Early Choriocapillaris Loss in a Porcine Model of RPE Cell Debridement Precedes Pathology That Simulates Advanced Macular Degeneration.

Purpose: No large-mammal surgical models exist for geographic atrophy (GA), choroidal neovascularization (CNV), and pachychoroidal vascular remodeling. Our goal was to develop a porcine RPE debridement model of advanced macular degeneration to study photoreceptor cell loss and choroidal remodeling. Methods: Seven 2-month-old female domestic pigs were used for this study. After 25G vitrectomy, the area centralis was detached via subretinal bleb. A nitinol wire (Finesse Flex Loop) was used to debride RPE cells across a 3- to 5-mm diameter region. Fluid-air exchange was performed, and 20% SF6 gas injected. Animals underwent fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT-angiography (OCTA) at 2 weeks, 1 month, 2 months, 3 months, and 6 months postoperatively. Retinal histology was obtained at euthanasia, 2 months (n = 3), 3 months (n = 2), or 6 months (n = 2) after surgery. Results: RPE debridement resulted in GA with rapid loss of choriocapillaris, progressive loss of photoreceptors, and pachychoroidal changes in Sattler's and Haller's layers in all seven eyes undergoing debridement within 2 months. OCT and histological findings included subretinal disciform scar with overlying outer retinal atrophy; outer retinal tubulations and subretinal hyper-reflective material. OCTA revealed type 2 CNV (n = 4) at the edges of the debridement zone by 2 months, but there was no significant exudation noted at any time point. Conclusions: Surgical debridement of the RPE results in GA, CNV, and pachychoroid and reproduced all forms of advanced macular degeneration. This surgical model may be useful in examining the role of RPE and other cell replacement in treating advanced macular disease.

Appropriateness of Ophthalmology Recommendations From an Online Chat-Based Artificial Intelligence Model.

Objective: To determine the appropriateness of ophthalmology recommendations from an online chat-based artificial intelligence model to ophthalmology questions. Patients and Methods: Cross-sectional qualitative study from April 1, 2023, to April 30, 2023. A total of 192 questions were generated spanning all ophthalmic subspecialties. Each question was posed to a large language model (LLM) 3 times. The responses were graded by appropriate subspecialists as appropriate, inappropriate, or unreliable in 2 grading contexts. The first grading context was if the information was presented on a patient information site. The second was an LLM-generated draft response to patient queries sent by the electronic medical record (EMR). Appropriate was defined as accurate and specific enough to serve as a surrogate for physician-approved information. Main outcome measure was percentage of appropriate responses per subspecialty. Results: For patient information site-related questions, the LLM provided an overall average of 79% appropriate responses. Variable rates of average appropriateness were observed across ophthalmic subspecialties for patient information site information ranging from 56% to 100%: cataract or refractive (92%), cornea (56%), glaucoma (72%), neuro-ophthalmology (67%), oculoplastic or orbital surgery (80%), ocular oncology (100%), pediatrics (89%), vitreoretinal diseases (86%), and uveitis (65%). For draft responses to patient questions via EMR, the LLM provided an overall average of 74% appropriate responses and varied by subspecialty: cataract or refractive (85%), cornea (54%), glaucoma (77%), neuro-ophthalmology (63%), oculoplastic or orbital surgery (62%), ocular oncology (90%), pediatrics (94%), vitreoretinal diseases (88%), and uveitis (55%). Stratifying grades across health information categories (disease and condition, risk and prevention, surgery-related, and treatment and management) showed notable but insignificant variations, with disease and condition often rated highest (72% and 69%) for appropriateness and surgery-related (55% and 51%) lowest, in both contexts. Conclusion: This LLM reported mostly appropriate responses across multiple ophthalmology subspecialties in the context of both patient information sites and EMR-related responses to patient questions. Current LLM offerings require optimization and improvement before widespread clinical use.

A Comparative Study of Responses to Retina Questions from Either Experts, Expert-Edited Large Language Models, or Expert-Edited Large Language Models Alone.

Objective: To assess the quality, empathy, and safety of expert edited large language model (LLM), human expert created, and LLM responses to common retina patient questions. Design: Randomized, masked multicenter study. Participants: Twenty-one common retina patient questions were randomly assigned among 13 retina specialists. Methods: Each expert created a response (Expert) and then edited a LLM (ChatGPT-4)-generated response to that question (Expert + artificial intelligence [AI]), timing themselves for both tasks. Five LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, and Bard) also generated responses to each question. The original question along with anonymized and randomized Expert + AI, Expert, and LLM responses were evaluated by the other experts who did not write an expert response to the question. Evaluators judged quality and empathy (very poor, poor, acceptable, good, or very good) along with safety metrics (incorrect information, likelihood to cause harm, extent of harm, and missing content). Main Outcome: Mean quality and empathy score, proportion of responses with incorrect information, likelihood to cause harm, extent of harm, and missing content for each response type. Results: There were 4008 total grades collected (2608 for quality and empathy; 1400 for safety metrics), with significant differences in both quality and empathy (P < 0.001, P < 0.001) between LLM, Expert and Expert + AI groups. For quality, Expert + AI (3.86 ± 0.85) performed the best overall while GPT-3.5 (3.75 ± 0.79) was the top performing LLM. For empathy, GPT-3.5 (3.75 ± 0.69) had the highest mean score followed by Expert + AI (3.73 ± 0.63). By mean score, Expert placed 4 out of 7 for quality and 6 out of 7 for empathy. For both quality (P < 0.001) and empathy (P < 0.001), expert-edited LLM responses performed better than expert-created responses. There were time savings for an expert-edited LLM response versus expert-created response (P = 0.02). ChatGPT-4 performed similar to Expert for inappropriate content (P = 0.35), missing content (P = 0.001), extent of possible harm (P = 0.356), and likelihood of possible harm (P = 0.129). Conclusions: In this randomized, masked, multicenter study, LLM responses were comparable with experts in terms of quality, empathy, and safety metrics, warranting further exploration of their potential benefits in clinical settings. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of the article.

Deep Learning and Machine Learning Algorithms for Retinal Image Analysis in Neurodegenerative Disease: Systematic Review of Datasets and Models.

Purpose: Retinal images contain rich biomarker information for neurodegenerative disease. Recently, deep learning models have been used for automated neurodegenerative disease diagnosis and risk prediction using retinal images with good results. Methods: In this review, we systematically report studies with datasets of retinal images from patients with neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and others. We also review and characterize the models in the current literature which have been used for classification, regression, or segmentation problems using retinal images in patients with neurodegenerative diseases. Results: Our review found several existing datasets and models with various imaging modalities primarily in patients with Alzheimer's disease, with most datasets on the order of tens to a few hundred images. We found limited data available for the other neurodegenerative diseases. Although cross-sectional imaging data for Alzheimer's disease is becoming more abundant, datasets with longitudinal imaging of any disease are lacking. Conclusions: The use of bilateral and multimodal imaging together with metadata seems to improve model performance, thus multimodal bilateral image datasets with patient metadata are needed. We identified several deep learning tools that have been useful in this context including feature extraction algorithms specifically for retinal images, retinal image preprocessing techniques, transfer learning, feature fusion, and attention mapping. Importantly, we also consider the limitations common to these models in real-world clinical applications. Translational Relevance: This systematic review evaluates the deep learning models and retinal features relevant in the evaluation of retinal images of patients with neurodegenerative disease.

The Effect of Scleral Buckle Surgery on Tonographic Outflow Facility, Positional Intraocular Pressure, and Ocular Biomechanics.

PURPOSE: To investigate the in vivo effect of scleral buckle surgery on ocular biomechanics and aqueous humor dynamics. DESIGN: Prospective observational cross-sectional study. PARTICIPANTS: Nine patients with unilateral 360 degree encircling scleral buckles without vitrectomy for rhegmatogenous retinal detachments, between 3 and 39 months postoperative. METHODS: All measurements were performed in both eyes of all participants. Intraocular pressure (IOP) was measured in the seated and supine positions using pneumatonometry. Outflow facility was measured using 2-minute weighted pneumatonography. Ocular rigidity coefficient was determined from the Friedenwald equations based on the difference in IOP with and without a weighted tonometer tip. The percentage change in IOP upon transitioning from seated to supine was calculated. Measurements for buckled and nonbuckled eyes were compared using paired Student t test of means. MAIN OUTCOME MEASURES: Sitting and supine IOP and percentage difference between the 2 positions; outflow facility; ocular rigidity coefficient. RESULTS: Seated IOP was similar between buckled and nonbuckled eyes (16.1 ± 2.5 vs. 16.7 ± 2.7 mmHg; P = 0.5) whereas supine IOP was lower in buckled eyes compared with nonbuckled eyes (18.7 ± 2.6 vs. 21.3 ± 2.5 mmHg; P = 0.008). The percentage increase in IOP upon change in body position from seated to supine was greater in nonbuckled eyes (17.4 ± 9.4% vs. 27.6 ± 9.5%; P = 0.005). Ocular rigidity coefficient was lower in buckled (9.9 × 10-3 ± 1.4 × 10-3 µL-1) vs. nonbuckled eyes (14.4 × 10-3 ± 3.1 × 10-3 µL-1; P = 0.006). Outflow facility was not significantly different in buckled and nonbuckled eyes. CONCLUSIONS: Scleral buckling decreases ocular rigidity but does not affect outflow facility. This change in ocular biomechanics likely results in the attenuated IOP change from seated to supine position. Decreased ocular rigidity may also reduce IOP fluctuations and potentially reduce the risk for glaucoma progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

EPIRETINAL MEMBRANE WITH FOVEAL HERNIATION: Visual and Surgical Outcomes.

PURPOSE: Foveal herniation occurs when neuroretinal tissue protrudes through and above the level of an epiretinal membrane. This study describes the visual symptoms and spectral domain optical coherence tomography findings associated with foveal herniation and evaluates the postoperative visual, anatomical, and surgical outcomes. METHODS: A multicenter retrospective review of patients diagnosed with epiretinal membrane identified 59 patients with preoperative foveal herniation on spectral domain optical coherence tomography. Data regarding visual symptoms, preoperative and postoperative best-corrected visual acuity (BCVA), central retinal thickness, macular volume, and size of foveal herniation were collected, and statistical analysis was performed. RESULTS: A total of 58 of the 59 patients with foveal herniation underwent surgical epiretinal membrane peeling, with foveal contour restored in 53.5% of patients after surgery. Average BCVA improved from 20/80 to 20/40 Snellen equivalent at most-recent postoperative visit (P < 0.0001). The average central retinal thickness decreased from 632 µm to 432 µm (P < 0.0001) and the average macular volume decreased from 11.3 mm3 to 9.5 mm3 (P < 0.0001) at 3 months postoperatively. Preoperatively, greater herniation height was associated with worse BCVA (P = 0.008), greater central retinal thickness (P = 0.01), retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone abnormality, and external limiting membrane abnormalities (P < 0.05). Postoperatively, there was a decrease in retinoschisis, cystoid macular edema, foveolar detachment, ellipsoid zone, and external limiting membrane abnormality (P < 0.05) on spectral domain optical coherence tomography. CONCLUSION: Patients with larger foveal herniation height had greater preoperative central retinal thickness, worse preoperative and postoperative BCVA, and more intraretinal abnormalities on spectral domain optical coherence tomography. Surgical epiretinal membrane peeling in patients with foveal herniation resulted in a significant improvement in patients' BCVA and microstructural abnormalities.

Incidence of metformin use in patients with age-related macular degeneration versus normal controls: A population-based study in Olmsted County, Minnesota.

PURPOSE: The purpose of this study is to compare the use of metformin in patients with both exudative and non-exudative age-related macular degeneration (AMD) versus control populations. DESIGN: Retrospective review of three age- and sex-matched cohorts from 1/1/2004 to 12/31/2013: patients with exudative AMD, a cohort of dry AMD patients, and a cohort of patients without AMD. The primary endpoint was the incidence of metformin use in all of the cohorts. RESULTS: There were 1512 patients, with 504 in each of the three cohorts. There was no difference in the prevalence of diabetes between cohorts. Compared to patients with dry AMD, patients with no AMD had increased likelihood of metformin use (p = 0.0168, OR 1.66 (1.09-2.51). There was no difference in the likelihood of metformin use between exudative AMD patients and non-AMD controls. CONCLUSIONS: There appears to be an increased incidence of metformin use in patients without AMD compared to patients with dry AMD. Metformin's current role in the treatment of anti-aging diseases makes it a plausible target for use in the treatment of AMD, particularly dry AMD.

EFFECT OF PHYSICIAN FACE MASK USE ON POSTINJECTION ENDOPHTHALMITIS.

PURPOSE: To examine the impact of physician face mask use on the rates and outcomes of postinjection endophthalmitis. METHODS: A multicenter retrospective, comparative cohort study comparing endophthalmitis rate and visual acuity of eyes that developed endophthalmitis after antivascular endothelial growth factor injections at Mayo Clinic Rochester (MCR) and at Mayo Clinic Health System sites depending on physician masking. RESULTS: A total of 164,824 injections were performed at MCR and Mayo Clinic Health System sites. Of these, 66,098 injections were in the no mask group and 98,726 injections were in the mask group. Overall, there were no differences in the rates of infectious endophthalmitis in the no mask versus mask cohorts (overall: no mask: 20 cases [0.0303%] vs. mask: 41 cases (0.0415%); P = 0.24; infectious: no mask: 12 cases [0.018%] versus mask: 13 cases [0.0132%]; P = 0.42). At MCR alone, there was a significant reduction in infectious endophthalmitis between the no mask versus mask groups (no mask: 9 cases [0.0297%] versus mask: 2 cases [0.003%]; P < 0.001). Only 2 cases of infectious endophthalmitis occurred at MCR after the face mask policy was implemented (1 in 30,000 injections). At presentation and at 6 months, the average visual acuity was similar for patients who developed endophthalmitis between the no mask versus mask groups. CONCLUSION: Physician face mask use did not affect the rate or outcome of postinjection endophthalmitis. However, there was a significant reduction at MCR after masking along with other quality improvement measures, including performance of injections in a dedicated procedure room and preparation of patients by nurses, that led to a low rate of endophthalmitis.

Risk, Prevalence, and Progression of Glaucoma in Eyes With Age-Related Macular Degeneration Treated With Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To examine the risk, prevalence, and progression of glaucoma development in age-related macular degeneration (AMD) eyes receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections compared to controls. DESIGN: Retrospective clinical cohort study. METHODS: Retrospective review of eyes receiving intravitreal anti-VEGF injections from January 1, 2004, to December 31, 2013, for exudative AMD. Age- and sex-matched control groups of eyes included eyes with nonexudative AMD (NEAMD) and no AMD. Eyes with a diagnosis of glaucoma or glaucoma suspect were reviewed for injection details, type and date of glaucoma diagnosis, glaucoma treatments, standard automated perimetry (SAP), and spectral domain optical coherence tomography (SD-OCT). Qualitative progression was determined by indication of glaucoma progression in provider notes. Quantitative progression was assessed based on change in mean deviation (MD) on SAP, retinal nerve fiber layer thickness on SD-OCT, and intraocular pressure (IOP). RESULTS: There were 707 eyes of 504 patients treated with anti-VEGF injections and 1008 eyes in the NEAMD and no-AMD cohorts. There was no difference in glaucoma or suspect prevalence at initial presentation between eyes treated with injections and NEAMD (6.9% vs 9.7%, P = .22) or no-AMD controls (vs 8.5%, P = .55). There was no difference in cumulative 5-year probability of new glaucoma diagnosis after anti-VEGF injections compared to NEAMD (1.9% vs 1.0%, P = .69) or no-AMD controls (vs 1.6%, P = .88). There was no difference in qualitative progression of glaucoma in the injection cohort vs NEAMD (P = .19) or no-AMD controls (P = .61). The rate of MD change in injection eyes was similar to NEAMD eyes (P = .74) but greater than no-AMD eyes (P = .02). Eyes receiving injections required more topical glaucoma medications compared with NEAMD (P = .03) and more glaucoma laser treatments compared with no-AMD controls (P = .009). Eyes receiving injections did not require more frequent incisional glaucoma surgery compared with NEAMD (21.0% vs 15.0%, P = .95) or no-AMD controls (vs 10.0%, P = .10). CONCLUSION: Eyes treated with intravitreal anti-VEGF injections for exudative AMD did not have increased risk of developing glaucoma compared with controls. Of those with a glaucoma diagnosis, exudative AMD eyes receiving injections required a greater number of topical glaucoma medications compared with NEAMD eyes and had a greater rate of MD loss than no-AMD controls.

Methodological Approach to Improve Surgical Outcomes of a Pig Subretinal Implantation Model.

Purpose: To improve outcomes for subretinal implantation surgery in pigs. Methods: Analysis of variables affecting the success of subretinal implantation surgery was performed on videos of 37 surgeries. Ex vivo experiments were conducted to measure intraocular pressure (IOP) and test various prototyped implanters for effectiveness at maintaining IOP. Results: A video analysis revealed a prolonged sclerotomy open time owing to a combination of uncontrolled bleeding and excessive fluid outflow often resulting in retinal prolapse. Precauterization of the choroid before full-thickness sclerotomy (n = 10) resulted in a reduced incidence of uncontrolled bleeding from 39.1% (9/23) versus 0% (0/10) (P = 0.005) and improved implantation success from 73% to 90%. An ex vivo analysis of the IOP revealed a mean decrease in the IOP from 30.2 ± 3.0 mm Hg to 5.0 ± 2.1 mm Hg after a fully penetrating sclerotomy. To address this situation, we produced a series of plugs that integrated with a custom implant insertion device to seal the sclerotomy during implantation. The use of the plugs was cumbersome, however, and so we opted instead to increase the width of the inserter tip to fill the open sclerotomy. This improved device restored and maintained IOP during implantation (27.1 ± 1.9 mm Hg). Combined with precauterization the improved inserter resulted in 100% successful implantation (n = 4). Conclusions: For subretinal implantation in pigs, a modified procedure to precauterize the choroid before sclerotomy combined with an instrument that better fills the scleral opening decreases bleeding, hypotony, and open sclerotomy time, improving the success rate. Translational Relevance: Better management of IOP and bleeding from a sclerotomy will improve implant-based therapies.

ASSOCIATION OF PIGMENTED PARAVENOUS RETINOCHOROIDAL ATROPHY WITH A PATHOGENIC VARIANT IN THE HK1 GENE.

PURPOSE: To report a case of pigmented paravenous retinochoroidal atrophy in a patient that was found to have an autosomal dominant pathogenic variant of the hexokinase 1 ( HK1 ) gene. METHODS: A case report. RESULTS: A 41-year-old White woman with a distant family history of retinitis pigmentosa presented with a 5-year history of bilateral blurry and decreased vision that led to eventual loss of ability to drive. Color funduscopic photographs revealed retinochoroidal atrophy, hyper-reflective spots within the retina, and a paravenous distribution of pigment bilaterally. Given the patient's familial ocular history and workup, she was diagnosed with inherited retinal degeneration with phenotype suggestive of pigmented paravenous retinochoroidal atrophy. Genetic testing revealed a single rare variant, c.2551 G>A in the HK1 gene. DISCUSSION: This case describes a pathogenic variant in HK1 , a gene that has been associated with RP, but has not been previously reported in association with the pigmented paravenous retinochoroidal atrophy phenotype. This expands the phenotypes associated with HK1 pathogenic variant, p.Glu851Lys, and the genetic association of pigmented paravenous retinochoroidal atrophy to include HK1 . Although pigmented paravenous retinochoroidal atrophy has been previously reported to be associated with CRB1 gene, no previous relationship to the HK1 gene has been described.

Inkjet-Printed Graphene Sensors for the Bedside Detection of Tear Film pH.

Purpose: To determine whether an inexpensive, graphene thin-film electronic pH sensor could be used to measure tear film pH. Methods: The pH-sensitive electrolyte-gated graphene field-effect transistors (EG-GFETs) were fabricated by patterning graphene ink and ultraviolet-cured dielectric onto 125 µm-thick polyimide substrate using a nanomaterials inkjet printer. A flow-cell was used to exchange test solutions and record current flow through the EG-GFET. Laboratory reference pH test solutions were used to calibrate the sensor. Contrived tears with lipids were pH buffered using HCL (1 M) or NAOH (1 M) to produce tear solutions ranging in pH from 2.0 to 9.5. A laboratory-reference pH meter was used to verify the pH of each solution. Dirac curves that demonstrate pH-dependent changes in current flow through the EG-GFET were measured for each test solution, using dual sourcemeters. Results: Graphene EG-GFET devices were highly sensitive to changes in artificial tear-film pH. The Dirac voltage was defined as the gate voltage at which minimum source drain current was measured. The relationship between Dirac voltage and tear film pH was highly linear with a slope of 17.2 mV per pH unit over the range of solutions tested, from pH 2.0 to pH 9.5 (r2 = 0.977). Conclusions: Graphene field-effect transistors accurately measure tear film pH and may be useful in the emergency management of ocular adnexal exposure to acids or bases. Translational Relevance: Thin-film graphene sensors are low cost and can rapidly map tear-film pH at multiple sites on the ocular surface and within the conjunctival fornices, avoiding subjective, colorimetric test-paper methods.

Outcomes of Patients With Active Diabetic Macular Edema at the Time of Cataract Surgery Managed With Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To investigate the outcomes of cataract surgery in patients with active diabetic macular edema (DME) who are receiving active treatment with intravitreal anti-vascular endothelial growth factor (VEGF) injections in the perioperative period. DESIGN: Retrospective clinical cohort study. METHODS: We reviewed all patients who underwent cataract surgery and were receiving intravitreal anti-VEGF injections from January 1, 2012 through December 31, 2017. Thirty-seven eyes underwent cataract surgery and received ≥1 intravitreal anti-VEGF injection for a diagnosis of DME within 6 months before surgery. Outcome measures included the development of subretinal or intraretinal fluid in the 6 months after surgery, timing of injections, number of injections, best-corrected visual acuity, and central subfield thickness. RESULTS: There was a significant improvement between pre- and postoperative best-corrected visual acuity when comparing all eyes (Ps < .0001) and no significant difference in central subfield thickness before and after surgery (P > .05). There were 30 eyes (81.1%) that had fluid on the preoperative optical coherence tomography scan. Seventeen eyes (45.9%) developed new or worsening postoperative DME. Comparing the eyes that did or did not develop worsening DME, there were no differences in postoperative visual acuities (P > .05). Eyes that did develop new fluid had significant increases in postoperative central subfield thickness at both 1 month (350 vs 320 µm, P = .036) and 6 months (342 vs 305 µm, P = .013). CONCLUSION: In a real-world setting, patients with cataracts and actively treated DME may undergo cataract surgery but may see a worsening of DME not immediately affecting the best-corrected visual acuity.

Clinical Utility of Antiretinal Antibody Testing.

IMPORTANCE: The clinical utility of most antiretinal antibodies (retina antibodies) currently available for testing remains unclear and unproven. Despite this, the presence of retinal antibodies is included in current diagnostic autoimmune retinopathy criteria. OBJECTIVE: To evaluate the clinical significance of comprehensive retinal antibody evaluations currently offered in North America. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, 14 patients without autoimmune retinopathy were recruited into the Mayo Clinic Neuroimmunology Biorepository for this study between January 1, 2019, and October 1, 2019. These serum samples without autoimmune retinopathy were sent in masked fashion to a Clinical Laboratory Improvement Amendments-certified laboratory. Using similar methods, the Mayo Clinic Neuroimmunology Research Laboratory independently assessed the same sample to ascertain reproducibility of the findings. MAIN OUTCOMES AND MEASURES: Results of the autoimmune retinopathy and cancer-associated retinopathy panels. RESULTS: Thirteen of 14 (93%; 95% CI, 66%-100%) serum samples tested positive for retinal antibodies, with a median of 5 retinal antibodies (range, 0-8) per patient at the Clinical Laboratory Improvement Amendments-certified laboratory, which provides a specificity of 7% (95% CI, 0%-34%). Confirmatory immunohistochemistry staining in human retina was present in 12 of 14 samples (86%). α-Enolase was found in 9 (64%). The only retinal antibody not present was recoverin. These nonspecific retinal antibody results were replicated at the Mayo Clinic Laboratory on Western blot using pig retina proteins as substrate. CONCLUSIONS AND RELEVANCE: The presence of retinal antibodies in 93% of the patients without autoimmune retinopathy indicates a lack of specificity and that most detectable retinal antibodies have limited clinical relevance in the evaluation of patients for suspected autoimmune retinopathy. Current retinal antibody testing, other than recoverin, should be interpreted with caution, especially for cases of low clinical suspicion. The poor specificity is important to recognize to prevent the potentially unnecessary commencement of systemic immunosuppressants that may result in significant extraocular adverse effects. Identification of biomarkers that have a high predictive value for inflammatory or autoimmune retinal diseases is needed to move the field forward.

Time to Unplanned Return to the Operating Room and Associated Risk Factors in Patients With Surgical Retinal Detachment Repair.

PURPOSE: To assess the incidence of unplanned return to the operating room (ROR) at ≤45 days or ≥46 days after primary retinal detachment (RD) surgery and correlate ROR with preoperative risk factors and visual outcomes. DESIGN: Retrospective cohort study. METHODS: This was a retrospective review of patients with primary RD surgery to assess for unplanned ROR between January 1, 2012 and June 30, 2014, with follow-up of 90 days to 8 years (mean, 1.5 years). We assessed 268 patients receiving 270 primary rhegmatogenous RD surgeries between January 1, 2012 and June 30, 2014 in an academic tertiary referral center. RESULTS: Of the 270 RD surgeries, 82 were complicated (history of proliferative vitreoretinopathy or trauma-related RDs at presentation) and 188 were uncomplicated (RD unrelated to trauma or proliferative vitreoretinopathy at presentation). The ROR rate for all surgeries was 12.2% (33/270) over the follow-up period, with 51.5% (17/33) having reoperations within 45 days. The complicated detachment group had a ROR rate of 14.6% (12/82) over the follow-up period, and 50% of those (6/12) had reoperations within 45 days. The uncomplicated detachment group had a ROR rate of 11.2% (21/188) over the follow-up period. Of those, 52.4% (11/21) had reoperations within 45 days. CONCLUSIONS: Given that only 51.5% of all RORs occurred within 45 days, a 45-day ROR surgical quality metric that has been previously used may be of limited value for RD surgery. Factors such as age at presentation, number of retinal breaks, number of detached clock hours, use of silicone oil tamponade for pars plana vitrectomy, history of choroidal detachment, high myopia, ocular trauma, and open globe were associated with increasing risk of ROR. Implementing risk-adjusted metrics may provide a more accurate and useful quality improvement metric for evaluating quality of surgical care in vitreoretinal surgery. Am J Ophthalmol 2021;221:•••-•••. © 2021 Elsevier Inc. All rights reserved.

Binocular Interference vs Diplopia in Patients With Epiretinal Membrane.

Importance: Patients with epiretinal membrane (ERM) sometimes close 1 eye for improved vision, but associations have not been rigorously studied. Objective: To evaluate associations with monocular eye closure in patients with ERM, and to report binocular interference (closing 1 eye to improve visual quality). Design, Setting, and Participants: Retrospective medical record review of an adult strabismus clinic at a tertiary referral center. Patients with ERM referred from retina clinicians between June 2010 and October 2019 who completed the Adult Strabismus (AS)-20 questionnaire, including the question: "I cover or close one eye to see things better." Two groups were identified: (1) patients reporting eye closure sometimes or more, and (2) patients reporting no eye closure (as control patients). Main Outcomes and Measures: Frequencies of (1) central-peripheral rivalry (CPR)-type diplopia (dragged fovea diplopia); (2) binocular interference (monocular eye closure but no diplopia or strabismus); and (3) other, associated with monocular eye closure. Visual acuity, metamorphopsia, aniseikonia, and AS-20 quality of life domain scores (self-perception, interactions, reading function, and general function) compared between binocular interference, CPR-type diplopia, and control patients. Results: A total of 124 patients with ERM (58 of 124 were women [47%]; mean [SD] age, 70 [9] years) reported monocular eye closure. Associations were binocular interference in 36 (29%; 95% CI, 21%-38%), CPR-type diplopia in 34 (27%; 95% CI, 20%-36%), and other (primarily strabismus) in 54 (44%). Compared with control patients with ERM (n = 11), patients with ERM and binocular interference had worse quality of life on AS-20 reading function (95 vs 62; mean difference, 22 points; 95% CI, 7-27 points; P = .007) and general function (89 vs 68; mean difference, 23 points; 95% CI, 13-34 points; P = .01) domains. Compared with CPR-type diplopia, patients with binocular interference had poorer worst-eye visual acuity (median 0.50 vs 0.30 logMAR [20/63 vs 20/40]; mean difference, 0.13 logMAR; 95% CI, 0.00-0.25 logMAR [20/20 to 20/35]; P = .03), and a larger interocular difference (0.46 vs 0.19 logMAR [20/58 vs 20/30]; mean difference, 0.15 logMAR; 95% CI, 0.03-0.28 logMAR [20/21 to 20/38]; P = .004). Conclusions and Relevance: Study findings suggest that binocular interference, manifesting as monocular eye closure (without diplopia or strabismus), is a distinct entity affecting quality of life in patients with epiretinal membrane.

Visual and Anatomic Outcomes following Cataract Surgery in Patients with Pre-operative Macular Edema Due to Retinal Vein Occlusions Managed with Intravitreal anti-VEGF.

PURPOSE: The purpose of this study was to investigate the visual and anatomic outcomes in patients with macular edema due to retinal vein occlusions (RVO) who were actively managed with intravitreal anti-vascular endothelial growth factor (VEGF) before and after cataract surgery. METHODS: Retrospective, cohort study of all patients with RVO who underwent cataract surgery and were receiving intravitreal anti-VEGF injections from January 1st, 2012 through October 31st, 2018. There were 31 eyes that underwent cataract surgery and received at least one intravitreal anti-VEGF injection for a diagnosis of RVO within 6 months prior to surgery. Data collected included the development of subretinal or intraretinal macular fluid in the 6 months following surgery, timing of injections, number of injections, best corrected visual acuity (BCVA), and central subfield thickness (CST). RESULTS: There was a significant improvement between pre- and post-operative BCVA when comparing all eyes (p values < .0001) and no significant difference in CST before and after surgery (p > .05). Eyes without fluid pre-operatively saw an improvement in visual acuity, but with an initial significant increase in CST (p = .03) that normalized over time (p = .33) without an increase in frequency of anti-VEGF injections. CONCLUSION: Patients with cataracts who are actively managed for macular edema due to RVO with anti-VEGF agents may undergo cataract surgery, knowing they will have a transient increase in macular thickness that resolves without adjusting the frequency of intravitreal injections and is not visually significant.

Twenty-Year Incidence of Macular Telangiectasia Type 2 and Associated Systemic Comorbidities in Olmsted County, Minnesota.

BACKGROUND AND OBJECTIVE: To identify the incidence and associated systemic and ocular risk factors of macular telangiectasia (MacTel) type 2 using a population-based study. PATIENTS AND METHODS: In this retrospective cohort study, patients with MacTel type 2 were identified using the Rochester Epidemiology Project. An age- and sex-matched 4:1 cohort of healthy control patients was created to identify systemic medical comorbidities, medications, and ophthalmic risk factors with MacTel type 2. RESULTS: Over a 20-year time period, 18 patients with MacTel type 2 were identified. The overall incidence was 0.0007% per year. Adjusting for the age and sex of the Caucasian population in the 2010 U.S. census, the overall incidence was 0.0008% (95% CI, 0.4-1.2) per year. There were significantly more MacTel type 2 patients with type 2 diabetes (P = .007), hyperlipidemia (P = .03), and hypertriglyceridemia (P = .004). CONCLUSION: The incidence of MacTel type 2 in Olmsted County, Minnesota, is 0.7 per 100,000 persons per year. These patients are more likely to have type 2 diabetes and high cholesterol. The use of aspirin and nonsteroidal anti-inflammatory drugs may be protective factors. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S35-S42.].

Fibrin hydrogels are safe, degradable scaffolds for sub-retinal implantation.

Retinal pigment epithelium (RPE) transplantation for the treatment of macular degeneration has been studied for over 30 years. Human clinical trials have demonstrated that RPE monolayers exhibit improved cellular engraftment and survival compared to single cell suspensions. The use of a scaffold facilitates implantation of a flat, wrinkle-free, precisely placed monolayer. Scaffolds currently being investigated in human clinical trials are non-degradable which results in the introduction of a chronic foreign body. To improve RPE transplant technology, a degradable scaffold would be desirable. Using human fibrin, we have generated scaffolds that support the growth of an RPE monolayer in vitro. To determine whether these scaffolds are degraded in vivo, we developed a surgical approach that delivers a fibrin hydrogel implant to the sub-retinal space of the pig eye and determined whether and how fast they degraded. Using standard ophthalmic imaging techniques, the fibrin scaffolds were completely degraded by postoperative week 8 in 5 of 6 animals. Postmortem histologic analysis confirmed the absence of the scaffold from the subretinal space at 8 weeks, and demonstrated the reattachment of the neurosensory retina and a normal RPE-photoreceptor interface. When mechanical debridement of a region of native RPE was performed during implantation surgery degradation was accelerated and scaffolds were undetectable by 4 weeks. These data represent the first in situ demonstration of a fully biodegradable scaffold for use in the implantation of RPE and other cell types for treatment of macular degeneration and other retinal degenerative diseases.