American Journal of Ophthalmology最新文献

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.

Purpose: To investigate the effect of tamsulosin on iris morphology, ciliary muscle thickness (CMT), pupil diameter (PD), and pupil responses to light using anterior segment optical coherence tomography and corneal topography.

Design: Prospective clinical before-and-after study METHODS: The right eyes of 43 patients with newly diagnosed benign prostatic hyperplasia were included in this study. Iris dilator muscle region (DMR) thickness, sphincter muscle region (SMR) thickness, DMR/SMR ratio, PD (scotopic, mesopic and photopic light conditions), CMT1 (1 mm posterior to the scleral spur), CMT2 (2 mm posterior to the scleral spur), CMT3 (3 mm posterior to the scleral spur) and anterior chamber depth (ACD) were measured before and after dilation. Measurements were performed twice firstly before starting tamsulosin treatment and secondly at the 3rd month of tamsulosin treatment.

Results: Pre-dilation DMR thickness (P < .001), post-dilation DMR thickness (P < .001) pre-dilation DMR/SMR ratio (P = .001), and post-dilation DMR/SMR ratio (P = .001) were reduced significantly after tamsulosin treatment. Pre-dilation PD decreased after treatment in scotopic, mesopic and photopic conditions, but only photopic conditions showed a significant difference (P = .733, P = .142, and P = .04, respectively). Post-dilation PD was significantly reduced after tamsulosin treatment (P < .001). No significant differences were found in pre- and post-dilation iris SMR thickness (P = .08 and P = .784, respectively), pre-dilation CMT1, CMT2, and CMT3 (P = .841, 0.794, 0.880, respectively), post-dilation CMT1, CMT2, and CMT3 (P = .367, 0.114, 0.256, respectively), pupil dilation speed (P = .463), pre-dilation ACD (P = .583), and post-dilation ACD(P = .305) after treatment.

Conclusion: Tamsulosin treatment does not change the iris SMR thickness, CMT1, CMT2, CMT3, and ACD but statistically significantly reduces the iris DMR thickness, DMR/SMR ratio, pre-dilation photopic PD, and post-dilation PD.

Purpose: Primarily, to evaluate the repeatability and reproducibility of the new noncontact esthesiometer (NCE) in healthy subjects. Secondarily, the corneal sensitivity threshold measurements of the NCE were compared with those of the Cochet-Bonnet esthesiometer (CBE).

Design: Assessment reliability study.

Methods: Two examiners measured bilateral corneal sensitivity thresholds by NCE and CBE. Triple NCE measurements were performed per eye at all 5 levels, whereas single CBE measurements were performed per eye. When appropriate, NCE (mBar) and CBE (mm) measurements were converted to millinewtons (mN) for direct comparison between devices. The NCE measurement variations were calculated with the intra-class correlation coefficients (ICC) for the primary objective. For the secondary objective, Bland-Altman plots with 95% limits of agreement (95%-LoA) and Spearman's rank correlation coefficients were used to evaluate the level of agreement and linear relationship between the corneal sensitivity thresholds obtained with both devices. Generalized estimating equation models were used to account for the inter-eye correlation of the same study participant.

Results: Fifty subjects (100 eyes) aged 29 years (median) were included. There were no statistically significant differences in the pressure measured by both observers at each NCE level (all P > .05). There was a high intra-observer and inter-observer repeatability of the NCE measurements (ICC > 0.90) and a strong linear correlation (rho > 0.7) at each NCE level. The difference between the mean corneal sensitivity thresholds (mN) measured with the NCE (0.052 ± 0.021 mN) and CBE (0.046 ± 0.005 mN) was statistically significant (P = .001). Bland-Altman analysis revealed a differential bias of +0.00578 mN (95%-LoA -0.03677 - +0.04833 mN) between threshold measurements.

Conclusions: The NCE provides reliable user-independent corneal sensitivity measurements. The NCE and CBE do not yield similar values. Thus, both devices cannot be used interchangeably.

Purpose: Adalimumab, a TNF-alpha inhibitor, is the only FDA-approved biologic for non-infectious uveitis (NIU). However, treatment responses vary, potentially due to interindividual pharmacokinetic differences influenced by body mass index (BMI). This study aimed to evaluate the impact of BMI on adalimumab serum trough levels and therapeutic efficacy in patients with NIU.

Design: cross-sectional, clinical study.

Method: Setting: Single-center study. - Study Population: 80 patients with NIU treated with Adalimumab - Observation Procedure: Adalimumab serum trough levels and anti-Adalimumab antibody (AAA) levels were measured. BMI was calculated at treatment initiation, and patients were categorized into normal weight, overweight, obese, and morbidly obese groups. - Main Outcome Measures: The correlation between BMI, adalimumab levels, and clinical response was analyzed using Pearson correlation, chi-square tests, and logistic regression.

Results: Higher BMI was associated with lower adalimumab serum levels and a reduced likelihood of clinical response. A significant negative correlation was found between BMI and adalimumab levels (r = -0.408, P = .007). Logistic regression identified BMI as a significant predictor of treatment response (P = .017). A BMI threshold of 26.4 was identified, above which the probability of a positive response significantly decreased. Additionally, 51.2% of patients were non-responders, all of whom demonstrated detectable AAA.

Conclusions: Higher BMI is associated with lower adalimumab trough levels and reduced treatment efficacy in NIU patients. A BMI threshold of 26.4 may serve as a clinical marker for tailoring adalimumab therapy, highlighting the need for personalized dosing strategies in patients with elevated BMI.

Topic: evaluation of clinical outcomes of patients with retinoblastoma treated with intravitreal chemotherapy (IvitC).

Design: Systematic review and single-arm meta-analysis CLINICAL RELEVANCE: Clinical outcomes with IVitC vary across reports according to patient characteristics and concomitant treatment modalities, mainly intravenous chemotherapy (IVC) and intra-arterial chemotherapy (IAC). There are currently no large clinical trials or meta-analyses focusing on the topic.

Methods: A systematic search was conducted in MEDLINE, EMBASE and Cochrane. All articles reporting use of IVitC for RB and safety or efficacy outcomes were included regardless of publication date. Studies with fewer than 10 eyes were excluded. Enucleation rates (ER) were calculated using proportions and 95% confidence intervals (CIs). The analysis was performed using the Random Effects model in R Studio.

Results: 25 studies comprising 1082 eyes met inclusion criteria. Melphalan was exclusively used in 687 eyes (63.49%), 104 eyes received topotecan exclusively (9.61%), and the remaining 291 (26.90%) used a combination. General ER was 24.70% (95% CI 19.20-31.18%). Subgroup analysis showed an ER of 27.76% (95% CI 19.05-38.55%) for melphalan, 14.23% (95% CI 5.61-21.66%) for topotecan, and 23.82% (95% CI 11.95-41.87%) for combination therapy (p<0.05). It also revealed an ER of 21.54% (95% CI 15.57-29.01%) for studies that implemented IAC+IVitC versus 35.50% (95% CI 20.73-53.66%) for those who used IVC+IVitC (p<0.05). Pigmentary retinopathy rate was 36.56% (95% CI 24.61-50.44%) in subjects treated with melphalan and 2.42% (95% CI 0.70-8.01%) for those receiving topotecan (p<0.05). Other adverse events were cataract (17.76%) followed by vitreous hemorrhage (12.10%) and retinal detachment (5.62%). All studies, except one, were determined to have a serious risk of bias.

Conclusion: IVitC represents an effective strategy for retinoblastoma, especially when administered after IAC; however, melphalan retinal toxicity still poses a challenge. Results with topotecan are promising but scarce. Comparing both drugs is needed to define the best treatment strategy. This study is limited by the lack of large, randomized studies on this subject.