Skip to main content
eScholarship
Open Access Publications from the University of California

School of Medicine

Department of Ophthalmology - Open Access Policy Deposits bannerUC San Diego

This series is automatically populated with publications deposited by UC San Diego School of Medicine Department of Ophthalmology researchers in accordance with the University of California’s open access policies. For more information see Open Access Policy Deposits and the UC Publication Management System.

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

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

(2025)

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 results highlight the crucial role of HTRA1 in the retina and RPE. Furthermore, this study allows for the Htra1-/- mouse model to be utilized for deciphering mechanisms that lead to sub-RPE deposit phenotypes including AMD.

Cover page of Robotic Visible-Light Optical Coherence Tomography Visualizes Segmental Schlemms Canal Anatomy and Segmental Pilocarpine Response.

Robotic Visible-Light Optical Coherence Tomography Visualizes Segmental Schlemms Canal Anatomy and Segmental Pilocarpine Response.

(2025)

PURPOSE: To use robotic visible-light optical coherence tomography (vis-OCT) to study circumferential segmental Schlemms 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 larger (pilocarpine, 26.8 ± 5.0% vs. control, 8.9 ± 4.6% volume increase; P = 0.030). However, the pilocarpine alteration was also segmental, with a greater increase observed superior (pilocarpine, 31.6 ± 8.9% vs. control, 1.8 ± 5.7% volume increase; P = 0.023) and nasal (pilocarpine, 41.1 ± 15.3% vs. control, 13.9 ± 4.5% volume increase; P = 0.045). CONCLUSIONS: Circumferential noninvasive imaging of the AHO pathways was done in vivo. Segmental SC anatomy was seen, consistent with the known segmental nature of trabecular AHO. Segmental SC anatomical response to a muscarinic agonist was also observed. Segmental glaucoma drug response around the circumference of AHO pathways is an observation that may influence patient response to glaucoma treatments.

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

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

(2025)

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 worlds 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 containing over 10 domains, including vitals, retinal imaging, electrocardiogram, cognitive function, continuous glucose monitoring, physical activity, home air quality, blood and urine collection for laboratory testing and psychosocial variables including social determinants of health. There are three study sites: Birmingham, Alabama; San Diego, California; and Seattle, Washington.

Ethics and dissemination

AI-READI aims to establish standards, best practices and guidelines for collection, preparation and sharing of the data for the purposes of AI/ML, including guidance from bioethicists. Following Findable, Accessible, Interoperable, Reusable principles, AI-READI can be viewed as a model for future efforts to develop other medical/health data sets targeted for AI/ML. AI-READI opens the door for novel insights in understanding T2DM salutogenesis. The AI-READI Consortium are disseminating the principles and processes of designing and implementing the AI-READI data set through publications. Those who download and use AI-READI data are encouraged to publish their results in the scientific literature.

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

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

(2025)

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 included in this study. Across all subgroups, RGB provided significantly more accurate clinical imaging with CFP as ground truth and compared to other modalities. This was true comparing RGB to both RG (P = 0.0225) and MCI (P < 0.001) overall. Although RGB provided more accurate clinical information overall, it was inferior to RG for melanocytic choroidal lesions (P = 0.011).

Conclusions

RGB can be considered as a useful tool to detect characteristics of central, midperipheral, and peripheral retinal lesions. Regarding melanocytic choroidal lesions, RGB was inferior to RG, and MCI was inferior to both RG and RGB modalities due to color changes.

Translational relevance

Traditional retinal ultra-widefield imaging uses two wavelengths. Here, we evaluated three wavelengths for ultra-widefield imaging. We examined new optics (basic science) effect on patient imaging (clinical care).

Cover page of Horizontal Gaze Tolerance and Its Effects on Visual Sensitivity in Glaucoma.

Horizontal Gaze Tolerance and Its Effects on Visual Sensitivity in Glaucoma.

(2025)

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 deviation) age was 68.0 (11.0) years, with a mean deviation of -9.9 (6.6) dB for POAG and -1.0 (1.9) dB for healthy eyes using Humphrey field analysis 24-2. MS did not significantly differ among central gaze (27.0 [1.8] dB), abduction (27.1 [1.9] dB), and adduction (26.9 [2.2] dB) in healthy eyes (P = 0.650). However, MS was significantly lower for adduction (17.2 [5.9] dB) compared to central gaze (18.1 [5.9] dB) and abduction (17.9 [5.9] dB) in glaucoma eyes (P = 0.001 and P = 0.022, respectively). CONCLUSIONS: Horizontal gaze, especially in adduction, significantly reduces visual sensitivity in glaucoma, suggesting a specific vulnerability associated with eye movement. This finding highlights the importance of eye positioning in glaucoma, warranting further investigation of its clinical significance.

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

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

(2025)

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 binary glaucoma classification. The diagnostic accuracy of RETFound was iteratively tested across different combinations of dataset sample sizes (50-2000 optic disc photographs), training cycles (5-50), and study subpopulations stratified by severity of glaucoma, age, and race).

Main outcome measures

Diagnostic accuracy area under the receiver operating characteristic curve (AUC) for classifying CFP as "Glaucomatous" or "Non-glaucomatous."

Results

Performance increased with larger training datasets and more training cycles, improving from 50 training images and 5 epochs (AUC: 0.52) to 2000 training images and 50 epochs (AUC: 0.86), with reduced gain in performance from approximately 500 and 1000 training images (AUC of 0.82 and 0.83, respectively). Performance was consistent across race and age for all training size and cycle number combinations: Black (AUC = 0.87) vs. other (AUC = 0.86), and >60 years (AUC = 0.84) vs. <60 years (AUC = 0.87). Performance was significantly higher in patients with moderate to severe vs. mild glaucoma (AUC = 0.95 vs. 0.84, respectively).

Conclusions

Good RETFound performance was observed with a relatively small sample size of optic disc photographs used for fine-tuning and across differences in race and age. RETFound's ability to adapt across a range of CFP training conditions and populations suggests it is a promising tool to automate glaucoma detection in a variety of use cases.

Financial disclosures

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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

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

(2025)

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 discussions were sent to participating ophthalmologists to identify the author of the discussions. Response confidence was assessed using a 5-point Likert scale score, and subjective feedback was manually reviewed. MAIN OUTCOME MEASURES: Accuracy of ophthalmologist identification of discussion author, as well as subjective perceptions of human-generated versus ChatGPT-generated discussions. RESULTS: Overall, ChatGPT correctly identified the primary diagnosis in 15 of 17 (88.2%) cases. Two cases were excluded from the paired comparison due to hallucinations or fabrications of nonuser-provided data. Ophthalmologists correctly identified the author in 77.9% ± 26.6% of the 13 included cases, with a mean Likert scale confidence rating of 3.6 ± 1.0. No significant differences in performance or confidence were found between board-certified and board-eligible ophthalmologists. Subjectively, ophthalmologists found that discussions written by ChatGPT tended to have more generic responses, irrelevant information, hallucinated more frequently, and had distinct syntactic patterns (all P < 0.01). CONCLUSIONS: Large language models have the potential to synthesize clinical data and generate ophthalmic discussions. While these findings have exciting implications for artificial intelligence-assisted health care delivery, more rigorous real-world evaluation of these models is necessary before clinical deployment. FINANCIAL DISCLOSURES: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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

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

(2025)

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 with AMD, regardless of retinal disease severity. This highlights the importance of treating coexisting ocular surface conditions to enhance patient outcomes, even in the presence of significant maculopathy.

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

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

(2025)

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: Overall, 64 patients (119 eyes) with SCD and 57 age- and race-matched controls (106 eyes) were included. The majority of the patients with SCD were females (65.6%) and of Black or African descent (78.1%), with an average age of 35.1 ± 20.1 years. The mean number of crises per patient was 3.4 ± 5.2, and the patients took 0.7 ± 0.9 medications. The mean CTI for eyes with SCD was higher than controls (1.06 ± vs. 1.03 ± 0.02, P < 0.001). On subgroup analysis, hemoglobin S, hemoglobin C, and HbS/beta-thalassemia variants had significantly higher CTIs compared with controls (1.07 vs. 1.03, P < 0.001), but not with sickle cell trait variant (1.04 vs. 1.03 control, P = .2). Univariable analysis showed a higher CTI in patients diagnosed with proliferative SCR, most significantly among those with sea-fan neovascularization (1.06 ± 0.02 vs. 1.04 ± 0.01, P < 0.001) and those with >3 sickle cell crises (1.07 ± 0.02 vs. 1.05 ± 0.02, P < 0.001). CONCLUSIONS: A DL-based metric of cumulative vascular tortuosity associates with and may be a potential biomarker for SCD and SCR disease severity. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.