Frequency and Distribution of Ophthalmic Surgical Procedures among Patients with Inherited Retinal Diseases.

OBJECTIVE: In this study, we aimed to characterize the frequency and distribution of ocular surgeries in patients with inherited retinal diseases (IRDs) and evaluate associated patient and disease factors. DESIGN: Retrospective cohort. PARTICIPANTS: Subjects aged ≥ 18 years who were followed at the Johns Hopkins Genetic Eye Disease Center. METHODS: We studied a retrospective cohort of patients with an IRD diagnosis to analyze the occurrence of laser and incisional surgeries. Subjects were categorized into 2 groups: central dysfunction (macular/cone/cone-rod dystrophy, "MCCRD group") and panretinal or peripheral dysfunction (retinitis pigmentosa-like, "RP group"). Genetic testing status was recorded. The association of patient and disease factors on the frequency, distribution, and timing of surgeries was analyzed. MAIN OUTCOME MEASURES: Prevalence, prevalence odds ratio (POR), hazard ratio (HR) of ophthalmic procedures by phenotype. RESULTS: A total of 1472 eyes of 736 subjects were evaluated. Among them, 31.3% (n = 230) had undergone ocular surgery, and 78.3% of those (n = 180/230) had a history of more than 1 surgery. A total of 602 surgical procedures were analyzed. Cataract extraction with intraocular lens implantation (CEIOL) was the most common (51.2%), followed by yttrium aluminum garnet capsulotomy, refractive surgery, retinal surgery, and others. Cataract extraction with intraocular lens implantation occurred more frequently in RP than in MCCRD subjects (POR, 2.59; P = 0.002). Retinitis pigmentosa subjects underwent CEIOL at a younger age than patients with MCCRD (HR, 2.11; P < 0.001). CONCLUSIONS: Approximately one-third of patients with IRD had a history of laser or incisional surgery. Cataract extraction with intraocular lens implantation was the most common surgery; its frequency and timing may be associated with the IRD phenotype. This data may inform the design of prospective research. Such efforts may illuminate routine clinical decision-making and contribute to surgical strategy development for cell and gene therapy delivery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Automated identification of fleck lesions in Stargardt disease using deep learning enhances lesion detection sensitivity and enables morphometric analysis of flecks.

PURPOSE: To classify fleck lesions and assess artificial intelligence (AI) in identifying flecks in Stargardt disease (STGD). METHODS: A retrospective study of 170 eyes from 85 consecutive patients with confirmed STGD. Fundus autofluorescence images were extracted, and flecks were manually outlined. A deep learning model was trained, and a hold-out testing subset was used to compare with manually identified flecks and for graders to assess. Flecks were clustered using K-means clustering. RESULTS: Of the 85 subjects, 45 were female, and the median age was 37 years (IQR 25-59). A subset of subjects (n=41) had clearly identifiable fleck lesions, and an AI was successfully trained to identify these lesions (average Dice score of 0.53, n=18). The AI segmentation had smaller (0.018 compared with 0.034 mm2, p<0.001) but more numerous flecks (75.5 per retina compared with 40.0, p<0.001), but the total size of flecks was not different. The AI model had higher sensitivity to detect flecks but resulted in more false positives. There were two clusters of flecks based on morphology: broadly, one cluster of small round flecks and another of large amorphous flecks. The per cent frequency of small round flecks negatively correlated with subject age (r=-0.31, p<0.005). CONCLUSIONS: AI-based detection of flecks shows greater sensitivity than human graders but with a higher false-positive rate. With further optimisation to address current shortcomings, this approach could be used to prescreen subjects for clinical research. The feasibility and utility of quantifying fleck morphology in conjunction with AI-based segmentation as a biomarker of progression require further study.

Deep Learning Model for Static Ocular Torsion Detection Using Synthetically Generated Fundus Images.

Purpose: The objective of the study is to develop deep learning models using synthetic fundus images to assess the direction (intorsion versus extorsion) and amount (physiologic versus pathologic) of static ocular torsion. Static ocular torsion assessment is an important clinical tool for classifying vertical ocular misalignment; however, current methods are time-intensive with steep learning curves for frontline providers. Methods: We used a dataset (n = 276) of right eye fundus images. The disc-foveal angle was calculated using ImageJ to generate synthetic images via image rotation. Using synthetic datasets (n = 12,740 images per model) and transfer learning (the reuse of a pretrained deep learning model on a new task), we developed a binary classifier (intorsion versus extorsion) and a multiclass classifier (physiologic versus pathologic intorsion and extorsion). Model performance was evaluated on unseen synthetic and nonsynthetic data. Results: On the synthetic dataset, the binary classifier had an accuracy and area under the receiver operating characteristic curve (AUROC) of 0.92 and 0.98, respectively, whereas the multiclass classifier had an accuracy and AUROC of 0.77 and 0.94, respectively. The binary classifier generalized well on the nonsynthetic data (accuracy = 0.94; AUROC = 1.00). Conclusions: The direction of static ocular torsion can be detected from synthetic fundus images using deep learning methods, which is key to differentiate between vestibular misalignment (skew deviation) and ocular muscle misalignment (superior oblique palsies). Translational Relevance: Given the robust performance of our models on real fundus images, similar strategies can be adopted for deep learning research in rare neuro-ophthalmologic diseases with limited datasets.

NOVEL OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN SEROUS MACULAR DETACHMENT AFTER PANRETINAL PHOTOCOAGULATION.

PURPOSE: To describe a novel optical coherence tomography finding in a case of macular serous retinal detachment after pars plana vitrectomy and panretinal photocoagulation. METHODS: Retrospective case report. RESULTS: A 52 year old male with diabetes underwent uncomplicated pars plana vitrectomy with panretinal photocoagulation for non-clearing vitreous hemorrhage, Postoperative course was complicated by significantly decreased vision and a macular serous retinal detachment that was characterized on optical coherence tomography by a reticular network of hyperreflective bands in the subretinal space. Fluid and hyperreflective material in the subretinal space resolved by postoperative Week 6 with standard postoperative eye drops. However, persistent ellipsoid zone disruption was seen up to postoperative Week 20. CONCLUSION: Extensive subretinal bands can be seen after panretinal photocoagulation. This novel finding can pose diagnostic and management challenges but may resolve with conservative medical management.

Prediction of visual impairment in retinitis pigmentosa using deep learning and multimodal fundus images.

BACKGROUND: The efficiency of clinical trials for retinitis pigmentosa (RP) treatment is limited by the screening burden and lack of reliable surrogate markers for functional end points. Automated methods to determine visual acuity (VA) may help address these challenges. We aimed to determine if VA could be estimated using confocal scanning laser ophthalmoscopy (cSLO) imaging and deep learning (DL). METHODS: Snellen corrected VA and cSLO imaging were obtained retrospectively. The Johns Hopkins University (JHU) dataset was used for 10-fold cross-validations and internal testing. The Amsterdam University Medical Centers (AUMC) dataset was used for external independent testing. Both datasets had the same exclusion criteria: visually significant media opacities and images not centred on the central macula. The JHU dataset included patients with RP with and without molecular confirmation. The AUMC dataset only included molecularly confirmed patients with RP. Using transfer learning, three versions of the ResNet-152 neural network were trained: infrared (IR), optical coherence tomography (OCT) and combined image (CI). RESULTS: In internal testing (JHU dataset, 2569 images, 462 eyes, 231 patients), the area under the curve (AUC) for the binary classification task of distinguishing between Snellen VA 20/40 or better and worse than Snellen VA 20/40 was 0.83, 0.87 and 0.85 for IR, OCT and CI, respectively. In external testing (AUMC dataset, 349 images, 166 eyes, 83 patients), the AUC was 0.78, 0.87 and 0.85 for IR, OCT and CI, respectively. CONCLUSIONS: Our algorithm showed robust performance in predicting visual impairment in patients with RP, thus providing proof-of-concept for predicting structure-function correlation based solely on cSLO imaging in patients with RP.

PSEUDOMONAL CHOROIDAL ABSCESS AFTER ROUTINE PARS PLANA VITRECTOMY IN AN IMMUNOSUPPRESSED PATIENT.

PURPOSE: To describe an unusual case of pseudomonal choroidal abscess which developed after a routine pars plana vitrectomy in an immunosuppressed patient. METHODS: Case report. A 61-year-old woman with a history of rheumatoid arthritis and ulcerative colitis on abatacept underwent pars plana vitrectomy. A few days after the patient's operation, a partially serous choroidal detachment was identified. Her choroidal detachment increased in size despite prednisone therapy, and she was taken to the operating room for repeat vitrectomy and choroidal drainage. Intraoperatively, there was no significant intraocular inflammation, but purulent whitish material was expressed during external choroidal drainage which grew Pseudomonas aeruginosa. RESULTS: The patient was given intravenous antibiotics. Systemic infectious workup was negative for blood and urine cultures. The patient was transitioned to oral antibiotics, but had persistent eye pain after discharge and vision remained at count fingers. A computed tomography orbit scan with contrast showed persistent choroidal abscess, and intravitreal ceftazidime injections were administered. The patient's subjective pain resolved within several days of the first intravitreal injection; repeat ultrasound also showed interval resolution of the choroidal elevation. One year after the resolution of her choroidal abscess, her visual acuity was Snellen 20/250 in the affected eye. CONCLUSION: Isolated choroidal bacterial abscess is a possible, but rare, complication of pars plana vitrectomy. Although visual prognosis is poor, especially for pseudomonal choroidal abscesses, aggressive treatment with timely choroidal drainage, systemic antibiotics, and intravitreal antibiotics may allow recovery of some ambulatory vision.

Global Current Practice Patterns for the Management of Open Globe Injuries.

PURPOSE: To determine global current practice patterns for the management of open globe injuries and identify areas of variation. DESIGN: Cross-sectional survey. METHODS: An online survey assessed global management paradigms for open globe injuries from August 2020 to January 2021. Responses were collected from experts at eye trauma centers and emergency departments worldwide who manage ≥1 open globe injury per month. The survey assessed the use/selection of antibiotics and steroids, procedural and imaging decisions, and admission practices for open globe injuries. RESULTS: Responses were received from representatives of 36 of 42 institutions (85.7%), of which 33 (78.6%) had sufficient trauma volume to be included. Included responses were distributed across North America (n=12, 36.4%), Asia (n=12, 36.4%), South America (n=4, 12.1%), Africa (n=3, 9.1%), Europe (n=1, 3.0%), and Australia (n=1, 3.0%). Preoperative systemic antibiotics for open globe injuries were administered by 75.8% (n = 25/33) of institutions, while 30.3% (n = 10/33) administered preoperative topical antibiotics. Intraoperative ophthalmic antibiotics for open globe injuries were used by 54.5% (n = 18/33) of experts. Most institutions also administered postoperative systemic antibiotics (n = 23 [69.7%]) and topical steroids (n = 29 [87.9%]), although specific medication choices diverged. At 19 responding centers (61.3% of the 31 that had trainees), residents participated in surgical repairs. Many institutions discharged patients after repair, but 54.5% (n = 18/33) of locations routinely admitted them for observation. CONCLUSIONS: Preferred management practices for open globe injuries vary widely. To ensure the highest standard of care for all patients, evidence-based international guidelines for the treatment of these injuries are needed.

Application of Deep Learning to Retinal-Image-Based Oculomics for Evaluation of Systemic Health: A Review.

The retina is a window to the human body. Oculomics is the study of the correlations between ophthalmic biomarkers and systemic health or disease states. Deep learning (DL) is currently the cutting-edge machine learning technique for medical image analysis, and in recent years, DL techniques have been applied to analyze retinal images in oculomics studies. In this review, we summarized oculomics studies that used DL models to analyze retinal images-most of the published studies to date involved color fundus photographs, while others focused on optical coherence tomography images. These studies showed that some systemic variables, such as age, sex and cardiovascular disease events, could be consistently robustly predicted, while other variables, such as thyroid function and blood cell count, could not be. DL-based oculomics has demonstrated fascinating, "super-human" predictive capabilities in certain contexts, but it remains to be seen how these models will be incorporated into clinical care and whether management decisions influenced by these models will lead to improved clinical outcomes.

Prevalence of diabetic retinopathy in children and adolescents at an urban tertiary eye care center.

BACKGROUND: Diabetic retinopathy (DR) is a serious complication that can progress to sight-threatening disease. The prevalence of DR in youth with diabetes has been reported to be 3.8% to 20%. OBJECTIVE: We aimed to evaluate the prevalence of DR among youth with diabetes at a large ophthalmologic referral center. Secondary goals were to determine the risk factors for DR and severity of disease. METHODS: Retrospective chart review of 343 patients with diabetes, <21 years of age, seen at a tertiary referral eye care center from 2013 to 2018. RESULTS: The study included 343 patients, of which 293 had type 1 diabetes (T1D) and 50 had type 2 diabetes (T2D). Thirteen of 343 patients had DR, with an overall incidence of 3.8% (3.4% in T1D and 6% T2D). DR severity included nine with mild non-proliferative, three moderate non-proliferative, and one with proliferative DR. Patients with hemoglobin A1c (HbA1c) > 8% had a higher risk of DR (P = .049). In this cohort, none of the patients with an HbA1c <8% had DR. In the multivariate analysis, a higher systolic blood pressure was marginally associated with risk for DR (P = .07). CONCLUSIONS: We found lower prevalence of DR in youth with diabetes than previously reported. The incidence of DR was higher among patients with T2D and occurred with a shorter duration of disease, as compared with T1D. While the incidence of DR in youth with T1D is low, with the increasing incidence of T2D in adolescents and early risk for DR, early screening must be emphasized.

Multimodal Retinal Imaging in Incontinentia Pigmenti Including Optical Coherence Tomography Angiography: Findings From an Older Cohort With Mild Phenotype.

Importance: Incontinentia pigmenti (IP) is a rare, X-linked dominant disease with potentially severe ocular complications that predominantly affect the peripheral retina. However, little is known about its effects on the macula. Objective: To describe the structural and vascular abnormalities observed in the maculas of patients with IP and to correlate these findings with peripheral pathologies. Design, Setting, and Participants: Prospective, cross-sectional study at Wilmer Eye Institute, Johns Hopkins University. Five participants with a clinical diagnosis of IP were included and underwent multimodal imaging with ultra-wide-field fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT), and OCT angiography. Main Outcomes and Measures: The structural and vascular abnormalities observed on spectral-domain OCT and OCT angiography and their correlation with peripheral pathologies seen on ultra-wide-field FA. Results: A total of 9 eyes from 5 patients (median age, 20.5 years; range, 8.4-54.2 years) were included. Median Snellen visual acuity was 20/32 (range, 20/16 to 20/63). ultra-wide-field FA-identified retinal vascular abnormalities in all 7 eyes in which FA was obtained. These abnormalities included microaneurysms, areas of nonperfusion, and vascular anastomoses, most of which were peripheral to the standard view of 30° FA with peripheral sweeps. Structural abnormalities were observed in 6 eyes on spectral-domain OCT, including inner retinal thinning and irregularities in the outer plexiform layer. Optical coherence tomography angiography abnormalities were noted in all 9 eyes, including decreased vascular density, abnormal vascular loops, and flow loss in the superficial and deep plexuses, which corresponded to areas of retinal thinning on spectral-domain OCT. Conclusions and Relevance: Although our study is limited by the small sample size, the findings suggest that multimodal imaging is useful for detecting structural and vascular abnormalities that may not be apparent on ophthalmoscopy in patients with IP. Macular pathologies, especially a decrease in vascular density on OCT angiography, are common. Further studies are needed to characterize further the association between macular and peripheral abnormalities in patients with IP.

Evolution of Leukemic Retinal Hemorrhages Documented by Spectral-Domain OCT and Color Fundus Photography.

PURPOSE: Retinal hemorrhages are observed frequently in patients with leukemia. However, little is known about the impact and natural history of these hemorrhages. The purpose of this study was to describe leukemic retinal hemorrhages using multimodal imaging and to monitor their evolution longitudinally. DESIGN: Retrospective case series. PARTICIPANTS: A total of 11 eyes of 7 symptomatic leukemic patients with posterior segment hemorrhages. METHODS: Single-center study performed at the Johns Hopkins Hospital. Symptomatic leukemic patients with posterior segment hemorrhages underwent serial dilated fundus examinations. The hemorrhages were documented longitudinally with color fundus photographs and spectral-domain (SD) OCT. MAIN OUTCOMES MEASURES: Microanatomic locations of leukemic retinal hemorrhages and their impact on vision and evolution over time. RESULTS: A total of 7 patients (71.4% men; 57.1% white, 28.6% black, and 14.3% Hispanic) were included, with 11 eyes showing posterior segment hemorrhages. The median age at presentation was 49.8 years. All patients had intraretinal hemorrhages; these involved the vitreous and sub-internal limiting membrane (ILM) space in 1 and 3 patients, respectively. The median total follow-up duration was 4.0 months. At the final follow-up visits, 4 of 6 patients showed complete resolution of hemorrhages on examination and color fundus photographs. The final SD-OCT images of all patients did not show any retinal thinning, disruption of the ellipsoid zone, disorganization of the retinal layers, intraretinal fluid, or subretinal fluid. CONCLUSIONS: Symptomatic leukemic retinal hemorrhages are associated with anemia and thrombocytopenia. These hemorrhages, including visually significant central sub-ILM hemorrhages, tend to be self-limiting and resolve within a few months with treatment of the underlying disease.

Correlation of Ultra-Widefield Fluorescein Angiography and OCT Angiography in Sickle Cell Retinopathy.

PURPOSE: To determine whether the degree of peripheral nonperfusion seen on ultra-widefield (UWF) fluorescein angiography (FA) correlates with measures of macular vascular flow as seen on OCT angiography (OCTA) in sickle cell retinopathy. DESIGN: Prospective, observational study. PARTICIPANTS: Patients with sickle cell disease undergoing an eye examination at an urban, tertiary medical center. METHODS: All patients underwent dilated fundus examination as well as UWF FA and macular OCTA imaging on the same day. The peripheral nonperfusion seen on UWF FA was measured to calculate an ischemic index (visualized nonperfusion/total visualized retinal area × 100%), and OCTA measurements of macular vessel density were recorded. The degree of peripheral nonperfusion and vessel density were then correlated. MAIN OUTCOME MEASURES: Correlation between ischemic index as seen on UWF FA and macular vessel density on OCTA. RESULTS: Thirty-six eyes from 19 patients (10 women, 9 men) with a mean age of 30.8 years were included. Sickle genotypes included 14 patients with SS (73.7%), 4 with SC (21.1%), and 1 with ß-thalassemia (5.2%). Average ischemic index was 4.4% for all eyes and was found to be higher in patients with sickle SC (8.0%) than in those with sickle SS (3.2%; P = 0.01). Ischemic index also was higher in those with proliferative sickle cell retinopathy (9.3%) than in those without (2.8%; P < 0.01). Ischemic index on UWF FA showed a statistically significant correlation (P < 0.05) with vessel density on OCTA in the temporal subfield of the superficial capillary plexus and in all subfields of the deep capillary plexus. CONCLUSIONS: Peripheral nonperfusion seen on UWF FA is greater in those with sickle SC disease and proliferative retinopathy and is correlated with macular vessel density on OCTA, especially the deep retinal plexus.

Peripheral Retinal Neovascularization with Vitreous Hemorrhage in HIV Retinopathy.

We report a case of peripheral retinal neovascularization and vitreous hemorrhage in the setting of HIV retinopathy that can serve to extend the clinical spectrum of this condition. A 53-year-old African-American woman with AIDS was referred for decreased vision in the left eye and was found to have peripheral retinal neovascularization and vitreous hemorrhage. She had a workup that was negative for etiologies of retinal ischemia. Peripheral laser photocoagulation was used to treat areas of nonperfusion. To our knowledge, this is the first reported case of peripheral retinal neovascularization and vitreous hemorrhage in the setting of HIV retinopathy, and it can serve to extend the clinical spectrum of this condition.

Retinal optical coherence tomography manifestations of intraocular lymphoma.

PURPOSE: Primary central nervous system lymphoma (PCNSL) is a rare disease. The index report describes a patient with intraocular lymphoma secondary to recurrent PCNSL and corresponding retinal findings on spectral domain optical coherence tomography (SD-OCT). METHODS: Case report. RESULTS: OCT changes were documented and correlated with the clinical course of intraocular lymphoma progression in the index patient. The OCT changes, manifested as hyperreflective material accumulation in the intraretinal and subretinal pigment epithelial spaces, were caused by lymphomatous infiltration. CONCLUSION: SD-OCT can be useful in diagnosing and monitoring the progression or regression of intraocular lymphoma with retinal involvement.