Margin Reflex Distance: Differences Based on Camera and Flash Positions.

PURPOSE: To evaluate the effect of camera flash position on the measurement of photographic margin reflex distances (MRD). METHODS: Subjects without any ophthalmic disease were prospectively enrolled after institutional review board approval. Clinical measurements of MRD1 and interpalpebral fissure were obtained. Photographs were then taken with a digital single lens reflex with built-in pop-up flash (dSLR-pop), a dSLR with lens-mounted ring flash (dSLR-ring), a point-and-shoot camera, and a smartphone, each in 4 positions: with the camera upright, rotated 90°, 180°, and 270°. The images were analyzed using ImageJ software to measure MRD1, interpalpebral fissure, horizontal white-to-white, and distance from nasal limbus to the corneal light reflex. RESULTS: Thirty-two eyes of 16 subjects were included (ages 27-65). When using the dSLR-ring, point-and-shoot, and smartphone, the difference between clinical and photographic MRD1 did not reach statistical significance. There was, however, a statistically significant difference in the upright position with dSLR-pop (mean difference 0.703 mm, σ = 0.984 mm, p = 0.0008). For dSLR-pop, photographic MRD1 in upright versus inverted position differed significantly (mean difference -0.562 mm, σ =0.348 mm, p < 0.0001). Photographic MRD1 between dSLR-pop and dSLR-ring showed significant difference in upright position (mean difference -0.572 mm, σ = 0.701 mm, p = 0.0002). There were no statistically significant differences between clinical and photographic interpalpebral fissure, and among white-to-white and nasal limbus to light reflex measurements in any position in all 4 cameras. CONCLUSIONS: When using photographs for measurement of MRD1, cameras with a near-coaxial light source and aperture have values that are most similar to clinical measurements.

Comparison of Ophthalmologist and Large Language Model Chatbot Responses to Online Patient Eye Care Questions.

Importance: Large language models (LLMs) like ChatGPT appear capable of performing a variety of tasks, including answering patient eye care questions, but have not yet been evaluated in direct comparison with ophthalmologists. It remains unclear whether LLM-generated advice is accurate, appropriate, and safe for eye patients. Objective: To evaluate the quality of ophthalmology advice generated by an LLM chatbot in comparison with ophthalmologist-written advice. Design, Setting, and Participants: This cross-sectional study used deidentified data from an online medical forum, in which patient questions received responses written by American Academy of Ophthalmology (AAO)-affiliated ophthalmologists. A masked panel of 8 board-certified ophthalmologists were asked to distinguish between answers generated by the ChatGPT chatbot and human answers. Posts were dated between 2007 and 2016; data were accessed January 2023 and analysis was performed between March and May 2023. Main Outcomes and Measures: Identification of chatbot and human answers on a 4-point scale (likely or definitely artificial intelligence [AI] vs likely or definitely human) and evaluation of responses for presence of incorrect information, alignment with perceived consensus in the medical community, likelihood to cause harm, and extent of harm. Results: A total of 200 pairs of user questions and answers by AAO-affiliated ophthalmologists were evaluated. The mean (SD) accuracy for distinguishing between AI and human responses was 61.3% (9.7%). Of 800 evaluations of chatbot-written answers, 168 answers (21.0%) were marked as human-written, while 517 of 800 human-written answers (64.6%) were marked as AI-written. Compared with human answers, chatbot answers were more frequently rated as probably or definitely written by AI (prevalence ratio [PR], 1.72; 95% CI, 1.52-1.93). The likelihood of chatbot answers containing incorrect or inappropriate material was comparable with human answers (PR, 0.92; 95% CI, 0.77-1.10), and did not differ from human answers in terms of likelihood of harm (PR, 0.84; 95% CI, 0.67-1.07) nor extent of harm (PR, 0.99; 95% CI, 0.80-1.22). Conclusions and Relevance: In this cross-sectional study of human-written and AI-generated responses to 200 eye care questions from an online advice forum, a chatbot appeared capable of responding to long user-written eye health posts and largely generated appropriate responses that did not differ significantly from ophthalmologist-written responses in terms of incorrect information, likelihood of harm, extent of harm, or deviation from ophthalmologist community standards. Additional research is needed to assess patient attitudes toward LLM-augmented ophthalmologists vs fully autonomous AI content generation, to evaluate clarity and acceptability of LLM-generated answers from the patient perspective, to test the performance of LLMs in a greater variety of clinical contexts, and to determine an optimal manner of utilizing LLMs that is ethical and minimizes harm.

Patient Co-Participation in Narrative Medicine Curricula as a Means of Engaging Patients as Partners in Healthcare: A Pilot Study Involving Medical Students and Patients Living with HIV.

This paper describes a pilot study of a new model for narrative medicine training, "community-based participatory narrative medicine" (CBPNM), which centers on shared narrative work between healthcare trainees and patients. Nine medical students and eight patients participated in one of two, five-week-long pilot workshop series. A case study of participants' experiences of the workshop series identified three major themes: (1) the reciprocal and collaborative nature of participants' relationships; (2) the interplay between self-reflection and receiving feedback from others; and (3) the clinical and pedagogical implications of the CBPNM model. Principles and proposed outcomes of the CBPNM model are presented.

A Value-Added Health Systems Science Intervention Based on My Life, My Story for Patients Living with HIV and Medical Students: Translating Narrative Medicine from Classroom to Clinic.

In 2018-2019, at the Keck School of Medicine of the University of Southern California (KSOM), we developed and piloted a narrative-based health systems science intervention for patients living with HIV and medical students in which medical students co-wrote patients' life narratives for inclusion in the electronic health record. The pilot study aimed to assess the acceptability of the "life narrative protocol" (LNP) from multiple stakeholder positions and characterize participants' experiences of the clinical and pedagogical implications of the LNP. Students were recruited from KSOM. Patients and staff were recruited from the Maternal, Child, and Adolescent/Adult Center for Infectious Disease and Virology (MCA) at Los Angeles County+USC Medical Center. Ten patients, seventeen students, and ten MCA staff participated in the pilot study. Qualitative methods were used to gather data from students', patients', and staff's perspectives. Three themes emerged from the thematic analysis: (1) patients' life narratives conveyed their unique life experiences and voices; (2) the protocol could result in wide-ranging effects on HIV care; (3) the LNP enabled students to contribute value to patients' healthcare. Across groups, participants considered the LNP an acceptable intervention. The LNP, its limitations, and implications for HIV care, narrative medicine, and health information technology are presented.

Densitometric Profiles of Optic Disc Hemorrhages in the Ocular Hypertension Treatment Study.

PURPOSE: The origin of blood in glaucoma-related disc hemorrhages (DH) remains unknown. A prior clinic-based study of primary open-angle glaucoma (POAG)-related DH showed that they had grayscale pixel intensities more similar to blood from retinal macroaneurysms and adjacent retinal arterioles than to blood from retinal vein occlusions or adjacent retinal venules, suggesting an arterial source. Here we assessed the densitometric profile of DH from fundus photographs in the Ocular Hypertension Treatment Study (OHTS). DESIGN: Retrospective cross-sectional study of prospectively collected images. METHODS: Stereo disc photographs of 161 DH events from 83 OHTS participants (mean age [standard deviation (SD)]: 65.6 [9.2] years; 46.6% female; 13.0% black race) were imported into ImageJ to measure densitometry differences (adjacent arterioles minus DH [ΔA] or venules minus DH [ΔV]). Their size as percentage of disc area, ratio of length to midpoint width, and location relative to the disc margin were also analyzed. We performed t tests to compare ΔA and ΔV, analysis of variance to compare ΔA and ΔV across DH recurrent events, and multivariable linear regression to identify determinants of ΔA and ΔV. RESULTS: Mean (SD) ΔA and ΔV were -2.2 (8.7) and -11.4 (9.7) pixel intensity units, respectively (P < .001). ΔA and ΔV each did not differ significantly across recurrence of DH (P ≥ .92) or between DH events with and without POAG (P ≥ .26). CONCLUSIONS: OHTS DH had densitometric measurements more similar in magnitude to adjacent arterioles than venules, supporting an arterial origin for DH. Vascular dysregulation may contribute to disc hemorrhage formation in ocular hypertension.

Resting nailfold capillary blood flow in primary open-angle glaucoma.

BACKGROUND/AIMS: An altered haemodynamic profile for various ocular posterior segment capillary beds has been documented in primary open-angle glaucoma (POAG). POAG may also involve abnormal non-ocular blood flow, and the nailfold capillaries, which are not affected by elevated intraocular pressure (IOP), are readily assessable. METHODS: We measured resting nailfold capillary blood flow in 67 POAG and 63 control subjects using video capillaroscopy. Masked readers tracked blood column voids between consecutive, registered image sequence frames, measured vessel diameter and calculated blood flow. We used multiple logistic regression to investigate the relation between nailfold capillary blood flow and POAG. In secondary analyses, we stratified cases by maximum IOP and concurrent topical beta-blocker use. RESULTS: Mean (±SD) blood flow in picolitres per second was 26.8±17.6 for POAG cases and 50.1±24.2 for controls (p<0.0001). After adjustment for demographic and clinical factors including blood pressure and pulse, every picolitre per second increase in resting nailfold blood flow was associated with a 6% (95% CI 0.92 to 0.96) reduced odds of POAG (p<0.0001). Similar relations between nailfold capillary blood flow and POAG were found for cases stratified by maximum known IOP and for cases stratified by concurrent topical beta-blocker use. CONCLUSION: Reduced resting nailfold capillary blood flow is present in POAG independent of covariates such as blood pressure, pulse and IOP.

Microvasculature of the Optic Nerve Head and Peripapillary Region in Patients With Primary Open-Angle Glaucoma.

PURPOSE: To assess optic nerve head (ONH) and peripapillary microvasculature in primary open-angle glaucoma (POAG) of mild to moderate severity using swept-source optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: In a cross-sectional study, swept-source OCTA images were analyzed for 1 eye from each of 30 POAG patients with glaucomatous Humphrey visual field loss and 16 controls. The anatomic boundary of ONH was manually delineated based on Bruch's membrane opening and large vessels were removed from en face angiography images to measure vessel density (VD) and the integrated OCTA by ratio analysis signal (IOS), suggestive of flow, in the ONH and peripapillary region. POAG subgroup analysis was performed based on a history of disc hemorrhage (DH) matched by visual field mean deviation (MD). RESULTS: POAG (mean MD±SD, -3.3±3.0 dB) and control groups had similar demographic characteristics and intraocular pressure on the day of imaging. Groups did not differ in superficial ONH VD or flow indicated by IOS (P≥0.28). POAG eyes showed significantly lower VD (39.4%±4.0%) and flow (38.8%±5.6%) in deep ONH, peripapillary VD (37.9%±2.9%) and flow (43.6%±4.0%) compared with control eyes (44.1%±5.1%, 44.7%±6.9%, 40.7%±1.7%, 47.8%±2.5%, respectively; P≤0.007 for all). In the subgroup analysis, POAG eyes with (n=14) and without DH (n=16) had similar measured OCTA parameters (P>0.99 for all). CONCLUSIONS: The image processing methodology based on the anatomic boundary of ONH demonstrated compromised microvasculature in the deep ONH and peripapillary region in eyes with mild to moderate POAG, regardless of the history of DH.

Fundus Densitometry Findings Suggest Optic Disc Hemorrhages in Primary Open-Angle Glaucoma Have an Arterial Origin.

PURPOSE: To analyze optic disc hemorrhages (DH) associated with primary open-angle glaucoma by quantifying their geometric profile and comparing their densitometry with hemorrhages from retinal vein occlusions (RVO) and retinal macroaneurysms (MA), which have venous and arterial sources of bleeding, respectively. DESIGN: Retrospective cross-sectional study. METHODS: Setting: Massachusetts Eye & Ear. POPULATION: Fundus images of DH (n = 40), MA (n = 14), and RVO (n = 25) were identified. Patient clinical backgrounds and demographics were obtained. MAIN OUTCOME MEASURES: Grayscale pixel intensity units of hemorrhages and adjacent arteriole and venule over the same background tissue were measured. Densitometry differentials (arteriole or venule minus hemorrhage [ΔA and ΔV, respectively]) were calculated. The ratios of length (radial) to midpoint width for DH were calculated. Mean ΔA and ΔV between groups were compared with t tests. Multiple linear regression assessed the relation of retinal hemorrhage diagnosis to ΔA and ΔV and of DH shape to ΔA and ΔV. RESULTS: Mean (± standard deviation) ΔA and ΔV for DH (6.9 ± 7.1 and -4.7 ± 8.0 pixel intensity units, respectively) and MA (5.3 ± 5.9 and -6.0 ± 4.6, respectively) were comparable (P ≥ .43). Mean ΔA (14.6 ± 7.7) and ΔV (6.4 ± 6.3) for RVO were significantly higher compared to DH and MA (P < .0001) and remained significant in multivariable analyses. A unit increase in DH length-to-width ratio was associated with 1.2 (0.5) and 1.3 (0.5) pixel intensity unit (standard error) decrease in ΔA and ΔV, respectively (P ≤ .014). CONCLUSIONS: DH have densitometry profiles comparable to MA and different from RVO, suggesting that DH in glaucoma have an arterial origin.

Endothelin receptor-A antagonist attenuates retinal vascular and neuroretinal pathology in diabetic mice.

PURPOSE: We sought to determine the effects of atrasentan, a selective endothelin-A receptor antagonist, on the retinal vascular and structural integrity in a db/db mouse, an animal model of type 2 diabetes and diabetic retinopathy. METHODS: Diabetic mice, 23 weeks old, were given either atrasentan or vehicle treatment in drinking water for 8 weeks. At the end of the treatment period, eyes underwent trypsin digest to assess the retinal vascular pathology focusing on capillary degeneration, endothelial cell, and pericyte loss. Paraffin-embedded retinal cross sections were used to evaluate retinal sublayer thickness both near the optic nerve and in the retinal periphery. Immunohistochemistry and TUNEL assay were done to evaluate retinal cellular and vascular apoptosis. RESULTS: Compared with untreated db/db mice, atrasentan treatment was able to ameliorate the retinal vascular pathology by reducing pericyte loss (29.2% ± 0.4% vs. 44.4% ± 2.0%, respectively, P < 0.05) and capillary degeneration as determined by the percentage of acellular capillaries (8.6% ± 0.3% vs. 3.3% ± 0.41%, respectively, P < 0.05). A reduction in inner retinal thinning both at the optic nerve and at the periphery in treated diabetic mice was also observed in db/db mice treated with atrasentan as compared with untreated db/db mice (P < 0.05). TUNEL assay suggested that atrasentan may decrease enhanced apoptosis in neuroretinal layers and vascular pericytes in the db/db mice. CONCLUSIONS: Endothelin-A receptor blockade using atrasentan significantly reduces the vascular and neuroretinal complications in diabetic mice. Endothelin-A receptor blockade is a promising therapeutic target in diabetic retinopathy.

Sildenafil attenuates vaso-obliteration and neovascularization in a mouse model of retinopathy of prematurity.

PURPOSE: We sought to determine the effect of sildenafil on retinal vascular changes in a mouse model of oxygen-induced retinopathy (OIR). METHODS: Vascular defects in OIR mice were quantified by measuring vaso-obliteration at postnatal days 12 and 17 (P12 and P17) and neovascularization at P17 to compare sildenafil-treated to dextrose-treated OIR mice. Retinal HIF1α protein expression was quantified by Western blotting and normalized to that of ß-actin. Right ventricular hypertrophy was measured by Fulton's index as a surrogate for hyperoxia-induced pulmonary hypertension. RESULTS: At P12, OIR mice treated with sildenafil demonstrated a 24% reduction in vaso-obliteration (P < 0.05), whereas at P17, treated animals showed a 50% reduction in neovascularization (P < 0.05) compared to dextrose-treated controls. Sildenafil-treated OIR mice had stabilization of retinal HIF1α at P12, immediately after hyperoxia. At P17, sildenafil-treated OIR mice had decreased HIF1α relative to untreated mice. OIR mice developed right ventricle hypertrophy that was significant compared to that in room air controls, which was abrogated by sildenafil. CONCLUSIONS: Sildenafil treatment significantly decreased retinal vaso-obliteration and neovascularization in a mouse OIR model. These effects are likely due to sildenafil-induced HIF1α stabilization during hyperoxia exposure. Furthermore, we confirm disease overlap by showing that OIR mice also develop hyperoxia-induced right ventricular hypertrophy, which is prevented by sildenafil. This study is a first step toward delineating a potential therapeutic role for sildenafil in OIR and further suggests that there may be common pathophysiologic mechanisms underlying hyperoxia-induced retinal and pulmonary vascular disease.

Trypsin digest protocol to analyze the retinal vasculature of a mouse model.

Trypsin digest is the gold standard method to analyze the retinal vasculature (1-5). It allows visualization of the entire network of complex three-dimensional retinal blood vessels and capillaries by creating a two-dimensional flat-mount of the interconnected vascular channels after digestion of the non-vascular components of the retina. This allows one to study various pathologic vascular changes, such as microaneurysms, capillary degeneration, and abnormal endothelial to pericyte ratios. However, the method is technically challenging, especially in mice, which have become the most widely available animal model to study the retina because of the ease of genetic manipulations (6,7). In the mouse eye, it is particularly difficult to completely remove the non-vascular components while maintaining the overall architecture of the retinal blood vessels. To date, there is a dearth of literature that describes the trypsin digest technique in detail in the mouse. This manuscript provides a detailed step-by-step methodology of the trypsin digest in mouse retina, while also providing tips on troubleshooting difficult steps.