The USC Gayle and Edward Roski Eye Institute, part of Keck School of Medicine of USC, is a center for ophthalmic care, research and education located in downtown Los Angeles, California. It has subsidiary clinics in Pasadena, Beverly Hills and Arcadia. It was allied with the Doheny Eye Institute from 1975 until 2013, when Doheny allied with University of California Los Angeles....
center dot PURPOSE: In this study the safety and efficacy of silk- derived protein 4 (SDP-4), also known as amlisimod, , eye drops against a vehicle control formulation in patients with moderate to severe dry eye disease (DED) was assessed. SDP-4 is a novel, naturally derived, antiinflammatory wetting agent that enhances coating on the ocular surface. center dot DESIGN: Exploratory Phase 2, 12- and 8-week, serial cohort, multicenter, double-masked, randomized, vehicle- controlled study. center dot METHODS: In the first cohort (N = 305), patients were randomized 1:1:1:1 to SDP-4 (0.1%, 1%, 3% wt./wt.) or vehicle control and dosed 2 times per day (BID), while in the second cohort patients were randomized 1:1 with 1% wt./wt. SDP-4, the best performing formulation from the first cohort, or vehicle control BID (N = 151). Diagnosed DED patients were treated in the United States between April 2019 and May 2021. The first cohort of subjects had moderate to severe baseline symptoms, while the second cohort had moderate baseline symptoms to study the impact of baseline symptoms on SDP-4 performance. Key sign and symptom end points were mean change from baseline in TBUT and total SANDE score (0-100 visual analog scale) throughout the study. center dot RESULTS: SDP-4 (1%) significantly increased TBUT vs the vehicle control ( P < .05) at days 28 and 56 in the first cohort, and patient symptomatology from baseline was reduced by 46% based on subject reported SANDE VAS scores at day 84. Patients with more severe baseline DED symptoms experienced a significantly greater amount of relief than when compared to patients with moderate DED ( P < .05). All treatment groups were well tolerated with a 2.6% total discontinuation rate. center dot CONCLUSIONS: To the best of our knowledge, this was the first-in-human use of SDP-4 in a clinical trial. SDP- 4 is a first-in-class protein ingredient that offers a safe and multi-modal treatment approach for alleviating severe DED symptoms within a novel formulation. (Am J Ophthalmol 2025;269: 315-326. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
Exfoliation Syndrome is an age-related systemic condition characterized by large aggregated fibrillar material deposition in the anterior eye tissues. This aggregate formation and deposition on the aqueous humor outflow pathway are significant risk factors for developing Exfoliation Glaucoma (XFG). XFG is a multifactorial late-onset disease that shares common features of neurodegenerative diseases, such as increased protein aggregation, impaired protein degradation, and oxidative and cellular stress. XFG patients display decreased mitochondrial membrane potential and mitochondrial DNA deletions. Here, using Tenon Capsule Fibroblasts (TFs) from patients without glaucoma (No Glaucoma, NG) and XFG patients, we found that XFG TFs have impaired mitochondrial bioenergetics and increased reactive oxygen species accumulation. These defects are associated with mitochondrial abnormalities as XFG TFs exhibit smaller mitochondria that contain dysmorphic cristae, with increased mitochondrial localization to lysosomes and slowed mitophagic flux. Mitochondrial dysfunction in the XFG TFs was associated with hyperdynamic microtubules, decreased acetylated tubulin, and increased HDAC6 activity. Treatment of XFG TFs with a mitophagy inducer, Urolithin A (UA), and a mitochondrial biogenesis inducer, Nicotinamide Ribose (NR), improved mitochondrial bioenergetics and reduced ROS accumulation. Our results demonstrate that XFG TFs have abnormal mitochondria and suggest that mitophagy inducers may represent a potential class of therapeutics for reversing mitochondrial dysfunction in XFG patients.
PURPOSE:To describe clinical features, treatment outcomes, and microbiological isolates in eyes with presumed post-injection endophthalmitis (PIE) following anti-vascular endothelial growth factor (anti-VEGF) injection for retinopathy of prematurity (ROP). METHODS:Medical records data of preterm infants diagnosed with PIE, from multiple centres, between October 2017 and March 2025 were reviewed. Details of the type of anti-VEGF, setting of the procedure, duration between injection and diagnosis, and clinical features were recorded. The details of treatment, microbiological evaluation, additional treatment for endophthalmitis or ROP, and final structural outcomes were documented. RESULTS:Twenty-three eyes of 23 infants treated with Ranibizumab (n = 13), Bevacizumab (n = 9), and Aflibercept (n = 1) were diagnosed with presumed PIE at a median of four days (IQR-4) after injection. Clinical features included conjunctival congestion (12, 52.8%), corneal edema (10, 43.8%), fibrinous membrane, or hypopyon in anterior chamber (10, 43.5%), posterior synechiae (6, 26.1%), and vitritis with exudation (19, 82.6%). Eighteen eyes (78.3%) were initially treated with intravitreal antibiotic, of which 11 eyes needed vitrectomy for persistent vitritis. The globe was salvaged in 14 eyes (60.9%), with attached retina in 12 eyes (52.2%). Nine eyes (39.1%) had phthisis bulbae. Five eyes had culture proven PIE (5/17, 29.4%) and isolates included Pseudomonas aeruginosa (n = 2), Streptococcus salivaris (n = 1), Streptococcus mitis (n = 1) and Candida tropicalis (n = 1). CONCLUSION:Examination within a week after the injection can identify most eyes with presumed PIE, with vitreous exudation being the most consistent clinical feature. Isolated microorganisms are virulent. Following treatment, the possibility of poor structural outcome is higher than in adults with PIE.
