Associations between steady-state pattern electroretinography and estimated retinal ganglion cell count in glaucoma suspects.

PURPOSE: To estimate retinal ganglion cell (RGC) count in glaucoma suspects (GS) and ascertain its relationships with steady-state pattern electroretinography (ssPERG) parameters. METHODS: In this prospective cross-sectional study, 22 subjects (44 eyes) were recruited at the Manhattan Eye, Ear, and Throat Hospital. Subjects underwent complete eye examinations, optical coherence tomography, standard automated perimetry, and ssPERG testing. Eyes were divided into two groups based upon clinical data: healthy subjects and GS. RGC count was estimated using the combined structure-function index. RESULTS: Estimated RGC count, average retinal nerve fiber layer thickness (ARNFLT), and average ganglion cell layer and inner plexiform layer thickness (GCIPLT) were reduced in GS eyes (p ≤ 0.001 for all parameters). Pearson correlations revealed that ssPERG magnitude and magnitudeD correlated with ARNFLT (r ≥ 0.53, p < 0.001), GCIPLT (r > 0.38, p < 0.011), and estimated RGC count (r > 0.46, p < 0.002). Six mediation analyses revealed that estimated RGC count mediated the relationships among ssPERG parameters, ARNFLT, and GCIPLT. CONCLUSION: Steady-state PERG parameters demonstrated linear correlations with estimated RGC count. The associations among ssPERG parameters and structural measures were mediated by estimated RGC count.

Structure-function models for estimating retinal ganglion cell count using steady-state pattern electroretinography and optical coherence tomography in glaucoma suspects and preperimetric glaucoma: an electrophysiological pilot study.

PURPOSE: To derive and validate structure-function models for estimating retinal ganglion cell (RGC) count using optical coherence tomography (OCT) and steady-state pattern electroretinography (ssPERG) parameters in glaucoma suspects (GS) and preperimetric glaucoma (PPG). METHODS: In this prospective cross-sectional study, 25 subjects (50 eyes) were recruited at the Manhattan Eye, Ear, and Throat Hospital. Subjects underwent comprehensive eye examinations, OCT, standard automated perimetry (SAP), and ssPERG testing. Eyes were divided into three groups based on the Global Glaucoma Staging System: healthy (N = 30), GS (N = 10), and PPG (N = 10) eyes. The combined structure-function index (CSFI), which estimates retinal ganglion cell count (eRGCCSFI) from SAP and OCT parameters, was calculated in each study subject. Two prediction formulas were derived using a generalized linear mixed model (GLMM) to predict eRGCCSFI from ssPERG parameters, age, and average retinal nerve fiber layer thickness (ARNFLT) in 30 eyes selected at random (training group). GLMM predicted values were cross-validated with the remaining 20 eyes (validation group). RESULTS: The ARNFLT, ssPERG parameters magnitude (Mag) and magnitudeD (MagD), and eRGCCSFI were significantly different among study groups (ANOVA p ≤ 0.001). Pearson correlations demonstrated significant associations among ARNFLT, ssPERG parameters, and eRGCCSFI (r2 ≥ 0.31, p < 0.001). Two GLMMs predicted eRGCCSFI from Mag (eRGCMag) and MagD (eRGCMagD), respectively, with significant equations (F(3,18), F(3,19) ≥ 58.37, R2 = 0.90, p < 0.001). eRGCMag and eRGCMagD in the validation group (R2 = 0.89) correlated with eRGCCSFI similarly to the training group. Multivariate pairwise comparisons revealed that eRGCMag and eRGCMagD distinguished between healthy, GS, and PPG eyes (p ≤ 0.035), whereas independent Mag, MagD, and ARNFLT measures did not distinguish between GS and PPG eyes. CONCLUSION: This pilot study offers the first combined structure-function models for estimating RGC count using ssPERG parameters. RGC counts estimated with these models were generalizable, strongly associated with CSFI estimates, and performed better than individual ssPERG and OCT measures in distinguishing healthy, GS, and PPG eyes.

Agreement and Predictors of Discordance of 6 Visual Field Progression Algorithms.

PURPOSE: To determine the agreement of 6 established visual field (VF) progression algorithms in a large dataset of VFs from multiple institutions and to determine predictors of discordance among these algorithms. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Visual fields from 5 major eye care institutions in the United States were analyzed, including a subset of eyes with at least 5 Swedish interactive threshold algorithm standard 24-2 VFs that met our reliability criteria. Of a total of 831 240 VFs, a subset of 90 713 VFs from 13 156 eyes of 8499 patients met the inclusion criteria. METHODS: Six commonly used VF progression algorithms (mean deviation [MD] slope, VF index slope, Advanced Glaucoma Intervention Study, Collaborative Initial Glaucoma Treatment Study, pointwise linear regression, and permutation of pointwise linear regression) were applied to this cohort, and each eye was determined to be stable or progressing using each measure. Agreement between individual algorithms was tested using Cohen's κ coefficient. Bivariate and multivariate analyses were used to determine predictors of discordance (3 algorithms progressing and 3 algorithms stable). MAIN OUTCOME MEASURES: Agreement and discordance between algorithms. RESULTS: Individual algorithms showed poor to moderate agreement with each other when compared directly (κ range, 0.12-0.52). Based on at least 4 algorithms, 11.7% of eyes progressed. Major predictors of discordance or lack of agreement among algorithms were more depressed initial MD (P < 0.01) and older age at first available VF (P < 0.01). A greater number of VFs (P < 0.01), more years of follow-up (P < 0.01), and eye care institution (P = 0.03) also were associated with discordance. CONCLUSIONS: This extremely large comparative series demonstrated that existing algorithms have limited agreement and that agreement varies with clinical parameters, including institution. These issues underscore the challenges to the clinical use and application of progression algorithms and of applying big-data results to individual practices.

Comparison of Gemini Advanced and ChatGPT 4.0's Performances on the Ophthalmology Resident Ophthalmic Knowledge Assessment Program (OKAP) Examination Review Question Banks.

Background With advancements in natural language processing, tools such as Chat Generative Pre-Trained Transformers (ChatGPT) version 4.0 and Google Bard's Gemini Advanced are being increasingly evaluated for their potential in various medical applications. The objective of this study was to systematically assess the performance of these language learning models (LLMs) on both image and non-image-based questions within the specialized field of Ophthalmology. We used a review question bank for the Ophthalmic Knowledge Assessment Program (OKAP) used by ophthalmology residents nationally to prepare for the Ophthalmology Board Exam to assess the accuracy and performance of ChatGPT and Gemini Advanced. Methodology A total of 260 randomly generated multiple-choice questions from the OphthoQuestions question bank were run through ChatGPT and Gemini Advanced. A simulated 260-question OKAP examination was created at random from the bank. Question-specific data were analyzed, including overall percent correct, subspecialty accuracy, whether the question was "high yield," difficulty (1-4), and question type (e.g., image, text). To compare the performance of ChatGPT-4 and Gemini on the difficulty of questions, we utilized the standard deviation of user answer choices to determine question difficulty. In this study, a statistical analysis of Google Sheets was conducted using two-tailed t-tests with unequal variance to compare the performance of ChatGPT-4.0 and Google's Gemini Advanced across various question types, subspecialties, and difficulty levels. Results In total, 259 of the 260 questions were included in the study as one question used a video that any form of ChatGPT could not interpret as of May 1, 2024. For text-only questions, ChatGPT-4.0.0 correctly answered 57.14% (148/259, p < 0.018), and Gemini Advanced correctly answered 46.72% (121/259, p < 0.018). Both versions answered most questions without a prompt and would have received a below-average score on the OKAP. Moreover, there were 27 questions utilizing a secondary prompt in ChatGPT-4.0 compared to 67 questions in Gemini Advanced. ChatGPT-4.0 performed 68.99% on easier questions (<2 on a scale from 1-4) and 44.96% on harder questions (>2 on a scale from 1-4). On the other hand, Gemini Advanced performed 49.61% on easier questions (<2 on a scale from 1-4) and 44.19% on harder questions (>2 on a scale from 1-4). There was a statistically significant difference in accuracy between ChatGPT-4.0 and Gemini Advanced for easy (p < 0.0015) but not for hard (p < 0.55) questions. For image-only questions, ChatGPT-4.0 correctly answered 39.58% (19/48, p < 0.013), and Gemini Advanced correctly answered 33.33% (16/48, p < 0.022), resulting in a statistically insignificant difference in accuracy between ChatGPT-4.0 and Gemini Advanced (p < 0.530). A comparison against text-only and image-based questions demonstrated a statistically significant difference in accuracy for both ChatGPT-4.0 (p < 0.013) and Gemini Advanced (p < 0.022). Conclusions This study provides evidence that ChatGPT-4.0 performs better on the OKAP-style exams and is improved compared to Gemini Advanced within the context of ophthalmic multiple-choice questions. This may show an opportunity for increased worth for ChatGPT in ophthalmic medical education. While showing promise within medical education, caution should be used as a more detailed evaluation of reliability is needed.

Decreased Ocular Perfusion Pressure Associated With Reverse Ophthalmic Artery Flow on Transcranial Doppler Ultrasonography.

Innovative applications of clinical ocular diagnostic tools are emerging to help identify systemic disorders that extend beyond ocular diseases. Ophthalmodynamometry (ODM) is a screening tool that non-invasively determines mean central retinal artery pressure (MCRAP) and ocular perfusion pressure (OPP). Decreased OPP and MCRAP on Falck Medical Multifunctional Device (FMD, Falck Medical, Inc., Mystic, CT), along with reverse ophthalmic artery flow (ROAF) on transcranial Doppler ultrasonography (TCD), indicate increased collateral brain perfusion and possible stenosis of the ophthalmic artery or internal carotid artery (ICA). In this case report, we describe the case of a 78-year-old female with ROAF, reduced MCRAP, and OPP in the right eye, confirmed by carotid duplex of 50-79% right ICA stenosis. Early application of ODM and TCD allowed for prompt diagnosis and management with a vascular specialist.

Repeatability and Comparability of Retinal Blood Vessel Caliber Measurements by OCTA.

BACKGROUND: To investigate the repeatability in vessel caliber measurements by optical coherence tomography angiography (OCTA). METHODS: In this prospective study, 28 patients (47 eyes) underwent sequential OCTA imaging of the optic nerve head and macula. Two independent masked graders measured vessel caliber for sequential images of the optic nerve head and macula. The average vessel width was determined and variability between graders and images. RESULTS: A total of 8400 measurements of 420 vessels from 84 OCTA images were included in the analysis. Overall, inter-grader agreement was excellent (ICC 0.90). The coefficient of variation (CoV) for all repeated OCTA images was 0.10. Greater glaucoma severity, older age, macular location, and diagnosis of diabetes were associated with thinner vessels (p < 0.05). CoV was higher in the peripapillary region (0.07) as compared to the macula (0.15). ICC was high for all subgroups except for the macula (ICC = 0.72). CONCLUSIONS: Overall, the repeatability of vessel caliber measurements by OCTA was high and variability low. There was greater variability in the measurement of macular vessels, possibly due to technical limitations in acquiring accurate vessel widths for smaller macular vessels.

Pituitary Macroadenoma with Optic Cupping Masquerading as Normal Tension Glaucoma.

When non-glaucomatous disease with disc cupping mimics normal-tension glaucoma (NTG), diagnosis is challenging. The typical optic disc features of glaucomatous disease are often subjective, and often overlap with disc changes in compressive intracranial lesions. Ancillary diagnostic testing such as retinal nerve fiber layer (RNFL) analysis and visual field testing can elevate the index of suspicion of an underlying non-glaucomatous process. We present a case of a nonfunctional macroadenoma coexisting with NTG, although it is unclear if the concurrent brain lesion aggravated or caused it. This case highlights the diagnostic challenge of recognizing optic cupping and non-matching abnormalities in the visual field from a coexisting intracranial lesion, even in the absence of other neurological signs.

Posterior Pole Asymmetry Analysis as a Diagnostic Tool in Glaucoma Suspects: An Electrophysiological Approach.

Purpose: Spectral domain optical coherence tomography (SD-OCT) with posterior pole asymmetry analysis (PPAA) provides a mapping of posterior pole retinal thickness with asymmetry analysis between hemispheres of each eye. We investigated whether these structural abnormalities were correlated with functional retinal ganglion cell (RGC) loss, quantified by steady state pattern electroretinogram (ssPERG), in glaucoma suspects (GS). Methods: Twenty GS (34 eyes) were enrolled in a prospective study at the Manhattan Eye, Ear, and Throat Hospital. All subjects underwent ophthalmological examination, including Humphrey visual field, Spectralis Glaucoma Module Premium Edition (GMPE) SD-OCT PPAA, and ssPERG testing. The ability of ssPERG parameters (Magnitude [Mag, µv], MagnitudeD [MagD, µv], and MagD/Mag ratio) to predict PPAA thickness (total, superior, and inferior thickness, [µm]) was tested via adjusted multivariate linear regression analysis. Results: Mag explained 8% of variance in total PPAA change (F(1,29)=6.33, B=6.86, 95% CI: 1.29-12.44, p=0.018), 8% in superior PPAA change (F(1,29)=5.57, B=6.92, 95% CI: 0.92-12.92, p=0.025), and 7.1% in inferior PPAA change (F(1,29)=5.83, B=6.80, 95% CI: 1.04-12.56, p=0.022). Similarly, MagD explained 9.7% of variance in total PPAA change (F(1,29)=8.09, B=6.47, 95% CI: 1.82-11.13, p=0.008), 10% in superior PPAA change (F(1,29)=7.33, B=6.63, 95% CI: 1.62-11.63, p=0.011), and 8.5% in inferior PPAA change (F(1,29)=7.25, B=6.36, 95% CI: 1.53-11.18, p=0.012). MagD/Mag ratio and PPAA were not significantly associated. Conclusion: To the best of our knowledge, this is the first study demonstrating a positive relationship between RGC dysfunction and retinal thickness changes between the superior and inferior hemispheres. The detection of asymmetrical structural loss, combined with functional RGC assessment using ssPERG, may be an informative tool for early glaucoma diagnosis.

Retinal Ganglion Cell Functional Recovery after Intraocular Pressure Lowering Treatment Using Prostaglandin Analogs in Glaucoma Suspects: A Prospective Pilot Study.

Aim and background: To evaluate the ability of pattern electroretinogram (PERG) to detect improvement of retinal ganglion cell (RGC) function in glaucoma suspects (GS) after medically reducing intraocular pressure (IOP) using prostaglandin analog drops. Materials and methods: Six subjects (eight eyes) received topical IOP lowering treatment based on their clinical examination and were observed at Manhattan Eye, Ear & Throat Hospital over an average of 3.1 ± 2.2 months. During this time, participants underwent a full ophthalmologic exam and were evaluated with a Humphrey visual field analyzer (HFA) 24-2 [24-2 mean deviation (MD), 24-2 pattern standard deviation (PSD), and 24-2 visual field indices (VFI)], Diopsys NOVA PERG optimized for glaucoma [magnitude (Mag), magnitudeD (MagD), and magnitudeD/magnitude ratio (MagD/Mag ratio)] and optical coherence tomography (OCT)-derived average retinal nerve fiber layer thickness (avRNFLT) and average ganglion cell layer + inner plexiform layer (avGCL + IPL) thicknesses at baseline visit (pretreatment) and 3 months later (posttreatment). Goldman applanation tonometry was used to measure IOP at each visit. Paired sample t-tests were conducted to determine the statistical significance of the change in IOP, HFA indices, PERG parameters, and OCT thickness measurements between the two visits. Results: Lowering IOP by 22.29% resulted in a significant increase (32.98 and 15.49%) in MagD [t (7) = -3.174, 95% confidence interval (CI) = -0.53, -0.08, p = 0.016] and MagD/Mag ratio [t (7) = -3.233, 95% CI = -0.20, -0.03, p = 0.014], respectively. There was a positive percentage change for all variables of interest, however, 24-2 MD, Mag, avRNFLT, and GCL+ IPLT did not reach statistical significance. Conclusion: After reducing IOP by 22.29% for a duration of 3.1 months, the PERG parameters, MagD and MagD/Mag ratio, significantly improved by 32.98 and 15.49%, respectively. Clinical significance: Pattern electroretinogram (PERG) may be a crucial tool for clinicians to locate a window of opportunity in which degenerating yet viable RGCs could be rescued from irreversible damage. We suggest consideration of PERG as a tool in early retinal ganglion cell (RGC) dysfunction detection as well as for monitoring IOP lowering treatment. How to cite this article: Tirsi A, Gliagias V, Sheha H, et al. Retinal Ganglion Cell Functional Recovery after Intraocular Pressure Lowering Treatment Using Prostaglandin Analogs in Glaucoma Suspects: A Prospective Pilot Study. J Curr Glaucoma Pract 2023;17(4):178-190.

Ehlers-Danlos syndromes and their manifestations in the visual system.

Ehlers-Danlos syndrome (EDS) is a rare, genetically variable, heterogenous group of (currently recognized) thirteen connective tissue disorders characterized by skin hyperextensibility, tissue fragility, and generalized joint hypermobility. In addition to these commonly recognized phenotypes, recent studies have notably highlighted variable ophthalmic features in EDS. In this review, we comprehensively gather and discuss the ocular manifestations of EDS and its thirteen subtypes in the clinical setting.

Development and Comparison of Machine Learning Algorithms to Determine Visual Field Progression.

Purpose: To develop and test machine learning classifiers (MLCs) for determining visual field progression. Methods: In total, 90,713 visual fields from 13,156 eyes were included. Six different progression algorithms (linear regression of mean deviation, linear regression of the visual field index, Advanced Glaucoma Intervention Study algorithm, Collaborative Initial Glaucoma Treatment Study algorithm, pointwise linear regression [PLR], and permutation of PLR) were applied to classify each eye as progressing or stable. Six MLCs were applied (logistic regression, random forest, extreme gradient boosting, support vector classifier, convolutional neural network, fully connected neural network) using a training and testing set. For MLC input, visual fields for a given eye were divided into the first and second half and each location averaged over time within each half. Each algorithm was tested for accuracy, sensitivity, positive predictive value, and class bias with a subset of visual fields labeled by a panel of three experts from 161 eyes. Results: MLCs had similar performance metrics as some of the conventional algorithms and ranged from 87% to 91% accurate with sensitivity ranging from 0.83 to 0.88 and specificity from 0.92 to 0.96. All conventional algorithms showed significant class bias, meaning each individual algorithm was more likely to grade uncertain cases as either progressing or stable (P ≤ 0.01). Conversely, all MLCs were balanced, meaning they were equally likely to grade uncertain cases as either progressing or stable (P ≥ 0.08). Conclusions: MLCs showed a moderate to high level of accuracy, sensitivity, and specificity and were more balanced than conventional algorithms. Translational Relevance: MLCs may help to determine visual field progression.

Measurement of Retinal Microvascular Blood Velocity Using Erythrocyte Mediated Velocimetry.

Changes in retinal blood flow may be involved in the pathogenesis of glaucoma and other ocular diseases. Erythrocyte mediated velocimetry (EMV) is a novel technique where indocyanine green (ICG) dye is sequestered in erythrocyte ghosts and autologously re-injected to allow direct visualization of erythrocytes for in vivo measurement of speed. The purpose of this study is to determine the mean erythrocyte speed in the retinal microvasculature, as well as the intravisit and intervisit variability of EMV. Data from 23 EMV sessions from control, glaucoma suspect, and glaucoma patients were included in this study. In arteries with an average diameter of 43.11 µm ± 6.62 µm, the mean speed was 7.17 mm/s ± 2.35 mm/s. In veins with an average diameter of 45.87 µm ± 12.04 µm, the mean speed was 6.05 mm/s ± 1.96 mm/s. Intravisit variability, as measured by the mean coefficient of variation, was 3.57% (range 0.44-9.68%). Intervisit variability was 4.85% (range 0.15-8.43%). EMV may represent reliable method for determination of retinal blood speed, potentially allowing insights into the effects of pharmacologic agents or pathogenesis of ocular diseases.

Delineation of Novel Compound Heterozygous Variants in LTBP2 Associated with Juvenile Open Angle Glaucoma.

Juvenile open angle glaucoma (JOAG), which is an uncommon form of primary open angle glaucoma, is a clinically and genetically heterogeneous disorder. We report on a family with a recessively inherited form of JOAG. The proband has a superior and an inferior never fiber layer thinning in both the eyes and the nasal visual field (VF) defects in the left eye, which are clinical findings consistent with glaucomatous optic neuropathy. Whole exome sequencing revealed two novel compound heterozygous variants [c.2966C>G, p.(Pro989Arg); c.5235T>G, p.(Asn1745Lys)] in latent transforming growth factor-beta-binding protein 2 (LTBP2) segregating with the phenotype. Both these variants are predicted to replace evolutionary conserved amino acids, have a pathogenic effect on the encode protein, and have very low frequencies in the control databases. Mutations in LTBP2 are known to cause the Weill-Marchesani syndrome and a Weill-Marchesani-like syndrome, which include glaucoma in their clinical presentation. However, to our knowledge, this is the first published case of a JOAG subject associated with recessively inherited variants of LTPB2 and, thus, expands the repertoire of the known genetic causes of JOAG and the phenotypic spectrum of LTBP2 alleles.

Pulmonary Perfusion Changes Following Single-Lung Transplantation.

Following single-lung transplantation (SLT), there is significant redistribution of flow preferentially to the transplanted lung. Altered lung perfusion leads to unusual results when performing pulmonary scintigraphy, which could result in interpretation errors. We present pulmonary scintigraphy images from a 67-year-old female patient with history of chronic obstructive pulmonary disease that were obtained before SLT, 10 days after SLT, and 3 months after SLT.