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.

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.

Efficacy and Safety of Trabeculectomy Versus Nonpenetrating Surgeries in Open-angle Glaucoma: A Meta-analysis.

PURPOSE: The purpose of this study was to conduct a meta-analysis on the efficacy and safety of trabeculectomy (TE) and nonpenetrating glaucoma surgery (NPGS) techniques in patients with primary open-angle glaucoma, pseudoexfoliation glaucoma, pigmentary glaucoma, and normal-tension glaucoma. METHODS: All studies were identified by searching electronic sources (PubMed, Medline, Scopus, and Embase) until February 5, 2018. Primary outcome was mean intraocular pressure (IOP) reduction at 6, 12, and 24 months. Complications, number of antiglaucomatous medications, and visual outcomes were also evaluated. RESULTS: Twenty-one studies were included. Ten studies compared TE with deep sclerectomy (DS), 5 with viscocanalostomy (VC), 1 study with both DS and VC, and 5 with canaloplasty (CP). TE was superior to DS, VC, and CP in reducing IOP at 6 and 12 months, and to DS at 24 months. When comparing TE to VC and to CP at 24 months, there was no significant difference in IOP reduction. Hypotony, choroidals, anterior chamber shallowing or flattening, and cataract formation or progression were more associated with TE than with NPGSs. TE was more effective in reducing antiglaucomatous medications than VC and CP. CONCLUSIONS: TE is more effective in reducing IOP. TE presents a higher risk of complications as compared with NPGS, except for hyphema.

One-year outcome of ranibizumab for neovascular age-related macular degeneration: a thorough analysis in a real-world clinical setting.

PURPOSE: To verify the safety and efficacy of ranibizumab in neovascular age-related macular degeneration (nAMD) and factors influencing the outcome in a real-world setting. METHODS: Retrospective 12-month follow-up analysis of 100 naive nAMD eyes treated with as-needed ranibizumab. Changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), lesion, and leakage size were recorded. Type and characteristics of lesions and indicators of protocol adherence were analyzed. RESULTS: Mean BCVA at baseline was 61.6 ± 14.8 Early Treatment Diabetic Retinopathy Study letters and 59.6 ± 16 at 12 months. Sixty-three eyes maintained or improved BCVA; the number of injections and follow-up visits were 4.8 and 5.1, respectively. First injection and pro re nata retreatments were administered 22.7 and 20.5 days after prescription, respectively. Seventy-two eyes received 3 initial monthly injections. Patients were not reinjected despite BCVA loss >5 letters one or more times in 37% of cases. No adverse events were reported. The CRT diminished by 26 ± 101 µm; choroidal neovascularization size and leakage area increased by 0.53 ± 1.31 mm² and 0.34 ± 1.33 mm², respectively. The BCVA gain was correlated with CRT reduction (r = 0.24, p = 0.016), mean baseline BCVA (r = -0.25, p = 0.01), age (r = -0.25, p = 0.01), and decrease in CNV size and leakage area (r = 0.56 and r = 0.59, respectively, p<0.001). CONCLUSIONS: Our results compare unfavorably with those of controlled trials. Treatment and follow-up regimens in real-world settings seem to have a major role in determining outcome. Lower age and BCVA at baseline were associated with better response to treatment.