 
mean, standard deviation (SD), median, minimum, and maximum. Minima and maxima will be reported with 
the same precision as the raw values; means and medians will be presented to one additional decimal 
place than reported in the raw values. Standard deviations will be presented to two additional decimal 
places than reported in the raw values.  
Summaries for discrete variables will include counts and percentages. All percentages will be rounded to 
one decimal place (i.e., XX.X%). Differences between active treatment groups and placebo (vehicle) will 
be calculated as active minus placebo (vehicle) and change from baseline will be calculated as follow-up 
visit minus baseline.  
All statistical tests will be two-sided with a significance level of 0.05 (α = 0.05) unless otherwise specified. 
Confidence intervals (CI) for differences between treatment groups will be two-sided at 95% confidence. 
All p-values will be rounded to 4 decimal places; p-values less than 0.0001 will be presented as “<0.0001”; 
p-values greater than 0.9999 will be presented as “>0.9999.” 
Unless otherwise specified, tabular summaries will be presented by treatment group and, where 
appropriate, visit. Listings will be based on all randomized subjects, unless specified otherwise, and sorted 
by subject number, visit, and parameter as applicable. 


 
 
 
 
 
  
9. Disposition of Subjects 
Subject disposition will be presented in terms of the numbers of subjects who were screened, screen 
failures, and randomized, by treatment group and overall for all screened subjects. The numbers and 
percentages of subjects who were included in the FAS, Per-Protocol, and Safety analysis populations as 
well as who completed the study and discontinued from the study will be presented by treatment group and 
overall for all randomized subjects. Subjects who are not discontinued from the study will be considered 
study completers. The reasons for discontinuation will be summarized by treatment group and overall for 
all discontinued subjects. Percentages will be calculated using discontinued subjects as the denominator. 
The reasons for study discontinuation that will be summarized include: adverse event (AE), lost to follow-
up, protocol violation, study terminated by sponsor, withdrawal by subject, lack of efficacy, and other. The 
number and percentage of subjects with any deviation, major deviation, and minor deviation will be 
summarized by treatment group and overall for all randomized subjects. 
The reasons for screen failure (i.e., subject did not meet eligibility criteria) will be displayed with the 
percentages calculated using total number of screen failures as the denominator. 
Details of the study randomization, including study site, randomization date, randomized treatment, and 
actual treatment, will be provided within a subject listing. 
A subject listing for subject disposition will include study completion or discontinuation date, study 
completion status, and the primary reason for study discontinuation (if applicable). 
For protocol deviations, a subject listing will be provided that includes the date of the deviation, visit at which 
the deviation occurred, the deviation category, the deviation description, if the deviation was related to 
COVID-19, and the classification of whether the deviation was judged to be major or minor in a masked 
review prior to database lock. 
A subject listing of inclusion/exclusion criteria will include whether if all eligibility criteria were met, the 
specific eligibility criterion which was not met (if applicable), and the visit at which the eligibility criterion was 
not met (if applicable). 
A subject listing of analysis population inclusion will include whether criteria were met for inclusion in the 
FAS, Per-Protocol population, and Safety population. 


10. Demographic and Pretreatment Variables 
10.1 
Demographic Variables 
The demographic variables collected in this study include age, gender, ethnicity, race, and iris color. 
Subjects who record more than one race will be grouped into a single category denoted as multi-racial. Iris 
color will be summarized at the eye level. Demographic variables will be summarized for the FAS. 
Age (years) will be summarized, overall and by treatment, using continuous descriptive statistics. Age will 
also be categorized as follows: < 65 years and ≥ 65 years.   
The number and percentage of subjects will be presented, overall and by treatment, for age category, 
gender, ethnicity, race, iris color, and study site. 
A subject listing that includes all demographic variables will be provided. 
11. Medical History and Concomitant Medications 
11.1 
Medical History 
Medical history will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 25.0. 
Ocular medical history will be summarized using discrete summary statistics and presented by treatment 
group and overall separately for study eyes and fellow eyes by System Organ Class (SOC) and Preferred 
Term (PT) using the Safety population. Non-ocular medical history will be similarly summarized at the 
subject level. If a subject reports the same PT multiple times within the same SOC, that PT will only be 
reported once within that SOC. As with the PT, if a subject reports multiple conditions within the same SOC, 
that SOC will only be reported once. In the summaries, SOCs will be sorted in alphabetical order, and PTs 
within an SOC will be sorted in order of descending frequency across all subjects. 
Listings of medical history will be generated separately for ocular and non-ocular data. 
11.2 
Concomitant Medications 
Concomitant medications will be coded using World Health Organization Drug Dictionary (WHODrug) 
Global B3 01Mar2022 and summarized to the therapeutic drug class (Anatomical Therapeutic Chemical 
[ATC] 4 classification) and preferred name. If the ATC 4 classification is not provided, then the next highest 
classification that is provided in the coding dictionary will be used. The preferred name will be defined as 
the active ingredient; if the active ingredient is not provided or includes more than two ingredients (e.g., 
multivitamins), then the drug name will be summarized as the preferred name.  
Prior medications are defined as those medications with an end date before the date of initiation of study 
drug administration. Concomitant medications are defined as those medications listed as having been taken 
(1) prior to initiation of study drug administration and continuing for any period of time following the first 
administration of study drug or (2) at any time following the first administration of study drug.  
Concomitant medications will be summarized using the FAS. Medications will be tabulated for each 
treatment group using frequencies and percentages. Subjects may have more than one medication per 


ATC text. At each level of subject summarization, a subject will be counted once if they report one or more 
medications. Percentages will be based on the number of subjects in each treatment group. In the 
summaries, ATC classes and preferred names within an ATC class will be sorted in alphabetical order. 
All medications utilized for lowering IOP or for rescue will be noted in the subject listing of prior and 
concomitant medications. IOP-lowering medications and rescue medications are each a subset of 
medications where the investigator has indicated on the eCRF that the medication was used to lower IOP 
or rescue. Rescue medications and criteria are described in Section 4.3. 
The number and percentage of subjects initiating IOP-lowering medications will be presented by treatment 
group for each post-baseline visit as well as across all post-baseline visits for the Safety population. 
Listings of prior and concomitant medications will be generated separately for ocular and non-ocular data. 
A separate listing will be generated for IOP-lowering medications. 
11.3 
IOP-Lowering Procedures 
All IOP-lowering procedures will be coded using MedDRA Version 25.0 and presented in a subject listing.  
12. Dosing Compliance and Treatment Exposure 
12.1 
Dosing Compliance 
Details of individual administrations of study medication done at home by subjects are not captured within 
the clinical database, therefore dosing compliance will not be summarized. 
12.2 
Treatment Exposure 
The number and percent of subjects receiving at least one dose of study medication (i.e., Safety population) 
will be summarized as part of subject disposition. 
Although not captured directly on the eCRF, additional variables related to study drug administration will 
also be derived for summarization: 
• 
Study drug interruption (yes/no), where interruptions will be identified via presence of a TEAE 
where action taken with study drug was marked as “drug interrupted” or a protocol deviation 
indicating study drug was interrupted. 
• 
Premature discontinuation of study drug (yes/no), where discontinuations will be identified via 
presence of a TEAE where action taken with study drug was marked as “drug withdrawn” or a 
protocol deviation indicating study drug was prematurely discontinued. Subjects who discontinue 
the study prior to Visit 6 (
) will also be reviewed to verify if study drug was prematurely 
discontinued or not. 
• 
Study drug completion, defined as those subjects where premature discontinuation of study drug 
is not equal to “yes”. 
A masked data review will be conducted prior to database lock and unmasking to identify any other cases 
of study drug interruption or premature discontinuation of study drug which are known to have occurred, 


but are not identified through the criteria above. The classifications from this final review will be used for 
analysis. 
The number and percentage of subjects with study drug interruption, premature discontinuation of study 
drug, and study drug completion will be presented by treatment group. 
Subject data listings will be generated to present details of study drug assignment, study drug replacement, 
as well as first instillation of study medication performed in-clinic on Visit 2 
 Details about study drug 
accountability will also be listed. 
13. Efficacy Analyses 
13.1 
Primary Analysis 
The primary efficacy variables are the following: 
• 
Absence of anterior chamber cells, defined as a score of “0,” at Visit 6 (
 
• 
Absence of pain, defined as a score of “0,” at Visit 4 (
 
The anterior chamber cell score for study eyes will be recorded as well as the anterior chamber cell count 
if the actual number of cells observed is 10 cells or fewer (only white blood cells should be counted; red 
blood cells and pigment cells should not be counted). The assessment of anterior chamber cells will be 
performed prior to any other procedure that requires dilation of the pupil, such as dilated indirect 
ophthalmoscopy, to avoid cells from being introduced into the anterior chamber. The 5-unit grading scale 
for anterior chamber cells is from 0 to 4 where 0 = 0 cells, 1 = 1 to 10 cells, 2 = 11 to 25 cells, 3 = 26 to 50 
cells, and 4 = >50 cells. Anterior chamber cell status will be classified as “Absent” for a grade of ‘0’ or 
“Present” for a grade of 1 to 4. 
Ocular pain in study eyes will be assessed by the subject utilizing a pain rating number scale graded from 
0 to 10. Subjects will assess the level of pain they are experiencing in the study eye at the time of the 
assessment. The examiner will ask the subject the following question in reference to the below figure and 
will record the number selected by the subject on the appropriate eCRF: 
On a scale of 0 to 10, in which 0 is no pain and 10 is the worst possible or unbearable pain, please mark 
on the scale the number that best describes the pain or discomfort you are feeling in the operated eye at 
this time. The middle of the scale (around 5) can be used to describe “moderate pain”. Only whole number 
scores are allowed. 








 
 
13.1.3 SENSITIVITY ANALYSIS III 
The primary efficacy analysis will be performed using the PP population with observed data only. Treatment 
comparisons will be made using Pearson’s chi-squared test. If any of the expected cell counts are less than 
five, an exact 95% CI for the difference in proportions and Fisher’s exact test will be used instead. 
13.1.4 SENSITIVITY ANALYSIS IV 
The primary efficacy analysis will be performed using the FAS with observed data only. Treatment 
comparisons will be made using Pearson’s chi-squared test. If any of the expected cell counts are less than 
five, an exact 95% CI for the difference in proportions and Fisher’s exact test will be used instead. 
13.1.5 SENSITIVITY ANALYSIS V 
The handling of intercurrent events will be updated as follows: 
• 
Receipt of rescue medication: observed data for visits after receipt of rescue medication will be 
singly imputed as failure [hypothetical strategy]. 
• 
Missing data for any reason: missing data will be singly imputed as failure [hypothetical strategy]. 
Treatment comparisons will be made using Pearson’s chi-squared test. If any of the expected cell counts 
are less than five, an exact 95% CI for the difference in proportions and Fisher’s exact test will be used 
instead. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
14. Safety Analyses 
All safety analyses will be conducted using the Safety population. 
14.1 
Adverse Events 
An Adverse Event (AE) is defined as any untoward medical occurrence associated with the use of a drug 
in humans, whether or not the event is considered drug-related. An AE can therefore be any unfavorable 
and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease occurring after the subject 
started dosing with the study drug, without any judgment about causality. Any pre-existing medical condition 
that worsens after administration of the study drug will also be considered a new AE. Study drug includes 
the study drug under evaluation (OCS-01) and any comparator drug, placebo (vehicle), or any other 
medications required by the protocol given during any stage of the study. All AEs will be coded using 
MedDRA Version 25.0. 
Treatment-emergent adverse events (TEAEs) are defined as any event that occurs or worsens on or after 
the day that randomized study treatment is initiated. 
Severity of an AE is defined as a qualitative assessment of the degree of intensity of an AE as determined 
by the Investigator or reported to them by the subject. The assessment of severity is made irrespective of 
the relationship to study drug or the seriousness of the event and should be evaluated according to the 
following scale: 
• 
Mild: AE is noticeable to the subject but is easily tolerated and does not interfere with the subject’s 
daily activities. 
• 
Moderate: AE is bothersome, possibly requiring additional therapy, and may interfere with the 
subject’s daily activities. 
• 
Severe: AE is intolerable, necessitates additional therapy or alteration of therapy, and interferes 
with the subject’s daily activities. 
The relationship of each AE to the study drug should be determined by the Investigator using these 
explanations: 
• 
Suspected: A reasonable possibility exists that the study drug caused the AE. 


• 
Not Suspected: A reasonable possibility does not exist that the study drug caused the AE. 
Only suspected TEAEs are considered treatment-related TEAEs. 
The expectedness of an AE should be determined based upon existing safety information about the study 
drug using these explanations: 
• 
Unexpected: an AE that is not listed in the Investigator’s Brochure (IB) or is not listed at the 
specificity or severity that has been observed. 
• 
Expected: an AE that is listed in the IB at the specificity and severity that has been observed. 
An AE is considered serious if, in the view of either the Investigator or Sponsor, it results in any of the 
following outcomes: 
• 
Death 
• 
A life-threatening AE 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions 
• 
A congenital anomaly/birth defect 
TEAEs with a missing relationship to study drug will be counted as suspected treatment-related TEAEs for 
all summaries of suspected treatment-related TEAEs. All summaries of expected and unexpected TEAEs 
will include only suspected treatment-related TEAEs. TEAEs with missing severities will be counted as 
severe for all summaries by maximum severity. 
An overall summary will be presented that includes the number of events and the number and percentage 
of subjects who experienced at least one TEAE by treatment group. This summary will also include 
breakdowns of TEAEs further categorized as treatment-emergent serious adverse events (TE-SAEs), 
suspected treatment-related TEAEs, expected TEAEs, unexpected TEAEs, TEAEs leading to study drug 
discontinuation, TEAEs leading to death, and TEAEs by maximum severity. Separate summaries will be 
created for all events, ocular events in study eyes, ocular events in fellow eyes, and non-ocular events.  
TEAEs will be summarized using discrete summary statistics and presented by treatment group at the 
subject and event level by SOC and PT for the following categories of TEAEs:  
• 
Ocular TEAEs by SOC and PT 
• 
Non-Ocular TEAEs by SOC and PT 
• 
Ocular TE-SAEs by SOC and PT 
• 
Non-Ocular TE-SAEs by SOC and PT 
• 
Suspected Treatment-related Ocular TEAEs by SOC and PT 
• 
Suspected Treatment-related Non-Ocular TEAEs by SOC and PT 
• 
Expected Ocular TEAEs by SOC and PT 


• 
Expected Non-Ocular TEAEs by SOC and PT 
• 
Unexpected Ocular TEAEs by SOC and PT 
• 
Unexpected Non-Ocular TEAEs by SOC and PT 
• 
Ocular TEAEs by SOC, PT, and Maximum Severity 
• 
Non-Ocular TEAEs by SOC, PT, and Maximum Severity 
Ocular TEAEs will be summarized at the subject level for study and fellow eyes separately. If a subject 
reports the same PT multiple times within the same SOC, that PT will only be reported once within that 
SOC. As with the PT, if a subject reports multiple conditions within the same SOC, that SOC will only be 
reported once. To count the number of subjects with any TEAEs by maximum severity, if a subject has 
multiple TEAEs coded to the same SOC or PT within an SOC, the subject will be counted once under the 
maximum severity for that SOC or PT. In the summary, SOCs will be listed in ascending alphabetical order,. 
and PTs within each SOC will be listed in order of descending frequency for the OCS-01 treatment group.   
All AEs will be presented in a subject listing. In addition, all SAEs and AEs leading to study drug 
discontinuation will be presented in separate listings. 
14.2 
Pin-Hole Visual Acuity 
Pin-hole visual acuity (VA) is assessed at each visit using an Early Treatment Diabetic Retinography Study 
(ETDRS) chart. Pin-hole VA testing will be done with a pin-hole occluder at a viewing distance of 4 meters 
at the beginning of each study visit (i.e., prior to slit lamp examination). If less than 20 letters are read at 4 
meters the subject will perform the assessment again at a viewing distance of 1 meter. If at least 20 letters 
are read correctly at 4 meters, pin-hole VA is computed as 30 plus the number of letters correct at 4 meters. 
If less than 20 letters are read correctly at 4 meters, pin-hole VA is computed as the number of letters 
correct at 4 meters plus the number of letters correct at 1 meter. 
For presentations in tables and listings, pin-hole VA will be converted from number of letters correct to a 
logarithm of the minimum angle of resolution (logMAR) score using the following formula: 
logMAR VA = 1.70 – 0.02*(Number of letters correct) 
Summaries of pin-hole VA will be based on study eyes. 
Pin-hole VA actual values at Visits 1, 2, 4, 5, 6, and 7 (
 and change from 
baseline at Visits 4, 5, 6, and 7 (
) will be summarized by visit and treatment group 
using continuous summary statistics. 
Worsening of pin-hole visual acuity by at least 2 lines (10 letters) from the ETDRS scale from the previous 
visit at Visits 4, 5, 6, and 7 (
) will be summarized by visit and treatment group using 
discrete summary statistics. 
A subject listing of pinhole visual acuity by visit will be presented. 


14.3 
Intraocular Pressure (IOP) 
Intraocular pressure (IOP) in mmHg will be measured using a Goldmann application tonometer. Both eyes 
will be tested, with the right eye preceding the left eye. Two IOP measurements will initially be collected per 
eye. If the two IOP measurements differ by 2 mmHg or less, the mean of the two IOP measurements will 
be calculated and recorded as the final IOP measurement. If the two IOP measurements differ by more 
than 2 mmHg, a third (consecutive) IOP measurement will be collected and the median IOP measurement 
will be recorded as the final IOP measurement. For a given subject for a given eye, the dataset will have 
either the mean or median of the IOP measurements, but not both. The available measure will be used as 
the analysis value for IOP listings, summaries, and analyses. 
Summaries of IOP will be based on study eyes. 
IOP actual values at Visits 1, 4, 5, 6, and 7 (
) and change from baseline at 
Visits 4, 5, 6, and 7 (
) will be summarized by visit and treatment group using continuous 
summary statistics. 
Eyes with IOP of 30 mmHg or more at Visits 1, 4, 5, 6, and 7 (
) as well as 
eyes with an increase from baseline in IOP of 10 mmHg or more at Visits 4, 5, 6, and 7 (D
 
) will be summarized by visit and treatment group using discrete summary statistics. 
A subject listing of IOP by visit will be presented. 
14.4 
Endothelial Cell Parameters 
Endothelial cell density will be assessed by specular microscopy. The image of the corneal endothelium 
will be obtained when the instrument captures the light reflected from the optical interface between the 
corneal endothelium and the aqueous humor. Multiple microphotographs will be performed for each eye, 
after which the device will perform an automatic analysis of the selected area and calculate the average 
number of cells per 1 mm2. The microscope will then provide a histogram determining the endothelial cell 
population size and specify the minimum, maximum, and average cell size of the selected area. The 
pleomorphism of endothelial cells will also be evaluated, indicating the percentage of hexagonality. 
Summaries of endothelial cell parameters will be based on study eyes. 
Endothelial cell parameters (density, %hexagonal, and %CV) actual values at Visits 1 and 8 (
 and change from baseline at Visit 8 
 will be summarized by visit and treatment group 
using continuous summary statistics. The p-values from two-sample t-tests comparing changes from 
baseline in endothelial cell density parameters between treatment groups will also be presented. 
A subject listing of endothelial cell parameters by visit will be presented. 


14.5 
Dilated Indirect Ophthalmoscopy 
A dilated indirect ophthalmoscopic examination of the vitreous, retina, macula, choroid, optic nerve, and 
lens will be performed at Visits 1 and 7 (
). The results for each region will be graded 
as normal, abnormal not clinically significant (NCS), and abnormal clinically significant (CS). 
Summaries of dilated ophthalmoscopy parameters will be based on study eyes. 
The results for each region at Visits 1 and 7 (
) will be summarized by visit and 
treatment group using discrete summary statistics. Percentages will be based on the number of subjects in 
each treatment group with responses. 
Shifts from baseline at Visit 7 (
 for the dilated ophthalmoscopy parameters will be summarized by 
treatment group using discrete summary statistics. Percentages will be based on the number of subjects in 
each treatment group with responses at both Visits 1 and 7 (
 
A subject listing of the dilated ophthalmoscopy parameters will also be produced. 
14.6 
Slit-Lamp Biomicroscopy Examination 
A slit-lamp biomicroscopy examination of the eyelid, conjunctiva, cornea, anterior chamber, iris, and lens 
will be performed at each visit. The results will be graded as normal, abnormal NCS, or abnormal CS. 
Summaries of slit-lamp biomicroscopy parameters will be based on study eyes. 
The results for each region at Visits 1, 4, 5, 6, and 7 (
) will be summarized 
by visit and treatment group using discrete summary statistics. Percentages will be based on the number 
of subjects in each treatment group with responses. 
Shifts from baseline at Visits 4, 5, 6, and 7 (
) for the dilated ophthalmoscopy 
parameters will be summarized by visit and treatment group using discrete summary statistics. Percentages 
for each visit will be based on the number of subjects in each treatment group with responses at both Visit 
1 and the respective visit. 
A subject listing of the slit-lamp biomicroscopy parameters will also be produced. 
14.7 
Clinical Laboratory Data 
Results from the urine pregnancy test at Visits 1 and 7 
) will be provided in a subject 
listing. 
15. Interim Analyses 
Interim analyses will not be performed for this study. 
16. Changes from Protocol-Stated Analyses 
The SAP includes the following changes from the protocol-stated analyses: 








Listing 
16.2.4.3.3 
Prior and Concomitant IOP Lowering Medications 
All Randomized 
Subjects 
Listing 16.2.4.4 
IOP Lowering Procedures 
All Randomized 
Subjects 
Listing 16.2.4.5 
Cataract Surgery 
All Randomized 
Subjects 
Listing 16.2.5.1 
Study Drug Administration 
All Randomized 
Subjects 
Listing 16.2.5.2 
Study Drug Accountability 
All Randomized 
Subjects 
Listing 16.2.6.1 
Anterior Chamber Cells and Flare 
All Randomized 
Subjects 
Listing 16.2.6.2 
Ocular Pain 
All Randomized 
Subjects 
Listing 16.2.7.1 
Adverse Events 
All Randomized 
Subjects 
Listing 16.2.7.2 
Serious Adverse Events 
All Randomized 
Subjects 
Listing 16.2.7.3 
Adverse Events Leading to Study Drug Discontinuation 
All Randomized 
Subjects 
Listing 16.2.8 
Urine Pregnancy Test - Subjects of Childbearing Potential  
Subjects of 
Childbearing Potential 
Listing 16.2.9.1 
Pin-Hole Visual Acuity 
All Randomized 
Subjects 
Listing 16.2.9.2 
Intraocular Pressure 
All Randomized 
Subjects 
Listing 16.2.9.3 
Endothelial Cell Density 
All Randomized 
Subjects 
Listing 16.2.9.4 
Dilated Indirect Ophthalmoscopy 
All Randomized 
Subjects 
Listing 16.2.9.5 
Slit Lamp Biomicroscopy 
All Randomized 
Subjects