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Brown A, Cousins H, Cousins C, Esquenazi K, Elze T, Harris A, Filipowicz A, Barna L, Yonwook K, Vinod K, Chadha N, Altman RB, Coote M, Pasquale LR. Deep Learning for Localized Detection of Optic Disc Hemorrhages. Am J Ophthalmol 2023;255:161-169.Abstract
PURPOSE: To develop an automated deep learning system for detecting the presence and location of disc hemorrhages in optic disc photographs. DESIGN: Development and testing of a deep learning algorithm. METHODS: Optic disc photos (597 images with at least 1 disc hemorrhage and 1075 images without any disc hemorrhage from 1562 eyes) from 5 institutions were classified by expert graders based on the presence or absence of disc hemorrhage. The images were split into training (n = 1340), validation (n = 167), and test (n = 165) datasets. Two state-of-the-art deep learning algorithms based on either object-level detection or image-level classification were trained on the dataset. These models were compared to one another and against 2 independent glaucoma specialists. We evaluated model performance by the area under the receiver operating characteristic curve (AUC). AUCs were compared with the Hanley-McNeil method. RESULTS: The object detection model achieved an AUC of 0.936 (95% CI = 0.857-0.964) across all held-out images (n = 165 photographs), which was significantly superior to the image classification model (AUC = 0.845, 95% CI = 0.740-0.912; P = .006). At an operating point selected for high specificity, the model achieved a specificity of 94.3% and a sensitivity of 70.0%, which was statistically indistinguishable from an expert clinician (P = .7). At an operating point selected for high sensitivity, the model achieves a sensitivity of 96.7% and a specificity of 73.3%. CONCLUSIONS: An autonomous object detection model is superior to an image classification model for detecting disc hemorrhages, and performed comparably to 2 clinicians.
Jabs DA, Sugar EA, Burke AE, Altaweel MM, Dunn JP, Gangaputra S, Kempen JH, Pepple KL, Stawell RJ, Holbrook JT, and Group MUST (MUST) TF-up SR. Cataract Surgery in Patients With Uveitis Treated With Systemic Therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study: Risk Factors and Outcomes. Am J Ophthalmol 2023;254:210-220.Abstract
PURPOSE: To evaluate the rate of, risk factors for, and outcomes of cataract surgery in patients with intermediate, posterior, and panuveitides treated with systemic corticosteroids and immunosuppression. DESIGN: Cohort study of participants from a randomized clinical trial. METHODS: A multicenter clinical trial with extended follow-up comprised the study setting. From the cohort of participants assigned to systemic therapy in the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study, 125 phakic eyes of 74 patients with intermediate, posterior, or panuveitides treated with systemic therapy were included. The main outcome measures were cataract surgery and visual acuity after cataract surgery. RESULTS: The cumulative incidence of cataract surgery was 43% at 7 years of follow-up, and the risk did not plateau. Risk factors for cataract surgery included age >50 years (hazard ratio [HR] 2.86, 95% CI 1.52, 5.42; P = .001), topical corticosteroid use (time-updated HR 3.13, 95% CI 1.42, 6.94; P = .005), glaucoma medication use (HR 2.75, 95% CI 1.38, 5.47; P = .004), and possibly history of anterior chamber inflammation (HR 1.90, 95% CI 0.95, 3.84; P = .07). Median gain in acuity and median best corrected visual acuity 1 year after cataract surgery were 4.8 lines and 20/25, respectively, among 42 eyes undergoing cataract surgery with 1-year follow-up data. CONCLUSIONS: Among patients with intermediate, posterior, and panuveitides, treated with oral corticosteroids and immunosuppression, there is a substantial long-term risk of cataract surgery. Visual acuity outcomes after cataract surgery are generally good.
Somisetty A, Hoyek S, Yuan M, Somisetty S, Kim LA, Patel NA. The Use of Additional Facedown Positioning with Silicone Oil Tamponade for the Treatment of Retinal Re-detachment. Retin Cases Brief Rep 2023;Abstract
PURPOSE: To highlight a potential alternative to additional surgery for management of retinal re-detachment through the use of additional facedown positioning with silicone oil tamponade. METHODS: Retrospective case-series of two patients evaluated with examination, multimodal imaging, including fundus photography, optical coherence tomography (OCT), and fluorescein angiography. RESULTS: In case 1, a 70-year-old female patient underwent surgery for a full-thickness macular hole with associated macula-off retinal detachment, but experienced a recurrent detachment and underwent a second surgery with silicone oil placement. Another recurrent detachment was found. The case was managed conservatively with face-down positioning, resulting in resolution of subretinal fluid and improvement in vision. At follow-up, the retina remained attached with stable vision. In case 2, a 25-year-old male patient underwent a surgical repair for PVR retinal detachment with a scleral buckle, cryotherapy, and external drainage. After multiple re-detachment surgeries with retinectomy and oil placement there was another tractional re-detachment of the fovea was noted. Management was with facedown positioning and follow-up evaluation showed resolution of the subretinal fluid and improvement in vision with stability for greater than 2 months. CONCLUSIONS: For recurrent retinal re-detachments with silicone oil in place, an additional week of facedown positioning can result in anatomic success and be a viable alternative or bridge to invasive surgical interventions. This approach may have greatest utility for patients who are poor surgical candidates without new peripheral pathology.
Lin LY, Stone JH, Liou VD, Stagner AM, Lee GN. Eosinophilic Angiocentric Fibrosis of the Orbit: A Clinicopathologic Review of 6 Novel Cases With Review of the Literature. Am J Ophthalmol 2023;256:9-19.Abstract
PURPOSE: To describe 6 cases and review the current state of knowledge of eosinophilic angiocentric fibrosis (EAF) involving the orbit. DESIGN: Retrospective clinicopathologic case series and review of the current literature METHODS: Clinical records and histopathologic data of orbit-involving EAF were gathered between 2004 and 2022 from a single academic institution. The patients' presenting clinical symptoms and signs, laboratory data, radiographic studies, and management documentation were collected. RESULTS: Retrospective review identified 6 novel cases, totaling 31 cases of EAF involving the orbit described as of this writing. Fourteen patients were male, and the average age of presentation was 49.8 years (range 25-78 years). Eighteen patients had concurrent sinonasal involvement, whereas 13 had primary orbital involvement. The median duration of symptoms prior to evaluation was 24 months, with nasal symptoms, proptosis, periorbital swelling, and pain being the most common presenting symptoms. The majority of patients underwent surgical debulking, as well as treatment with glucocorticoids and steroid-sparing agents, such as rituximab, with varied results. CONCLUSION: EAF involving the orbit is uncommon. The histopathologic findings include a perivascular, eosinophil-rich infiltrate and a pauci-inflammatory storiform type of fibrosis concentrated around small vessels. Orbital involvement usually results from local extension from adjacent sinuses, but primary orbital involvement has been described. Surgical debulking and immunosuppressive agents such as rituximab have been shown to stabilize disease.
Oke I, Ness SD, Peeler CE. Gaze-Evoked Vision Changes. J Binocul Vis Ocul Motil 2023;73(3):75-76.Abstract
We describe an atypical presentation of aberrant regeneration of the 3rd cranial nerve causing vision changes with ocular motility. Abnormal communication between axons destined for the medial rectus and those destined for muscles involved in the accommodative response resulted in simultaneous pupil constriction and myopic shift of approximately 2.5 diopters with adduction. While there have been several reports of this pupillary response (Czarnecki sign), no cases have documented the change in refraction from ciliary muscle involvement.
Papaliodis GN, Rosner BA, Dreger KA, Fitzgerald TD, Artornsombudh P, Kothari S, Gangaputra SS, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Sen NH, Suhler EB, Thorne JE, Bhatt NP, Foster SC, Jabs DA, Pak CM, Ying G-S, Kempen JH, for Group SITED (SITE) CSR. Incidence of and Risk Factors for Cataract in Anterior Uveitis. Am J Ophthalmol 2023;254:221-232.Abstract
PURPOSE: To estimate the incidence/risk factors for cataract in noninfectious anterior uveitis. DESIGN: Retrospective multicenter cohort study (6 US tertiary uveitis sites, 1978-2010). METHODS: Data were harvested by trained expert reviewers, using protocol-driven review of experts' charts. We studied cataract incidence-newly reduced visual acuity worse than 20/40 attributed to cataract; or incident cataract surgery-in 3923 eyes of 2567 patients with anterior uveitis. RESULTS: Cataract developed in 507 eyes (54/1000 eye-years, 95% CI 49-59). Time-updated risk factors associated with cataract included older age (≥65 vs <18 years: adjusted hazard ratio [aHR] 5.04, 95% CI 3.04-8.33), higher anterior chamber cell grade (P(trend)=0.001), prior incisional glaucoma surgery (aHR 1.86, 95% CI 1.10-3.14), band keratopathy (aHR 2.23, 95% CI 1.47-3.37), posterior synechiae (aHR 3.71, 95% CI 2.83-4.87), and elevated intraocular pressure ≥30 vs 6-20 mm Hg (aHR 2.57, 95% CI 1.38-4.77). Primary acute (aHR 0.59, 95% CI 0.30-1.15) and recurrent acute (aHR 0.74, 95% CI 0.55-0.98) had lower cataract risk than chronic anterior uveitis. Higher-dose prednisolone acetate 1%-equivalent use (≥2 drops/day) was associated with >2-fold higher cataract risk in eyes with anterior chamber cell grades 0.5+ or lower but was not associated with higher cataract risk in the presence of anterior chamber cells of grade 1+ or higher. CONCLUSIONS: Cataract complicates anterior uveitis in ∼5.4/100 eye-years. Several fixed and modifiable risk factors were identified, yielding a point system to guide cataract risk minimization. Topical corticosteroids only were associated with increased cataract risk when anterior chamber cells were absent or minimally present, suggesting their use to treat active inflammation (which itself is cataractogenic) does not cause a net increase in cataract incidence.
Soleimani M, Ebrahimi Z, Ebrahimi KS, Farhadian N, Shahlaei M, Cheraqpour K, Ghasemi H, Moradi S, Chang AY, Sharifi S, Baharnoori SM, Djalilian AR. Application of biomaterials and nanotechnology in corneal tissue engineering. J Int Med Res 2023;51(7):3000605231190473.Abstract
Corneal diseases are among the most common causes of blindness worldwide. Regardless of the etiology, corneal opacity- or globe integrity-threatening conditions may necessitate corneal replacement procedures. Several procedure types are currently available to address these issues, based on the complexity and extent of injury. Corneal allograft or keratoplasty is considered to be first-line treatment in many cases. However, a significant proportion of the world's population are reported to have no access to this option due to limitations in donor preparation. Thus, providing an appropriate, safe, and efficient synthetic implant (e.g., artificial cornea) may revolutionize this field. Nanotechnology, with its potential applications, has garnered a lot of recent attention in this area, however, there is seemingly a long way to go. This narrative review provides a brief overview of the therapeutic interventions for corneal pathologies, followed by a summary of current biomaterials used in corneal regeneration and a discussion of the nanotechnologies that can aid in the production of superior implants.
Finkelstein JB, Hauptman M, Acosta K, Flanagan S, Cahill D, Smith B, Bernstein A, Shah SH, Kaur R, Meyers H, Shah AS, Meara JG, Estrada CR. Environmental Impact of a Pediatric and Young Adult Virtual Medicine Program: A Lesson from the COVID-19 Pandemic. Acad Pediatr 2023;Abstract
OBJECTIVES: The Coronavirus Disease 2019 (COVID-19) pandemic led to the expansion of virtual medicine as a method to provide patient care. We aimed to determine the impact of pediatric and young adult virtual medicine use on fossil fuel consumption, greenhouse gas and non-greenhouse traffic-related air pollutant emissions. METHODS: We conducted a retrospective analysis of all virtual medicine patients at a single quaternary-care children's hospital with a geocoded address in the Commonwealth of Massachusetts prior to (3/16/2019-3/15/2020) and during the COVID-19 pandemic (3/16/2020-3/15/2021). Primary outcomes included patient travel distance, gasoline consumption, carbon dioxide and fine particulate matter emissions as well as savings in main hospital energy use. RESULTS: There were 3,846 and 307,273 virtual visits performed with valid Massachusetts geocoded addresses prior to and during the COVID-19 pandemic, respectively. During one year of the pandemic, virtual medicine services resulted in a total reduction of 620,231 gallons of fossil fuel use and $1,620,002 avoided expenditure as well as 5,492.9 metric tons of carbon dioxide and 186.3 kilograms of fine particulate matter emitted. There were 3.1 million fewer kilowatt hours used by the hospital intra-pandemic compared to the year prior. Accounting for equipment emissions, the combined intra-pandemic emission reductions are equivalent to the electricity required by 1,234 homes for one year. CONCLUSIONS: Widespread pediatric institutional use of virtual medicine provided environmental benefits. The true potential of virtual medicine for decreasing the environmental footprint of healthcare lies in scaling this mode of care to patient groups across the state and nation when medically feasible.
Seresirikachorn K, Thiamthat W, Aramtiantamrong N, Traichaiyaporn S, Wanichwecharungruang B, Patel NA, Vu DM. Two types of childhood glaucoma secondary to familial exudative vitreoretinopathy. J AAPOS 2023;Abstract
BACKGROUND: Glaucoma secondary to familial exudative vitreoretinopathy presents as angle closure by either neovascular or non-neovascular mechanisms. We analyze the presentation and outcomes of two types of childhood glaucoma secondary to familial exudative vitreoretinopathy (FEVR). METHODS: This retrospective cross-sectional study included all patients <18 years of age diagnosed with glaucoma after or concurrently with a diagnosis of FEVR between 2010 and 2020 from Queen Sirikit National Institute of Child Health in Bangkok, Thailand. Two groups were analyzed: neovascular or non-neovascular angle-closure status. Primary outcome measures were final visual acuity and intraocular pressure (IOP) in both groups. RESULTS: Of 144 FEVR patients, 8 children (5.5%; 11 eyes, 3 bilateral cases) developed childhood glaucoma. Mean time between FEVR presentation and glaucoma was 42.2 ± 40.0 months. In the neovascular group, 3 of 9 eyes presented with glaucoma at FEVR diagnosis; 3 of 9 eyes (33%) required glaucoma surgery. In the non-neovascular group, 2 eyes presented with acute angle closure secondary to a phacomorphic lens. Both were treated with trabeculectomy, with resolution of pupillary block. All eyes had stage 4B FEVR or greater. Six of 8 eyes had stable or better visual acuity, and 10 eyes (91%) had IOP <21 mm Hg at final follow-up. CONCLUSIONS: Childhood glaucoma secondary to FEVR is a rare complication caused by later stages of the disease. It may present as neovascular or non-neovascular angle closure, often requiring complex care. Therefore, awareness and adequate management of FEVR can help prevent additional morbidity from childhood glaucoma.
Azad AD, Reshef ER, Lee NG. Hyperglobus and Pseudoptosis in Type 1 Lipogenic Thyroid Eye Disease. Am J Ophthalmol Case Rep 2023;32:101890.Abstract
PURPOSE: We present a case of Type 1 (lipogenic) Thyroid Eye Disease (TED) and our aim is to describe an atypical presentation of a rare orbital process. OBSERVATIONS: A man in his 50s presented with left-sided eyelid drooping. His exam showed no evidence of active inflammation but did show left hyperglobus and ipsilateral upper eyelid pseudoptosis. He had no prior history or symptoms of Graves' Disease and imaging did not show evidence of extraocular muscle enlargement, bony asymmetries, or masses in the orbit. Subsequent lab work showed a low TSH (thyroid-stimulating hormone), elevated free T4 (thyroxine) and T3 (triiodothyronine), and elevated TSI (thyroid-stimulating immunoglobulin) index. CONCLUSIONS AND IMPORTANCE: This is a unique and atypical presentation of a patient diagnosed with Type 1 (lipogenic) TED causing hyperglobus and pseudoptosis secondary to fat expansion in the absence of other classic TED findings such as contralateral eyelid retraction or extraocular muscle enlargement. Thyroid eye disease can have a heterogenous disease presentation, as evidenced by this case, and should always be considered in the differential diagnosis of pseudoptosis.
Peli E, Goldstein R, Jung J-H. The Invisibility of Scotomas I: The Carving Hypothesis. Optom Vis Sci 2023;Abstract
SIGNIFICANCE: Veridical depictions of scene appearance with scotomas allow better understanding of the impact of field loss and may improve the development and implementation of rehabilitation. Explanation and depiction of the invisibility of scotoma may lead to patients' understanding and thus better compliance with related treatments. PURPOSE: Simulations of perception with scotomas guide training, patient education, and rehabilitation research. Most simulations incorrectly depict scotomas as black patches, though the scotomas and the missing contents are usually invisible to patients. We present a novel approach to capture the reported appearance of scenes with scotomas. METHODS: We applied a content-aware image resizing algorithm to carve out the content elided under the scotoma. With video sequences we show how and why eye movements fail to increase the visibility of the carved scotomas. RESULTS: Numerous effects, reported by patients, emerge naturally from the scotoma carving. Carving-eliminated scotomas over natural images are barely visible, despite causing substantial distortions. Low resolution and contrast sensitivity at farther eccentricities and saccadic blur reduce the visibility of the distortions. In a walking scenario, static objects moving smoothly to the periphery disappear into, and then reemerge out of peripheral scotomas invisibly. CONCLUSIONS: Scotoma carving provides a viable hypothetical simulation of vision with scotomas, due to loss of neurons at the retinal ganglion cell level and higher. As a hypothesis, it generates predictions that lend themselves to future clinical testing. The different effects of scotomas due to loss of photoreceptors are left for follow-up work.
Spaide RF, Vavvas DG. COMPLEMENT INHIBITION FOR GEOGRAPHIC ATROPHY: Review of Salient Functional Outcomes and Perspective. Retina 2023;43(7):1064-1069.Abstract
PURPOSE: To evaluate available rationale and outcomes of randomized trial results for complement inhibition for geographic atrophy. METHODS: Data from recently completed randomized trials of complement inhibition, particularly for pegcetacoplan and avacincaptad pegol, were evaluated for both the outcome, area of autofluorescence loss, and functional vision tests. RESULTS: Pegcetacoplan 2 mg showed statistically significant reduction in expansion of the area of autofluorescence loss with monthly, but not every-other-month dosing, in a 12-month phase two trial. Nearly 40% of patients recruited for the monthly arm did not complete the treatment. In two parallel phase 3 studies there was a statistically significant reduction in the area of atrophy in one but not both studies as compared with untreated controls. Data released at 24 months follow-up showed statistically significant reduction in the area of autofluorescence-detected atrophy in both studies compared with sham. Patients did not show functional difference in best-corrected visual acuity, maximum reading speed, Functional Reading Independence Index, and mean microperimetry threshold sensitivities in the treatment versus sham arms. Avacincaptad pegol was evaluated in two randomized pivotal studies and showed a statistically significant reduction in the expansion of autofluorescence loss at 12 months. Patients in the treatment arms did not show any difference as compared with sham in the best-corrected visual acuity or low luminance visual acuity, the only functional outcomes mentioned. Both drugs increased the risk of macular neovascularization. CONCLUSION: Both avacincaptad pegol and pegcetacoplan show significant differences compared with sham in autofluorescence imaging but no benefit in visual function at 12 and 24 months, respectively.
Ambrosio L, Akula JD, Harman JC, Arellano IA, Fulton AB. Do the retinal abnormalities in X-linked juvenile retinoschisis include impaired phototransduction?. Exp Eye Res 2023;234:109591.Abstract
X-linked juvenile retinoschisis (XLRS), a hereditary retinal disorder primarily affecting males, is characterized by the formation of cystic spaces between the outer plexiform layer and outer nuclear layer of the retina. Mutations in the RS1 gene, which encodes the extracellular binding protein retinoschisin, are responsible for XLRS pathogenesis. While the role of retinoschisin in maintaining retinal integrity is well established, there is growing evidence suggesting compromised photoreceptor function in XLRS. To investigate the molecular pathways affected by RS1 deficiency, particularly in phototransduction, we performed electroretinographic (ERG) and proteomic analyses on retinae from Rs1 knockout mice, a model of human XLRS. The Rs1 knockout mice had reduced ERG a-wave amplitudes. Correspondingly, differential expression analysis revealed downregulation of proteins crucial for phototransduction, with Ingenuity Pathway Analysis (IPA) highlighting "phototransduction" as the most significantly downregulated biological theme. Compensatory mechanisms were also observed in the IPA, including upregulation of synaptic remodeling, inflammation, cell adhesion, and G-protein signaling. These findings strongly implicate an underrecognized role of photoreceptor dysfunction in XLRS pathology. We speculate that entrapment of mutant retinoschisin protein within photoreceptor inner segments as well as disrupted reciprocal regulation between L-type voltage-gated calcium channels and retinoschisin contribute to the dysfunction in photoreceptors.

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