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Open Access Publications from the University of California

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

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

(2024)

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.

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

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

(2024)

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 and corrected STMN2 splicing. Our findings suggest that early ALS pathogenesis is driven by SMN complex dysregulation.

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

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

(2024)

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 and 67 controls were included in the development dataset. Setting the GHS cutoff at 75 points out of 100, test dataset 1, which comprised 41 subjects with glaucoma and 41 healthy controls, achieved an area under the receiver operating characteristic curve (AUROC) of 0.98, with a sensitivity of 71% and specificity of 98%; test dataset 2, which included 53 patients with glaucoma and 53 healthy controls, resulted in an AUROC of 0.95, with a sensitivity of 75% and specificity of 96%. A decision curve analysis across all datasets demonstrated a higher net benefit for the GHS model compared to individual OCT parameters. Conclusions: The GHS offers a feasible, standardized approach for early detection of glaucoma, providing strong specificity and acceptable sensitivity, with clear decision-making benefits in screening settings.

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

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

(2024)

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 test strategy. Standard VF reliability indices were assessed. For each subject, 24-2 and 10-2 test results from 1 randomly selected eye were analyzed.

Main outcome measures

Perimetric threshold sensitivity and reference limits for each test analysis parameter.

Results

The ages of the study cohort were widely distributed, with a mean age (standard deviation [SD]) of 52.3 (18.5) years. Sex assignment was 44.0% male and 56.0% female. The majority of subjects self-identified as White (67.4%), followed by Black or African American (13.5%) and Asian (8.7%), with 14.6% self-identified as Hispanic or Latino ethnicity. Mean sensitivity (SD) was 29.1 (1.3) decibels (dB) for the 24-2 and 32.4 (1.0) dB for the 10-2 test. For the 24-2 and 10-2, mean sensitivity (SD) age-related changes averaged -0.06 (0.01) dB and -0.05 (0.01) dB per year, respectively. The normal range of pointwise threshold sensitivity increased with eccentricity and showed asymmetry around the mean, particularly notable in the 24-2 test. Mean (SD) binocular test duration was 3.18 (0.38) minutes (1 minute 35 seconds per eye) for the 24-2 test and 3.58 (0.43) minutes (1 minute 47 seconds per eye) for the 10-2 test.

Conclusions

An RDB for the TEMPO/IMOvifa perimeter was established, highlighting the significance of considering both age and stimulus eccentricity in interpreting threshold VF test results.

Financial disclosures

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

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

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

(2024)

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 on day 1 and day 2 were significantly correlated at the group level (R=0.83, p<0.001) and in four individual patients (1, 2, 6 and 7). IOP time-pairs of self-measurements and day 2 were significantly correlated at the group level (R=0.4, p<0.001) and in four individual patients (2, 5, 6 and 7). CONCLUSIONS: Twenty-four hour automatic measurements of IOP are correlated on consecutive days and, though to a lesser degree, with self-measurements. Therefore a virtual 24-hour IOP curve might be constructed from self-measurements. Both options provide an alternative to frequent in-office IOP measurements.

Cover page of Long-term variability of retinal nerve fibre layer thickness measurement in patients with glaucoma of African and European descents

Long-term variability of retinal nerve fibre layer thickness measurement in patients with glaucoma of African and European descents

(2024)

Background

To examine long-term retinal nerve fibre layer thickness (RNFLT) variability and associated clinical factors in African (AD) and European descent (ED) individuals with glaucoma.

Methods

This retrospective cohort study included glaucoma eyes of AD and ED from Diagnostic Innovations in Glaucoma Study/The African Descent and Glaucoma Evaluation Study with ≥4 visits/2 years of follow-up. We calculated optic nerve head RNFLT variability per-examination/visit as the absolute error of its residuals across follow-up. Full, baseline and parsimonious linear-mixed models were fit to evaluate the effects of clinical factors (demographics and ocular characteristics, prior/intervening glaucoma surgeries and cataract extraction (CE), RNFLT thinning rate, scan quality, visit/testing frequency, etc) on RNFLT variability in both races.

Results

There were 376 and 625 eyes (226 and 349 participants) of AD and ED, and the mean (95% CI) RNFLT variability was 1.62 (1.52, 1.71) µm and 1.42 (1.34, 1.50) µm, respectively (p=0.002). AD and ED had some shared predictors of RNFLT variability, including intraocular pressure fluctuation and scan quality, although the effects varied (p<0.05). In both races, intervening CE was most strongly correlated with higher RNFLT variability (β: 0.24-0.92, p<0.05). After excluding eyes with intervening CE, RNFLT variability was reduced and the small racial difference was no longer significant (AD: 1.40 (1.31, 1.48) µm vs ED: 1.34 (1.27, 1.40) µm; p=0.280).

Conclusions

Although some predictors were identified, long-term RNFLT variability appeared small for both AD and ED eyes. Moreover, the racial difference did not remain once intervening CE, the strongest predictor of variability, was eliminated. Our findings inform on strategies to optimise structural assessment and suggest that, when accounting for relevant factors, RNFLT is reliable across races.

Cover page of Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression

Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression

(2024)

Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted. Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity. Nanopore sequencing confirmed the lower transcription of the TMEM216 c.-69G>T allele in blood-derived RNA from a heterozygous carrier, and reduced expression was further recapitulated by qPCR, using both leukocytes-derived RNA of c.-69G>T homozygotes and total RNA from genome-edited hTERT-RPE1 cells carrying homozygous TMEM216 c.-69G>A. In conclusion, these variants explain a significant proportion of unsolved cases, specifically in individuals of African ancestry, suggesting that reduced TMEM216 expression might lead to abnormal ciliogenesis and photoreceptor degeneration.