Relationship between duration and extent of oedema and visual acuity outcome with ranibizumab in diabetic macular oedema: A post hoc analysis of Protocol I data

BACKGROUND/OBJECTIVES: This post hoc analysis explores the relationship between residual oedema exposure after ranibizumab treatment initiation and long-term visual acuity outcome in eyes with centre-involved diabetic macular oedema (DMO). SUBJECTS/METHODS: Eyes randomised to the ranibizumab + prompt or deferred laser treatment arms in the Protocol I trial and with observed central retinal thickness (CRT) readings at baseline and ≥1 follow-up visits (n = 367) were stratified by 1) oedema duration (number of study visits with CRT ≥ 250 µm during the first 52 weeks of ranibizumab treatment); and 2) oedema extent (amount of excess CRT [≥ 250 µm] at each study visit, averaged over the first 52 weeks). Associations between measures of residual oedema and best-corrected visual acuity (BCVA) were assessed in multiple regression analyses. RESULTS: Oedema duration and oedema extent during the first 52 weeks of ranibizumab treatment showed significant negative associations with BCVA improvement at weeks 52, 104 and 156. Eyes with the most persistent oedema gained (mean) 4.4 (95% CI 0.1─8.7) fewer Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 156 than eyes with the least persistent oedema (P = 0.044). Eyes with the greatest amount of oedema gained (mean) 9.3 (95% CI 4.0─14.5) fewer ETDRS letters at week 156 than eyes with the least amount of oedema (P \u3c 0.001). CONCLUSIONS: Macular oedema exposure over the first 52 weeks of ranibizumab treatment is a negative prognostic factor for long-term visual acuity improvement in centre-involved DMO

A case study of choroideremia carrier – Use of multi-spectral imaging in highlighting clinical features

Purpose: To report the use of non-invasive multi-spectral imaging of a female choroideremia (CHM) carrier with mild visual symptoms and extensive fundus mottling. Observation: This was an observational case report study. A symptomatic 42-year-old female with a history of binocular CHM presented for routine ocular examination and underwent review of her clinical and photographic records, optical coherence tomography (OCT), intravenous fluorescein angiography (IVFA) and multi-spectral imaging (MSI). Dilated fundus examination and photography revealed similar outcomes of diffuse mottling with normal looking vessels. IVFA showed large irregular and confluent patches of RPE atrophy in the peripapillary and parapapillary areas as well as the midperiphery, corresponding to the OCT findings. The entire range of MSI imaging (520–940 nm) clearly illustrated the anomalies of the fundus including retinal pigment epithelium (RPE) mottling with melanin clumping not readily seen with the other imaging modalities. MSI fundus autofluorescence (MSI-FAF) showed a spotty hypo and hyperautofluorescent appearance of the fundus, consistent with the observations seen on IVFA and OCT images. Conclusion and Importance: MSI significantly improves visualization of the retinal pigment epithelium in choroideremia. The non-invasive nature of MSI technique is a valuable tool in monitoring the effect of retinal and choroidal presentation in patients with CHM

Results Of The 2-Year Ocriplasmin For Treatment For Symptomatic Vitreomacular Adhesion Including Macular Hole (Oasis) Randomized Trial

Purpose The Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (OASIS) trial was designed to evaluate the long-term efficacy and safety profile of ocriplasmin for the treatment of symptomatic vitreomacular adhesion (VMA)/vitreomacular traction, including full-thickness macular hole (FTMH). Design Phase 3b, randomized, sham-controlled, double-masked, multicenter clinical trial. Participants Sample size was 220 subjects (146 ocriplasmin, 74 sham) randomized in a 2:1 ratio to receive intravitreal ocriplasmin 0.125 mg or sham injection. Methods The trial involved 12 visits over 24-months. Inclusion criteria included presence of VMA and best-corrected visual acuity (BCVA) of 20/32 or worse in the study eye. Exclusion criteria included FTMH \u3e400 μm, presence of epiretinal membrane (ERM), and aphakia in the study eye. Main Outcome Measures The primary efficacy end point was the proportion of subjects with pharmacologic VMA resolution at day 28. Secondary efficacy end points were assessed at month 24 and included proportion of subjects with BCVA gain from baseline, nonsurgical FTMH closure, vitrectomy, and Visual Function Questionnaire 25 (VFQ-25) outcomes. Results The OASIS trial met its primary end point with pharmacologic VMA resolution at day 28 being significantly higher in the ocriplasmin group (41.7%) compared with the sham group (6.2%). The treatment effect was maintained until study end. In the ocriplasmin group, pharmacologic VMA resolution at day 28 was higher in subgroups with the following baseline characteristics compared with the complementary subgroups without them: presence of focal VMA, presence of FTMH, absence of ERM, and phakic lens status. In the ocriplasmin group, 50.5% of subjects had a ≥2-line improvement in BCVA from baseline compared with 39.1% of subjects in the sham group. The nonsurgical FTMH closure rate was 30.0% for the ocriplasmin group compared with 15.4% for the sham group. All other secondary end points also favored ocriplasmin over sham. Regarding safety, most adverse events were mild to moderate, had a short onset time, and were transient, with no new safety signals identified. Conclusions The OASIS trial demonstrates the long-term efficacy and safety of ocriplasmin, providing improved resolution of symptomatic VMA compared with previous phase 3 trials with no additional safety signals identified

Innovative therapies for neovascular age-related macular degeneration

Introduction: Investigational anti-VEGF treatments for neovascular age-related macular degeneration (nAMD) aim to improve visual outcomes and reduce treatment burden; these include long-acting agents, combination strategies, topical agents, sustained-release, and genetic therapies. Areas covered: The authors provide a comprehensive review of investigational therapies for nAMD, focusing on therapies currently in clinical trial. Expert opinion: Long-acting anti-VEGF agents have demonstrated promising results in phase 3 studies, and include Brolucizumab, a single-chain antibody fragment, and Abicipar, a designed ankyrin repeat protein (DARPin). Other unique anti-VEGF agents in current trials include Conbercept - a fusion protein of the VEGF receptor domains, KSI-301 - an anti-VEGF antibody biopolymer conjugate, and OPT-302 - an inhibitor of VEGF-C/D. Strategies to activate the Tie-2 receptor, some in combination with VEGF inhibition, are of interest, with recent trials of Faricimab, ARP-1536, and nesvacumab. Topical anti-VEGF ± anti-PDGF agents, such as pazopanib, squalamine lactate, regorafenib, and LHA510 have shown limited efficacy and/or have not been advanced, although PAN-90806 continues to advance with promising initial results. Sustained-release anti-VEGF treatments, to address treatment burden, include the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305. Similarly, genetic therapies, including RGX-314 and ADVM-022, aim to provide sustained anti-VEGF expression from the retina