A Phase I, Single Ascending Dose Study of GEM103 (Recombinant Human Complement Factor H) in Patients with Geographic Atrophy.

Purpose: To establish the safety, tolerability, pharmacokinetics, and pharmacodynamics of an intravitreal injection of recombinant human complement factor H (CFH), GEM103, in individuals with genetically defined age-related macular degeneration (AMD) and geographic atrophy (GA). Design: Phase I single ascending-dose, open-label clinical trial (ClinicalTrials.gov identifier, NCT04246866). Participants: Twelve individuals 50 years of age or older with a confirmed diagnosis of foveal GA in the study eye. Methods: Participants were assigned to the increasing dose cohorts and received 1 50-µl intravitreal injection of GEM103 at doses of 50 µg/eye, 100 µg/eye, 250 µg/eye, or 500 µg/eye; dose escalation was dependent on the occurrence of dose-limiting toxicities. Main Outcome Measures: Safety assessments included ocular and systemic adverse events (AEs), ocular examinations, clinical laboratory and vital signs, and serum antidrug antibody levels. Biomarkers, measured in the aqueous humor (AH), included CFH and complement activation biomarkers factor Ba and complement component 3a. Results: No dose-limiting toxicities were reported, enabling escalation to the maximum study dose. No anti-GEM103 antidrug antibodies were detected during the study. Four participants experienced AEs; these were nonserious, mild or moderate in severity, and unrelated to GEM103. The AEs in 2 of these participants were related to the intravitreal injection procedure. No clinically significant ophthalmic changes and no ocular inflammation were observed. Visual acuity was maintained and stable throughout the 8-week follow-up period. No choroidal neovascularization occurred. CFH levels increased in a dose-dependent manner after GEM103 administration with supraphysiological levels observed at week 1; levels were more than baseline for 8 weeks or more in all participants receiving single doses of 100 µg or more. Complement activation biomarkers were reduced 7 days after dose administration. Conclusions: A single intravitreal administration of GEM103 (up to 500 µg/eye) was well tolerated in individuals with GA. Of the few mild or moderate AEs reported, none were determined to be related to GEM103. No intraocular inflammation or choroidal neovascularization developed. CFH levels in AH were increased and stable for 8 weeks, with pharmacodynamic data suggesting that GEM103 restored complement regulation. These results support further development in a repeat-dose trial in patients with GA with AMD.

Intravitreal ranibizumab for macular edema secondary to central retinal vein occlusion.

PURPOSE: To evaluate the safety and efficacy of intravitreal ranibizumab for macular edema secondary to central retinal vein occlusion. METHODS: Patients with macular edema secondary to perfused central retinal vein occlusion were enrolled in this ongoing, prospective, open-label study. Treatment was initiated with monthly intravitreal ranibizumab for 3 months. In the first year, additional injections were administered for edema in quarterly intervals as needed (PRN) for Cohort 1 (n = 10) and monthly PRN for Cohort 2 (n = 10). In the second year of treatments, all patients received monthly PRN treatment. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, central retinal thickness, fundus photographs, and fluorescein angiograms were evaluated, and the incidence and severity of adverse events were documented. RESULTS: Mean change in best-corrected visual acuity and central retinal thickness improved during the induction phase in both groups. During the remainder of the first year for Cohort 1, initial gains were lost during quarterly treatment but returned with monthly PRN treatment in the second year. For Cohort 2, improvement in best-corrected visual acuity and central retinal thickness from the induction phase was maintained through Month 24. Nineteen of 20 patients experienced a reduction in intraretinal hemorrhage, optic nerve swelling, and/or venous diameter after treatment. One myocardial infarction, one cerebrovascular accident, and no serious ocular adverse events were reported. Iris neovascularization was developed in none of the eyes. CONCLUSION: Ranibizumab was well tolerated and associated with a greater reduction in macular edema and improvement in visual acuity in the monthly PRN regimen compared with quarterly treatment. Vision lost during the quarterly PRN injection intervals in the first year of Cohort 1 could be regained by switching to monthly PRN dosing.

Spectral domain optical coherence tomography for proliferative diabetic retinopathy with subhyaloid hemorrhage.

A prototype 6-microm axial resolution spectral domain optical coherence tomography (SD-OCT) device was used to image the retina of a patient with uncontrolled diabetes mellitus who had proliferative diabetic retinopathy with subhyaloid hemorrhage. A raster scan pattern with 128 B-scans covering a 6 X 6 X 2-mm volume of the retina was obtained. SD-OCT showed the presence of blood localized between the internal limiting membrane and the posterior hyaloid face and allowed visualization of the cross sectional retinal architecture and the vitreoretinal interface at different horizontal levels that could be registered with the color fundus photograph. SD-OCT provided useful information about the relationship of the hemorrhage to the posterior hyaloid and the retina.

Outcomes of surgery for idiopathic macular hole: a case-control study comparing silicone oil with gas tamponade.

BACKGROUND AND OBJECTIVE: To compare outcomes of macular hole surgery using silicone oil with C3F8 gas tamponade. PATIENTS AND METHODS: A retrospective case-control study of patients who underwent macular hole surgery for stage 2, 3, or 4 macular holes. RESULTS: Forty-six eyes of 44 patients underwent macular hole surgery involving injection of silicone oil (23 cases) or gas tamponade (23 controls). Anatomic closure occurred in 19 (82.6%) cases and 20 (86.9%) controls. Visual acuity improved to 20/70 or better in 4 (17.3%) of the cases and in 17 (73%) of the controls. CONCLUSION: In the current study of macular hole surgery, outcomes were better among patients with gas tamponade.

Laser treatment of Coats' disease.

A 9-year-old boy presented with an exudative retinal detachment, vascular telangiectasias, subretinal lipid, and retinal macrocyst formation. He underwent three sessions of large-spot diode laser for the treatment of Coats' disease. Serial examinations and fundus photography documented an excellent involutional response with an improvement in visual acuity.

Diffuse neonatal hemangiomatosis presenting as bilateral iris hemangiomas in an infant.

PURPOSE: To describe a case of diffuse neonatal hemangiomatosis presenting as bilateral iris hemangiomas. METHOD: Case report. PATIENT: A 2-month-old girl presented with bilateral enlarging red masses of her irises, congestive heart failure, and abdominal distension. The iris masses were diagnosed as hemangiomas, and she was found to have diffuse neonatal hemangiomatosis also involving her skin, liver, heart, and cerebellum. RESULTS: The patient's systemic hemangiomas were successfully treated with four cycles of weekly intravenous vincristine (0.05 mg/kg/dose) with concurrent resolution of her right iris hemangioma within 6 weeks. The left iris lesion then regressed within 1 month following 1 subTenon injection of 20 mg of triamcinolone acetonide with residual iridocorneal adhesions at the site. CONCLUSION: Diffuse neonatal hemangiomatosis should be considered in the setting of bilateral iris hemangiomas. Also, this case demonstrates that iris hemangiomas associated with diffuse neonatal hemangiomatosis may respond to systemic vincristine, and that periocular steroids may be useful for treating iris hemangiomas that are unresponsive to systemic vincristine alone.