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.

Aggressive amelanotic choroidal melanoma with extrascleral extension after brachytherapy.

PURPOSE: The purpose of this study was to report a case of amelanotic choroidal melanoma, previously treated with brachytherapy, subsequently exhibiting local extension through pars plana vitrectomy sites. METHOD: The authors present a retrospective interventional case report from a clinical practice. RESULTS: An amelanotic choroidal melanoma, previously responsive to brachytherapy, underwent two pars plana vitrectomies for nonclearing vitreous hemorrhage with double-freeze cryotherapy to sclerotomy sites. Recurrent melanoma extended through the sclerotomies presenting as subconjunctival nodules requiring exenteration. CONCLUSION: Vitrectomy sclerotomy sites may serve as a route of extrascleral extension in previous brachytherapy treatment-responsive choroidal melanomas. Caution should be exercised in performing vitrectomy for choroidal melanomas with subsequent vitreous hemorrhage.

The role of difluprednate ophthalmic emulsion in clinical practice.

The mainstay in the treatment of ocular inflammation, either post-surgical or endogenous, is the use of steroids. While these agents effectively address inflammation, they are not without their risks, including ocular hypertension and acceleration of cataract formation. The most notorious culprits are the strong steroids, such as prednisolone acetate and betamethasone. This review aims to cover the biochemistry and drug development of difluprednate, a novel synthetic strong steroid emulsion. In vivo pharmacokinetics as well as ocular distribution and metabolism are discussed, followed by a comprehensive summary of phase I, II, and III clinical trials evaluating safety and efficacy in patients suffering from postoperative inflammation or anterior uveitis. The objective is to provide an increased familiarity with this newly approved medication as a welcome addition to the ophthalmologist's armamentarium.

An improved technique of eye drop self-administration for patients with limited vision.

PURPOSE: To describe a new, highly accurate, tactile technique to increase accuracy in the self-administration of eye drops. DESIGN: Interventional case series. METHODS: Ten adult patients with loss of fixation (< or = 20/400) in one eye and ten adult patients with loss of fixation in both eyes instilled one drop of artificial tears in each eye using the technique normally employed at home. The time required to instill each drop, the number of drops squeezed from the bottle, and location of the drops' landing points on the face or eye were recorded. The patients were then instructed in a new technique for instillation, guided through the procedure once, and allowed to practice until comfortable with it. All measurements were then repeated. RESULTS: In patients with loss of fixation in one eye, an additional 3.2 +/- 4.1 seconds were required to instill a drop using the new technique (P <.0001, paired t test; range, -7-18 seconds). The mean number of drops dispensed decreased by 0.1 +/- 0.6 drops (P =.60, paired t test; range, -2-1 drop). The accuracy of drop placement increased from 80.0% to 82.5% (P =.32, paired t test). In subjects with loss of fixation in both eyes, using the new technique increased the time needed to instill a drop by 3.8 +/- 3.8 seconds (P <.0001, paired t test; range, -3-13 seconds). The average number of drops dispensed decreased by 0.1 +/- 0.6 drops (P =.25, paired t test; range, -2-1 drop). The accuracy of placement increased from 63.0% to 85.0% (P =.001, paired t test). CONCLUSIONS: This technique of drop instillation may be beneficial for patients with significant visual impairment in both eyes.

Attempted eyelid closure affects intraocular pressure measurement in open-angle glaucoma patients.

PURPOSE: To evaluate the effect of attempted eyelid closure on intraocular pressure (IOP) measurements in normal-tension (NTG) and high-tension (HTG) open-angle glaucoma patients. DESIGN: Prospective clinical trial. METHODS: Forty randomly selected eyes of 40 patients underwent corneal pachymetry and IOP measurements using both Goldmann applanation tonometry and Tono-pen XL (Mentor, Inc., Norwell, Massachusetts, USA). Intraocular pressure was measured by the same examiner holding the eyelids open, both with and without the subject simultaneously attempting forced eyelid closure. Subjects were seated during all measurements and waited 5 minutes between measurements with each instrument; the order of measurement was randomized. RESULTS: Twenty NTG and 20 HTG eyes were enrolled. The mean age was 63.0 +/- 13.0 years (range, 31-80 years). The average corneal thickness was 540 +/- 32 microm (range, 480-608 microm) in NTG patients and 552 +/- 40 microm (range, 449-610 microm) in HTG patients (P =.07, analysis of variance [ANOVA]). Using Goldmann applanation tonometry, IOP measurement in eyes with NTG increased by 3.9 +/- 2.0 mm Hg with attempted eyelid closure (P <.0001, paired t test; range, 2-11 mm Hg). With the Tono-pen XL, IOP measurements increased 4.2 +/- 2.7 mm Hg (P <.0001, paired t test; range, 1-14 mm Hg). With attempted forced eyelid closure, the Goldmann applanation measurement in eyes with HTG increased 4.1 +/- 2.1 mm Hg (P <.0001, paired t test; range, 1-9 mm Hg). Using the Tono-pen XL, measurements increased 4.5 +/- 2.0 mm Hg (P <.0001, paired t test; range, 2-11 mm Hg). CONCLUSION: Attempted eyelid closure during tonometry is a significant and common source of error in eyes with glaucoma and may influence the clinical management and decision-making in the treatment of NTG and HTG.