PURPOSE:The NEW DAY (ClinicalTrials.gov identifier, NCT04469595) study assessed the efficacy and safety of the fluocinolone acetonide (FAc; 0.19 mg) intravitreal implant as baseline therapy in diabetic macular edema (DME). DESIGN:Prospective, randomized, single-masked, active-controlled, multicenter, 18-month, phase 4 study. PARTICIPANTS:Adults with type 1 or 2 diabetes and center-involving DME confirmed by central subfield thickness (CST). METHODS:Treatment regimens were FAc implant followed by rescue supplemental injections of aflibercept if needed (2 mg/0.05 ml) for 17 months versus aflibercept loading dose (2 mg every 4 weeks for 5 consecutive doses) followed by rescue supplemental injections of aflibercept if needed (2 mg/0.05 ml) for 13 months. MAIN OUTCOME MEASURES:The primary end point was mean rescue supplemental injections of aflibercept needed during the study by treatment group. Additional outcomes included time to first rescue supplemental injection, best-corrected visual acuity (BCVA), CST, rates of cataract procedures, and increases in intraocular pressure (IOP). RESULTS:Five hundred seventeen participants were screened, and 306 participants randomized. Mean (standard deviation [SD]) rescue supplemental injections were 2.4 (3.2) with FAc and 2.5 (3.1) with aflibercept (P = 0.76; primary end point). Counting both protocol-mandated and rescue supplemental injections, the FAc group received fewer injections compared with the aflibercept group (mean [SD], 3.4 [3.2] vs. 7.2 [3.4] injections; nominal P < 0.001). Time to first rescue supplemental injection was longer with FAc than with aflibercept (mean [SD], 185.4 [97.9] days vs. 132.8 [94.0] days; nominal P < 0.001). Proportions of participants who did not receive rescue supplemental injections were similar (32.5% vs. 30.3%; nominal P = 0.68). Mean change in BCVA was similar between groups (1.8 letters vs. 5.5 letters; nominal P = 0.08), as was the change in CST (mean [SD], -119 [112] μm vs. -114 [103] μm; nominal P = 0.71). In the FAc group, 27.9% underwent a cataract procedure versus 6.6% in the aflibercept group. Increased IOP occurred in 15.6% and 3.3% of participants in the FAc and aflibercept groups, respectively. CONCLUSIONS:Although the primary end point of rescue supplemental injection superiority was not met, FAc-treated participants achieved similar visual and anatomic improvements as those receiving aflibercept with fewer than half the number of total injections throughout the study. Safety data results were consistent with previous FAc implant studies. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PURPOSE:Knobloch syndrome is a rare autosomal recessive condition characterized by lack of functional collagen type XVIII (COL18A1), occipital defects, high myopia, and vitreoretinal degeneration. Clinical features, retinal detachment (RD) rates, and role of prophylactic treatment are not well established. The purpose is to 1) report clinical/systemic features, 2) RD rates and 3) the role of prophylactic treatment in a U.S.-based genetically confirmed cohort. DESIGN:Retrospective, nonrandomized multi-center case cohort SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Genetically confirmed Knobloch patients from 12 US -based pediatric retina tertiary referral centers MAIN OUTCOMES MEASURES: Baseline characteristics, RD rates, risk of RD with or without a history of prophylactic treatment RESULTS: 72 eyes (36 patients) were included. Mean follow up was 5.2 years. 14 patients (38.9%) were female. Most common systemic features included 1) occipital defects (n=17 (47.2%)), 2) intracranial abnormalities (n=10 (27.8%); polymicrogyria, plagiocephaly, cortical dysplasia, encephalomalacia, periventricular heterotopia), and 3) skin (n=5 (13.9%)); hemangioma, eczema). Mean +/-SE refractive error was - 9.85 (range -20.12 - +7.50). 18 eyes (25.0%) had cataracts, 16 (20.0%) iris defects (transillumination defects, absent crypts, pupillary membrane), 40 (57.1%) optically empty/vitreous condensations, and 64/70 eyes (91.4%) had macular abnormalities ranging from tessellated fundus to generalized macular atrophy.Of 72 eyes, 23 (31.9 %) experienced an RD, 12 (52.2%) at baseline. Two eyes (8.7%) had a concurrent macular hole. Mean age at RD was 6.24 years and time to RD was 18.6 months (0 - 86). 20 eyes (87.0%) underwent RD surgery (laser, SB, PPV, or PPV/SB). Single and final anatomic success was 60% and 85%. 21/72 eyes (29.2%) received laser or scleral buckle prophylaxis - only two of which (9.0%) developed an RD. Age-adjusted GEE logistic model demonstrated lower odds of RD in eyes that received prophylaxis than not (OR 0.20, P = 0.022). 4/19 fellow eyes (21%) developed an RD (n=1 with previous RD prophylaxis). There was a nonsignificant lower odds of RD in fellow eyes that received RD prophylaxis versus no prophylaxis (OR = 0.42, p = 0.41). CONCLUSION:In genetically confirmed Knobloch, RD rates are high, and RD prophylaxis appeared to reduce risk of RD. Early diagnosis and prophylaxis should be considered in this population.
Allogeneic ocular surface stem cell transplantation (OSST) is an established therapeutic approach for limbal stem cell deficiency, utilizing techniques such as keratolimbal allograft (KLAL), living-related conjunctival limbal allograft (lr-CLAL), allogeneic cultivated limbal epithelial transplantation (allo-CLET), and allogeneic simple limbal epithelial transplantation (allo-SLET). This review synthesizes evidence from 35 studies encompassing 1, 268 eyes with at least 24 months of follow-up to evaluate intermediate- and long-term outcomes. Overall, OSST is associated with improvement in visual acuity and restoration of ocular surface stability, although success rates vary widely by technique, ranging from 13% to 87%. Outcomes appear to be influenced by the intensity of systemic immunosuppression, with triple-agent regimens demonstrating higher rates of long-term success compared with single- or dual-agent approaches. Among techniques, lr-CLAL may offer advantages over KLAL due to lower rejection rates. Despite encouraging results, long-term data remain limited for newer approaches such as allo-CLET and allo-SLET. Careful postoperative monitoring and management of complications, including rejection, glaucoma, and microbial keratitis, remain essential to optimize outcomes.
