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.

Recent Advances of Adipose-Tissue-Derived Mesenchymal Stem Cell-Based Therapy for Retinal Diseases.

With the rapid development of stem cell research in modern times, stem cell-based therapy has opened a new era of tissue regeneration, becoming one of the most promising strategies for currently untreatable retinal diseases. Among the various sources of stem cells, adipose tissue-derived mesenchymal stem cells (ADSCs) have emerged as a promising therapeutic modality due to their characteristics and multiple functions, which include immunoregulation, anti-apoptosis of neurons, cytokine and growth factor secretion, and antioxidative activities. Studies have shown that ADSCs can facilitate the replacement of dying cells, promote tissue remodeling and regeneration, and support the survival and growth of retinal cells. Recent studies in this field have provided numerous experiments using different preclinical models. The aim of our review is to provide an overview of the therapeutic strategies, modern-day clinical trials, experimental models, and potential clinical use of this fascinating class of cells in addressing retinal disorders and diseases.

Innovative Strategies for Drug Delivery to the Ocular Posterior Segment.

Innovative and new drug delivery systems (DDSs) have recently been developed to vehicle treatments and drugs to the ocular posterior segment and the retina. New formulations and technological developments, such as nanotechnology, novel matrices, and non-traditional treatment strategies, open new perspectives in this field. The aim of this mini-review is to highlight promising strategies reported in the current literature based on innovative routes to overcome the anatomical and physiological barriers of the vitreoretinal structures. The paper also describes the challenges in finding appropriate and pertinent treatments that provide safety and efficacy and the problems related to patient compliance, acceptability, effectiveness, and sustained drug delivery. The clinical application of these experimental approaches can help pave the way for standardizing the use of DDSs in developing enhanced treatment strategies and personalized therapeutic options for ocular pathologies.

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.

Fundus autofluorescence applications in retinal imaging.

Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications.

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.