Recent ucsdsom_oph_oapdeposits items

Bridging the gap: socioeconomic disparities in pediatric vision referrals from the UCSD EyeMobile Program

Thu, 30 Jul 2026 00:00:00 +0000

PURPOSE: To evaluate demographic and socioeconomic factors associated with pediatric ophthalmology referrals from the UC San Diego (UCSD) EyeMobile, a school-based mobile vision program. METHODS: The records of children screened from 2021 to 2025 were reviewed retrospectively. Children who failed a screening received a comprehensive eye examination by an optometrist. Referrals to a pediatric ophthalmologist were made for those with potentially significant ocular pathology and no established eye care provider. Socioeconomic status was assessed using the national Child Opportunity Index (COI), analyzed as continuous scores and quintiles. Referral rates were compared across quintiles using two-proportion z tests, and multivariable logistic regression was used to identify factors associated with referrals. RESULTS: Of 42,166 children screened during the study period, 5,657 (14.1%) received a comprehensive examination, and 217 (0.51%) were referred to an ophthalmologist. Leading reasons...

Bupivacaine-Induced Regeneration in Rabbit Extraocular Muscles: Implications for the Treatment of Strabismus

Thu, 4 Jun 2026 00:00:00 +0000

Objective Local injections such as bupivacaine are used to treat strabismus, although the mechanism of its clinical effects is unknown. The purpose of this study is to analyze the effects of bupivacaine on extraocular muscle regeneration in a pre-clinical model. Design Laboratory study. Subjects, Participants, and/or Controls Three-month-old male New Zealand white rabbits with age- and sex-matched saline injection controls and un-injected controls. Methods One superior rectus per animal was injected with either 3% bupivacaine or saline control and harvested at 1 week, 1 month, or 3 months after treatment. Histomorphometric analysis was used to determine the effects of bupivacaine on extraocular muscles. Data were analyzed for the global and orbital layer separately, as well as the entire muscle cross-sectional area. Main Outcome Measures. Muscle morphology, markers of muscle regeneration, muscle size. Results 3% bupivacaine treatment has a myodestructive effect on the injected...

Retinal nerve fibre layer optical texture analysis: retinal nerve fibre bundle defect patterns and the extent of macular involvement across different stages of glaucoma

Wed, 3 Jun 2026 00:00:00 +0000

BACKGROUND/AIMS: To apply retinal nerve fibre layer (RNFL) optical texture analysis (ROTA) to investigate (1) the patterns of RNFL bundle defects, and (2) the frequency of papillomacular and papillofoveal bundle involvement across early, moderate and advanced glaucoma. METHODS: All eyes underwent 24-2 visual field (VF) testing and optical coherence tomography (OCT) for ROTA. The borders of RNFL defects were delineated from ROTA, and the involvement of the arcuate, papillomacular and papillofoveal bundles was determined for each eye. 24-2 VF stimulus projections were mapped onto the corresponding topographic areas of ROTA images. Multilevel logistic regression analysis was applied to evaluate the structure-function association. RESULTS: Papillomacular bundle defects were highly prevalent in glaucoma, increasing from 87.7% in early to 95.35% in moderate and 100% in advanced glaucoma. Papillofoveal bundle defects were also common, increasing from 29.7% in early to 36.05% in moderate...

Biorthogonal Tunable Wavelet Unit with Lifting Scheme in Convolutional Neural Network

Thu, 26 Mar 2026 00:00:00 +0000

This work introduces a novel biorthogonal tunable wavelet unit constructed using a lifting scheme that relaxes both the orthogonality and equal filter length constraints, providing greater flexibility in filter design. The proposed unit enhances convolution, pooling, and downsampling operations, leading to improved image classification and anomaly detection in convolutional neural networks (CNN). When integrated into an 18-layer residual neural network (ResNet-18), the approach improved classification accuracy on CIFAR-10 by $\mathbf{2. 1 2} \boldsymbol{\%}$ and on the Describable Textures Dataset (DTD) by 9.73%, demonstrating its effectiveness in capturing fine-grained details. Similar improvements were observed in ResNet-34. For anomaly detection in the hazelnut category of the MVTec Anomaly Detection dataset, the proposed method achieved competitive and wellbalanced performance in both segmentation and detection tasks, outperforming existing approaches in terms of accuracy...

Tunable Wavelet Unit Based Convolutional Neural Network in Optical Coherence Tomography Analysis Enhancement for Classifying Type of Epiretinal Membrane Surgery

Thu, 26 Mar 2026 00:00:00 +0000

In this study, we developed deep learning-based method to classify the type of surgery performed for epiretinal membrane (ERM) removal—either internal limiting membrane (ILM) removal or ERM-alone removal. Our model, based on the ResNet18 convolutional neural network (CNN) architecture, utilizes postoperative optical coherence tomography (OCT) center scans as inputs. We evaluated the model using both original scans and scans preprocessed with energy crop and wavelet denoising, achieving 72% accuracy on preprocessed inputs, outperforming the 66% accuracy achieved on original scans. To further improve accuracy, we integrated tunable wavelet units with two key adaptations: Orthogonal Lattice-based Wavelet Units (OrthLatt-UwU) and Perfect Reconstruction Relaxation-based Wavelet Units (PR-Relax-UwU). These units allowed the model to automatically adjust filter coefficients during training and were incorporated into downsampling, stride-two convolution, and pooling layers, enhancing...

Disagreement of Radial Peripapillary Capillary Density Among Four Optical Coherence Tomography Angiography Devices.

Mon, 2 Mar 2026 00:00:00 +0000

Purpose

This prospective study evaluated the agreement among four optical coherence tomography angiography (OCTA) devices in the assessment of radial peripapillary capillary (RPC) density.

Methods

The study included 48 eyes of 48 subjects (14 healthy, 19 glaucomatous, and 15 non-glaucomatous optic neuropathy). Each participant was scanned using four OCTA devices in a random sequence: RTVue XR Avanti (RTVue), DRI OCT Triton (Triton), Revo NX 130 (Revo), and PLEX Elite 9000 (PlexE). All 6 × 6-mm grayscale OCTA images from each device were analyzed for RPC density using a customized algorithm. Agreement between each pair of devices was assessed using intraclass correlation coefficients (ICCs) and Bland-Altman plots.

Results

There was a poor correlation between devices in all comparisons (RTVue-Triton, ICC = 0.34; RTVue-Revo, ICC = 0.31; RTVue-PlexE, ICC = 0.28; Triton-Revo, ICC = 0.31; Triton-PlexE, ICC = 0.17; Revo-PlexE, ICC = 0.34). Significant proportional...

Epidemiology of strabismus among adults in the United States: insights from the All of Us database

Thu, 6 Nov 2025 00:00:00 +0000

PURPOSE: To determine the prevalence of adult-diagnosed strabismus and its associations with sex, age, and race in a large, diverse population database in the United States. METHODS: Sex, age, and race data were collected from 413,457 individuals in the All of Us database. The χ² test with post hoc pairwise comparisons was used to determine significant differences in distributions of sex, age, and race data in 3,734 strabismus patients compared with the overall database. RESULTS: There is a higher proportion of males among patients with strabismus compared with the overall database (43.34% vs 38.34% [P < 0.001]). There is a significantly higher proportion of patients aged over 65 years among patients with strabismus compared with the overall database (45.77% vs 24.7% [P < 0.001]). There is also a significantly different racial distribution of individuals with strabismus compared with the overall database (P < 0.001). Pairwise comparisons showed a significantly...

Socioeconomic trends of adult strabismus in the United States: an analysis of the All of Us database

Thu, 6 Nov 2025 00:00:00 +0000

PURPOSE: To determine associations of income and education level with a diagnosis of strabismus and to identify socioeconomic variables that may affect timely access to diagnosis. METHODS: Annual income, highest level of education completed, and ZIP code income, high school completion, poverty, and socioeconomic deprivation metrics were collected from 413,360 participants in the database. A χ² test was used to determine significant differences in distributions of income, education, and ZIP code metrics in 3,734 strabismus patients compared with the overall database. RESULTS: Participants living in ZIP codes with lower multidimensional deprivation indices (less deprivation) are more likely to be diagnosed with strabismus. Participants with annual income below $10,000 (10.10%) or who completed education between fifth grade and a high school diploma or GED (20.06%) are less likely to receive a diagnosis for certain strabismus subtypes. Participants with annual income over...

Differential change in extraocular muscle volume after teprotumumab for thyroid eye disease

Thu, 6 Nov 2025 00:00:00 +0000

PURPOSE: To evaluate the effects of teprotumumab on individual extraocular muscle (EOM) volume and proptosis in thyroid eye disease (TED). METHODS: A retrospective review was performed using exophthalmometry, clinical activity score (CAS), and orbital imaging before and after teprotumumab treatment. The lateral rectus (LR), medial rectus (MR), superior rectus (SR), inferior rectus (IR) muscles, and the globe were manually segmented individually. Individual and total EOM volumes were calculated and compared between pre- and post-treatment magnetic resonance imaging (MRI). RESULTS: Mean proptosis reduction after teprotumumab treatment was 3.69 mm (95% CI: 2.82, 4.17, p < 0.001), with an improvement in all orbits. Significant muscle volume reductions occurred in the MR (-20%, p < 0.001) and IR (-28%, p = 0.002) but not the LR (-11%, p = 0.063) or SR (-19%, p = 0.053). Total EOM volume decreased by 20%, while globe volume remained unchanged....

Faricimab for treatment-resistant choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD): seven-months results using artificial intelligence and OCTA

Fri, 18 Jul 2025 00:00:00 +0000

BackgroundTo analyze the therapeutic response to faricimab 6 mg/0.05 ml in eyes with neovascular AMD (nAMD) with refractory intra- and/or subretinal fluid due to choroidal neovascularization (CNV), previously unresponsive to 4 mg monthly aflibercept and combination therapy with anti-VEGF and long-acting steroids.MethodsA retrospective case series study of 22 eyes with unresponsive CNV, despite monthly intravitreal treatment (mean number of pre-faricimab injections: 35.52 ± 17.12). We evaluated therapeutic response in eyes with persistent intra/subretinal fluid (IRF/SRF) unresponsive to anti-VEGF double-dose (DD) monotherapy (4-mg aflibercept) and/or simultaneous DD anti-VEGF (4-mg aflibercept) with steroids (triamcinolone). Best-corrected visual acuity (BCVA), intraocular pressure (IOP), and optical coherence tomography (OCT) measurements of central retinal thickness (CRT) were recorded for 7 follow-ups. Baseline and follow-up OCTs were examined by an AI-developed...

Elucidating VEGF Biology: A Journey of Discovery and Clinical Translation

Thu, 19 Jun 2025 00:00:00 +0000

Elucidating VEGF Biology: A Journey of Discovery and Clinical Translation

Time to Glaucoma Progression Detection by Optical Coherence Tomography in Individuals of African and European Descents

Mon, 14 Apr 2025 00:00:00 +0000

PURPOSE: To examine the time to detectable retinal nerve fiber layer thickness (RNFLT) progression by optical coherence tomography (OCT) among glaucoma patients of African descent (AD) and European descent (ED). DESIGN: Retrospective cohort study. METHODS: AD and ED glaucoma eyes from the Diagnostic Innovations in Glaucoma Study (DIGS)/African Descent and Glaucoma Evaluation Study (ADAGES) with ≥2 years/4 visits of optic nerve head RNFLT measurements were included after homogenization on age, diagnosis, and baseline visual field (VF) measurement. RNFLT variability estimates based on linear mixed-effects models were used to simulate longitudinal RNFLT data for both races. Times to trend-based RNFLT progression detection were calculated under standardized scenarios (same RNFLT baseline/thinning rates for both races) and real-world scenarios (AD and ED cohort-specific RNFLT baseline/thinning rates). RESULTS: We included 332 and 542 eyes (216 and 317 participants) of AD and ED, respectively....

Differences in macular thickness associated with peripheral retinal vessel whitening in diabetic patients

Fri, 11 Apr 2025 00:00:00 +0000

This study aimed to determine the difference in macular thickness among patients with diabetes mellitus (DM) with and without peripheral retinal vessel whitening (PRVW). PRVW was defined by retinal vessel whitening outside the standard seven ETDRS fields. Subjects were divided into DM with PRVW, DM without PRVW, and normal age-matched controls. Optical coherence tomography scans were divided into total, inner, and outer retinal layer thicknesses and were compared in the macula's central, inner, and outer rings. Forty-seven eyes were included: DM with PRVW = 15, DM without PRVW = 16, and Controls = 16. Overall, the mean retinal thickness in patients with DM with PRVW was lower than in patients with DM without PRVW and controls. In the inner macula, DM patients with PRVW showed a significantly lower mean inner superior, nasal, inferior, and temporal macula compared to DM patients without PRVW (p = 0.014, 0.008, 0.005, < 0.001, respectively). DM patients with PRVW also showed...

Prevalence of peripheral retinal findings in retinal patients using ultra-widefield pseudocolor fundus imaging

Fri, 11 Apr 2025 00:00:00 +0000

Ultra-widefield retinal imaging is increasingly used in ophthalmology and optometry practices to image patients identifying peripheral abnormalities. However, the clinical relevance of these peripheral retinal abnormalities is unclear. This cross-sectional study aims to firstly validate a new grading system, secondly, assess the prevalence of peripheral retinal abnormalities in retinal patients, and finally understand how peripheral findings may associate with retinal disease. Ultra-widefield pseudocolor fundus images were taken from the eyes of clinic patients. Demographic data and clinical diagnosis for each patient was noted. The grading system was validated using masked retinal specialists. Logistic regression identified associations between retinal disease and peripheral retinal findings. Using the grading system, inter-observer agreement was 76.1% with Cohen’s Kappa coefficient 0.542 (p < 0.0001) and the test–retest agreement was 95.1% with Kappa 0.677(p < 0.0001)....

Geographic Patterns of Ocular Oncologist Supply and Patient Demand for Uveal Melanoma Treatment in the United States: A Supply and Demand Analysis.

Fri, 11 Apr 2025 00:00:00 +0000

PURPOSE: To study geographic patterns of supply and demand for uveal melanoma and other ocular oncology healthcare by ocular oncology physicians in the United States. METHODS: Google search interest data was obtained through trends.google.com. The combined-state density of ocular oncology physicians was calculated by dividing the number of practicing ocular oncologists in each state and its surrounding states by the state population. Relative search volume (RSV) values were divided by ocular oncology physician density to calculate the Google relative demand index (gRDI) for each state. Medicare (mRDI) and IRIS® Registry (iRDI) relative demand indices were calculated using prevalence data obtained through the Vision and Eye Health Surveillance System (VEHSS). Data from the US Census Bureau and Centers for Disease Control (CDC) databases were also utilized to analyze associations with poverty rates, percent living in urban or rural areas, vision screening rates, and ocular...

Developing an image-based grading scale for peripheral drusen to investigate associations of peripheral drusen type with age-related macular degeneration

Fri, 11 Apr 2025 00:00:00 +0000

Age-related macular degeneration (AMD) is a leading cause of blindness. It is associated with peripheral drusen which has not been categorized. We investigated peripheral drusen to validate an image grading system and to understand possible associations between peripheral drusen and AMD. We collated clinical data, ultra-widefield (UWF) pseudocolor fundus images and Spectral-Domain Optical Coherence Tomography (SD-OCT) scans from consecutive retinal patients. SD-OCT scans were used to determine AMD stage. A masked retinal specialist recorded the types of peripheral drusen observed in UWF images. Eyes whose UWF images did not pass quality screening and those without AMD and peripheral drusen were excluded from the study. Statistical tests were utilized to determine the validity of our grading system and associations of peripheral drusen with AMD. A total of 481 eyes (283 subjects) were included in the study (mean age 73.1 ± 1.2years, 64.3% female). Interobserver and test–retest...

Detection and agreement of event-based OCT and OCTA analysis for glaucoma progression

Wed, 9 Apr 2025 00:00:00 +0000

ObjectiveTo examine event-based glaucoma progression using optical coherence tomography (OCT) and OCT angiography (OCTA).MethodsIn this retrospective study, glaucoma eyes with ≥2-year and 4-visits of OCT/OCTA imaging were included. Peripapillary capillary density (CD) and retinal nerve fibre layer thickness (RNFL) were obtained from 4.5 mm × 4.5 mm optic nerve head (ONH) scans. Event-based OCT/OCTA progression was defined as decreases in ONH measurements exceeding test-retest variability on ≥2 consecutive visits. Visual field (VF) progression was defined as significant VF mean deviation worsening rates on ≥2 consecutive visits. Inter-instrument agreement on progression detection was compared using kappa(κ) statistics.ResultsAmong 147 eyes (89 participants), OCTA and OCT identified 33(22%) and 25(17%) progressors, respectively. They showed slight agreement (κ = 0.06), with 7(5%) eyes categorized as progressors by both. When incorporating both instruments, the rate of progressors...

Effect of Corneal Hysteresis on the Rates of Microvasculature Loss in Glaucoma

Tue, 8 Apr 2025 00:00:00 +0000

PURPOSE: To investigate the association between corneal hysteresis (CH) and rates of optic nerve head whole image capillary density (wiCD) loss over time in open-angle glaucoma (OAG). DESIGN: Observational cohort. PARTICIPANTS: One hundred seventy-four eyes (122 OAG and 52 glaucoma suspect eyes) from 112 patients over more than 2 years and 4 visits or more. METHODS: Baseline CH measurements were acquired with the Ocular Response Analyzer. Linear mixed-effect models were designed to investigate the effect of CH, average intraocular pressure (IOP) during follow-up, and baseline visual field (VF) mean deviation (MD) on the rates of wiCD loss and circumpapillary retinal nerve fiber layer (cpRNFL) thinning over time, while adjusting for confounders. Interaction between CH or baseline MD and average IOP during follow-up were included in final models to evaluate the effect of baseline MD or average IOP during follow-up on structural changes for different values of CH. MAIN OUTCOME MEASURE:...

A case of iatrogenic CNV following macular surgery

Fri, 4 Apr 2025 00:00:00 +0000

Purpose: To report a case of iatrogenic trauma related choroidal neovascularization (CNV). Methods: A 66 year old female presented with complaints of distortion of vision in the right eye. A diagnosis of epiretinal membrane (ERM) foveoschisis was made and the patient was recommended surgery. During surgery an inadvertent touch of the retina occurred. Post operatively, an iatrogenic choroidal neovascular membrane was diagnosed. Results: Post-operative optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) revealed a CNV which was treated with intravitreal Bevacizumab. The visual acuity improved remarkably. The intraretinal and subretinal fluid resolved and the macula was almost completely dry at final visit. Conclusion: ERM surgery is one of the common procedures in vitreoretinal surgery. Iatrogenic CNV is a reported but rare complication following inadvertent trauma during surgery. We report a successful outcome of iatrogenic CNV treated with intravitreal...

Mechanical countermeasures for spaceflight-associated neuro-ocular syndrome during 30-days of head down tilt bed rest: design, implementation, and tolerability

Fri, 4 Apr 2025 00:00:00 +0000

After longer duration space missions, some astronauts experience structural and functional changes in the eye and structural changes in the brain, termed Spaceflight-Associated Neuro-Ocular Syndrome (SANS). Countermeasures against SANS are required to minimize potential operation impacts and negative long-term health consequences. Headward fluid shifts, which appear to promote SANS, provide a target for countermeasures. The SANS countermeasures study, a 30 days strict head down tilt bed rest (HDTBR) study, tested two mechanical countermeasures aimed at reversing cephalad fluid overload. This work presents design and methodology of the study with a focus on countermeasure implementation and tolerability. Following baseline evaluations, participants were randomized to four groups and HDTBR commenced: Daily application of 25 mmHg lower body negative pressure for 6 h, six-hour bilateral venous constrictive thigh cuffs following moderate cycling exercise on 6 days per week,...

OCTA-based AMD Stage Grading Enhancement via Class-Conditioned Style Transfer

Wed, 2 Apr 2025 00:00:00 +0000

Optical Coherence Tomography Angiography (OCTA) is a promising diagnostic tool for age-related macular degeneration (AMD), providing non-invasive visualization of sub-retinal vascular networks. This research explores the effectiveness of deep neural network (DNN) classifiers trained exclusively on OCTA images for AMD diagnosis. To address the challenge of limited data, we combine OCTA data from two instruments-Heidelberg and Optovue-and leverage style transfer technique, CycleGAN, to convert samples between these domains. This strategy introduces additional content into each domain, enriching the training dataset and improving classification accuracy. To enhance the CycleGAN for downstream classification tasks, we propose integrating class-related constraints during training, which can be implemented in either supervised or unsupervised manner with a pretrained classifier. The experimental results demonstrate that the proposed class-conditioned CycleGAN is effective and elevates...

Deep Learning Approach Predicts Longitudinal Retinal Nerve Fiber Layer Thickness Changes

Wed, 2 Apr 2025 00:00:00 +0000

This study aims to develop deep learning (DL) models to predict the retinal nerve fiber layer (RNFL) thickness changes in glaucoma, facilitating the early diagnosis and monitoring of disease progression. Using the longitudinal data from two glaucoma studies (Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES)), we constructed models using optical coherence tomography (OCT) scans from 251 participants (437 eyes). The models were trained to predict the RNFL thickness at a future visit based on previous scans. We evaluated four models: linear regression (LR), support vector regression (SVR), gradient boosting regression (GBR), and a custom 1D convolutional neural network (CNN). The GBR model achieved the best performance in predicting pointwise RNFL thickness changes (MAE = 5.2 μm, R² = 0.91), while the custom 1D CNN excelled in predicting changes to average global and sectoral RNFL thickness, providing greater resolution...

Large Language Models in Ophthalmology: A Review of Publications from Top Ophthalmology Journals

Wed, 2 Apr 2025 00:00:00 +0000

Purpose: To review and evaluate the current literature on the application and impact of large language models (LLMs) in the field of ophthalmology, focusing on studies published in high-ranking ophthalmology journals. Design: This is a retrospective review of published articles. Participants: This study did not involve human participation. Methods: Articles published in the first quartile (Q1) of ophthalmology journals on Scimago Journal & Country Rank discussing different LLMs up to June 7, 2024, were reviewed, parsed, and analyzed. Main Outcome Measures: All available articles were parsed and analyzed, which included the article and author characteristics and data regarding the LLM used and its applications, focusing on its use in medical education, clinical assistance, research, and patient education. Results: There were 35 Q1-ranked journals identified, 19 of which contained articles discussing LLMs, with 101 articles eligible for review. One-third were original investigations...

Comparison of manual versus automated thermal lid therapy with expression for meibomian gland dysfunction in patients with dry eye disease

Tue, 1 Apr 2025 00:00:00 +0000

To compare two types of lipid expression procedures to treat dry eye disease. Standardized treatment and evaluation methods were used in patients treated with either manual thermoelectric lipid expression (MiBoFlo) or automated lipid expression (Lipiflow) of the Meibomian glands. This was a contemporaneous, non-randomized study of both treatment methods. Treatment was per the manufacturers’ recommendation. The primary outcome included two types of dry eye questionnaires as well as objective analysis of ocular surface including tear break up time, Schirmer testing, Osmolarity, and fluorescein staining. Baseline characteristics analyzed included floppy lid, conjunctivochalasis and lagophthalmos. Statistical analysis was performed correcting for baseline factors such as age and co existing pathology using multivariable analysis. Both treatments improved the results of the OSDI and SPEED dry eye questionnaire results. Both treatments resulted in improvement of many objective findings...

The Benefit of Nocturnal IOP Reduction in Glaucoma, Including Normal Tension Glaucoma

Tue, 1 Apr 2025 00:00:00 +0000

Nocturnal intraocular pressure (IOP) profiling has shown that the peak IOP usually occurs at night, particularly in patients with glaucoma. Multiple studies have demonstrated that these nocturnal IOP elevations drive glaucomatous progression, often despite stable daytime IOP. Existing vascular dysregulation and decreased nighttime blood pressure compound the damage via low ocular perfusion pressure while elevated nocturnal IOP disrupts axonal transport. These findings are consistent with studies that indicate lowering nocturnal IOP is important for slowing glaucoma progression. Many of the current treatment options lower nighttime IOP significantly less than daytime IOP. Non-invasive IOP-lowering treatments that effectively lower nocturnal IOP remain an unmet need in the treatment of glaucoma.

Federated Learning in Glaucoma A Comprehensive Review and Future Perspectives

Tue, 1 Apr 2025 00:00:00 +0000

CLINICAL RELEVANCE: Glaucoma is a complex eye condition with varied morphological and clinical presentations, making diagnosis and management challenging. The lack of a consensus definition for glaucoma or glaucomatous optic neuropathy further complicates the development of universal diagnostic tools. Developing robust artificial intelligence (AI) models for glaucoma screening is essential for early detection and treatment but faces significant obstacles. Effective deep learning algorithms require large, well-curated datasets from diverse patient populations and imaging protocols. However, creating centralized data repositories is hindered by concerns over data sharing, patient privacy, regulatory compliance, and intellectual property. Federated Learning (FL) offers a potential solution by enabling data to remain locally hosted while facilitating distributed model training across multiple sites. METHODS: A comprehensive literature review was conducted on the application of Federated...

Variations in Using Diagnosis Codes for Defining Age-Related Macular Degeneration Cohorts

Fri, 21 Mar 2025 00:00:00 +0000

Data harmonization is vital for secondary electronic health record data analysis, especially when combining data from multiple sources. Currently, there is a gap in knowledge as to how studies identify cohorts of patients with age-related macular degeneration (AMD), a leading cause of blindness. We hypothesize that there is variation in using medical condition codes to define cohorts of AMD patients that can lead to either the under- or overrepresentation of such cohorts. This study identified articles studying AMD using the International Classification of Diseases (ICD-9, ICD-9-CM, ICD-10, and ICD-10-CM). The data elements reviewed included the year of publication; dataset origin (Veterans Affairs, registry, national or commercial claims database, and institutional EHR); total number of subjects; and ICD codes used. A total of thirty-seven articles were reviewed. Six (16%) articles used cohort definitions from two ICD terminologies. The Medicare database was the most used dataset...

Racial Differences in Diagnostic Accuracy of Retinal Nerve Fiber Layer Thickness in Primary Open-Angle Glaucoma

Wed, 19 Mar 2025 00:00:00 +0000

Purpose: To evaluate the diagnostic accuracy of retinal nerve fiber layer thickness (RNFLT) by spectral-domain optical coherence tomography (OCT) in primary open-angle glaucoma (POAG) in eyes of African (AD) and European descent (ED). Design: Comparative diagnostic accuracy analysis by race. Participants: 379 healthy eyes (125 AD and 254 ED) and 442 glaucomatous eyes (226 AD and 216 ED) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Methods: Spectralis (Heidelberg Engineering GmbH) and Cirrus (Carl Zeiss Meditec) OCT scans were taken within one year from each other. Main Outcome Measures: Diagnostic accuracy of RNFLT measurements. Results: Diagnostic accuracy for Spectralis-RNFLT was significantly lower in eyes of AD compared to those of ED (area under the receiver operating curve [AUROC]: 0.85 and 0.91, respectively, P=0.04). Results for Cirrus-RNFLT were similar but did not reach statistical significance (AUROC:...

ARTIFICIAL INTELLIGENCE FOR OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY–BASED DISEASE ACTIVITY PREDICTION IN AGE-RELATED MACULAR DEGENERATION

Wed, 19 Mar 2025 00:00:00 +0000

PURPOSE: The authors hypothesize that optical coherence tomography angiography (OCTA)-visualized vascular morphology may be a predictor of choroidal neovascularization status in age-related macular degeneration (AMD). The authors thus evaluated the use of artificial intelligence (AI) to predict different stages of AMD disease based on OCTA en face 2D projections scans. METHODS: Retrospective cross-sectional study based on collected 2D OCTA data from 310 high-resolution scans. Based on OCT B-scan fluid and clinical status, OCTA was classified as normal, dry AMD, wet AMD active, and wet AMD in remission with no signs of activity. Two human experts graded the same test set, and a consensus grading between two experts was used for the prediction of four categories. RESULTS: The AI can achieve 80.36% accuracy on a four-category grading task with 2D OCTA projections. The sensitivity of prediction by AI was 0.7857 (active), 0.7142 (remission), 0.9286 (dry AMD), and 0.9286 (normal) and...

Effect of Testing Frequency on the Time to Detect Glaucoma Progression With Optical Coherence Tomography (OCT) and OCT Angiography

Tue, 18 Mar 2025 00:00:00 +0000

PURPOSE: To determine how the frequency of testing affects the time required to detect statistically significant glaucoma progression for circumpapillary retinal nerve fiber layer (cpRNFL) with optical coherence tomography (OCT) and circumpapillary capillary density (cpCD) with OCT angiography (OCTA). DESIGN: Retrospective, observational cohort study. METHODS: In this longitudinal study, 156 eyes of 98 patients with glaucoma followed up over an average of 3.5 years were enrolled. Participants with 4 or more OCT and OCTA tests were included to measure the longitudinal rates of cpRNFL thickness and cpCD change over time using linear regression. Estimates of variability were then used to re-create real-world cpRNFL and cpCD data by computer simulation to evaluate the time required to detect progression for various loss rates and different testing frequencies. RESULTS: The time required to detect a statistically significant negative cpRNFL and cpCD slope decreased as the testing...

A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma

Fri, 7 Mar 2025 00:00:00 +0000

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities...

Robotic Visible-Light Optical Coherence Tomography Visualizes Segmental Schlemm's Canal Anatomy and Segmental Pilocarpine Response

Fri, 28 Feb 2025 00:00:00 +0000

Purpose: To use robotic visible-light optical coherence tomography (vis-OCT) to study circumferential segmental Schlemm's canal (SC) anatomy in mice after topical pilocarpine administration. Methods: Anterior segment imaging using a robotic vis-OCT to maintain perpendicular laser illumination aimed at SC was performed. Sixteen mice were studied for repeatability testing and to study aqueous humor outflow (AHO) pathway response to topical drug. Pharmaceutical-grade pilocarpine (1%; n = 5) or control artificial tears (n = 9) were given, and vis-OCT imaging was performed before and 15 minutes after drug application. SC areas and volumes were measured circumferentially. Results: Circumferential vis-OCT provided high-resolution imaging of the AHO pathways. Segmental SC anatomy was visualized with the average cross-sectional area greatest temporal (3971 ± 328 µm2) and the least nasal (2727 ± 218 µm2; P = 0.018). After pilocarpine administration, the SC became...

Current and Future Directions in Developing Effective Treatments for PRPH2-Associated Retinal Diseases: A Workshop Report

Fri, 28 Feb 2025 00:00:00 +0000

Purpose and Methods: A workshop of affected individuals and their families, clinicians, researchers, and industry representatives was convened in March 2023 to define the knowledge landscape of peripherin 2 (PRPH2) biology and identify challenges and opportunities towards developing PRPH2-associated inherited retinal disease (IRD) treatments. Results: The results of an online survey and presentations from affected individuals and their family members revealed disease characteristics and impacts on daily living. Scientific sessions highlighted the significant heterogeneity in clinical presentation of PRPH2-related retinopathy; PRPH2's crucial function in rod and cone outer segment formation and maintenance; the usefulness of existing animal and cellular models for understanding disease pathophysiology; and possible therapeutic approaches for autosomal dominant PRPH2-associated IRDs, including gene-specific therapies and gene-agnostic approaches. Priority gaps identified by the...

MFRP in Early Onset Retinal Degeneration: Clinical and Molecular Perspectives

Thu, 27 Feb 2025 00:00:00 +0000

The membrane-frizzled related protein (MFRP) is a retinal pigment epithelium (RPE) and ciliary epithelium-expressed gene of unknown function. Interest in MFRP stems from clinical manifestations that range from acute-angle closure glaucoma to microphthalmia and Retinitis pigmentosa in patients with MFRP mutations. Furthermore, the genetic ablation of Mfrp in mice results in an early-onset retinal disease with visible degeneration around 1mo of age and primary rod photoreceptor loss. Yet, little is known regarding the exact role of MFRP in the RPE, its underlying contribution to pathology, and the impacted mechanisms at the early stages of MFRP-related disease. This review presents a current overview of MFRP studies and poses outstanding questions that are crucial for understanding the involvement of MFRP in early-onset retinal degeneration. Such insight could pave the way for deciphering the molecular mechanisms associated with MFRP that are impacted during early stages in the...

Dry eye disease treatment improves subjective quality-of-life responses in patients with AMD, independent of disease stage

Thu, 27 Feb 2025 00:00:00 +0000

Purpose

To determine the impact of severity of age-related macular degeneration (AMD) on subjective treatment response in patients treated for dry eye disease.

Methods

A total of 203 eyes diagnosed with evaporative dry eye disease (DED) due to meibomian gland dysfunction were treated using the LipiFlow or MiBoFlo systems. From this cohort, 40 eyes with stable dry AMD (early, intermediate, or late stages) were included. Each participant completed the Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation of Eye Dryness Questionnaire (SPEED) before treatment and at a 6-month follow-up. Changes in questionnaire scores were analyzed using one-way analysis of variance (ANOVA) to assess differences between AMD severity groups.

Results

Improvement in SPEED and OSDI scores, including vision related OSDI scores were observed across all AMD stages, with no significant differences between groups (p<0.05).

Conclusion

Managing DED improved quality...

Progressive Visual Field Loss and Subsequent Quality of Life Outcomes in Glaucoma

Tue, 25 Feb 2025 00:00:00 +0000

PURPOSE: To evaluate the association between baseline severity of visual field (VF) damage and the initial rates of VF progression with quality of life (QOL) outcomes over an extended follow-up in glaucoma. DESIGN: Retrospective cohort study. METHODS: Both eyes of 167 glaucoma or suspected glaucoma patients were followed for 10.0±0.3 years. The National Eye Institute Visual Function Questionnaire (NEI-VFQ)-25 was performed at the end of the follow-up. Separate linear regression models included the VF parameters of the better eye, the worse eye, and the central and peripheral points of the integrated binocular VF to evaluate the association of baseline and initial rates of change of VF parameters (first half of the follow-up) with NEI-VFQ-25 Rasch-calibrated disability scores over an extended follow-up. RESULTS: All models demonstrated association of worse baseline severity of VF damage with worse subsequent NEI-VFQ-25 scores. Faster rates of decline in VF mean deviation of the...

Glaucoma Detection and Feature Identification via GPT-4V Fundus Image Analysis

Fri, 21 Feb 2025 00:00:00 +0000

Purpose: The aim is to assess GPT-4V's (OpenAI) diagnostic accuracy and its capability to identify glaucoma-related features compared to expert evaluations. Design: Evaluation of multimodal large language models for reviewing fundus images in glaucoma. Subjects: A total of 300 fundus images from 3 public datasets (ACRIMA, ORIGA, and RIM-One v3) that included 139 glaucomatous and 161 nonglaucomatous cases were analyzed. Methods: Preprocessing ensured each image was centered on the optic disc. GPT-4's vision-preview model (GPT-4V) assessed each image for various glaucoma-related criteria: image quality, image gradability, cup-to-disc ratio, peripapillary atrophy, disc hemorrhages, rim thinning (by quadrant and clock hour), glaucoma status, and estimated probability of glaucoma. Each image was analyzed twice by GPT-4V to evaluate consistency in its predictions. Two expert graders independently evaluated the same images using identical criteria. Comparisons between GPT-4V's assessments,...

Horizontal Gaze Tolerance and Its Effects on Visual Sensitivity in Glaucoma

Thu, 20 Feb 2025 00:00:00 +0000

Purpose: This study evaluates the effect of 6° horizontal gaze tolerance on visual field mean sensitivity (MS) in patients with glaucoma using a binocular head-mounted automated perimeter, following findings of structural changes in the posterior globe from magnetic resonance imaging and optical coherence tomography. Methods: In this cross-sectional study, a total of 161 eyes (85 primary open-angle glaucoma [POAG] and 76 healthy) from 117 participants were included. Logistic regression and 1:1 matched analysis assessed the propensity score for glaucoma and healthy eyes, considering age, sex, and axial length as confounders. Visual field tests were performed with the imo perimeter (CREWT Medical Systems, Inc., Tokyo, Japan) at central gaze, 6° abduction, and 6° adduction positions as fixation points. A mixed-effects model was used to compare MS under all conditions. Results: The analysis included a total of 82 eyes, with 41 POAG and 41 healthy after matching. The mean (standard...

Implementing a Common Data Model in Ophthalmology: Mapping Structured Electronic Health Record Ophthalmic Examination Data to Standard Vocabularies

Mon, 17 Feb 2025 00:00:00 +0000

Objective: To identify and characterize concept coverage gaps of ophthalmology examination data elements within the Cerner Millennium electronic health record (EHR) implementations by the Observational Health Data Sciences and Informatics Observational Medical Outcomes Partnership (OMOP) common data model (CDM). Design: Analysis of data elements in EHRs. Subjects: Not applicable. Methods: Source eye examination data elements from the default Cerner Model Experience EHR and a local implementation of the Cerner Millennium EHR were extracted, classified into one of 8 subject categories, and mapped to the semantically closest standard concept in the OMOP CDM. Mappings were categorized as exact, if the data element and OMOP concept represented equivalent information, wider, if the OMOP concept was missing conceptual granularity, narrower, if the OMOP concept introduced excess information, and unmatched, if no standard concept adequately represented the data element. Descriptive statistics...

Combining Optical Coherence Tomography and Optical Coheremce Tomography Angiography Longitudinal Data for the Detection of Visual Field Progression in Glaucoma

Fri, 14 Feb 2025 00:00:00 +0000

PURPOSE: To use longitudinal optical coherence tomography (OCT) and OCT angiography (OCTA) data to detect glaucomatous visual field (VF) progression with a supervised machine learning approach. DESIGN: Prospective cohort study. METHODS: One hundred ten eyes of patients with suspected glaucoma (33.6%) and patients with glaucoma (66.4%) with a minimum of 5 24-2 VF tests and 3 optic nerve head and macula images over an average follow-up duration of 4.1 years were included. VF progression was defined using a composite measure including either a "likely progression event" on Guided Progression Analysis, a statistically significant negative slope of VF mean deviation or VF index, or a positive pointwise linear regression event. Feature-based gradient boosting classifiers were developed using different subsets of baseline and longitudinal OCT and OCTA summary parameters. The area under the receiver operating characteristic curve (AUROC) was used to compare the classification performance...

Adenosine diphosphate stimulates VEGF-independent choroidal endothelial cell proliferation: A potential escape from anti-VEGF therapy

Fri, 14 Feb 2025 00:00:00 +0000

We hypothesized that a strategy employing tissue-specific endothelial cells (EC) might facilitate the identification of tissue- or organ-specific vascular functions of ubiquitous metabolites. An unbiased approach was employed to identify water-soluble small molecules with mitogenic activity on choroidal EC. We identified adenosine diphosphate (ADP) as a candidate, following biochemical purification from mouse EL4 lymphoma extracts. ADP stimulated the growth of bovine choroidal EC (BCEC) and other bovine or human eye-derived EC. ADP induced rapid phosphorylation of extracellular signal-regulated kinase in a dose- and time-dependent manner. ADP-induced BCEC proliferation could be blocked by pretreatment with specific antagonists of the purinergic receptor P2Y1 but not with a vascular endothelial growth factor (VEGF) inhibitor, indicating that the EC mitogenic effects of ADP are not mediated by stimulation of the VEGF pathway. Intravitreal administration of ADP expanded the neovascular...

Automated Quantitative Assessment of Retinal Vascular Tortuosity in Patients with Sickle Cell Disease

Fri, 14 Feb 2025 00:00:00 +0000

Objective: To quantitatively assess the retinal vascular tortuosity of patients with sickle cell disease (SCD) and retinopathy (SCR) using an automated deep learning (DL)-based pipeline. Design: Cross-sectional study. Subjects: Patients diagnosed with SCD and screened for SCR at an academic eye center between January 2015 and November 2022 were identified using electronic health records. Eyes of unaffected matched patients (i.e., no history of SCD, hypertension, diabetes mellitus, or retinal occlusive disorder) served as controls. Methods: For each patient, demographic data, sickle cell diagnosis, types and total number of sickle cell crises, SCD medications used, ocular and systemic comorbidities, and history of intraocular treatment were extracted. A previously published DL algorithm was used to calculate retinal microvascular tortuosity using ultrawidefield pseudocolor fundus imaging among patients with SCD vs. controls. Main Outcome Measures: Cumulative tortuosity index (CTI). Results:...

Cross-sectional design and protocol for Artificial Intelligence Ready and Equitable Atlas for Diabetes Insights (AI-READI)

Thu, 13 Feb 2025 00:00:00 +0000

INTRODUCTION: Artificial Intelligence Ready and Equitable for Diabetes Insights (AI-READI) is a data collection project on type 2 diabetes mellitus (T2DM) to facilitate the widespread use of artificial intelligence and machine learning (AI/ML) approaches to study salutogenesis (transitioning from T2DM to health resilience). The fundamental rationale for promoting health resilience in T2DM stems from its high prevalence of 10.5% of the world's adult population and its contribution to many adverse health events. METHODS: AI-READI is a cross-sectional study whose target enrollment is 4000 people aged 40 and older, triple-balanced by self-reported race/ethnicity (Asian, black, Hispanic, white), T2DM (no diabetes, pre-diabetes and lifestyle-controlled diabetes, diabetes treated with oral medications or non-insulin injections and insulin-controlled diabetes) and biological sex (male, female) (Clinicaltrials.org approval number STUDY00016228). Data are collected in a multivariable protocol...

Ablation of Htra1 leads to sub-RPE deposits and photoreceptor abnormalities

Thu, 13 Feb 2025 00:00:00 +0000

The high-temperature requirement A1 (HTRA1), a serine protease, has been demonstrated to play a pivotal role in the extracellular matrix (ECM) and has been reported to be associated with the pathogenesis of age-related macular degeneration (AMD). To delineate its role in the retina, the phenotype of homozygous Htra1-KO (Htra1-/-) mice was characterized to examine the effect of Htra1 loss on the retina and retinal pigment epithelium (RPE) with age. The ablation of Htra1 led to a significant reduction in rod and cone photoreceptor function, primary cone abnormalities followed by rods, and atrophy in the RPE compared with WT mice. Ultrastructural analysis of Htra1-/- mice revealed RPE and Bruch's membrane (BM) abnormalities, including the presence of sub-RPE deposits at 5 months (m) that progressed with age accompanied by increased severity of pathology. Htra1-/- mice also displayed alterations in key markers for inflammation, autophagy, and lipid metabolism in the retina. These...

Dry eye disease treatment improves subjective quality-of-life responses in patients with AMD, independent of disease stage

Thu, 13 Feb 2025 00:00:00 +0000

PURPOSE: To determine the impact of severity of age-related macular degeneration (AMD) on subjective treatment response in patients treated for dry eye disease. METHODS: A total of 203 eyes diagnosed with evaporative dry eye disease (DED) due to meibomian gland dysfunction were treated using the LipiFlow or MiBoFlo systems. From this cohort, 40 eyes with stable dry AMD (early, intermediate, or late stages) were included. Each participant completed the Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation of Eye Dryness Questionnaire (SPEED) before treatment and at a 6-month follow-up. Changes in questionnaire scores were analyzed using one-way analysis of variance (ANOVA) to assess differences between AMD severity groups. RESULTS: Improvement in SPEED and OSDI scores, including vision related OSDI scores were observed across all AMD stages, with no significant differences between groups (p<0.05). CONCLUSION: Managing DED improved quality of life (QOL) in patients...

Deep Learning Estimation of 10-2 Visual Field Map Based on Circumpapillary Retinal Nerve Fiber Layer Thickness Measurements

Mon, 10 Feb 2025 00:00:00 +0000

PURPOSE: To estimate central 10-degree visual field (VF) map from spectral-domain optical coherence tomography (SD-OCT) retinal nerve fiber layer thickness (RNFL) measurements in glaucoma with artificial intelligence. DESIGN: Artificial intelligence (convolutional neural networks) study. METHODS: This study included 5352 SD-OCT scans and 10-2 VF pairs from 1365 eyes of 724 healthy patients, patients with suspected glaucoma, and patients with glaucoma. Convolutional neural networks (CNNs) were developed to estimate the 68 individual sensitivity thresholds of 10-2 VF map using all-sectors (CNN_A) and temporal-sectors (CNN_T) RNFL thickness information of the SD-OCT circle scan (768 thickness points). 10-2 indices including pointwise total deviation (TD) values, mean deviation (MD), and pattern standard deviation (PSD) were generated using the CNN-estimated sensitivity thresholds at individual test locations. Linear regression (LR) models with the same input were...

Experiences of older adult Filipino-Americans surrounding eye surgery and factors in health decision-making: a qualitative study

Fri, 31 Jan 2025 00:00:00 +0000

BackgroundThe greater San Francisco metropolitan bay area is home to 270,000 Filipino immigrants and the second largest Filipino-American population in the United States. Despite this, Filipino-Americans are aggregated with the general “Asian-American” category, making it a challenge to obtain accurate population health data on social determinants of health. One area that is concerning is the lack of research on Filipino-American eye health experiences. The Filipino-American population is an older community with a median age of 48 years old that experiences a high prevalence of diabetes and hypertension. Preserving sight in high risk patients against age-related eye disease depends on routine eye examinations and timely treatment. Therefore, it is important to explore older adult Filipino-American eye surgery experiences and factors in eye health decision-making.MethodsAn exploratory qualitative study was conducted with thirteen Filipino-American adults residing in the nine...

Comparison of a Novel Ultra-Widefield Three-Color Scanning Laser Ophthalmoscope to Other Retinal Imaging Modalities in Chorioretinal Lesion Imaging

Fri, 31 Jan 2025 00:00:00 +0000

Purpose: To compare the assessment of clinically relevant retinal and choroidal lesions as well as optic nerve pathologies using a novel three-wavelength ultra-widefield (UWF) scanning laser ophthalmoscope with established retinal imaging techniques for ophthalmoscopic imaging. Methods: Eighty eyes with a variety of retinal and choroidal lesions were assessed on the same time point using Topcon color fundus photography (CFP) montage, Optos red/green (RG), Heidelberg SPECTRALIS MultiColor 55-color montage (MCI), and novel Optos red/green/blue (RGB). Paired images of the optic nerve, retinal, or choroidal lesions were initially diagnosed based on CFP imaging. The accuracy of the imaging was then evaluated in comparison to CFP using a grading scale ranging from -1 (losing imaging information) to +1 (gaining imaging information). Results: Eighty eyes of 43 patients with 116 retinal or choroidal pathologies, as well as 59 eyes with optic nerve imaging using CFP, MCI, RG, and RGB, were...

Development of an Open-Source Dataset of Flat-Mounted Images for the Murine Oxygen–Induced Retinopathy Model of Ischemic Retinopathy

Fri, 31 Jan 2025 00:00:00 +0000

Purpose: To describe an open-source dataset of flat-mounted retinal images and vessel segmentations from mice subject to the oxygen-induced retinopathy (OIR) model. Methods: Flat-mounted retinal images from mice killed at postnatal days 12 (P12), P17, and P25 used in prior OIR studies were compiled. Mice subjected to normoxic conditions were killed at P12, P17, and P25, and their retinas were flat-mounted for imaging. Major blood vessels from the OIR images were manually segmented by four graders (JSC, HKR, KBL, JM), with cross-validation performed to ensure similar grading. Results: Overall, 1170 images were included in this dataset. Of these images, 111 were of normoxic mice retina, and 1048 were mice subject to OIR. The majority of images from OIR mice were obtained at P17. The 50 images obtained from an external dataset, OIRSeg, did not have age labels. All images were manually segmented and used in the training or testing of a previously published deep learning algorithm. Conclusions:...

Effects of Short-Term Treatment of Rabbit Extraocular Muscle With Ciliary Neurotrophic Factor

Thu, 23 Jan 2025 00:00:00 +0000

Purpose: Little is known about the effect of ciliary neurotrophic factor (CNTF) on extraocular muscles, but microarray studies suggested CNTF might play a role in the development and/or maintenance of strabismus. The effect of short-term treatment of adult rabbit extraocular muscle with injected CNTF was examined for its ability to alter muscle characteristics. Methods: Eight adult New Zealand white rabbits received an injection into one superior rectus muscle of 2 µg/100 µL CNTF on 3 consecutive days. One week after the first injection, the rabbits were euthanized, and the treated and contralateral superior rectus muscles were assessed for force generation capacity and contraction characteristics using an in vitro stimulation protocol and compared to naïve control superior rectus muscles. All muscles were analyzed to determine mean cross-sectional areas and expression of slow twitch myosin heavy chain isoform. Results: Short-term treatment of rabbit superior rectus muscles with...

Indocyanine Green Aided Schlemm Canal Identification During Gonioscopic Assisted Transluminal Trabeculotomy

Wed, 22 Jan 2025 00:00:00 +0000

Performing procedures like gonioscopic assisted transluminal trabeculotomy in eyes with congenital glaucoma may be difficult many a times due to difficult visualization of angle structures. Inaccurate identification of the angle landmark may lead to various inadvertent surgical complications. Hence, there is a need for techniques to improve visualization of surgical landmarks during these procedures. In this study, 0.2% indocyanine green was used to stain the trabecular meshwork before the surgeon proceeded with gonioscopic assisted transluminal trabeculotomy. It yielded excellent differentiation of the trabecular meshwork by imparting a bright green hue. This led to successful identification of the site of incision and subsequent 360 degrees cannulation of Schlemm canal in 5/5 cases. Indocyanine green aided Schlemm canal identification is helpful in children with congenital glaucoma undergoing angle surgeries, especially in eyes with poor structure differentiation.

Assessing Educational Impact of Worldwide Webinar on Management of Myopia Progression in Children

Sat, 18 Jan 2025 00:00:00 +0000

OBJECTIVE: To assess the educational impact of a worldwide webinar approach to myopia progression management in children <8 years and 8-12 years old. DESIGN: Cross-sectional study. METHODS: A self-administered survey was conducted for attendees of a 3 h worldwide webinar held in two parts on consecutive days on the management of myopia progression in children. The survey was administered before, immediately after completion of the webinar, and 8 weeks later; responses were recorded on a Likert scale. Questions were posed to assess (a) the confidence of attendees in managing myopia in children <12 years old, (b) attendees' understanding of latest treatment options, (c) any improvement in attendees' knowledge after the webinar, and (d) any changes made to practice 8 weeks after the webinar. Pre- and post-responses were analyzed using an unpaired two-tailed t-test. RESULTS: The webinar had 701 and 606 global attendees on the first and second days, respectively. Based...

Consensus Recommendations for Studies of Outflow Facility and Intraocular Pressure Regulation Using Ex Vivo Perfusion Approaches

Sat, 18 Jan 2025 00:00:00 +0000

Intraocular pressure (IOP) elevation is the primary risk factor and currently the main treatable factor for progression of glaucomatous optic neuropathy. In addition to direct clinical and living animal in vivo studies, ex vivo perfusion of anterior segments and whole eyes is a key technique for studying conventional outflow function as it is responsible for IOP regulation. We present well-tested experimental details, protocols, considerations, advantages, and limitations of several ex vivo model systems for studying IOP regulation. These include: (1) perfused whole globes, (2) stationary anterior segment organ culture, (3) perfused human anterior segment organ culture, (4) perfused animal anterior segment organ culture, (5) perfused human corneal rims, and (6) perfused human anterior segment wedges. These methods, with due consideration paid to their strengths and limitations, comprise a set of very strong tools for extending our understanding of IOP regulation.

Single cell RNA-seq of human cornea organoids identifies cell fates of a developing immature cornea

Fri, 17 Jan 2025 00:00:00 +0000

The cornea is a protective and refractive barrier in the eye crucial for vision. Understanding the human cornea in health, disease, and cell-based treatments can be greatly advanced with cornea organoids developed in culture from induced pluripotent stem cells. While a limited number of studies have investigated the single-cell transcriptomic composition of the human cornea, its organoids have not been examined similarly. Here, we elucidated the transcriptomic cell fate map of 4-month-old human cornea organoids and human donor corneas. The organoids harbor cell clusters that resemble cells of the corneal epithelium, stroma, and endothelium, with subpopulations that capture signatures of early developmental states. Unlike the adult cornea where the largest cell population is stromal, the organoids contain large proportions of epithelial and endothelial-like cells. These corneal organoids offer a 3D model to study corneal diseases and integrated responses of different cell types.

Proteome Landscape of Epithelial-to-Mesenchymal Transition (EMT) of Retinal Pigment Epithelium Shares Commonalities With Malignancy-Associated EMT

Fri, 17 Jan 2025 00:00:00 +0000

Stress and injury to the retinal pigment epithelium (RPE) often lead to dedifferentiation and epithelial-to-mesenchymal transition (EMT). These processes have been implicated in several retinal diseases, including proliferative vitreoretinopathy, diabetic retinopathy, and age-related macular degeneration. Despite the importance of RPE-EMT and the large body of data characterizing malignancy-related EMT, comprehensive proteomic studies to define the protein changes and pathways underlying RPE-EMT have not been reported. This study sought to investigate the temporal protein expression changes that occur in a human-induced pluripotent stem cell-based RPE-EMT model. We utilized multiplexed isobaric tandem mass tag labeling followed by high-resolution tandem MS for precise and in-depth quantification of the RPE-EMT proteome. We have identified and quantified 7937 protein groups in our tandem mass tag-based MS analysis. We observed a total of 532 proteins that are differentially regulated...

Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

Fri, 17 Jan 2025 00:00:00 +0000

X-linked juvenile retinoschisis (XLRS), linked to mutations in the RS1 gene, is a degenerative retinopathy with a retinal splitting phenotype. We generated human induced pluripotent stem cells (hiPSCs) from patients to study XLRS in a 3D retinal organoid in vitro differentiation system. This model recapitulates key features of XLRS including retinal splitting, defective retinoschisin production, outer-segment defects, abnormal paxillin turnover, and impaired ER-Golgi transportation. RS1 mutation also affects the development of photoreceptor sensory cilia and results in altered expression of other retinopathy-associated genes. CRISPR/Cas9 correction of the disease-associated C625T mutation normalizes the splitting phenotype, outer-segment defects, paxillin dynamics, ciliary marker expression, and transcriptome profiles. Likewise, mutating RS1 in control hiPSCs produces the disease-associated phenotypes. Finally, we show that the C625T mutation can be repaired precisely and...

A Tet-Inducible CRISPR Platform for High-Fidelity Editing of Human Pluripotent Stem Cells

Thu, 16 Jan 2025 00:00:00 +0000

Pluripotent stem cells (PSCs) offer an exciting resource for probing human biology; however, gene-editing efficiency remains relatively low in many cell types, including stem cells. Gene-editing using the CRISPR-Cas9 system offers an attractive solution that improves upon previous gene-editing approaches; however, like other technologies, off-target mutagenesis remains a concern. High-fidelity Cas9 variants greatly reduce off-target mutagenesis and offer a solution to this problem. To evaluate their utility as part of a cell-based gene-editing platform, human PSC lines were generated with a high-fidelity (HF) tetracycline-inducible engineered Streptococcus pyogenes SpCas9 (HF-iCas9) integrated into the AAVS1 safe harbor locus. By engineering cells with controllable expression of Cas9, we eliminated the need to include a large Cas9-expressing plasmid during cell transfection. Delivery of genetic cargo was further optimized by packaging DNA targeting guide RNAs (gRNAs) and...

IKKβ Inhibition Attenuates Epithelial Mesenchymal Transition of Human Stem Cell-Derived Retinal Pigment Epithelium

Thu, 16 Jan 2025 00:00:00 +0000

Epithelial-mesenchymal transition (EMT), which is well known for its role in embryonic development, malignant transformation, and tumor progression, has also been implicated in a variety of retinal diseases, including proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), and diabetic retinopathy. EMT of the retinal pigment epithelium (RPE), although important in the pathogenesis of these retinal conditions, is not well understood at the molecular level. We and others have shown that a variety of molecules, including the co-treatment of human stem cell-derived RPE monolayer cultures with transforming growth factor beta (TGF-β) and the inflammatory cytokine tumor necrosis factor alpha (TNF-α), can induce RPE-EMT; however, small molecule inhibitors of RPE-EMT have been less well studied. Here, we demonstrate that BAY651942, a small molecule inhibitor of nuclear factor kapa-B kinase subunit beta (IKKβ) that selectively targets NF-κB signaling, can modulate...

Temporal and Isoform-Specific Expression of CTBP2 Is Evolutionarily Conserved Between the Developing Chick and Human Retina

Thu, 16 Jan 2025 00:00:00 +0000

Complex transcriptional gene regulation allows for multifaceted isoform production during retinogenesis, and novel isoforms transcribed from a single locus can have unlimited potential to code for diverse proteins with different functions. In this study, we explored the CTBP2/RIBEYE gene locus and its unique repertoire of transcripts that are conserved among vertebrates. We studied the transcriptional coregulator (CTBP2) and ribbon synapse-specific structural protein (RIBEYE) in the chicken retina by performing comprehensive histochemical and sequencing analyses to pinpoint cell and developmental stage-specific expression of CTBP2/RIBEYE in the developing chicken retina. We demonstrated that CTBP2 is widely expressed in retinal progenitors beginning in early retinogenesis but becomes limited to GABAergic amacrine cells in the mature retina. Inversely, RIBEYE is initially epigenetically silenced in progenitors and later expressed in photoreceptor and bipolar cells where they localize...

Restoring vision and rebuilding the retina by Müller glial cell reprogramming

Thu, 16 Jan 2025 00:00:00 +0000

Müller glia are non-neuronal support cells that play a vital role in the homeostasis of the eye. Their radial-oriented processes span the width of the retina and respond to injury through a cellular response that can be detrimental or protective depending on the context. In some species, protective responses include the expression of stem cell-like genes which help to fuel new neuron formation and even restoration of vision. In many lower vertebrates including fish and amphibians, this response is well documented, however, in mammals it is severely limited. The remarkable plasticity of cellular reprogramming in lower vertebrates has inspired studies in mammals for repairing the retina and restoring sight, and recent studies suggest that mammals are also capable of regeneration, albeit to a lesser degree. Endogenous regeneration, whereby new retinal neurons are created from existing support cells, offers an exciting alternative approach to existing tissue transplant, gene therapy,...

Transcriptome Landscape of Epithelial to Mesenchymal Transition of Human Stem Cell–Derived RPE

Thu, 16 Jan 2025 00:00:00 +0000

Purpose

RPE injury often induces epithelial to mesenchymal transition (EMT). Although RPE-EMT has been implicated in a variety of retinal diseases, including proliferative vitroretinopathy, neovascular and atrophic AMD, and diabetic retinopathy, it is not well-understood at the molecular level. To contribute to our understanding of EMT in human RPE, we performed a time-course transcriptomic analysis of human stem cell-derived RPE (hRPE) monolayers induced to undergo EMT using 2 independent, yet complementary, model systems.

Methods

EMT of human stem cell-derived RPE monolayers was induced by either enzymatic dissociation or modulation of TGF-β signaling. Transcriptomic analysis of cells at different stages of EMT was performed by RNA-sequencing, and select findings were confirmed by reverse transcription quantitative PCR and immunostaining. An ingenuity pathway analysis (IPA) was performed to identify signaling pathways and regulatory networks associated with EMT.

Results

Proteocollagenolytic...

Thyroid hormone signaling specifies cone subtypes in human retinal organoids

Thu, 16 Jan 2025 00:00:00 +0000

The mechanisms underlying specification of neuronal subtypes within the human nervous system are largely unknown. The blue (S), green (M), and red (L) cones of the retina enable high-acuity daytime and color vision. To determine the mechanism that controls S versus L/M fates, we studied the differentiation of human retinal organoids. Organoids and retinas have similar distributions, expression profiles, and morphologies of cone subtypes. S cones are specified first, followed by L/M cones, and thyroid hormone signaling controls this temporal switch. Dynamic expression of thyroid hormone-degrading and -activating proteins within the retina ensures low signaling early to specify S cones and high signaling late to produce L/M cones. This work establishes organoids as a model for determining mechanisms of human development with promising utility for therapeutics and vision repair.

Potential of Ocular Transmission of SARS-CoV-2: A Review

Thu, 16 Jan 2025 00:00:00 +0000

PURPOSE OF REVIEW: to provide a prospective on the current mechanisms by which SARS-CoV-2 enters cells and replicates, and its implications for ocular transmission. The literature was analyzed to understand ocular transmission as well as molecular mechanisms by which SARS-CoV-2 enters cells and replicates. Analysis of gene expression profiles from available datasets, published immunohistochemistry, as well as current literature was reviewed, to assess the likelihood that ocular inoculation of SARS-CoV-2 results in systemic infection. RECENT FINDINGS: The ocular surface and retina have the necessary proteins, Transmembrane Serine Protease 2 (TMPRSS2), CD147, Angiotensin-Converting Enzyme 2 (ACE2) and Cathepsin L (CTSL) necessary to be infected with SARS-CoV-2. In addition to direct ocular infection, virus carried by tears through the nasolacrimal duct to nasal epithelium represent a means of ocular inoculation. SUMMARY: There is evidence that SARS-CoV-2 may either directly infect...

A Combinatorial Library of Biodegradable Polyesters Enables Non-viral Gene Delivery to Post-Mitotic Human Stem Cell-Derived Polarized RPE Monolayers

Thu, 16 Jan 2025 00:00:00 +0000

Safe and effective delivery of DNA to post-mitotic cells, especially highly differentiated cells, remains a challenge despite significant progress in the development of gene delivery tools. Biodegradable polymeric nanoparticles (NPs) offer an array of advantages for gene delivery over viral vectors due to improved safety, carrying capacity, ease of manufacture, and cell-type specificity. Here we demonstrate the use of a high-throughput screening (HTS) platform to synthesize and screen a library of 148 biodegradable polymeric nanoparticles, successfully identifying structures that enable efficient transfection of human pluripotent stem cell differentiated human retinal pigment epithelial (RPE) cells with minimal toxicity. These NPs can deliver plasmid DNA (pDNA) to RPE monolayers more efficiently than leading commercially available transfection reagents. Novel synthetic polymers are described that enable high efficacy non-viral gene delivery to hard-to-transfect polarized human...

CRISPR Generated SIX6 and POU4F2 Reporters Allow Identification of Brain and Optic Transcriptional Differences in Human PSC-Derived Organoids

Thu, 16 Jan 2025 00:00:00 +0000

Human pluripotent stem cells (PSCs) represent a powerful tool to investigate human eye development and disease. When grown in 3D, they can self-assemble into laminar organized retinas; however, variation in the size, shape and composition of individual organoids exists. Neither the microenvironment nor the timing of critical growth factors driving retinogenesis are fully understood. To explore early retinal development, we developed a SIX6-GFP reporter that enabled the systematic optimization of conditions that promote optic vesicle formation. We demonstrated that early hypoxic growth conditions enhanced SIX6 expression and promoted eye formation. SIX6 expression was further enhanced by sequential inhibition of Wnt and activation of sonic hedgehog signaling. SIX6 + optic vesicles showed RNA expression profiles that were consistent with a retinal identity; however, ventral diencephalic markers were also present. To demonstrate that optic vesicles lead to bona fide "retina-like"...

Teprotumumab for Thyroid Eye Disease-related Strabismus

Tue, 14 Jan 2025 00:00:00 +0000

PURPOSE: To assess and quantify teprotumumab's effect on thyroid eye disease-related strabismus by change in measured horizontal and vertical deviations and change in extraocular motility. METHODS: We reviewed a series of patients with thyroid eye disease-related strabismus treated with teprotumumab. Exclusion criteria included age under 18 years, strabismus of alternate etiology, or thyroid eye disease-related reconstructive surgery during the treatment course. Primary outcomes were absolute (prism diopters) and relative (%) differences in horizontal and vertical deviations in primary position at distance, as well as change in ductions of the more affected eye. Secondary outcomes included incidence and timing of strabismus surgery postteprotumumab. RESULTS: Thirty-one patients were included, with mean age 63 years and thyroid eye disease duration 10 months. After teprotumumab, there was 6 prism diopters (39%) mean reduction in vertical deviation ( p < 0.001), without significant...

Characterization of Facial Trauma Associated with Standing Electric Scooter Injuries

Mon, 13 Jan 2025 00:00:00 +0000

Characterization of Facial Trauma Associated with Standing Electric Scooter Injuries

Evaluating a Foundation Artificial Intelligence Model for Glaucoma Detection Using Color Fundus Photographs

Tue, 7 Jan 2025 00:00:00 +0000

Purpose: To evaluate RETFound, a foundation artificial intelligence model, using a diverse clinical research dataset to assess its accuracy in detecting glaucoma using optic disc photographs. The model's accuracy for glaucoma detection was evaluated across race, age, glaucoma severity, and various training cycles (epochs) and dataset sample sizes. Design: Evaluation of a diagnostic technology. Participants: The study included 9787 color fundus photographs (CFPs) from 2329 participants of diverse race (White [73.4%], Black [13.6%] and other [13%]), disease severity (21.8% mild glaucoma, 7.2% moderate or advanced glaucoma, 60.3% not glaucoma, and 10.7% unreported), and age (48.8% <60 years, 51.1% >60 years) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. All fundus photographs were graded as "Glaucomatous" or "Non-glaucomatous." Methods: The study employed RETFound, a self-supervised learning model, to perform...

Clinical Factors Associated With Long-Term OCT Variability in Glaucoma

Sat, 4 Jan 2025 00:00:00 +0000

PURPOSE: To examine clinical factors associated with long-term optical coherence tomography (OCT)-measured retinal nerve fiber layer thickness (RNFLT) variability in glaucoma. STUDY DESIGN: Retrospective cohort study. METHODS: Glaucoma eyes from Diagnostic Innovations in Glaucoma Study (DIGS)/the African Descent and Glaucoma Evaluation Study (ADAGES) with ≥2-years and 4-visit follow-up were included. RNFLT variability was calculated per visit as the absolute error of optic nerve head RNFLT residuals across longitudinal follow-up. Clinical factors examined included general demographics, baseline ocular measurements, prior and intervening cataract extraction (CE) or glaucoma surgery, scan quality, baseline RNFLT and RNFLT thinning rate, follow-up duration, and visit/testing frequency. Three multivariable linear mixed models (full model, baseline model, and parsimonious model) were fit to evaluate the effects of clinical factors on RNFLT variability, with 10-fold cross-validation...

Retinal OCT Layer Segmentation via Joint Motion Correction and Graph-Assisted 3D Neural Network

Fri, 3 Jan 2025 00:00:00 +0000

Optical Coherence Tomography (OCT) is a widely used 3D imaging technology in ophthalmology. Segmentation of retinal layers in OCT is important for diagnosis and evaluation of various retinal and systemic diseases. While 2D segmentation algorithms have been developed, they do not fully utilize contextual information and suffer from inconsistency in 3D. We propose neural networks to combine motion correction and segmentation in 3D. The proposed segmentation network utilizes 3D convolution and a novel graph pyramid structure with graph-inspired building blocks. We also collected one of the largest OCT segmentation dataset with manually corrected segmentation covering both normal examples and various diseases. The experimental results on three datasets with multiple instruments and various diseases show the proposed method can achieve improved segmentation accuracy compared with commercial softwares and conventional or deep learning methods in literature. Specifically, the proposed...

Biotissue stent for supraciliary outflow in open-angle glaucoma patients: surgical procedure and first clinical results of an aqueous drainage biostent

Tue, 24 Dec 2024 00:00:00 +0000

BACKGROUND/AIMS: To report a first-in-human trial in open-angle glaucoma (OAG) subjects treated with a new microinterventional biostent-reinforced cyclodialysis technique to enhance supraciliary aqueous drainage. METHODS: Subjects (N=10; 74.1±7.9 years old) with OAG and cataracts underwent combined phacoemulsification cataract surgery with implantation of a permanent endoscleral supraciliary biostent to reinforce a controlled cyclodialysis cleft. The biostent comprised decellularised scleral allograft tissue microtrephined into a polymer tubular implant intraoperative/postoperative safety, intraocular pressure (IOP) and glaucoma medications were tracked through 12 months postimplantation. RESULTS: Baseline medicated IOP averaged 24.2±6.9 mm Hg with subjects using 1.3±0.8 IOP-lowering medications. Successful biostent implantation was achieved in all individuals without significant complications. Immediate IOP lowering was sustained through 1 year. Twelve-month mean IOP was reduced...

Bio-Interventional Cyclodialysis and Allograft Scleral Reinforcement for Uveoscleral Outflow Enhancement in Open-Angle Glaucoma Patients: One-Year Clinical Outcomes

Tue, 24 Dec 2024 00:00:00 +0000

Background: To evaluate the one-year safety and effectiveness of bio-interventional cyclodialysis and scleral reinforcement in open-angle glaucoma (OAG) patients undergoing cataract surgery. Methods: An ab-interno approach was used to create a sectoral cyclodialysis in OAG patients who were prospectively followed in a consecutive case series. Subsequent visco-cycloplasty with scleral reinforcement using homologous minimally modified allograft scaffold was completed to maintain patency of the cyclodialysis reservoir and increase uveoscleral outflow. Outcomes were mean medicated IOP and mean number of IOP-lowering medications. Safety outcomes were adverse events (AEs) and best-corrected visual acuity (BCVA) changes. Results: Successful cyclodialysis and allograft bio-scaffold reinforcement was achieved in 117 eyes. There was minimal intraoperatie bleeding and few post-operative adverse events. At baseline, mean BCVA was 0.48 (95% CI: 0.42‒0.54; 20/40 Snellen) and mean ± SD medicated...

Detection of TTR Amyloid in the Conjunctiva Using a Novel Fluorescent Ocular Tracer

Wed, 18 Dec 2024 00:00:00 +0000

Background: Transthyretin amyloidosis (ATTR) is a significant cause of cardiomyopathy and other morbidities in the elderly and Black Americans. ATTR can be treated with new disease-modifying therapies, but large shortfalls exist in its diagnosis. The objective of this study was to test whether TTR amyloid can be detected and imaged in the conjunctiva using a novel small-molecule fluorescent ocular tracer, with the implication that ATTR might be diagnosable by a simple eye examination. Methods: Three approaches were used in this study. First, AMDX-9101 was incubated with in vitro aggregated TTR protein, and changes in its excitation and emission spectra were quantified. Second, a cadaver eye from a patient with familial amyloid polyneuropathy type II TTR mutation and a vitrectomy sample from an hATTR patient were incubated with AMDX-9101 and counterstained with Congo Red and antibodies to TTR to determine whether AMDX-9101 labels disease-related TTR amyloid deposits in human conjunctiva...

Indocyanine green-assisted goniotomy in eyes with hazy cornea

Wed, 18 Dec 2024 00:00:00 +0000

Corneal haze, due to edema or opacity, is a major contraindication for performing ab interno angle surgeries such as goniotomy in children with primary congenital glaucoma (PCG), despite otherwise favorable surgical outcomes expected in these patients. In this case series involving patients of PCG with moderate corneal haze, the authors describe a technique for performing goniotomy in cases with compromised visibility by using indocyanine green (ICG) to aid in the visualization of angle structures. The authors used 0.2% ICG intracamerally, which stained the anterior and posterior trabecular meshwork (TM) with different intensities, before proceeding with goniotomy. The junction between the two zones was discernible due to the contrast imparted by ICG staining, despite poor visibility, allowing the surgeon to incise the TM at the correct site. The possibility of performing goniotomy in such patients with the help of ICG can revolutionize our surgical approach to patients with PCG...

Recruitment of Temporal Aqueous Outflow Channels After Bent Needle Ab-Interno Goniectomy Demonstrated by Aqueous Angiography

Wed, 18 Dec 2024 00:00:00 +0000

PURPOSE: To demonstrate the utility of operating on the temporal trabecular meshwork with in vivo - aqueous angiography demonstrating new aqueous outflow channels. METHOD: In a patient with primary open angle glaucoma, nuclear sclerosis, and medically uncontrolled intraocular pressure, Indocyanine green aqueous angiography (0.5%) was performed to visualize baseline functional aqueous outflow channels. This was followed by 30 degrees bent needle ab-interno goniectomy in the temporal quadrant, where no aqueous outflow channels were initially visualized. Aqueous angiography was repeated using 2% fluorescein to visualize aqueous outflow channels after bent needle ab-interno goniectomy. RESULTS: Prebent needle ab-interno goniectomy, aqueous angiography revealed functional outflow channels in the nasal quadrant although none were visible in the temporal quadrant. Postbent needle ab-interno goniectomy in temporal quadrant aqueous angiography demonstrated 2 new aqueous outflow channels. CONCLUSION:...

Clinical applications of aqueous angiography in glaucoma

Wed, 18 Dec 2024 00:00:00 +0000

Aqueous humor outflow (AHO) pathways are the main site of resistance causing elevated intraocular pressure in glaucoma, especially primary open-angle glaucoma patients. With the recently introduced technique of aqueous angiography (AA); functional, real time assessment of AHO from proximal (trabecuar meshwork) to distal pathways under physiological conditions has been made possible. AHO pathways are segmental, and AA can identify high-flow region (increased angiographic signals) and low flow region (decreased angiographic signals) in an individual. With the introduction of canal-based minimally invasive glaucoma surgeries (MIGS), the assessment of AHO can help guide the placement of stents/incisions during MIGS procedures. This can allow individualized and targeted MIGS procedures in glaucoma patients for better results. Based on the density of AHO pathways visualized on AA, surgeons can decide whether to perform MIGS or conventional glaucoma surgery for improved outcomes for...

Aqueous outflow channels and its lymphatic association: A review

Wed, 18 Dec 2024 00:00:00 +0000

The human eye has a unique immune architecture and behavior. While the conjunctiva is known to have a well-defined lymphatic drainage system, the cornea, sclera, and uveal tissues were historically considered "alymphatic" and thought to be immune privileged. The very fact that the aqueous outflow channels carry a clear fluid (aqueous humor) along the outflow pathway makes it hard to ignore its lymphatic-like characteristics. The development of novel lymphatic lineage markers and expression of these markers in aqueous outflow channels and improved imaging capabilities has sparked a renewed interest in the study of ocular lymphatics. Ophthalmic lymphatic research has had a directional shift over the last decade, offering an exciting new physiological platform that needs further in-depth understanding. The evidence of a presence of distinct lymphatic channels in the human ciliary body is gaining significant traction. The uveolymphatic pathway is an alternative new route for aqueous...

Automated expert-level scleral spur detection and quantitative biometric analysis on the ANTERION anterior segment OCT system

Wed, 18 Dec 2024 00:00:00 +0000

AIM: To perform an independent validation of deep learning (DL) algorithms for automated scleral spur detection and measurement of scleral spur-based biometric parameters in anterior segment optical coherence tomography (AS-OCT) images. METHODS: Patients receiving routine eye care underwent AS-OCT imaging using the ANTERION OCT system (Heidelberg Engineering, Heidelberg, Germany). Scleral spur locations were marked by three human graders (reference, expert and novice) and predicted using DL algorithms developed by Heidelberg Engineering that prioritise a false positive rate <4% (FPR4) or true positive rate >95% (TPR95). Performance of human graders and DL algorithms were evaluated based on agreement of scleral spur locations and biometric measurements with the reference grader. RESULTS: 1308 AS-OCT images were obtained from 117 participants. Median differences in scleral spur locations from reference locations were significantly smaller (p<0.001) for the FPR4 (52.6±48.6 µm)...

Aqueous Angiography-guided Minimally Invasive Glaucoma Surgery

Wed, 18 Dec 2024 00:00:00 +0000

How to cite this article: Dada T, Verma S, Bukke AN, et al. Aqueous Angiography-guided Minimally Invasive Glaucoma Surgery. J Curr Glaucoma Pract 2022;16(1):1-3.

Catastrophic retinal vascular occlusion and vision loss due to crystal deposition in end-stage kidney disease treated with peritoneal dialysis

Tue, 10 Dec 2024 00:00:00 +0000

Purpose: To report two cases of catastrophic retinal vascular occlusion and crystalline retinopathy due to presumed oxalosis and hyperphosphatemia. Observations: We describe two unrelated patients with end-stage kidney failure (ESKD) treated with peritoneal dialysis that developed rapid bilateral vision loss due to severe retinal vascular occlusion. Multi-modal retinal imaging studies demonstrated crystalline deposits. Plasma phosphorus and oxalate levels were markedly elevated compared to persons with normal kidney function. One patient harbored a heterozygous variant of unknown significance in the Alanine--Glyoxylate Aminotransferase (AGXT) gene. Intense hemodialysis and diet modification reduced phosphorus and oxalate levels. Conclusions and importance: This report serves to raise awareness of hyperphosphatemia and oxalosis in dialysis patients to alert providers so that they can act to decrease the potential risk of vision loss.

Barriers to Implementation of Teleretinal Diabetic Retinopathy Screening Programs Across the University of California

Fri, 6 Dec 2024 00:00:00 +0000

Aim: To describe barriers to implementation of diabetic retinopathy (DR) teleretinal screening programs and artificial intelligence (AI) integration at the University of California (UC). Methods: Institutional representatives from UC Los Angeles, San Diego, San Francisco, Irvine, and Davis were surveyed for the year of their program's initiation, active status at the time of survey (December 2021), number of primary care clinics involved, screening image quality, types of eye providers, image interpretation turnaround time, and billing codes used. Representatives were asked to rate perceptions toward barriers to teleretinal DR screening and AI implementation using a 5-point Likert scale. Results: Four UC campuses had active DR teleretinal screening programs at the time of survey and screened between 246 and 2,123 patients at 1-6 clinics per campus. Sites reported variation between poor-quality photos (<5% to 15%) and...

Reference Database for a Novel Binocular Visual Function Perimeter: A Randomized Clinical Trial

Wed, 4 Dec 2024 00:00:00 +0000
Purpose: To construct a comprehensive reference database (RDB) for a novel binocular automated perimeter. Design: A four-site prospective randomized clinical trial. Subjects and Controls: Three hundred fifty-six healthy subjects without ocular conditions that might affect visual function were categorized into 7 age groups. Methods: Subjects underwent comprehensive ocular examination of both eyes before enrollment. Using the TEMPO/IMOvifa automated perimeter (Topcon Healthcare/CREWT Medical Systems), each subject completed 4 binocular threshold visual field (VF) tests during a single visit: First, practice 24-2 and 10-2 tests were obtained from both eyes. Next, study 24-2 and 10-2 tests were obtained from both eyes. Test order of each sequence was randomized, and the tests were conducted under standard automated perimetry testing conditions: Goldmann stimulus size III, 3183 cd/m² maximum stimulus intensity, and background intensity of 10 cd/m², using AIZE-Rapid...

Social and Health Care Utilization Factors Associated With Ophthalmic Visit Nonadherence in Glaucoma: An All of Us Study

Tue, 3 Dec 2024 00:00:00 +0000
PRÉCIS: In a diverse nationwide cohort, lower education and income levels, cost saving on medications, fewer past-year medical/specialist visits, and concerns regarding dissimilarity with health care providers were risk factors for ophthalmic visit nonadherence among glaucoma patients. PURPOSE: The purpose of this study was to characterize social and health care utilization factors associated with nonadherence with ophthalmic visits among patients with glaucoma. MATERIALS AND METHODS: Glaucoma patients in the All of Us database who completed the Healthcare Access and Utilization Survey were included and categorized into "visit" and "nonvisit" groups based on visit adherence, defined by self-reported past-year encounters with eyecare providers (yes/no). Data regarding potential factors affecting ophthalmic visit adherence, including past-year medical visits, inabilities to afford health care, and self-reported reasons for delayed care, were extracted. χ 2 tests and logistic regression...

One-Vote Veto: Semi-Supervised Learning for Low-Shot Glaucoma Diagnosis

Tue, 3 Dec 2024 00:00:00 +0000
Convolutional neural networks (CNNs) are a promising technique for automated glaucoma diagnosis from images of the fundus, and these images are routinely acquired as part of an ophthalmic exam. Nevertheless, CNNs typically require a large amount of well-labeled data for training, which may not be available in many biomedical image classification applications, especially when diseases are rare and where labeling by experts is costly. This article makes two contributions to address this issue: 1) It extends the conventional Siamese network and introduces a training method for low-shot learning when labeled data are limited and imbalanced, and 2) it introduces a novel semi-supervised learning strategy that uses additional unlabeled training data to achieve greater accuracy. Our proposed multi-task Siamese network (MTSN) can employ any backbone CNN, and we demonstrate with four backbone CNNs that its accuracy with limited training data approaches the accuracy of backbone CNNs trained...

The Development and Validation of a Glaucoma Health Score for Glaucoma Screening Based on Clinical Parameters and Optical Coherence Tomography Metrics

Mon, 2 Dec 2024 00:00:00 +0000
Background/Objectives: This study aims to develop and validate a Glaucoma Health Score (GHS) that incorporates multiple individual glaucoma risk factors to enhance glaucoma detection in screening environments. Methods: The GHS was developed using a retrospective dataset from two clinical sites, including both eyes of glaucoma patients and controls. The model incorporated age, central corneal thickness, intraocular pressure, pattern standard deviation from a visual field threshold 24-2 test, and two parameters from an optical coherence tomography (OCT) test: the average circumpapillary retinal nerve fiber layer thickness and the minimum thickness of the six sectors of the macular ganglion cell plus the inner plexiform layer. The GHS was then validated in two independent datasets: one from primary care sites using Maestro OCT data (test dataset 1) and another from an academic center using DRI OCT Triton (test dataset 2). Results: Both eyes of 51 glaucoma patients...

Analysis of ChatGPT Responses to Ophthalmic Cases: Can ChatGPT Think like an Ophthalmologist?

Mon, 2 Dec 2024 00:00:00 +0000
Objective: Large language models such as ChatGPT have demonstrated significant potential in question-answering within ophthalmology, but there is a paucity of literature evaluating its ability to generate clinical assessments and discussions. The objectives of this study were to (1) assess the accuracy of assessment and plans generated by ChatGPT and (2) evaluate ophthalmologists' abilities to distinguish between responses generated by clinicians versus ChatGPT. Design: Cross-sectional mixed-methods study. Subjects: Sixteen ophthalmologists from a single academic center, of which 10 were board-eligible and 6 were board-certified, were recruited to participate in this study. Methods: Prompt engineering was used to ensure ChatGPT output discussions in the style of the ophthalmologist author of the Medical College of Wisconsin Ophthalmic Case Studies. Cases where ChatGPT accurately identified the primary diagnoses were included and then paired. Masked human-generated and ChatGPT-generated...

Cross-instrument optical coherence tomography-angiography (OCTA)-based prediction of age-related macular degeneration (AMD) disease activity using artificial intelligence

Mon, 25 Nov 2024 00:00:00 +0000
This study investigates the efficacy of predicting age-related macular degeneration (AMD) activity through deep neural networks (DNN) using a cross-instrument training dataset composed of Optical coherence tomography-angiography (OCTA) images from two different manufacturers. A retrospective cross-sectional study analyzed 2D vascular en-face OCTA images from Heidelberg Spectralis (1478 samples: 1102 training, 276 validation, 100 testing) and Optovue Solix (1003 samples: 754 training, 189 validation, 60 testing). OCTA scans were labeled based on clinical diagnoses and adjacent B-scan OCT fluid information, categorizing activity into normal, dry AMD, active wet AMD, and wet AMD in remission. Experiments explored cross-instrument disease classification using separate and combined datasets for training the DNN. Testing involved 100 Heidelberg and 60 Optovue samples. Training on Heidelberg data alone yielded 73% accuracy on Heidelberg images and 60% on Optovue images. Training on Optovue...

Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes

Thu, 21 Nov 2024 00:00:00 +0000
Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear pores and disrupting transport. Using CRISPR-based microRaft, followed by gRNA identification (CRaft-ID), we discovered 55 RNA-binding proteins (RBPs) that influence CHMP7 localization, including SmD1, a survival of motor neuron (SMN) complex component. Immunoprecipitation-mass spectrometry (IP-MS) and enhanced crosslinking and immunoprecipitation (CLIP) analyses revealed CHMP7's interactions with SmD1, small nuclear RNAs, and splicing factor mRNAs in motor neurons (MNs). ALS induced pluripotent stem cell (iPSC)-MNs show reduced SmD1 expression, and inhibiting SmD1/SMN complex increased CHMP7 nuclear localization. Crucially, overexpressing SmD1 in ALS iPSC-MNs restored CHMP7's cytoplasmic localization...

Wavelet Deep Learning Network for Objective Retinal Functional Estimation from Multimodal Retinal Imaging

Thu, 7 Nov 2024 00:00:00 +0000
Wavelet Deep Learning Network for Objective Retinal Functional Estimation from Multimodal Retinal Imaging

AIBP Protects Müller Glial Cells Against Oxidative Stress-Induced Mitochondrial Dysfunction and Reduces Retinal Neuroinflammation

Wed, 6 Nov 2024 00:00:00 +0000
Glaucoma, an optic neuropathy with the loss of retinal ganglion cells (RGCs), is a leading cause of irreversible vision loss. Oxidative stress and mitochondrial dysfunction have a significant role in triggering glia-driven neuroinflammation and subsequent glaucomatous RGC degeneration in the context of glaucoma. It has previously been shown that apolipoprotein A-I binding protein (APOA1BP or AIBP) has an anti-inflammatory function. Moreover, Apoa1bp^-/- mice are characterized by retinal neuroinflammation and RGC loss. In this study, we found that AIBP deficiency exacerbated the oxidative stress-induced disruption of mitochondrial dynamics and function in the retina, leading to a further decline in visual function. Mechanistically, AIBP deficiency-induced oxidative stress triggered a reduction in glycogen synthase kinase 3β and dynamin-related protein 1 phosphorylation, optic atrophy type 1 and mitofusin 1 and 2 expression, and oxidative phosphorylation, as well...

Avidity sequencing of whole genomes from retinal degeneration pedigrees identifies causal variants

Tue, 5 Nov 2024 00:00:00 +0000
Whole genome sequencing has been an effective tool in the discovery of variants that cause rare diseases. In this study, we determined the suitability of a novel avidity sequencing approach for rare disease applications. We built a sample to results workflow, combining this sequencing technology with standard library preparation kits, analysis workflows, and interpretation tools. We applied the workflow to ten pedigrees with inherited retinal degeneration (IRD) phenotype. Candidate variants of interest identified through whole genome sequencing were further evaluated using segregation analysis in the additional family members. Potentially causal variants in known IRD genes were detected in five of the ten cases. These high confidence variants were found in ABCA4, CERKL, MAK, PEX6 and RDH12 genes associated with retinal degeneration, that could be sufficient to cause pathology. Pending confirmatory clinical evaluation, we observed a 50% diagnostic yield, consistent with previously...

Relationship of macular ganglion cell complex thickness to choroidal microvasculature drop-out in primary open-angle glaucoma

Sun, 3 Nov 2024 00:00:00 +0000
BACKGROUND/AIMS: To investigate the rate of ganglion cell complex (GCC) thinning in primary open-angle glaucoma (POAG) patients with and without deep-layer microvasculature drop-out (MvD). METHODS: POAG patients who had at least 1.5 years of follow-up and a minimum of three visits were included from the Diagnostic Innovations in Glaucoma Study. MvD was detected at baseline by optical coherence tomography angiography (OCT-A). Area and angular circumference of MvD were evaluated on en face choroidal vessel density images and horizontal B-scans. Rates of global and hemisphere GCC thinning were compared in MvD and non-MvD eyes using linear mixed-effects models. RESULTS: Thirty-six eyes with MvD and 37 eyes without MvD of 63 patients were followed for a mean of 3.3 years. In 30 out of 36 eyes, MvD was localised in the inferotemporal region. While mean baseline visual field mean deviation was similar between the two groups (p=0.128), global GCC thinning was significantly faster in eyes...

Correlation of ganglion cell complex thinning with baseline deep and superficial macular vessel density in glaucoma

Sun, 3 Nov 2024 00:00:00 +0000
BACKGROUND/AIMS: To investigate the relationship between ganglion cell complex (GCC) thinning and baseline deep and superficial macular vessel density (VD) in glaucoma. METHODS: 97 eyes of 69 primary open-angle glaucoma (POAG) and glaucoma suspect patients from the Diagnostics Innovations in Glaucoma Study with a minimum of 4 visits and 2 years of follow-up after baseline optical coherence tomography angiography (OCTA) examination were included. OCTA 3×3 mm² macular scans were acquired at each visit and used to calculate superficial and deep parafoveal VD (pfVD) and OCT-based parafoveal GCC (pfGCC) thickness. Association of baseline superficial and deep pfVD with pfGCC thinning rate was evaluated using linear mixed model. RESULTS: The included subjects had a baseline mean visual field mean deviation (95% CI) of -2.9 (-3.7 to -2.1) dB and a mean follow-up period of 3.6 years. In the univariable model, lower baseline superficial pfVD and higher mean intraocular pressure...

Impact of smoking on glaucoma

Sun, 3 Nov 2024 00:00:00 +0000
PURPOSE OF REVIEW: Assessing whether lifestyle related factors play a role in causing primary open-angle glaucoma (POAG) is of great value to clinicians, public health experts and policy makers. Smoking is a major global public health concern and contributes to ocular diseases such as cataracts, and age-related macular degeneration through ischemic and oxidative mechanisms. Recently, smoking has been investigated as a modifiable risk factor for glaucoma. In the presence of an association with glaucoma, provision of advice and information regarding smoking to patients may help reduce the burden of disease caused by POAG. Therefore, the aim of this review is to summarize the current evidence regarding the effect of smoking in the pathogenesis of glaucoma and its incidence, progression as well as the benefits of smoking cessation. RECENT FINDINGS: While the association between glaucoma development and smoking history is controversial, in the last decade, several recent studies have...

Reproducibility of consecutive automated telemetric noctodiurnal IOP profiles as determined by an intraocular implant.

Fri, 1 Nov 2024 00:00:00 +0000
BACKGROUND: Intraocular pressure (IOP) monitoring in glaucoma management is evolving with novel devices. We investigated the reproducibility of 24 hour profiles on two consecutive days and after 30 days of self-measurements via telemetric IOP monitoring. METHODS: Seven primary patients with open-angle glaucoma previously implanted with a telemetric IOP sensor in one eye underwent automatic measurements throughout 24 hours on two consecutive days (day 1 and day 2). Patients wore an antenna adjacent to the study eye connected to a reader device to record IOP every 5 min. Also, self-measurements in six of seven patients were collected for a period of 30 days. Analysis included calculation of hourly averages to correlate time-pairs of day 1 versus day 2 and the self-measurements vers day 2. RESULTS: The number of IOP measurements per patient ranged between 151 and 268 on day 1, 175 and 268 on day 2 and 19 and 1236 during 30 days of self-measurements. IOP time-pairs of automatic measurements...

Association Between Ganglion Cell Complex Thinning and Vision-Related Quality of Life in Glaucoma

Thu, 31 Oct 2024 00:00:00 +0000
Importance: Faster structural changes may be associated with worse vision-related quality of life in patients with glaucoma. Objectives: To evaluate the association between the rate of ganglion cell complex thinning and the Vision Function Questionnaire in glaucoma. Design, Setting, and Participants: This retrospective analysis of a longitudinal cohort was designed in October 2021. Patients were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Two hundred thirty-six eyes of 118 patients with diagnosed or suspected glaucoma were followed up with imaging for a mean of 4.1 years from September 2014 to March 2020. Main Outcomes and Measures: The Vision Function Questionnaire was evaluated using the 25-item National Eye Institute Visual Function at the last follow-up visit. Ganglion cell complex thickness was derived from macular optical coherence tomography scans and averaged within 3 circular areas (3.4°, 5.6°, and...

Association of Initial Optical Coherence Tomography Angiography Vessel Density Loss With Faster Visual Field Loss in Glaucoma

Wed, 30 Oct 2024 00:00:00 +0000
IMPORTANCE: Rapid vessel density loss during an initial follow-up period may be associated with the rates of visual field loss over time. OBJECTIVES: To evaluate the association between the rate of vessel density loss during initial follow-up and the rate of visual field loss during an extended follow-up period in patients suspected of having glaucoma and patients with primary open-angle glaucoma. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed 124 eyes (86 with primary open-angle glaucoma and 38 suspected of having glaucoma) of 82 patients who were followed up at a tertiary glaucoma center for a mean of 4.0 years (95% CI, 3.9-4.1 years) from January 1, 2015, to February 29, 2020. Data analysis for the current study was undertaken in March 2021. MAIN OUTCOMES AND MEASURES: The rate of vessel density loss was derived from macular whole-image vessel density values from 3 optical coherence tomography angiography scans early during the study. The rate of...

Automated Evaluation of Parapapillary Choroidal Microvasculature in Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Wed, 30 Oct 2024 00:00:00 +0000
OBJECTIVE: To determine whether parapapillary choroidal microvasculature (PPCMv) density as measured by optical coherence tomography angiography differs between pseudoexfoliation syndrome (PXS) and pseudoexfoliation glaucoma (PXG). DESIGN: Cross-sectional study. METHODS: One hundred ninety-two eyes of 120 subjects from 2 academic referral institutions were enrolled. Automated PPCMv density was calculated using custom Matlab software in inner and outer annuli around the optic nerve region in addition to peripapillary superficial vasculature. Linear modeling was used to compare vessel densities among groups. RESULTS: Data from 64 eyes with PXS, 84 eyes with PXG, and 44 eyes healthy control subjects were analyzed. The differences of visual field mean deviation and peripapillary retinal nerve fiber layer thickness among study groups were statistically significant with lower values in PXG eyes compared with the PXS and control groups. Peripapillary superficial retinal vessel densities...

Hidden flaws behind expert-level accuracy of multimodal GPT-4 vision in medicine

Fri, 11 Oct 2024 00:00:00 +0000
Recent studies indicate that Generative Pre-trained Transformer 4 with Vision (GPT-4V) outperforms human physicians in medical challenge tasks. However, these evaluations primarily focused on the accuracy of multi-choice questions alone. Our study extends the current scope by conducting a comprehensive analysis of GPT-4V’s rationales of image comprehension, recall of medical knowledge, and step-by-step multimodal reasoning when solving New England Journal of Medicine (NEJM) Image Challenges—an imaging quiz designed to test the knowledge and diagnostic capabilities of medical professionals. Evaluation results confirmed that GPT-4V performs comparatively to human physicians regarding multi-choice accuracy (81.6% vs. 77.8%). GPT-4V also performs well in cases where physicians incorrectly answer, with over 78% accuracy. However, we discovered that GPT-4V frequently presents flawed rationales in cases where it makes the correct final choices (35.5%), most prominent in image comprehension...

Complication rates of resident-performed cataract surgery: Impact of early introduction of cataract surgery training

Sat, 14 Sep 2024 00:00:00 +0000
PURPOSE: To determine the effect of the early introduction of cataract surgery training on the complication rates of resident-performed cataract surgery. SETTING: University of California San Diego, San Diego, California, USA. DESIGN: Retrospective case series. METHODS: Two classes of ophthalmology residents were examined, one class with a late introduction of cataract surgery and one with an early introduction of cataract surgery. All cataract cases in which residents acted as primary surgeon were included. Patient charts were reviewed to collect data on patient characteristics, surgical details, and intraoperative and postoperative complications. RESULTS: The late-introduction cohort comprised 3 residents who performed 540 cataract cases, all during their final year of residency. The early-introduction cohort comprised 4 residents who performed 780 cataract cases beginning in the first year of residency. The late-introduction cohort had higher rates of major intraoperative complications...