Clinical Trials

1. Must have a confirmed clinical diagnosis of MacTel Type 2.

2. Must be 18 years of age or older.

Mild to Moderate NPDR

Vision 20/25 or better

No prior treatment for DME or DR

1. Each eye with one of the following qualifying diagnoses (diagnoses may differ between eyes):

a. High-risk ocular hypertension (OHT): IOP > 21 mmHg without glaucomatous optic neuropathy (excavation, diffuse or focal thinning or notching of the neuroretinal rim, visible nerve fiber layer defects, or asymmetry of the vertical cup-to-disc ratio of >0.2 between eyes) [enrollment of trial participants with High-risk OHT will be capped at 25% of total enrollment]

b. Mild primary open-angle glaucoma: glaucomatous optic neuropathy, visual field mean deviation better than -6.0 dB with no points in the central 5° <15 dB (see figure on next page)

c. Moderate primary open-angle glaucoma: glaucomatous optic neuropathy, visual field mean deviation equal to or worse than -6.0 dB but no worse than -12.0 dB and no central 5° points <15 dB or mean deviation -12.0 dB or better with 1 central 5° points <15 dB (see figure on next page).

2. Each eye with BCVA 20/200 (UK 6/60) or better

General Inclusion Criteria

• Ability and willingness to provide informed consent

• Age ≥ 18 and ≤65 years at time of signing Informed Consent Form

• Ability and willingness to comply with the study protocol and to participate in all study visits and assessments in the investigator’s judgement

• For candidates of childbearing potential: willingness to use a method of contraception

• Agreement not to take supplements other than vitamin A

Ocular Inclusion Criteria

• Both eyes must exhibit the RP phenotype with evidence of loss of night vision, gradual constriction of visual fields, and maintenance of visual acuity;

In addition, an eye must meet the following criteria to be included in the study:

• Gradable EZ on a horizontal SD-OCT scan through the fovea center with width ≤ 8000 μm and ≥1500 μm and with well-defined truncation at both the nasal and temporal sides;

ENG Version: 2.0 Version Date (YYYY-MM-DD) 2023-07-13

NAC Attack Protocol Page 39 of 40

• BCVA ≥ ETDRS letter score of 61 (20/60, [6/18] Snellen equivalent);

• Sufficiently clear ocular media and adequate pupillary dilation to allow good quality images sufficient for analysis and grading by central reading center.

General Exclusion Criteria

• Active cancer within the past 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer with Gleason score ≤ 6 and stable prostate specific antigen for > 12 months

• Renal failure requiring renal transplant, hemodialysis, peritoneal dialysis, or anticipated to require hemodialysis or peritoneal dialysis during the study

• History of thrombocytopenia not due to a reversible cause or other blood dyscrasia

• Uncontrolled blood pressure (defined as systolic > 180 and/or diastolic > 100 mmHg while at rest) at screening. If a patient's initial measurement exceeds these values, a second reading may be taken 30 or more minutes later. If the patient's blood pressure must be controlled by antihypertensive medication, the patient may become eligible if medication is taken continuously for at least 30 days.

• History of other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion that oral NAC may be contraindicated or that follow up may be jeopardized

• Cerebrovascular accident or myocardial infarction within 6 months of screening

• Patients taking slow-release formulations of nitrates

• Participation in an investigational study that involves treatment with any drug or device within 4 months of screening

• Use of any interventional treatment to the retina such as transcorneal electrical stimulation within 4 months of screening

• Three relatives already enrolled in study

• Pregnant or breast feeding females. Women of childbearing potential who have not had tubal ligation must have a urine pregnancy test at screening.

• Known history of allergy to NAC or any non-medicinal ingredients in the study medication including citric acid, aspartame, sodium bicarbonate, and lemon flavor

• Having taken NAC in any form in the past 4 months

• Phenylketonuria

• Fructose intolerance

• Histamine intolerance

• Glucose-galactose malabsorption

• Sucrase-isomaltase insufficiency

• Any major abnormal findings on blood chemistry, hematology, and renal function lab tests that in the opinion of the Site Investigator and/or the Study Chair makes the candidate not suitable to participate in the trial

• HIV or hepatitis B infection

Angina that requires administration of sustained delivery of nitrates Being on strict sodium restriction that is deemed by the patient’s general medical doctor to be incompatible with the added sodium intake from study medication.

Ocular Exclusion Criteria

• Evidence of cone-rod dystrophy or pattern dystrophy including focal areas of atrophy or pigmentary changes in the central macula

• Cystoid spaces involving the fovea substantially reducing vision

• Glaucoma or other optic nerve disease causing visual field loss or reduced visual acuity

• Intra ocular pressure >27 mm Hg from two measurements. If a patient's initial measurement exceeds 27 mm Hg, a second reading must be taken.

• Any retinal disease other than RP causing reduction in visual field or visual acuity

• Any prior macular laser photocoagulation

• Intraocular surgery within 3 months prior to screening

• High myopia with spherical equivalent refractive error > 8 diopters. If an eye has had cataract surgery or refractive surgery, a pre-operative refractive error spherical equivalent > 8 diopters is an exclusion

• Any concurrent ocular condition that might affect interpretation of results

• History of uveitis in either eye

Participants must meet all the following criteria to be eligible for inclusion in the study:

-Are ≥ 18 years of age at screening

-Have a clinical diagnosis of TED associated with onset of active TED within 12 months prior to screening active

- Moderate to severe TED.

-Are euthyroid with the baseline disease under control or have mild hypo- or

hyperthyroidism.

• Persistent Epithelial Defect (PED)
• Stage 2 or 3 Neurotrophic Keratopathy
• BCVA score of less than or equal to 75 letters
• At least 18 years of age