Uveal melanoma: Recent advances in immunotherapy.

Uveal melanoma (UM) is the most common primary intraocular cancer in adults. The incidence in Europe and the United States is 6-7 per million population per year. Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection, up to 50% of UM patients develop metastases that usually involve the liver and are fatal within 1 year. To date, chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM, which is still characterized by poor prognosis. No standard therapeutic approaches for its prevention or treatment have been established. The application of immunotherapy agents, such as immune checkpoint inhibitors that are effective in cutaneous melanoma, has shown limited effects in the treatment of ocular disease. This is due to UM's distinct genetics, natural history, and complex interaction with the immune system. Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations, UMs are usually triggered by a mutation in GNAQ or GNA11. As a result, more effective immunotherapeutic approaches, such as cancer vaccines, adoptive cell transfer, and other new molecules are currently being studied. In this review, we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.

Recent Developments in Gene Therapy for Neovascular Age-Related Macular Degeneration: A Review.

Age-related macular degeneration (AMD) is a complex and multifactorial disease and a leading cause of irreversible blindness in the elderly population. The anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionized the management and prognosis of neovascular AMD (nAMD) and is currently the standard of care for this disease. However, patients are required to receive repeated injections, imposing substantial social and economic burdens. The implementation of gene therapy methods to achieve sustained delivery of various therapeutic proteins holds the promise of a single treatment that could ameliorate the treatment challenges associated with chronic intravitreal therapy, and potentially improve visual outcomes. Several early-phase trials are currently underway, evaluating the safety and efficacy of gene therapy for nAMD; however, areas of controversy persist, including the therapeutic target, route of administration, and potential safety issues. In this review, we assess the evolution of gene therapy for nAMD and summarize several preclinical and early-stage clinical trials, exploring challenges and future directions.

360° Ab-Interno Schlemm's Canal Viscodilation with OMNI Viscosurgical Systems for Open-Angle Glaucoma-Midterm Results.

PURPOSE: To evaluate the effectiveness of ab-interno microcatheterization and 360° viscodilation of Schlemm's canal (SC) performed with OMNI viscosurgical system in open angle glaucoma (OAG) together or not with phacoemulsification. SETTING: Two surgical sites. DESIGN: Retrospective, observational. METHODS: Eighty eyes from 73 patients with mild to moderate OAG underwent ab- interno SC viscodilation performed with OMNI system. Fifty eyes (Group 1) underwent only SC viscodilation, while 30 eyes (Group 2) underwent glaucoma surgery + cataract extraction. Primary success endpoint at 12 months was an intraocular pressure (IOP) reduction higher than 25% from baseline with an absolute value of 18 mmHg or lower, either on the same number or fewer ocular hypotensive medications, without further interventions. Secondary effectiveness endpoints included mean IOP, number of medications and comparison of outcomes between groups. Safety endpoints consisted of best-corrected visual acuity (BCVA), adverse events (AEs), and subsequent surgical procedures. RESULTS: Primary success was achieved in 40.0% and 67.9% in Groups 1 and 2, respectively. Mean IOP at 12-month follow-up showed a significant reduction in both groups (from 23.0 to 15.6 mmHg, p < 0.001, and from 21.5 to 14.1, p < 0.001, in Groups 1 and 2, respectively). Mean medication number decreased in both groups (from 3.0 to 2.0, p < 0.001 and from 3.4 to 1.9, p < 0.001, in Groups 1 and 2, respectively). AEs included hyphema (2 eyes), mild hypotony (4 eyes), IOP spikes one month after surgery (1 eye). Twelve eyes (15.0%) required subsequent surgical procedures. No BCVA reduction was observed. CONCLUSIONS: Viscodilation of SC using OMNI viscosurgical systems is safe and relatively effective in reducing IOP in adult patients with OAG.

Enhanced surgical technique for sutureless intrascleral fixation of intraocular lenses.

A simplified intrascleral fixation technique involving implantation of the Carlevale intraocular lens (IOL) in the posterior chamber is described, which lodges the T-shaped IOL haptics in the scleral wall, not requiring scleral flaps. This surgical modification reduces operative time, limits iatrogenic damage to the sclera, and avoids friction between haptics and the conjunctiva, which may cause conjunctival erosion and infection in the long term. 13 patients with crystalline lens or IOL dislocation/subluxation had surgery to implant the Carlevale IOL in the posterior chamber. Mean corrected distance visual acuity preoperatively was 0.75 ± 0.5 logMAR (range, 0.2 to 1.5 logMAR) and improved to 0.28 ± 0.3 logMAR (range, 0 to 1.0 logMAR) postoperatively. Complications rarely occurred and were not sight-threatening. The sutureless scleral fixation of the Carlevale IOL using the modified surgical technique may represent a safe and effective procedure to restore visual function in patients with damaged zonular-capsular support.

Antibiotic prophylaxis for preventing endophthalmitis after intravitreal injection: a systematic review.

PURPOSE: To assess the effect of topical antibiotic prophylaxis on the rate of post-operative endophthalmitis after intravitreal injection (IVI). METHODS: We conducted a systematic review of studies comparing the rates of endophthalmitis in eyes receiving IVI of different drugs with and without topical antibiotic prophylaxis, by searching MEDLINE and EMBASE up to June 2016. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool and the Risk Of Bias in Non-randomized Studies of Interventions (ROBINS-I) for randomized clinical trials (RCTs) and non-randomized studies, respectively. We used a random-effects meta-analysis to compute the odds ratio (OR) of endophthalmitis with antibiotic prophylaxis compared with no prophylaxis and conducted subgroup analyses to compare the efficacy of different regimens and classes of antibiotics on endophthalmitis rates. RESULTS: We identified 1 randomized and 12 non-randomized studies that reported 74 cases of endophthalmitis in 147,203 IVIs using antibiotic prophylaxis compared with 55 cases in 211,418 IVIs with no prophylaxis. The overall OR of endophthalmitis for antibiotic prophylaxis vs. no prophylaxis was 1.33 (95% CI 0.75-2.38). Leave-one-out sensitivity analyses showed that the exclusion of the only study with a serious risk of bias significantly increased the risk of endophthalmitis in the antibiotic prophylaxis group compared with control (OR: 1.62, 95% CI: 1.17, 2.34). There was no difference in the endophthalmitis rate associated with any other factor analyzed, including type of antibiotic, type of drug injected, or antibiotic prophylaxis regimen. CONCLUSIONS: Antibiotic prophylaxis does not reduce the rate of endophthalmitis following IVI and might potentially be associated with an increased risk of post-operative infection.

Low-concentration infracyanine green-assisted internal limiting membrane peeling in idiopathic macular pucker 25-gauge surgery.

PURPOSE: To investigate the efficacy of 25-gauge infracyanine green-assisted idiopathic macular pucker surgery and to identify prognostic factors. METHODS: In this retrospective interventional case series, 83 patients with idiopathic macular pucker who underwent 25-gauge surgery with infracyanine green-assisted internal limiting membrane (ILM) peeling were retrospectively reviewed. Best-corrected visual acuity (BCVA) measurement, complete ophthalmologic evaluation, and optical coherence tomography were performed at baseline and during follow-up. Preoperative and postoperative prognostic factors were correlated with final visual outcomes. RESULTS: Mean follow-up was 10.5 months (range 3-44). Best-corrected visual acuity improved from 0.56±0.27 logMAR (±SD) to 0.26 ±0.18 logMAR (p<0.001); central retinal thickness decreased from 441±115 µm to 355±72 µm (p<0.001). Greater postoperative visual gain was correlated with baseline BCVA (r=-0.65, p<0.0001), and BCVA gain after 1 week (r=0.64, p<0.0001) and 1 month (r=0.58, p<0.0001). Final BCVA was influenced by baseline BCVA (r=0.46, p<0.0001), BCVA change after 1 month (r=0.34, p=0.002), and presence of intraretinal fluid (r=0.28, p=0.01). No cases of endophthalmitis, retinal tears, or retinal detachments were reported. CONCLUSIONS: Low-concentration infracyanine green-assisted ILM peeling during minimally invasive surgery is associated with significant visual acuity improvement. Preoperative BCVA and optical coherence tomography appearance may be helpful in predicting the final visual outcome.