American Journal of Ophthalmology最新文献

Introduction: In diabetics, glucagon-like peptide 1 (GLP-1) receptor agonists (RA) may protect against microvascular alterations and oxidative stress, both of which have been implicated in glaucoma. Multiple studies suggest a possible relation between GLP-1 RA use and the development of glaucoma. This study performs a systematic review of the literature regarding the incidence of glaucoma development in type 2 diabetes patients treated with GLP-1 receptor agonists compared to a control group.

Design: A systematic review and meta-analysis.

Methods: We searched PubMed, Embase, Web of Science, and Cochrane databases from July 1991 to May 2024 for studies comparing the incidence of glaucoma development in GLP-1 RA users versus non-users. We calculated the pooled HR for the GLP-1 RA group and control using a random-effects model.

Results: 194 studies were identified, of which five retrospective studies met the inclusion criteria, with a total of 156,042 participants based on routinely collected electronic data. The meta-analysis revealed no significant statistical difference in glaucoma incidence among GLP-1 RA users compared to controls (HR 0.779; 95% CI [0.585; 1.036]; p=0.086; I²=86%). During the leave-one-out sensitivity analysis, the inclusion of Shao et al. yielded opposite effects, suggesting that SGLT-2 inhibitors might be as effective as, or potentially more effective than GLP-1 RAs in preventing glaucoma. When this study was excluded from the analysis, the results demonstrated a significant reduction in the incidence of glaucoma among GLP-1 RA users compared to controls, with reduced heterogeneity (HR 0.71; 95% CI [0.60, 0.85], I² = 29%). Studies had moderate bias concerns due to confounding factors and intervention classification.

Conclusions: This systematic meta-analysis found that GLP-1 RA use is associated with reduced glaucoma development in retrospective studies. Future, well-designed, long-term studies focusing on GLP-1 RAs and SGLT-2 inhibitors are needed to validate these findings and evaluate their effects on glaucoma progression and vision loss. The overall interpretation should be cautious.

Current treatments for retinal and choroidal neovascular diseases suffer from insufficient durability, including anti-vascular endothelial growth factor-A (VEGF-A) agents. It is, therefore, of interest to explore alternative methods that could allow for robust improvement in visual acuity with fewer injections required. Amongst various pre-clinical and clinical studies in the literature, a promising approach is the use of suprachoroidal injection with viral and non-viral gene delivery vectors. Compared to other ocular injection methods, suprachoroidal injection has demonstrated wide biodistribution of injected agents and safety as an outpatient procedure. In terms of viral vectors, suprachoroidal injection of an AAV8 vector expressing an anti-VEGF-A antibody fragment has shown an excellent safety profile and evidence of biological activity. In terms of non-viral vectors, lipid nanoparticles (LNPs) and polymeric nanoparticles (PNPs) are both demonstrating strong promise for ocular gene therapy in large animal models. In particular, biodegradable poly(beta-amino ester) (PBAE) nanoparticles show excellent biodistribution, safety, and efficacy for gene therapy via the suprachoroidal route. Non-viral nanoparticle approaches can have notable advantages over viral vectors in terms of carrying capacity, redosability, and manufacturing costs. An advantage of gene therapy is that once a delivery vector has been optimized, genetic cargos can be readily tailored without changing the safety, efficacy, and pharmacokinetic properties of the delivery vector. This review highlights recent progress that has been made and compares viral and non-viral suprachoroidal gene delivery for the treatment of retinal and choroidal vascular diseases. Suprachoroidal gene therapy is an emerging biotechnology that holds substantial potential to make a translational impact in treating these diseases.

Purpose: To characterize the clinical phenotype and disease progression in patients with NMNAT1-associated Leber congenital amaurosis (LCA) within the Korean population.

Design: Retrospective, observational case series.

Subjects: Fourteen patients with LCA with biallelic variants of NMNAT1 at a single tertiary referral center.

Methods: Electronic medical records were reviewed for medical history, ophthalmic examinations, and molecular diagnoses, both cross-sectionally and longitudinally.

Main outcome measures: Ophthalmic examination findings were evaluated and retinal phenotypic characteristics were assessed using multimodal imaging.

Results: All patients exhibited early-onset, rapidly progressive bilateral retinal degeneration with pronounced central involvement. The condition was characterized by multiple atrophic lesions that coalesced into a large central retinal scar by age 2. The condition stabilized around 4 years of age. Fluorescein angiography demonstrated central hypofluorescence with visible choroidal vasculature. Optical coherence tomography showed significant retinal thinning, outer retinal layer disruption, and retinal pigment epithelial atrophy. Most patients maintained light perception vision or better, with minimal deterioration of visual acuity after the age of 2. All patients were hyperopic and exhibited undetectable electroretinography and visual-evoked potential responses.

Conclusions: NMNAT1-associated LCA is characterized by severe, early-onset retinal degeneration with rapid progression, followed by stabilization. This distinct temporal pattern of disease progression suggests a potential therapeutic window in early childhood, emphasizing the importance of early diagnosis and regular monitoring for potential interventions.

Purpose: Uveal melanoma (UM) represents the most prevalent and aggressive intraocular malignancy in adults. This study examined the outcomes of patients diagnosed with high-risk UM who underwent fractionated stereotactic radiosurgery (fSRS) treatment utilizing a novel Linear Accelerator (LINAC)-based frameless technique.

Design: Retrospective, interventional case series.

Methods: All patients received fSRS, 50 Gy in 10 Gy/fraction, every other day on a stereotactic LINAC with a novel in-house eye localization and monitoring system. Tumor control, vision outcome, as well as acute and late toxicities were evaluated.

Results: This study included 23 patients with high-risk UM. Median age was 64.8 years old (range 37.9-85.1 years). The Median Karnofsky Performance Score was 90 (range 70-100). The median tumor diameter was 13.5 mm (range 3.0-24.0 mm), and median tumor thickness was 5.05 mm (range 1.2-15.1 mm). There were 11 patients (47.8%) who received prior episcleral plaque. The other 12 patients received stereotactic radiotherapy for initial treatment. With a median follow-up of 38 months, the local control rate was 95.6% at 1 year, 90.1% at 2 years, and 85.6% at 3 years. There was no significant difference between treatment-naïve patients and those who had previously received plaque treatment. Eye preservation rate was 91.3%, with 2 patients required enucleation for tumor progression and/or toxicity. High-grade acute adverse events included 1 patient with grade 3 eye pain. The median best-corrected visual acuity by LogMAR was 0.5 pretreatment (Snellen conversion 20/63) and 1.0 (Snellen 20/200) post-treatment.

Conclusions: Our institution's novel LINAC-based frameless fSRS demonstrated favorable local control and toxicity profile for high-risk UM (tumors deemed unsuitable for episcleral plaque brachytherapy). Patients maintained a high rate of eye preservation. This approach provides an eye preservation option for patients unable to have plaque radiotherapy.