CORRELATION BETWEEN MICROPERIMETRY AND IMAGING IN EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN-LIKE APPEARANCE.

PURPOSE: To determine the correlation between microperimetry and imaging findings in extensive macular atrophy with pseudodrusen-like appearance (EMAP). METHODS: This cross-sectional, observational study included 44 consecutive patients with EMAP (88 eyes) and 30 healthy subjects (60 eyes). Both groups underwent visual acuity assessment, mesopic and scotopic microperimetry, fundus photography, autofluorescence, optical coherence tomography, and optical coherence tomography angiography. Retinal sensitivity was also subdivided in macular (0-4°) and paramacular areas (8-10°). Scotopic sensitivity loss was defined as the difference between scotopic and mesopic sensitivities for each tested point. Eyes with EMAP were further classified into the three stages described by Romano et al: 19 eyes in Stage 1, 31 in Stage 2, and 38 in Stage 3. RESULTS: Mesopic and scotopic retinal sensitivity were significantly reduced in patients with EMAP compared with controls, particularly in the macular area (all P < 0.001). Mesopic retinal sensitivity progressively declined in more advanced EMAP stages (all P < 0.01), but no scotopic differences were observed between Stages 2 and 3 ( P = 0.08). Remarkably, scotopic sensitivity loss was significantly higher in Stage 1 ( P < 0.05).On multivariate analysis, mesopic dysfunction was associated with larger atrophic areas ( P < 0.01), foveal involvement ( P = 0.03), and fibrosis ( P = 0.02). Conversely, no independent variable was associated with a reduced scotopic retinal sensitivity (all P > 0.05). CONCLUSION: The findings highlight that patients with EMAP suffer from a severe cone- and rod-mediated dysfunction on microperimetry. The predominant rod impairment in the early cases (Stage 1) emphasizes the importance of dark-adapted scotopic microperimetry as a clinical end point and suggests defective transportation across the RPE-Bruch membrane complex in its pathogenesis.

Vertebrobasilar dolichoectasia and other arterial abnormalities leading to abducens nerve palsy.

INTRODUCTION: Dolichoectatic vessels can cause cranial nerve dysfunction by either direct compression or ischemia. Abducens nerve palsy due to neurovascular compression by elongated, enlarged, tortuous or dilated arteries is an uncommon but important cause. AIM: To highlight neurovascular compression as a cause of abducens nerve palsy and discuss various diagnostic techniques. METHODS: Manuscripts were identified using the National Institutes of Health PubMed literature search system. Search terms included abducens nerve palsy, neurovascular compression, dolichoectasia and arterial compression. Inclusion criteria required that the articles were written in English. RESULTS: The literature search identified 21 case reports where abducens nerve palsy was due to vascular compression. Out of these 18 patients were male and the mean age was 54 years. Eight patients had unilateral right abducens nerve involvement; eleven patients had unilateral left nerve involvement and two patients had bilateral involvement. The arteries causing the compression were basilar, vertebral and anterior inferior cerebellar arteries. A compressed abducens nerve is not usually clearly detected on CT (Computed Tomography) or MRI (Magnetic Resonance Imaging). MRA (Magnetic Resonance Angiography), Heavy T2- WI (weighted imaging), CISS (constructive interference in steady state) and FIESTA (Fast Imaging Employing Steady-state Acquisition) are essential to demonstrate vascular compression of the abducens nerve. The various treatment options included controlling hypertension, glasses with prisms, muscle resection and microvascular decompression.

Prevalence of diabetic retinopathy and self-reported barriers to eye care among patients with diabetes in the emergency department: the diabetic retinopathy screening in the emergency department (DRS-ED) study.

BACKGROUND: Screening for diabetic retinopathy (DR) is suboptimal, and patients with diabetes who present to the emergency department (ED) may be at particularly high risk of undiagnosed DR. The purpose of this study is to determine the prevalence of DR among diabetic patients who present to the ED of our tertiary medical center using teleophthalmology and to assess self-reported barriers to eye care. METHODS: This cross-sectional, single-institution study recruited clinically stable diabetic patients who presented to the ED during daytime hours over 29 total weekdays across 2 months in 2018 and 2019. Participants had nonmydriatic, 45-degree, single-field digital retinal photographs taken on site (Digital Retinal System, Centervue). Following retinal imaging, participants then completed a survey about barriers to regular eye care and their acceptance of potential interventions to promote screening. Digital retinal photographs were interpreted remotely by a board-certified ophthalmologist and communicated to participants' primary care physician and/or endocrinologist. RESULTS: Over the study period, 275 ED patients had a documented diagnosis of diabetes, of whom 167 were deemed clinically stable for the study and 141 were invited to participate. Sixty-four were enrolled, of whom 50 had gradable-quality fundus images (78%). Of these 50 patients, almost all had type 2 diabetes (47, 94%), with an average disease duration of 12 ± 9 years and mean hemoglobin A1c of 8.1 ± 2.0% (mmol/mol). Based on fundus photography, 14 patients (28%) were diagnosed with DR, which was newly diagnosed for 10 (20% of the total study population). Severity was most commonly mild or moderate (12/14, 86%), with 1 case of severe nonproliferative DR and 1 proliferative DR. The majority (26, 52%) reported at least one barrier to routine eye care in our self-administered survey, of which having too many appointments (6, 12%) and cost (5, 10%) were frequently cited as most important. The majority were receptive to interventions to promote DR screening, including reminder phone calls (29, 58%) and text messages (28, 56%). CONCLUSIONS: Digital fundus photography in the ED detected a high rate of undiagnosed DR. Half of participants reported barriers to routine care, and most were receptive to messaging interventions to schedule an eye exam. Future studies are warranted to assess scalability of ED-based screening programs and their follow-through rates.

Surgical trends in glaucoma management: The current Indian scenario.

OBJECTIVES: To assess the current trend in the surgical management of glaucoma in India. METHODS: An anonymous online survey evaluating the preferred choices in the surgical management of glaucoma was circulated among the members of Glaucoma Society of India (GSI). Survey responses were compared to prior survey among GSI members in 2013 and members of American Glaucoma Society (AGS), 2016. RESULTS: A total of 175 of 879(20%) GSI members participated in the survey of which 75.3% of the survey participants were practicing in the private sector. Trabeculectomy with or without augmentation with Mitomycin C(MMC) was the first-choice glaucoma incisional surgery for 96.6% of the survey participants. Of the participants doing tube surgery, use of valved GDD was the preferred choice (83.4%). Re-trabeculectomy was the preferred approach (60.7%) in case of trabeculectomy failure. For paediatric glaucomas, combined trabeculotomy with trabeculectomy was the preferred surgical approach for both hazy cornea (84.5%) as well as clear cornea (66%). For a POAG patient without prior incisional surgery and presenting with visually significant cataract, phacoemulsification with trabeculectomy was the preferred management approach by 58.7% of the participants. CONCLUSION: Trabeculectomy continues to be the clear winner for the Indian glaucoma surgeon because of its cost effectiveness, lack of expensive instrumentation, and a more robust surgical training for trabeculectomy during residency programs. A higher proportion of angle closure disease precludes the use of minimally invasive glaucoma surgery and very often tube shunts also. Economics, ease of access and follow-up made a combined cataract and glaucoma surgery a preferred choice among Indian surgeons.

Breaking bad news about glaucoma: a SPIKES strategy primer.

PURPOSE: Most ophthalmic physicians are not formally trained for breaking the news of having sight threatening diseases, requiring lifelong therapy. This study aims to ascertain physician practices and patients' experiences regarding delivery of bad news. METHODS: An online, anonymous questionnaire was sent to 400 ophthalmologists practising glaucoma to gather information as to how they deliver bad news to their patients. A parallel survey was also conducted amongst 100 established glaucoma patients to know whether how their doctor had delivered the diagnosis of glaucoma to them. After this, resident doctors were trained in SPIKES strategy and the patient survey was repeated in 100 new patients. RESULTS: Two hundred and eighteen out of 400 ophthalmologists responded to our survey resulting in a survey yield of 54.5%. About 56.5% ophthalmologists dealt with disclosing the diagnosis >20 times a month; 70% of responders always discussed about the true severity of disease up-front. Only 8.70% respondents had formal training for breaking the bad news. Results of first phase of patient survey revealed that nearly one-third of patients (27%), felt that their doctor used incomprehensible medical terminology and 42% patients said that their doctor downplayed their diagnosis. Only 12% provided information to their patients about reliable sources to gather additional information. After the resident doctors were trained in SPIKES strategy, the second phase of patient survey had marked positive change in the way information was delivered. CONCLUSION: The current study shows that despite years of clinical experience, many ophthalmologists face difficulty in delivering bad news for a sight threatening disease such as glaucoma. Therefore, SPIKES strategy or a similar protocol must be taught to practising ophthalmologists at all levels, to alleviate worries of patients suffering from chronic, visually debilitating diseases.

A pilot study for smartphone photography to assess bleb morphology and vasculature post-trabeculectomy.

PURPOSE: The current grading systems used for bleb morphology assessment in patients post-trabeculectomy are based on standardized slit-lamp photographs and anterior segment imaging devices. The lack of availability of these expensive and non-portable devices in resource-deficient settings is a significant deterrent in their widespread utilization for proper post-operative management. The rapidly evolving utilization of smartphone photography has significantly benefited diagnostics of posterior segment disorders and is now being increasingly utilized for monitoring anterior segment pathologies as well as post-surgical course. In this study, we study a novel use of smartphones for bleb photography for assessing the morphological characteristics as vascularity and microcysts. METHODS: In this pilot, observational study, we compared the trabeculectomy bleb images of five subjects, obtained by iPhone X (dual lens) and iPhone 6S (single lens). We captured two image sets with both smartphones first with a focussed torchlight and then with a built-in flash video light. RESULTS: The images resulting from the newer iPhone X were substantially superior than those from iPhone 6S. For the 12-megapixel dual-camera set-up on the iPhone X, the 1 × lens resulted in better images than the 2 × lens with contrast and overall clarity of the area of interest. While the macro-lens attachment had promising results at 1 × zoom, there is no added advantage of the macro-lens attachment as it resulted in considerable loss of image quality at twice the zoom. Using a 20 D lens helped attain higher magnification and better framing as it reduced the focussing distance needed to get sharp images. The images obtained from both smartphones were of higher quality when illuminated from an external source when compared to the native iPhone flash due to even exposure and fewer autofocus artefacts. CONCLUSION: Analyses of all image sets showed that the current generation in-built camera app on IOS and newer iPhone camera optics resulted in high-quality images of the ocular surface with high magnification without any loss in clarity.

Longitudinal Quantitative Ultrawidefield Angiographic Features in Diabetic Retinopathy Treated with Aflibercept from the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement Trial.

OBJECTIVE: To report longitudinal trends of quantitative ultrawidefield fluorescein angiography (qUWFA) biomarkers in the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement (PRIME) diabetic retinopathy (DR) clinical trial. DESIGN: Post hoc analysis of the PRIME prospective randomized DR clinical trial comparing intravitreal aflibercept treatment based on the DR severity score (DRSS) or quantitative leakage index for DR improvement (ClinicalTrials.gov identifier: NCT03531294). PARTICIPANTS: Patients were enrolled with a DRSS level of 47A to 71A and best-corrected visual acuity of 20/800 or better. Key exclusion criteria were previous intravitreal injection, panretinal photocoagulation, vitrectomy, central-involving macular edema, or vitreous hemorrhage. METHODS: A previously validated, machine learning-based qUWFA analysis platform was used for panretinal leakage index assessment and differentiation of generalized and perivascular leakage phenotypes. Additionally, microaneurysm count and ischemic index were quantified in panretinal and macular regions. The trends in these biomarkers and therapeutic response were studied over 1 year. MAIN OUTCOME MEASURES: Longitudinal trends of qUWFA biomarkers. The impact of these qUWFA metrics on treatment response was assessed by studying their associations with time to 2-step DRSS improvement and number of treatment-free days. RESULTS: Forty eyes from 40 subjects with DR were enrolled. Lower baseline generalized leakage was noted in eyes that attained the 2-step DRSS improvement in < 16 weeks (1.9% vs. 2.8%; P = 0.026). Baseline macular perivascular-generalized leakage ratio had a significant correlation with the number of treatment-free days (r = 0.4; P = 0.012). At the end of 1 year, therapy significantly reduced the mean panretinal (3.9% vs. 5.8%; P = 0.002) and macular (6.2% vs. 12.2%; P = 0.008) generalized leakage indices compared with baseline, as well as the mean panretinal perivascular leakage index (1.5% vs. 2.3%; P = 0.002). The mean panretinal ischemic index demonstrated a small but likely clinically insignificant decrease from 12.5% at baseline to 11.6% at year 1 (P = 0.016). CONCLUSIONS: Down-trending leakage indices and microaneurysm counts were demonstrated over 1 year of anti-VEGF therapy. At baseline, DR eyes with lower generalized leakage responded to therapy more rapidly. Eyes with greater perivascular leakage relative to generalized leakage showed a longer-lasting anti-VEGF treatment response. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Automated Evaluation of Ellipsoid Zone At-Risk Burden for Detection of Hydroxychloroquine Retinopathy.

BACKGROUND: Screening for hydroxychloroquine (HCQ) retinopathy is crucial to detecting early disease. A novel machine-learning-based optical coherence tomography (OCT) biomarker, Ellipsoid Zone (EZ) At-Risk, can quantitatively measure EZ alterations and at-risk areas for progressive EZ loss in a fully automated fashion. The purpose of this analysis was to compare the EZ At-Risk burden in eyes with HCQ toxicity to eyes without toxicity. METHODS: IRB-approved image analysis study of 83 subjects on HCQ and 44 age-matched normal subjects. SD-OCT images were reviewed for evidence of HCQ retinopathy. A ML-based, fully automatic measurement of the percentage of the macular area with EZ At-Risk was performed. RESULTS: The mean age for HCQ subjects was 67.1 ± 13.2 years and 64.2 ± 14.3 years for normal subjects. The mean EZ At-Risk macular burden in the "toxic" group (n = 38) was significantly higher (10.7%) compared to the "non-toxic" group (n = 45; 2.2%; p = 0.023) and the "normal" group (1.4%; p = 0.012). Additionally, the amount of EZ At-Risk burden was significantly correlated with the HCQ dose based on the actual (p = 0.016) and ideal body weight (p = 0.033). CONCLUSIONS: The novel biomarker EZ-At Risk was significantly higher in subjects with evidence of HCQ retinopathy as well as significantly associated with HCQ dose. This novel biomarker should be further evaluated as a potential screening tool for subjects on HCQ.

Ellipsoid Zone Integrity and Visual Function in Dry Age-Related Macular Degeneration.

In this longitudinal retrospective image analysis, conducted on patients diagnosed with dry age-related macular degeneration (AMD) and 5 years of follow-up imaging data, the study aimed to investigate the relationship between ellipsoid zone (EZ) integrity on spectral domain optical coherence tomography (SD-OCT) and visual acuity (VA). Using a machine learning-enabled feature extraction tool, quantitative EZ parameters were derived from SD-OCT images. The analysis revealed significant correlations between EZ integrity metrics and VA. Eyes with excellent VA (≥20/25 Snellen) exhibited higher EZ integrity, including less EZ attenuation, thicker ellipsoid zone-retinal pigment epithelium (EZ-RPE) thickness, and higher EZ intensity, in contrast to eyes with worse VA (≤20/40 Snellen). Additionally, eyes with geographic atrophy (GA) in the foveal region displayed compromised EZ integrity compared to those without GA. Notably, baseline EZ integrity metrics were predictive of future VA loss. These findings suggest that quantitative SD-OCT measurements of EZ integrity could potentially detect early changes in dry AMD and serve as valuable indicators for predicting future functional outcomes. Furthermore, these measurements hold promise for use in clinical trial screenings, offering insights into the progression of the disease and its impact on visual acuity. This study underscores the importance of EZ integrity assessment in understanding and managing dry AMD.

Correlation Between Blue Fundus Autofluorescence and SD-OCT Measurements of Geographic Atrophy in Dry Age-Related Macular Degeneration.

PURPOSE: To compare fundus autofluorescence (FAF) and spectral domain optical coherence tomography (OCT) measurements of geographic atrophy (GA) area and to analyze lesion area changes measured by spectral domain OCT in GATHER1. DESIGN: An assessment reliability analysis using prospective, randomized, double-masked phase 2/3 clinical trial data. METHODS: GATHER1 examined the efficacy and safety of avacincaptad pegol (ACP) for GA treatment. A post hoc analysis was performed to identify correlations between FAF- and OCT-based measurements of GA. GA area was measured on blue-light FAF images using semiautomatic segmentation software with support from OCT and near-infrared imaging. Machine-learning enhanced, multilayer segmentation of OCT scans were reviewed by human readers, and segmentation errors were corrected as needed. GA area was defined as total RPE loss on cross-sectional B scans. Time points included Months 0, 6, 12, and 18. Additionally, OCT-based GA-area changes between ACP and sham were analyzed. RESULTS: There was a strong correlation (r = 0.93) between FAF and OCT GA area measurements that persisted through 18 months. Mean (SD) differences between OCT and FAF GA measurements were negligible: 0.11 mm2 (1.42) at Month 0, 0.03 mm2 (1.62) at Month 6, -0.17 mm2 (1.81) at Month 12, and -0.07 mm2 (1.78) at Month 18. OCT assessments of GA growth revealed a 30% and 27% reduction at Months 12 and 18, respectively, between ACP and sham, replicating FAF measurements from GATHER1. CONCLUSIONS: The strong correlation between blue FAF and OCT measurements of GA area supports OCT as a reliable method to measure GA lesion area in clinical trials.

Choroidal Mass in a Patient with Undiagnosed Pulmonary Langerhans' Cell Histiocytosis.

BACKGROUND: Langerhan cell histiocytosis (LCH), although not a common cause, should be kept in the differential diagnosis for a patient that presents with a choroidal mass. CASE PRESENTATION: A 28-year-old female presented with a 4-day history of vision loss and associated pain in her right eye. EXAMINATION AND INVESTIGATIONS: A dilated fundus examination revealed a deep subretinal, orange, mottled lesion with associated serous retinal detachment. Ultrasonography demonstrated a solid mass at the posterior pole. Fluorescein angiography revealed corresponding, small, punctate, hyperfluorescent areas with leakage and pooling in the late phase outlining the subretinal fluid. Optical coherence tomography confirmed the choroidal elevation and subretinal fluid. In addition to starting oral steroids for addressing the patient's acute symptoms, a metastatic workup was ordered due to the lesion's appearance. Diagnosis: Computed tomography (CT) of the chest showed nodular lesions and subsequent lung biopsy was S-100 and CD1a positive, diagnostic of Langerhan's cell histiocytosis (LCH). TREATMENT AND OUTCOME: The patient was treated with six cycles of vinblastine and prednisolone therapy followed with a subsequent taper of steroids. Complete resolution of signs and symptoms was noted. DISCUSSION: A review of all reported cases of ophthalmic LCH with or without choroidal involvement was conducted. Diagnostic and therapeutic approaches described in these reportshave been summarized in the current manuscript. This case highlights the importance of pursuing a systemic workup in patients with uveal mass lesions. LCH should be considered in the differential of every choroidal mass.

Automated Identification and Segmentation of Ellipsoid Zone At-Risk Using Deep Learning on SD-OCT for Predicting Progression in Dry AMD.

BACKGROUND: The development and testing of a deep learning (DL)-based approach for detection and measurement of regions of Ellipsoid Zone (EZ) At-Risk to study progression in nonexudative age-related macular degeneration (AMD). METHODS: Used in DL model training and testing were 341 subjects with nonexudative AMD with or without geographic atrophy (GA). An independent dataset of 120 subjects were used for testing model performance for prediction of GA progression. Accuracy, specificity, sensitivity, and intraclass correlation coefficient (ICC) for DL-based EZ At-Risk percentage area measurement was calculated. Random forest-based feature ranking of EZ At-Risk was compared to previously validated quantitative OCT-based biomarkers. RESULTS: The model achieved a detection accuracy of 99% (sensitivity = 99%; specificity = 100%) for EZ At-Risk. Automatic EZ At-Risk measurement achieved an accuracy of 90% (sensitivity = 90%; specificity = 84%) and the ICC compared to ground truth was high (0.83). In the independent dataset, higher baseline mean EZ At-Risk correlated with higher progression to GA at year 5 (p < 0.001). EZ At-Risk was a top ranked feature in the random forest assessment for GA prediction. CONCLUSIONS: This report describes a novel high performance DL-based model for the detection and measurement of EZ At-Risk. This biomarker showed promising results in predicting progression in nonexudative AMD patients.

Clinical, Genotypic, and Imaging Characterization of the Spectrum of ABCA4 Retinopathies.

PURPOSE: To investigate the clinical and genotypic differences in the spectrum of ABCA4-associated retinopathies (ABCA4Rs). DESIGN: Observational, cross sectional case series. PARTICIPANTS: Sixty-six patients (132 eyes) carrying biallelic ABCA4 variants. METHODS: Patients underwent visual acuity measurement and multimodal imaging. Clinical records were reviewed for age at onset, presenting symptoms, genetic variants, and electroretinogram (ERG). Each eye was assigned to a phenotype based on age at onset, imaging and ERG: cone dystrophy-bull's-eye maculopathy (CD-BEM, 40 eyes), cone-rod dystrophy (CRD, 12 eyes), Stargardt disease (SD, 28 eyes), late-onset SD (LO-SD, 38 eyes), and fundus flavimaculatus (14 eyes). Images were analyzed for: peripapillary sparing, retinal pigment epithelium (RPE) atrophy (definitely decreased autofluorescence, DDAF), flecks patterns using autofluorescence; type of atrophy according to Classification of Atrophy Meeting reports, macular and choroidal thickness on OCT; and choriocapillaris flow deficits on OCT angiography. MAIN OUTCOME MEASURES: Primary outcome was to report the demographic, genotypic, and imaging characteristics of the different ABCA4R phenotypes. Secondary objectives included the assessment of imaging biomarkers as outcome measures for clinical trials. RESULTS: Age at onset was lower in CRD (12 ± 8 years) and higher in patients with LO-SD (59 ± 9 years) (all P < 0.01). Central vision loss was a common presenting symptom in CD-BEM and SD, whereas patients with LO-SD primarily complained of difficult dark adaptation. Missense variants were more frequent in CD-BEM, and splice site in CRD and LO-SD (P < 0.05). Peripapillary sparing was absent in 3 eyes with LO-SD (8%). Cone dystrophy-bull's-eye maculopathy eyes typically had complete outer retinal atrophy alterations (98%), whereas CRD and SD eyes showed both complete outer retinal atrophy and complete RPE and outer retinal atrophy (cRORA) (71%-100%). Patients with LO-SD had larger areas of DDAF (100% cRORA) and of choriocapillaris flow deficits (all P < 0.01). Repeatability of DDAF measurements was low for some phenotypes (CD-BEM and CRD) and atrophic areas <7.5 mm2. Resorbed flecks were significantly associated with CRD and LO-SD (P < 0.01). CONCLUSIONS: This research provides a thorough evaluation of the spectrum of ABCA4R. Our findings suggest that certain phenotypes show preferential photoreceptor degeneration (e.g., CD-BEM), whereas others have substantial RPE and choriocapillaris alterations (e.g., LO-SD). We recommend that clinical trial end points take into consideration these imaging features to improve the interpretation of their results. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Challenges in posterior uveitis-tips and tricks for the retina specialist.

PURPOSE: Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic. The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases. Inflammation can be confined to the eye or may be a part of systemic disease. A useful outline is therefore proposed to aid in the correct diagnosis of these challenging entities. The situation is further complicated by the fact that many neoplastic conditions resemble features of posterior uveitis; they are known as "masqueraders of uveitis". Here, we summarize different posterior uveitides that present with rare findings, along with masqueraders that can be difficult to distinguish. These conditions pose a diagnostic dilemma resulting in delay in treatment because of diagnostic uncertainty. METHODS: An extensive literature search was performed on the MEDLINE/PUBMED, EBSCO and Cochrane CENTRAL databases from January 1985 to January 2022 for original studies and reviews of predetermined diagnoses that include posterior uveitic entities, panuveitis and masquerade syndromes. RESULTS: We described conditions that can present as mimickers of posterior uveitis (i.e., immune check-points inhibitors and Vogt-Koyanagi-Harada-like uveitis; leukemia and lymphoma associated posterior uveitis), inflammatory conditions that present as mimickers of retinal diseases (i.e., Purtscher-like retinopathy as a presentation of systemic lupus erythematosus; central serous chorioretinopathy masquerading inflammatory exudative retinal detachment), and uveitic conditions with rare and diagnostically challenging etiologies (i.e., paradoxical inflammatory effects of anti-TNF-α; post vaccination uveitis; ocular inflammation after intravitreal injection of antiangiogenic drugs). CONCLUSION: This review of unique posterior uveitis cases highlights the overlapping features of posterior uveitis (paradoxical inflammatory effects of anti -TNF α and uveitis; Purtscher-like retinopathy as a presentation of systemic lupus erythematosus, …) and the nature of retinal conditions (ischemic ocular syndrome, or central retinal vein occlusion, amyloidosis, inherited conditions like retinitis pigmentosa, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), etc.…) that may mimic them is represented. Careful review of past uveitis history, current medications and recent vaccinations, detailed examination of signs of past or present inflammation, eventually genetic testing and/ or multimodal retinal imaging (like fluorescein angiography, EDI-OCT, OCT-angiography for lupus Purtscher-like retinopathy evaluation, or ICG for central serous retinopathy, or retinal amyloid angiopathy) may aid in correct diagnosis.

Automated lesion segmentation and quantification for prediction of paradoxical worsening in patients with tubercular serpiginous-like choroiditis.

To develop and evaluate a fully automated pipeline that analyzes color fundus images in patients with tubercular serpiginous-like choroiditis (TB SLC) for prediction of paradoxical worsening (PW). In this retrospective study, patients with TB SLC with a follow-up of 9 months after initiation of anti-tubercular therapy were included. A fully automated custom-designed pipeline was developed which was initially tested using 12 baseline color fundus photographs for assessment of repeatability. After confirming reliability using Bland-Altman plots and intraclass correlation coefficient (ICC), the pipeline was deployed for all patients. The images were preprocessed to exclude the optic nerve from the fundus photo using a single-shot trainable WEKA segmentation algorithm. Two automatic thresholding algorithms were applied, and quantitative metrics were generated. These metrics were compared between PW + and PW- groups using non-parametric tests. A logistic regression model was used to predict probability of PW for assessing binary classification performance and receiver operator curves were generated to choose a sensitivity-optimized threshold. The study included 139 patients (139 eyes; 92 males and 47 females; mean age: 44.8 ± 11.3 years) with TB SLC. Pilot analysis of 12 images showed an excellent ICC for measuring the mean area, intensity, and integrated pixel intensity (all ICC > 0.89). The PW + group had significantly higher mean lesion area (p = 0.0152), mean pixel intensity (p = 0.0181), and integrated pixel intensity (p < 0.0001) compared to the PW- group. Using a sensitivity optimized threshold cut-off for mean pixel intensity, an area under the curve of 0.87 was achieved (sensitivity: 96.80% and specificity: 72.09%). Automated calculation of lesion metrics such as mean pixel intensity and segmented area in TB SLC is a novel approach with good repeatability in predicting PW during the follow-up.

Predictive Factors of Research Productivity among Ophthalmology Residents: A Benchmark Analysis.

Introduction Positive and negative associations between prior publications and future research productivity is described in other fields, but no such analysis exists for ophthalmology. We conducted a study to determine characteristics of residents exhibiting research productivity during residency. Methods Using San Francisco Match and Program Web sites, a roster of ophthalmology residents in 2019 to 2020 was compiled, and publication data was collected via PubMed and Google Scholar on a random sample of 100 third-year residents. Results The median number of publications generated by ophthalmology residents before residency is 2 (range 0-13). Thirty-seven, 23, and 40 residents had zero, one, and two or more papers published during residency, respectively, with a median of 1 (range 0-14). On univariate analysis, compared with residents who published zero or one paper, those who published ≥ 2 were more likely to have more preresidency publications (odds ratio [OR] 1.30; p = 0.005), attend a top-25 ranked residency program by multiple metrics including Doximity reputation (OR 4.92; p < 0.001), and have attended a top-25 ranked medical school program by U.S. News and World Report (OR 3.24; p = 0.03). However, on adjusted analyses, the only factor that remained significant for predicting publications in residency was whether the residency program attended was top 25 ranked (OR 3.54; p = 0.009). Discussion/Conclusion With the advent of the United States Medical Licensing Examination Step 1 pass/fail system, greater emphasis will be placed on other metrics, including research. This is the first benchmark analysis examining factors predictive of publication productivity in ophthalmology residents. Our study suggests that the residency program attended, not the medical school attended or prior publication history, plays an influential role in the number of publications produced during residency, highlighting the importance of factors to support research on the institutional level, such as mentorship and funding, rather than historical factors in research productivity by the resident.

Long-term retinal changes in progressive geographic atrophy.

BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of blindness with loss of retinal layers over long term. We aim to evaluate these changes in eyes with progressive non-exudative AMD with geographic atrophy (GA). METHODS: This retrospective study included patients with GA with a minimum of 4 years follow up. Retinal layers on spectral domain optical coherence tomography (SD-OCT) were segmented based on their reflectivity patterns using validated semi-automated segmentation algorithm. The thickness of the segmented retinal layers was measured. Horizontal length of GA at baseline and last follow-up were also measured. Regression analysis was performed to correlate changes in RPE layer thickness with other retinal layers and the length of GA on OCT. RESULTS: A total of 351-line scans including 17 foveal scans showing presence of GA at final visit that is, a total of 2457 retinal layer bands were analyzed. Outer nuclear layer (ONL) (p = 0.02), outer segment layers (OSL) (p = 0.01), and retinal pigment epithelium (RPE) (p = 0.01) showed a statistically significant variation between baseline and final visit. Regression analysis showed the change in ONL (r = 0.72; p = 0.01) and OSL (r = 0.93, p < 0.01) correlated significantly with change in RPE thickness whereas rest of the layers failed to show significant correlation. CONCLUSION: Outer retinal layers (ONL and OSL) show more significant and widespread changes in retinal thickness and correlated most significantly with RPE thickness changes in eyes with GA due to AMD. Assessment of various retinal layer bands can be used as surrogate quantitative parameters to study eyes with GA.

Optical coherence tomography (OCT) angiolytics: a review of OCT angiography quantitative biomarkers.

Optical coherence tomography angiography (OCTA) provides a non-invasive method to obtain angiography of the chorioretinal vasculature leading to its recent widespread adoption. With a growing number of studies exploring the use of OCTA, various biomarkers quantifying the vascular characteristics have come to light. In the current report, we summarize the biomarkers currently described for retinal and choroidal vasculature using OCTA systems and the methods used to obtain them. Further, we present a critical review of these methods and key findings in common retinal diseases and appraise future directions, including applications of artificial intelligence in OCTA .

Machine Learning-Based Automated Detection of Hydroxychloroquine Toxicity and Prediction of Future Toxicity Using Higher-Order OCT Biomarkers.

OBJECTIVE: Despite guidelines for hydroxychloroquine (HCQ) toxicity screening, there are clear challenges to accurate detection and interpretation. In the current report, the feasibility of automated machine learning (ML)-based detection of HCQ retinopathy and prediction of progression to toxicity in eyes without preexisting toxicity has been described. DESIGN: Retrospective, longitudinal cohort study. SUBJECTS: Subjects on HCQ therapy. METHODS: This was an institutional review board-approved, retrospective, longitudinal image analysis of 388 subjects on HCQ. Multilayer, compartmental, retinal segmentation with ellipsoid zone (EZ) mapping was used to harvest quantitative spectral-domain (SD)-OCT biomarkers. Using a combination of clinical features (i.e., cumulative HCQ dose and the duration of therapy) and quantitative imaging biomarkers (e.g., volumetric EZ integrity and compartmental measurements), ML models were created to detect toxicity and predict progression based on ground-truth OCT-based toxicity readings by 2 masked retina specialists. Furthermore, 10-fold cross-validation was performed. MAIN OUTCOME MEASURES: The model performance was visualized using receiver operator curves and calculating the area under the curve (AUC). The corresponding sensitivity and specificity values were evaluated for the feasibility of HCQ toxicity screening and prediction. RESULTS: The prevalence of HCQ toxicity in this cohort of 388 patients was 9.8% (n = 38). Twenty-one eyes progressed to toxicity during follow-up. OCT-based features (i.e., partial EZ attenuation, EZ volume, outer nuclear layer volume, and compartmental thicknesses) and clinical features (i.e., HCQ daily dose, HCQ cumulative dose, and duration of therapy) showed significant differences between the toxic and nontoxic groups. Percentage area with partial EZ attenuation (i.e., percentage of the macula with an EZ-retinal pigment epithelium thickness of ≤ 20 µm) was the most discriminating single feature (toxic, 35.7 ± 46.5%; nontoxic, 1.8 ± 4.4%; P < 0.0001). Using a random forest model, high-performance, automated toxicity detection was achieved, with a mean AUC of 0.97, sensitivity of 95%, and specificity of 91%. Furthermore, the toxicity progression prediction model had a mean AUC of 0.89, with a sensitivity and specificity of 90% and 80%, respectively. CONCLUSIONS: This report described the feasibility of high-performance automated classification models that used a combination of clinical and quantitative SD-OCT biomarkers to detect HCQ retinal toxicity and predict progression to toxicity in cases without toxicity. Future work is needed to validate these findings in an independent dataset.

Accuracy Assessment of Outpatient Telemedicine Encounters at an Academic Ophthalmology Department.

Purpose We assess the clinical accuracy of direct-to-patient real-time outpatient video visit encounters at our eye center. Design This was a retrospective longitudinal study. Subjects and Methods Patients who completed a video visit over a 3-week period between March and April 2020 were included. Accuracy assessment was determined by comparing diagnosis and management from the video visit with subsequent in-person follow-up over the next year. Results A total of 210 patients (mean age 55±18 years) were included, of whom 172 (82%) were recommended a scheduled in-person follow-up encounter after their video visit. Among the 141 total patients who completed in-person follow-up, 137 (97%) had a diagnostic agreement between telemedicine and in-person evaluation. Management plan agreed for 116 (82%), with the remainder of visits either escalating or deescalating treatment upon in-person follow-up with little substantive change. Compared with established patients, new patients had higher diagnostic disagreement following video visits (12 vs. 1%, p =0.014). Acute visits trended toward more diagnostic disagreement compared with routine visits (6 vs. 1%, p =0.28) but had a similar rate of management change on follow-up (21 vs. 16%, p =0.48). New patients were more likely to have early unplanned follow-up than established patients (17 vs. 5%, p =0.029), and acute video visits were associated with unplanned early in-person assessments compared with routine video visits (13 vs. 3%, p =0.027). There were no serious adverse events associated with the use of our telemedicine program in the outpatient setting. Conclusions Video visits had high diagnostic and management agreement with subsequent in-person follow-up encounters.