Multicenter, Double-Masked, Randomized, Safety and Efficacy Study of BRIMOCHOL™ PF and Carbachol PF Topical Ophthalmic Solution With Emmetropic Phakic and Pseudophakic Presbyopia
Phase: PHASE3
Conditions: Presbyopia
Sponsor: Visus Therapeutics

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 1 of 67 
 
 
 
 
Clinical Study Protocol VT-002 Amendment 4 
 
A 3-Arm, Multicenter, Randomized, Double-Masked, Crossover Safety and 
Efficacy Study of BRIMOCHOL™ PF (Carbachol/Brimonidine Tartrate 
Fixed-Dose Combination) Topical Ophthalmic Solution vs. Carbachol PF 
Monotherapy Topical Ophthalmic Solution vs. Brimonidine Tartrate 
Monotherapy Topical Ophthalmic Solution in Subjects with Emmetropic 
Phakic or Pseudophakic Presbyopia 
 
Sponsor: 
Visus Therapeutics, Inc. 
 
 
Medical Monitor: 
 
 
 
Development Phase: 
3 
IND number: 
150905 
Clinical Trial  
Compliance: 
This clinical trial will be conducted in accordance with standards of 
Good Clinical Practice, as defined by the International Council for 
Harmonisation (ICH) and all applicable federal and local regulations. 
Version and Date: 
Version 5.1/ 4 Apr 2023 
 
Confidential Information 
The confidential information in this document is provided to you as a Principal Investigator, potential Principal 
Investigator, or Consultant, for review by you, your staff, and applicable institutional review committees. This 
information will not be disclosed to others without written authorization from Visus Therapeutics, Inc. except 
to the extent necessary to obtain informed consent from those persons to whom the drug may be administered. 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 3 of 67 
Principal Investigator Signature Page 
Protocol Title 
A 3-Arm, Multicenter, Randomized, Double-Masked, Crossover 
Safety and Efficacy Study of BRIMOCHOL™ PF 
(Carbachol/Brimonidine Tartrate Fixed-Dose Combination) 
Topical Ophthalmic Solution vs. Carbachol PF Monotherapy 
Topical Ophthalmic Solution vs. Brimonidine Tartrate 
Monotherapy Topical Ophthalmic Solution in Subjects with 
Emmetropic Phakic or Pseudophakic Presbyopia 
Protocol Number 
VT-002 Amendment 4 
Version and Date 
Version 5.1/ 4 Apr 2023 
I, the undersigned, have read this protocol and agree to personally supervise conduct of this 
protocol in accordance with ethical principles as outlined in the ICH guidelines on GCP, any 
applicable laws and requirements (including Part 54: Financial Disclosure by Clinical 
Investigators) and any additional conditions mandated by a regulatory authority and/or 
Institutional Review Board (IRB). 
I acknowledge that I am responsible for the overall study conduct; I approve of and will comply 
with all conditions, instructions, and restrictions described in this protocol. I am aware that my 
adherence to the above protocol is mandatory and that any changes in the protocol or consent 
form, except those necessary to eliminate apparent immediate hazards to human subjects, must 
first be approved in writing by Visus Therapeutics, Inc., and the respective IRB. 
I also agree that all information provided to me by Visus Therapeutics, Inc., including this 
document, Investigator’s Brochure, case report form, and verbal and written information, will be 
kept strictly confidential and confined to the clinical personnel involved in conducting the study. 
It is recognized that this information may be related in confidence to the IRB. I also understand 
that reports of information about the study or its progress will not be provided to anyone not 
involved in the study other than to the Principal Investigator, or in confidence to the IRB or to 
the Food and Drug Administration (FDA) or other legally constituted authority. 
 
 
Principal Investigator Signature 
Date 
 
 
Printed Name 
Institution 
City, State 
 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 4 of 67 
TABLE OF CONTENTS 
SIGNATURE PAGE ......................................................................................................................2 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE ..............................................................3 
TABLE OF CONTENTS ..............................................................................................................4 
LIST OF FIGURES .......................................................................................................................5 
LIST OF ABBREVIATIONS .......................................................................................................6 
1 
PROTOCOL SUMMARY AND SCHEDULE ....................................................................8 
1.1 
Protocol Summary .............................................................................................................8 
1.2 
Schedule of Visits and Procedures..................................................................................17 
2 
BACKGROUND ...................................................................................................................19 
2.1 
Presbyopia ........................................................................................................................19 
2.2 
Investigational Products ..................................................................................................19 
3 
RATIONALE FOR THE STUDY AND STUDY DESIGN ..............................................21 
3.1 
Therapeutic Rationale for BRIMOCHOL PF and Carbachol PF in 
Presbyopia ........................................................................................................................21 
3.2 
Study Rationale ................................................................................................................22 
3.3 
Rationale for Dose and Regimen Selection ....................................................................23 
4 
STUDY OBJECTIVES AND ENDPOINTS ......................................................................23 
4.1 
Study Objectives...............................................................................................................23 
4.2 
Study Endpoints ...............................................................................................................23 
4.2.1 
Efficacy Endpoints .....................................................................................................23 
4.2.2 
Safety Endpoints ........................................................................................................24 
4.2.3 
Pharmacodynamic (PD) Endpoints ..........................................................................24 
 
 
5 
STUDY DESIGN ..................................................................................................................25 
5.1 
Study Design .....................................................................................................................25 
5.2 
Beginning and End of Study ...........................................................................................26 
6 
STUDY POPULATION .......................................................................................................26 
6.1 
Inclusion Criteria .............................................................................................................27 
6.2 
Exclusion Criteria ............................................................................................................28 
6.3 
Subject Discontinuation ..................................................................................................29 
7 
TREATMENTS ....................................................................................................................30 
7.1 
Study Treatment ..............................................................................................................30 
7.1.1 
Randomization/Treatment Assignment ...................................................................30 
7.1.2 
Study Treatment ........................................................................................................30 
7.1.3 
Masking/Unmasking ..................................................................................................31 
7.2 
Investigational Product Preparation and Dispensing ...................................................31 
7.2.1 
Investigational Product Packaging and Labeling ...................................................32 
7.2.2 
Investigational Product Storage ...............................................................................32 
7.2.3 
Investigational Product Compliance and Accountability ......................................32 
7.2.4 
Return and Disposal of Investigational Product .....................................................32 
7.3 
Permissible Concomitant Medications/Treatments ......................................................33 
7.4 
Prohibited Concomitant Medications/Treatments .......................................................33 
8 
STUDY VISIT SCHEDULE AND PROCEDURES ..........................................................33 
8.1 
Visit 1: Screening (-14 to -1 Days) ..................................................................................34 
8.2 
Visit 2: (Randomization), Visit 3, and Visit 4/Exit ........................................................36 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 5 of 67 
9 
SAFETY MONITORING AND REPORTING .................................................................38 
9.1 
Adverse Events .................................................................................................................38 
9.1.1 
Definition and Reporting ...........................................................................................38 
9.2 
Serious Adverse Events ...................................................................................................39 
9.2.1 
Definitions ...................................................................................................................39 
9.2.2 
Reporting ....................................................................................................................39 
9.2.3 
Classification of Severity of Adverse Event .............................................................40 
9.2.4 
Relationship to Investigational Product...................................................................40 
9.2.5 
Ocular Events of Special Interest .............................................................................41 
9.3 
Pregnancies .......................................................................................................................41 
10 DATA COLLECTION AND MANAGEMENT ................................................................42 
10.1 
Data Confidentiality.........................................................................................................42 
10.2 
Site Monitoring.................................................................................................................42 
10.3 
Data Collection .................................................................................................................42 
11 STATISTICAL METHODS AND DATA ANALYSIS .....................................................43 
11.1 
Analysis Sets .....................................................................................................................43 
11.1.1 
Safety Population .......................................................................................................43 
11.1.2 
Modified Intent-to-Treat (mITT) Population .........................................................43 
11.1.3 
Per-Protocol Population ............................................................................................43 
11.2 
Efficacy Analyses .............................................................................................................43 
11.3 
Pharmacodynamic Analyses ...........................................................................................46 
11.4 
Safety Analyses .................................................................................................................46 
 
 
11.6 
Sample Size Calculation ..................................................................................................47 
12 ETHICAL CONSIDERATIONS AND ADMINISTRATIVE PROCEDURES .............48 
12.1 
Regulatory and Ethical Compliance ..............................................................................48 
12.2 
Responsibilities of the Investigator and IRB .................................................................48 
12.3 
Informed Consent Procedures ........................................................................................48 
12.4 
Publication of Study Protocol and Results ....................................................................48 
12.5 
Study Documentation, Recordkeeping, and Retention of Documents ........................48 
12.6 
Confidentiality of Study Documents and Subject Records ..........................................49 
12.7 
Monitoring and Quality Assurance ................................................................................49 
12.8 
Protocol Adherence ..........................................................................................................49 
12.9 
Study Termination ...........................................................................................................49 
13 REFERENCES .....................................................................................................................50 
14 PROTOCOL AMENDMENT 4 SUMMARY ....................................................................52 
15 PROTOCOL AMENDMENT 3 SUMMARY ....................................................................61 
16 PROTOCOL AMENDMENT 2 SUMMARY ....................................................................63 
17 PROTOCOL AMENDMENT 1 SUMMARY ....................................................................65 
 
LIST OF FIGURES 
Figure 1: 
Study Design Schematic ......................................................................................26 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 6 of 67 
LIST OF ABBREVIATIONS 
_M 
Mesopic 
_P 
Photopic 
ADL 
Activities of daily living 
AE 
Adverse event 
ALR 
AUC 
AUC0-8h 
Alternating logistic regression 
Area under the curve 
Area under the curve from Hour 0 to Hour 8 
BAK 
Benzalkonium chloride 
BUCDVA 
Binocular uncorrected distance visual acuity 
BUCNVA 
Binocular uncorrected near visual acuity 
COVID-19 
Coronavirus Disease 2019 
CRA 
Clinical Research Associate 
CV 
Coefficient of variation 
D 
Diopters 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEE 
Generalized Estimating Equations 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IOL 
Intraocular lens 
IOP 
Intraocular pressure 
IP 
Investigational product 
IRB 
Institutional Review Board 
IRT 
Interactive response technology 
NRS 
Numeric rating scale 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified intent-to-treat 
MUCDVA 
Monocular uncorrected distance visual acuity  
MUCNVA 
Monocular uncorrected near visual acuity  
PD 
Pharmacodynamics 
PF 
Preservative free 
PI 
Principal Investigator 
PP 
Per-protocol 
PT 
Preferred term 
OD 
Oculus dexter (right eye) 
OD/OS 
Each eye separately 
OS 
Oculus sinister (left eye) 
OU 
Both eyes at the same time 
ROW 
Rest of world 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 7 of 67 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SOC 
System organ class 
SSRI 
Selective serotonin reuptake inhibitor 
SUSAR 
Suspected unexpected serious adverse reactions 
TEAE 
Treatment-emergent adverse event 
 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 11 of 67 
9. Not receiving eye drops in either eye other than topical artificial tears no more 
than twice a day 
10. Females of childbearing potential must agree to use one of the following methods 
of birth control from the date they sign the informed consent form (ICF) until 
after the last study visit (Visit 4 or Exit): 
a. 
Abstinence, when it is in line with the preferred and usual lifestyle of the 
subject 
b. Maintenance of a monogamous relationship with a male partner who has 
been surgically sterilized by vasectomy (vasectomy procedure must have 
been conducted at least 60 days prior to the Screening Visit or confirmed via 
sperm analysis) 
c. 
Barrier method (e.g., condom or occlusive cap) with spermicidal 
foam/gel/film/cream, AND either hormonal contraception (oral, implanted, 
or injectable) or an intrauterine device or system. 
Note: Non-childbearing potential is defined as surgical sterilization (i.e., 
bilateral oophorectomy, hysterectomy, or tubal ligation) or postmenopausal 
(defined as not having a period for at least 12 consecutive months prior to 
Screening).  
11. Able to give informed consent and willing and able to comply with all study visits 
and examinations. 
Exclusion Criteria 
A subject who meets any of the following criteria will be excluded from the study: 
1. Current use (within 4 weeks of Visit 1) or likely need for distance refractive 
correction or the use of contact lens at any time during the study 
2. Narrow iridocorneal angles (Shaffer grade ≤2 on gonioscopy examination or Van 
Herick grade ≤2 by slit-lamp exam) or previous iridotomy 
3. Iris or pupil abnormalities 
4. History of hyphema, microhyphema, cyclodialysis, iridodynesis, or trauma to 
either eye 
5. Use of systemic or topical antihistamines 48 hours prior to on-site study visits, 
anticholinergics (including tricyclic antidepressants or monoamine oxidase 
inhibitors; however, use of selective serotonin reuptake inhibitor [SSRI] is 
acceptable) or cholinergics (including pilocarpine [e.g., VUITY] or cevimeline), 
alpha-1 agonists (including tetryzoline, oxymetazoline, phenylephrine, 
pseudoephedrine, methoxamine, mephentermine, cirazoline, benzphetamine), and 
alpha-2 agonists (including methyldopa, brimonidine, clonidine, dipivefrin, 
guanabenz) within 90 days prior to Visit 1 or at any time during the study 
6. Use of systemic alpha-antagonists (including phenoxybenzamine, phentolamine, 
alfuzosin, doxazosin, terazosin, tamsulosin, prazosin, and yohimbine) within 90 
days prior to visit 1 or at any time during the study 
7. Participation in other investigational drug or device clinical trials within 30 days 
prior to Visit 1 or planning to participate in any other investigational drug or 
device clinical trials within 30 days of study completion. This includes 
interventional clinical trials investigating the use of a pharmacologic agent for the 
treatment of cataract or presbyopia.  
8. Any other ocular pathology requiring treatment with topical prescription 
ophthalmic drops or intravitreal injection (e.g., glaucoma, allergic conjunctivitis, 
retinal disease). Note: Mild dry eye requiring only topical artificial tears up to 
2 times a day is acceptable. 
9. Concurrent use of temporary or permanent punctal plugs or history of punctal 
cautery in one or both eyes 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 12 of 67 
10. Corneal abnormalities in either eye that interfere with visual acuity or 
measurement of IOP including total corneal staining grade of >1 and central 
corneal staining >0 on the National Eye Institute (NEI) corneal grading scale 
11. Congenital or traumatic cataracts or congenital aphakia, central lens opacity on 
visual axis. 
12. History of intraocular surgery other than uncomplicated cataract surgery. Note: 
Prior LASIK refractive surgery at least 12 months prior is acceptable if the 
subject meets all other eligibility criteria. 
13. For phakic subjects, phacodynesis or subluxation of the lens or suspected loose 
zonules 
14. For pseudophakic subjects, complicated cataract surgery resulting in capsular 
tear, placement of IOL outside the bag (e.g., sulcus, scleral or iris fixation or 
anterior chamber placement) or yttrium aluminum garnet (YAG) capsulotomy or 
an axial length of ≥25 mm  
15. History of uveitis 
16. Diagnosis of glaucoma or ocular hypertension or IOP of >21 mm Hg or 
pseudoexfoliation in either eye 
17. Any active ocular or peri-ocular infection; any history of recurrent or chronic 
infection, including herpetic infection, in either eye 
18. Current or previous retinal detachment or retinal pathology including age-related 
macular degeneration 
19. Concurrent disease in either eye that could require medical or surgical 
intervention during the study period 
20. Known to be immunocompromised or receiving immunosuppression  
21. History of allergic reaction to the investigational product or any of its 
components 
22. Women who are pregnant or lactating 
23. Unwilling or unable to give informed consent 
24. Any disease or medical condition that, in the opinion of the Investigator, would 
prevent the subject from participating in the study or might confound study 
results 
25. Previous participation in the Visus VT-003 clinical trial. 
 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 16 of 67 
 
Sample Size Calculation 
 will be enrolled to complete 
152 subjects.  
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 19 of 67 
 
2 
BACKGROUND 
2.1 
Presbyopia 
Presbyopia is an inevitable, age-related, gradual loss in the ability to focus at intermediate and 
near targets without spectacle or surgical correction due to a progressive loss of elasticity in the 
crystalline lens. Symptoms of presbyopia include blurred vision, ocular discomfort/headache, 
fatigue/drowsiness from near work, increased working distance (arms too short), and need for 
brighter light for reading. In childhood, an amplitude of accommodation of 12 diopters (D) is 
typical (Benzoni 2012). Amplitude of accommodation declines linearly at a rate of about 0.3 D 
per year, falling below a threshold at which near vision is noticeably impaired by approximately 
40 to 45 years of age. An estimated 1.27 billion people have presbyopia globally, and this 
number is projected to increase to 1.78 billion people by 2050 (Frick 2015), including virtually 
all adults >50 years old.  
Therapeutic approaches to presbyopia cover a spectrum of nonsurgical to surgical techniques 
(Moarefi 2017). Non-invasive methods of correcting presbyopia (e.g., bifocal, or multifocal 
progressive addition lenses) can be effective, but many patients are dissatisfied for cosmetic or 
other reasons and desire independence from spectacles. Various surgical techniques have been 
applied on the cornea, lens, or sclera (Gil-Cazorla 2016). However, surgery is invasive and 
difficult to reverse in the event of complications or patient dissatisfaction. Moreover, surgical 
corrections usually require that patients choose for one eye to be corrected for distance and one 
for near, or monovision. Many patients do not like this outcome as this leaves them without 
binocular vision or depth perception at distance and near (Goertz 2014, McDonnell 2003). There 
is currently one Food and Drug Administration (FDA)-approved drug product to treat 
presbyopia, VUITY (pilocarpine 1.25%), with a limited duration of action. 
2.2 
Investigational Products 
Visus Therapeutics, Inc. (Visus) is developing BRIMOCHOL™ PF (Preservative Free) 
(carbachol 2.75% / brimonidine tartrate 0.1% fixed-dose combination) Topical Ophthalmic 
Solution (hereafter BRIMOCHOL PF) and Carbachol PF 2.75% Monotherapy Topical 
Ophthalmic Solution (hereafter Carbachol PF) eye drop for improvement in near visual acuity in 
emmetropic phakic and pseudophakic presbyopia.  
The active pharmaceutical ingredients carbachol and brimonidine tartrate are currently approved 
for topical ophthalmic use. Both carbachol and brimonidine tartrate have been used extensively 
in ophthalmic applications and the approved products have been administered chronically at 
higher total daily doses than that in the BRIMOCHOL PF combination product.   
Five Investigator-initiated trials of a pharmacy-compounded formulation of BRIMOCHOL 
containing up to 3.0% carbachol and 0.2% brimonidine tartrate were conducted in presbyopic 
subjects; the results of 4 of these studies are published (Abdelkader 2015, 2016, 2018, 2019). 
These studies evaluated pupillometry and near visual acuity across a range of carbachol 
concentrations from 1.5% to 3.0%, the effects of BRIMOCHOL in older and younger presbyopes 
and in pseudophakes, the occurrence of tachyphylaxis over 3 months, and whether the fixed-dose 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 21 of 67 
 
Please see the Investigator Brochure (IB) for additional information on the nonclinical and 
clinical support for BRIMOCHOL PF development. 
3 
RATIONALE FOR THE STUDY AND STUDY DESIGN 
3.1 
Therapeutic Rationale for BRIMOCHOL PF and Carbachol PF in Presbyopia 
In recent years, various miotics have been investigated alone or in combination with one or more 
other agents as treatments for presbyopia (Benozzi 2012, Karanfil 2017, Renna 2017). Until 
recently, there are two currently marketed miotic agents in the US: pilocarpine (Isopto® Carpine 
[Prescribing Information]) for the lowering of intraocular pressure (IOP) and carbachol 
(MIOSTAT® 0.01% [Prescribing Information]) for obtaining miosis during surgery. Carbachol 
was also marketed as ISTOPO® CARBACHOL (Prescribing Information) for the lowering of 
IOP for more than 50 years but was withdrawn from the market for commercial and not safety 
reasons. Carbachol is generally regarded as a stronger and longer-acting miotic than pilocarpine 
(Gelatt 1984) with a dosing frequency of up to 3 times daily rather than up to 4 times daily for 
pilocarpine. Recently, VUITY® (pilocarpine 1.25%) was approved for the treatment of 
presbyopia. The efficacy of VUITY for the treatment of presbyopia was demonstrated in two 30-
Day Phase 3, randomized, double-masked, vehicle-controlled studies, namely GEMINI 1 
(NCT03804268) and GEMINI 2 (NCT03857542). A total of 750 participants aged 40 to 55 years 
old with presbyopia were randomized (375 to VUITY group) in the two studies and participants 
were instructed to administer one drop of VUITY or vehicle once daily in each eye. In both 
studies, the proportion of participants gaining 3 lines or more in mesopic, high contrast, 
binocular distance corrected near visual acuity (DCNVA), without losing more than 1 line 
(5 letters) of corrected distance visual acuity (CDVA) with the same refractive correction was 
statistically significantly greater in the VUITY group compared to the vehicle group at Day 30, 
Hour 3. Statistical significance was not achieved in both studies at Hour 6. 
Both carbachol and pilocarpine are parasympathomimetic agents that induce miosis by 
promoting contraction of the iris sphincter muscle through activation of muscarinic receptors. 
However, both miotics also contract the ciliary muscle. It is through this effect on the ciliary 
muscle that miotics can reduce IOP by putting traction on the scleral spur and uveoscleral 
meshwork, thereby increasing aqueous outflow (Nardin 1966). It is also by this mechanism that 
miotics cause their main AEs: browache/headache (a referred pain from the ciliary muscle 
contraction/spasm) and a decrease in distance acuity by inducing a myopic shift (Poinoosawmy 
1976).  
Brimonidine tartrate is a selective alpha-2 adrenergic agonist that works presynaptically in the 
management of elevated IOP to inhibit the release of norepinephrine (Kato 2018) at the nerve 
terminals, thereby decreasing aqueous production, episcleral venous pressure and improving 
uveoscleral outflow. By inhibiting norepinephrine’s release, brimonidine tartrate’s main effect on 
the pupil is to inhibit contraction of the iris dilator muscle, which is classically stimulated as part 
of the fight or flight sympathetic response or, more commonly, under dark lighting to let more 
light into the eye.  

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 28 of 67 
 
b. Maintenance of a monogamous relationship with a male partner who has been surgically 
sterilized by vasectomy (vasectomy procedure must have been conducted at least 60 days 
prior to the Screening Visit or confirmed via sperm analysis) 
c. Barrier method (e.g., condom or occlusive cap) with spermicidal foam/gel/film/cream, 
AND either hormonal contraception (oral, implanted, or injectable) or an intrauterine 
device or system. 
Note: Non-childbearing potential is defined as surgical sterilization (i.e., bilateral 
oophorectomy, hysterectomy, or tubal ligation) or postmenopausal (defined as not having a 
period for at least 12 consecutive months prior to Screening).  
11. Able to give informed consent and willing and able to comply with all study visits and 
examinations 
6.2 
Exclusion Criteria 
A subject who meets any of the following criteria will be excluded from the study: 
1. Current use (within 4 weeks of Visit 1) or likely need for distance refractive correction or the 
use of contact lens at any time during the study 
2. Narrow iridocorneal angles (Shaffer grade ≤2 on gonioscopy examination or Van Herick 
grade ≤2 by slit-lamp exam) or previous iridotomy 
3. Iris or pupil abnormalities 
4. History of hyphema, microhyphema, cyclodialysis, iridodynesis, or trauma to either eye 
5. Use of systemic or topical antihistamines 48 hours prior to on-site study visits, 
anticholinergics (including tricyclic antidepressants or monoamine oxidase inhibitors; 
however, use of selective serotonin reuptake inhibitor [SSRI] is acceptable) or cholinergics 
(including pilocarpine [e.g., VUITY] or cevimeline), alpha-1 agonists (including tetryzoline, 
oxymetazoline, phenylephrine, pseudoephedrine, methoxamine, mephentermine, cirazoline, 
benzphetamine), and alpha-2 agonists (including methyldopa, brimonidine, clonidine, 
dipivefrin, guanabenz) within 90 days prior to Visit 1 or at any time during the study. 
6. Use of systemic alpha-antagonists (including phenoxybenzamine, phentolamine, alfuzosin, 
doxazosin, terazosin, tamsulosin, prazosin, and yohimbine) within 90 days prior to visit 1 or 
at any time during the study 
7. Participation in other investigational drug or device clinical trials within 30 days prior to 
Visit 1 or planning to participate in any other investigational drug or device clinical trials 
within 30 days of study completion. This includes interventional clinical trials investigating 
the use of a pharmacologic agent for the treatment of cataract or presbyopia.  
8. Any other ocular pathology requiring treatment with topical prescription ophthalmic drops or 
intravitreal injection (e.g., glaucoma, allergic conjunctivitis, retinal disease).  
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 29 of 67 
 
9. Concurrent use of temporary or permanent punctal plugs or history of punctal cautery in one 
or both eyes 
10. Corneal abnormalities in either eye that interfere with visual acuity or measurement of IOP 
including total corneal staining grade of >1 and central corneal staining >0 on the National 
Eye Institute (NEI) corneal grading scale 
11. Congenital or traumatic cataracts or congenital aphakia, central lens opacity on visual axis. 
12. History of intraocular surgery other than uncomplicated cataract surgery.  
Note: Prior LASIK refractive surgery at least 12 months prior is acceptable if the subject 
meets all other eligibility criteria. 
13. For phakic subjects, phacodynesis or subluxation of the lens or suspected loose zonules 
14. For pseudophakic subjects, complicated cataract surgery resulting in capsular tear, placement 
of IOL outside the bag (e.g., sulcus, scleral or iris fixation or anterior chamber placement) or 
yttrium aluminum garnet (YAG) capsulotomy or an axial length of ≥25 mm  
15. History of uveitis 
16. Diagnosis of glaucoma or ocular hypertension or IOP of >21 mm Hg or pseudoexfoliation in 
either eye 
17. Any active ocular or peri-ocular infection; any history of recurrent or chronic infection, 
including herpetic infection, in either eye 
18. Current or previous retinal detachment or retinal pathology including age-related macular 
degeneration 
19. Concurrent disease in either eye that could require medical or surgical intervention during the 
study period 
20. Known to be immunocompromised or receiving immunosuppression  
21. History of allergic reaction to the investigational product or any of its components 
22. Women who are pregnant or lactating 
23. Unwilling or unable to give informed consent 
24. Any disease or medical condition that, in the opinion of the Investigator, would prevent the 
subject from participating in the study or might confound study results 
25. Previous participation in the Visus VT-003 clinical trial 
6.3 
Subject Discontinuation  
A subject may discontinue the study at any time during the study for any reason. When possible, 
the following assessments should be assessed at the Exit Visit:  pregnancy test, AEs, concomitant 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 39 of 67 
 
Subjects will be queried for resolution of ongoing AEs or until any unresolved AEs are judged 
by the Investigator to have stabilized or if lost to follow-up. Resolution of all AEs will be 
promptly documented by the site in the subject’s eCRF. 
All AEs regardless of causality will be reported by the Investigator to the Medical Monitor 
through the 30-day period after the last dose of study treatment.  
Any AE related to COVID-19 must be recorded as such. 
9.2 
Serious Adverse Events 
9.2.1 
Definitions  
An SAE is any untoward medical occurrence at any dose that results in any of the following 
outcomes: 
• Death 
• A life-threatening event (i.e., puts the subject, in the view of the Principal Investigator 
(PI), at immediate risk of death) 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant disability/incapacity 
• A congenital anomaly/birth defect 
• Important medical event that may require medical or surgical intervention to prevent one 
of the above outcomes 
An unexpected adverse drug event is any adverse drug event, the specificity or severity of which 
is not consistent with the current IB. 
An AE is associated with the use of the drug if a reasonable possibility exists that the drug may 
have caused the event. 
9.2.2 
Reporting 
SAEs that are unexpected and related to BRIMOCHOL PF and/or Carbachol PF are reportable to 
Regulatory Authorities. All SAEs, regardless of causality will be reported by the Investigator to 
the Medical Monitor through the 30-day period after the last dose of study treatment. Deaths and 
SAEs occurring after the 30-day safety follow-up period AND considered related to study 
treatment or study procedures must also be reported. 
Report all SAEs (initial and follow-up information) on an SAE form and send the form to the 
Sponsor or designee within 24 hours of the discovery of the event or information (see below). 
The Sponsor or designee may request follow-up and other additional information from the 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 40 of 67 
 
Investigator (e.g., hospital admission or discharge notes, laboratory results). SAEs will be 
followed up through resolution, stabilization, or treatment termination.  
Report all deaths with the primary cause of death as the SAE term, as death is the outcome of the 
event, not the event itself. If an autopsy was performed, report the primary cause of death on the 
autopsy report as the SAE term. Forward autopsy and postmortem report(s) to the Sponsor or 
designee, as outlined above. 
If study treatment is discontinued, temporarily suspended, or the dose reduced because of an 
SAE, include this information in the SAE report. 
Suspected unexpected serious adverse reactions (SUSARs) are SAEs that qualify for mandatory 
expedited reporting to regulatory authorities where the SAE is suspected to be caused by the 
study treatment and is considered unexpected (i.e., not defined as expected in the current IB 
clinical study protocol, or approved labeling for marketed drugs). In this case, the Sponsor or 
designee will report to the relevant regulatory authorities and forward a formal notification 
describing the SUSAR to Investigators, according to regulatory requirements. Each Investigator 
must then notify his or her institutional review board (IRB) of the SUSAR as required by local 
regulatory authorities and in accordance with IRB policy. 
Preplanned surgeries or procedures for pre-existing known medical conditions for which a 
patient requires hospitalization is not reportable as a serious adverse event and should be listed in 
medical history. 
9.2.3 
Classification of Severity of Adverse Event 
The severity of AEs will be categorized, as shown below.  
Categorization of Severity of Adverse Events   
Mild 
The event is minor and does not cause significant discomfort to subject or change in 
activities of daily living (ADL); subject is aware of symptoms, but symptoms are easily 
tolerated. 
Moderate 
The event is an inconvenience or concern to the subject and causes interference with ADL, 
but the subject is able to continue with ADL. 
Severe 
The event significantly interferes with ADL and the subject is incapacitated and/or unable 
to continue with ADL. 
Potentially 
life- 
threatening  
An event/reaction in which the subject was at risk of death at the time of the event/reaction; 
it does not refer to an event/reaction which hypothetically might have caused death if it 
were more severe. 
9.2.4 
Relationship to Investigational Product 
The Investigator will make a determination of the relationship of the AE to the IP using a 
4-category system (not related, possible, probable, definite), as shown below. 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 41 of 67 
 
Categorization for Determining Relationship of AEs to Study Treatment   
Not related 
An AE that does not follow a reasonable temporal sequence from administration of the drug 
and that can be reasonably explained by other factors, including underlying disease, 
complications, concomitant drugs, or concurrent treatment. 
Possible 
An AE that follows a reasonable temporal sequence from the administration of the drug 
(including the course after withdrawal of the drug) and that cannot be excluded as being 
possibly caused by the drug (e.g., existence of similar reports attributed to the drug and/or its 
analogues; reactions attributable to the pharmacological effect of the drug), although other 
factors such as underlying disease, complications, concomitant drugs, or concurrent treatment 
are presumable. 
Probable 
An AE that follows a reasonable temporal sequence from administration of the drug (including 
the course after withdrawal of the drug) and that can be excluded as being possibly caused by 
other factors, such as underlying disease, complications, concomitant drugs, or concurrent 
treatment. 
Definite 
An AE that follows a reasonable temporal sequence from administration of the drug (including 
the course after withdrawal of the drug), follows a known or hypothesized cause–effect 
relationship, and (if appropriate) satisfies the following: 
• 
Positive results obtained in drug sensitivity tests. 
• 
Toxic level of the drug present in blood or other body fluids. 
9.2.5 
Ocular Events of Special Interest 
For this study medically important events comprise the following ocular events, which are of 
special interest and by default are to be reported as SAEs:  
• Acute angle glaucoma or moderate to severe increase in IOP of >25 mm Hg 
• Retinal tear or detachment 
9.3 
Pregnancies 
Females of childbearing potential must have a negative urine pregnancy test at Visit 1 to 
participate. If a female has a positive urine pregnancy test during the study, the subject will be 
withdrawn from the study and the Investigator will notify IQVIA and/or the Sponsor within 
24 hours of knowledge of the positive pregnancy test. 
The pregnancy will be followed to term and/or outcome, and this outcome must be reported to 
the Sponsor. A pregnancy is not regarded as an AE or SAE unless the birth results in a 
congenital anomaly/birth defect, or there is suspicion that the study treatment may have 
interfered with the effectiveness of a contraceptive medication or method. 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 42 of 67 
 
10 DATA COLLECTION AND MANAGEMENT 
10.1 
Data Confidentiality 
All data collected during the study will be recorded in the subject’s eCRF. To maintain 
confidentiality, subjects will be identified only by Subject Number and initials. 
10.2 
Site Monitoring 
The Sponsor or designee (e.g., Clinical Research Associate [CRA]) will be responsible for 
monitoring this clinical trial. The CRA will monitor the study conduct, proper eCRF and source 
documentation completion and retention, and accurate IP accountability. To this end, the CRA 
will visit the study site at suitable intervals and be in frequent contact through verbal and written 
communication. The Investigator will grant access to all documents (related to the study and 
subjects) at any time these are requested. In turn, the CRA will adhere to all requirements for 
subject confidentiality as outlined in the ICF. The Investigator and study staff will be expected to 
cooperate with the CRA, to be available during a portion of the monitoring visit to answer 
questions, and to provide any missing information. 
10.3 
Data Collection 
All primary source data or copies thereof (e.g., laboratory records, eCRFs, data worksheets, 
correspondence, photographs, and computer records) that are a result of the original observations 
and activities of the study and are necessary for the reconstruction and evaluation of any study 
report will be retained in the clinic archives. 
 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 48 of 67 
 
12 ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES 
12.1 
Regulatory and Ethical Compliance 
The study will be conducted in accordance with the International Council for Harmonisation 
Good Clinical Practice (ICH GCP) guidelines, principles enunciated in the Declaration of 
Helsinki, and all applicable FDA regulations. 
12.2 
Responsibilities of the Investigator and IRB 
This protocol, the ICF, and all relevant supporting data must be submitted to the IRB for 
approval. IRB approval of the protocol, the ICF, any advertisement used to recruit study subjects 
must be obtained before initiating the study. 
The PI is responsible for keeping the IRB advised of the progress of the study and of any 
changes made to the protocol as deemed appropriate, but in any case, at least once a year. The PI 
is also responsible for notifying the IRB of any reportable AEs that occur during the study. 
12.3 
Informed Consent Procedures 
At the first visit, prior to initiation of any study-related procedures, subjects must give their 
written consent to participate in the study after having been informed about the nature and 
purpose of the study, participation/termination conditions, and risks and benefits. The ICF must 
be signed and dated by the subject prior to study participation. A copy of the ICF must be 
provided to the subject. Signed consent forms must remain in the subject’s study file and be 
available for verification by the Sponsor or its representative at any time. 
12.4 
Publication of Study Protocol and Results 
Visus will retain ownership of all data. All proposed publications based on this study will be 
subject to the Sponsor’s approval requirements. 
12.5 
Study Documentation, Recordkeeping, and Retention of Documents 
All study data will be captured using an EDC system. All source documents, records, and reports 
will be retained by the clinic. 
All primary source data or copies thereof (e.g., eCRFs, data worksheets, correspondence, and 
computer records) that are a result of the original observations and activities of the study and are 
necessary for the reconstruction and evaluation of any study report will be retained in the clinic 
archives. 
The Investigator must retain study documents for a period of 2 years following the date a 
marketing application is approved for the study product for the indication for which it is being 
investigated; or if no application is to be filed or if the application is not approved for such 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 49 of 67 
 
indication until 2 years after the investigation is discontinued and the FDA is notified. The site 
should not destroy records until authorized to do so by Visus. 
12.6 
Confidentiality of Study Documents and Subject Records 
All information provided regarding the study, as well as all information collected or documented 
during the study, will be regarded as confidential. The Investigator agrees not to disclose such 
information in any way without prior written permission from the Sponsor. 
Any publication of the results, either in part or in total (articles in journals or newspapers, oral 
presentations, abstracts, etc.) by the Investigator or their representative(s), shall require prior 
notification and review, within a reasonable time frame, by the Sponsor, and cannot be made in 
violation of the Sponsor’s confidentiality restrictions or to the detriment of the Sponsor’s 
intellectual property rights. 
The results from Screening and data collected during the study will be recorded in the subject’s 
eCRF. To maintain confidentiality, subjects will be identified only by numbers and initials. 
12.7 
Monitoring and Quality Assurance 
During the study, the Sponsor, an IQVIA Biotech CRA, or designee may complete routine 
monitoring visits to review protocol compliance, assess IP accountability, and ensure the study is 
being conducted according to regulatory requirements. The review of the subjects’ medical 
records will be performed in a manner that adequately maintains subject confidentiality.  
Further details of the study monitoring will be outlined in a clinical monitoring plan (CMP). 
Regulatory authorities of domestic and foreign agencies, the Sponsor, and IQVIA Biotech 
Quality Assurance and/or its designees may carry out on-site inspections and/or audits that may 
include source data checks. Therefore, direct access to the original source data will be required 
for inspections and/or audits.  
All inspections and audits will be carried out considering data protection as well as subject 
confidentiality to the extent that local, state, and federal laws apply.  
12.8 
Protocol Adherence 
The Investigator must adhere to the protocol as detailed in this document and agree that the 
Sponsor must approve any changes to the protocol prior to seeking approval from the IRB. There 
will be no alterations in the protocol without agreement between the Sponsor and the 
Investigator. There will be no alterations in the protocol affecting subject safety without the 
express written approval of the Sponsor, Investigator, and the IRB. 
12.9 
Study Termination 
The study may be stopped at a study site at any time by the Investigator. The Sponsor may stop 
the study (and/or the study site) for any reason with appropriate notification.  
 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 50 of 67 
 
13 REFERENCES 
Abdelkader A. A novel pharmacological treatment of pseudophakic presbyopia. Int J 
Ophthalmic Res. 2018;4(2):291-4. 
Abdelkader A. Improved presbyopic vision with miotics. Eye & Contact Lens 
2015;41(5):323–7. 
Abdelkader A. Influence of different concentrations of carbachol drops on the outcome of 
presbyopia treatment – a randomized study. Int J Ophthalmic Res. 2019;5(1):317-20. 
Abdelkader A, Kaufman HE. Clinical outcomes of combined versus separate carbachol and 
brimonidine drops in correcting presbyopia. Eye Vis (Lond). 2016 Dec 5; 3:31. 
Allergan patent application Pub. No.: US 2018 / 0078500 A1. 
Benozzi J, Benozzi G, Orman B. Presbyopia: a new potential pharmacological treatment. 
Med Hypothesis Discov Innov Ophthalmol. 2012 Spring;1(1):3-5. 
Benzoni JA, Rosenfield M. Clinical amplitude of accommodation in children between 5 and 
10 years of age. Optom Vis Dev. 2012;43(3):109-14. 
Carey V, Zeger S, Diggle P. Modelling multivariate binary data with alternating logistic 
regressions. Biometrika., 1993;80:517-526.  
Connor R. Sample size for testing differences in proportions for the paired-sample design. 
Biometrics. 1987;43(1), 207-11. 
EMA/CHMP/44762/2017, Guideline on multiplicity issues in clinical trials.  
Frick KD, Joy SM, Wilson DA, Naidoo KS, Holden BA. The global burden of potential 
productivity loss from uncorrected presbyopia. Ophthalmology. 2015 Aug;122(8):1706-10. 
FDA. Guidance for industry: multiple endpoints in clinical trials. 2017.  
Gelatt KN, Gum GG, Wolf ED, White MM. Dose response of topical carbamylcholine 
chloride (carbachol) in normotensive and early glaucomatous beagles. Am J Vet Res. 1984 
Mar;45(3):547-54. 
Gil-Cazorla R, Shah S, Naroo SA. A review of the surgical options for the correction of 
presbyopia. Br J Ophthalmol. 2016 Jan;100(1):62-70. 
Goertz DA, Stewart WC, Burns WR, et al. Review of the impact of presbyopia on quality of 
life in the developing and developed world. Acta Ophthalmol. 2014:92:497-500. 
ISOPTO® CARBACHOL (carbachol ophthalmic solution) 1.5% [prescribing information]. 
Fort Worth, TX: Alcon Laboratories, Inc.; 2007. 
Isopto® Carpine (pilocarpine hydrochloride ophthalmic solution) 1%, 2%, and 4% 
[prescribing information]. Fort Worth, TX: Alcon Laboratories, Inc.; 2010. 
Karanfil FC, Turgut B. Update on presbyopia-correcting drops. European Ophthalmic 
Review. 2017;11(2):99–102. 
Kato S, Shimizu K, Kamiya K, Ishikawa H, Igarashi A. Effects of brimonidine tartrate 0.1% 
ophthalmic solution on the pupil, refraction, and light reflex. Sci Rep. 2018; 8:9003. 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 51 of 67 
 
Kubo C, Suzuki R. Involvement of prejunctional alpha2-adrenoceptor in bovine ciliary 
muscle movement. J Ocul Pharmacol. 1992;8(3):225-31. 
McDonnell PJ, Lee P, Spritzer K, Lindblad AS, Hays RD. Associations of presbyopia with 
vision- targeted health-related quality of life. Arch Ophthalmol. 2003 Nov;121(11):1577-81. 
McNemar Q. Note on the sampling error of the difference between correlated proportions or 
percentages. Psychometrika. 1947;12:153–157. 
MIOSTAT® (Carbachol Intraocular Solution, USP) 0.01% [prescribing information (PI)]. 
Fort Worth, TX: Alcon Laboratories, Inc.; 2015. 
Moarefi MA, Bafna S, Wiley W. A review of presbyopia treatment with corneal inlays. 
Ophthalmol Ther. 2017 Jun;6(1):55-65. 
Nardin G, Zimmerman T. (1966). Ocular cholinergic agents. In Ritch R, Shields MB, 
Krupin T, eds. The glaucomas. 2nd ed. St. Louis: Mosby. 1966; 3:1399-1407. 
Renna A, Alió JL, Vejarano LF. Pharmacological treatments of presbyopia: a review of 
modern perspectives. Eye Vis (Lond). 2017 Feb 7; 4:3. 
Poinoosawmy D, Nagasubramanian S, Brown NA. Effect of pilocarpine on visual acuity and 
on the dimensions of the cornea and anterior chamber. Br J Ophthalmol. 1976; 60:676-9. 
Suzuki G, Kunikane E, Shinno K, Kozai S, Kurata M, Kawamura A. Ocular and systemic 
pharmacokinetics of brimonidine and timolol after topical administration in rabbits: 
comparison between fixed-combination and single drugs. Ophthalmol Ther. 2020; 9:115–25. 
 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 52 of 67 
 
14 PROTOCOL AMENDMENT 4 SUMMARY 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
Visus Therapeutics, Inc. 
Confidential 
Page 53 of 67 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5 1  4 Apr 2023 
Visus Therapeutics, Inc. 
Confidential 
Page 54 of 67 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
Visus Therapeutics, Inc. 
Confidential 
Page 55 of 67 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
Visus Therapeutics, Inc. 
Confidential 
Page 56 of 67 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
Visus Therapeutics, Inc. 
Confidential 
Page 57 of 67 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
Visus Therapeutics, Inc. 
Confidential 
Page 58 of 67 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
Visus Therapeutics, Inc. 
Confidential 
Page 59 of 67 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
Visus Therapeutics, Inc. 
Confidential 
Page 60 of 67 
 
 
 
 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 61 of 67 
 
15 PROTOCOL AMENDMENT 3 SUMMARY 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
Visus Therapeutics, Inc. 
Confidential 
Page 62 of 67 
 
 
 
 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 63 of 67 
 
16 PROTOCOL AMENDMENT 2 SUMMARY 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
Visus Therapeutics, Inc. 
Confidential 
Page 64 of 67 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
 
Visus Therapeutics, Inc. 
Confidential 
Page 65 of 67 
 
17 PROTOCOL AMENDMENT 1 SUMMARY 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
Visus Therapeutics, Inc. 
Confidential 
Page 66 of 67 
 

Protocol VT-002 Amendment 4 
Visus Therapeutics, Inc. 
Version 5.1, 4 Apr 2023 
Visus Therapeutics, Inc. 
Confidential 
Page 67 of 67