Comparing Three-Dimensional Digitally Enabled Intraoperative OCT With Conventional Microscope-Integrated OCT in Vitreoretinal Surgery: A Post Hoc Analysis of the DISCOVER Study.

BACKGROUND AND OBJECTIVE: This study compared the surgeon experience between conventional microscope-integrated intraoperative optical coherence tomography (iOCT) and digitally enabled microscope-integrated iOCT in vitreoretinal surgery. PATIENTS AND METHODS: This is a post hoc case-control analysis of the DISCOVER study. Conventional microscope-integrated iOCT (Rescan 700, Zeiss) was compared with digitally enabled iOCT (Artevo 800, Zeiss). Compared variables included surgical field-based visualization (ie, ocular heads-up display in the conventional group; three-dimensional screen-based visualization in the digital iOCT group) and non-surgical field-based visualization (ie, review on the external two-dimensional monitor). RESULTS: A total of 200 patients were included. Surgical field-based visualization of iOCT was significantly higher in the digitally enabled group (P < 0.0001). Required endoillumination level was significantly lower in the digital iOCT group (P < 0.0001). Surgeons reported "significant" back discomfort and headache more frequently when using conventional iOCT (P = 0.003 and P = 0.001, respectively). CONCLUSIONS: Digitally enabled iOCT resulted in greater surgical visualization efficiency, appeared to require a lower illumination level, and may provide advantages for ergonomic-related discomfort. [Ophthalmic Surg Lasers Imaging Retina 2024;55:270-277.].

Artificial Intelligence Improves Patient Follow-Up in a Diabetic Retinopathy Screening Program.

Purpose: We examine the rate of and reasons for follow-up in an Artificial Intelligence (AI)-based workflow for diabetic retinopathy (DR) screening relative to two human-based workflows. Patients and Methods: A DR screening program initiated September 2019 between one institution and its affiliated primary care and endocrinology clinics screened 2243 adult patients with type 1 or 2 diabetes without a diagnosis of DR in the previous year in the San Francisco Bay Area. For patients who screened positive for more-than-mild-DR (MTMDR), rates of follow-up were calculated under a store-and-forward human-based DR workflow ("Human Workflow"), an AI-based workflow involving IDx-DR ("AI Workflow"), and a two-step hybrid workflow ("AI-Human Hybrid Workflow"). The AI Workflow provided results within 48 hours, whereas the other workflows took up to 7 days. Patients were surveyed by phone about follow-up decisions. Results: Under the AI Workflow, 279 patients screened positive for MTMDR. Of these, 69.2% followed up with an ophthalmologist within 90 days. Altogether 70.5% (N=48) of patients who followed up chose their location based on primary care referral. Among the subset of patients that were seen in person at the university eye institute under the Human Workflow and AI-Human Hybrid Workflow, 12.0% (N=14/117) and 11.7% (N=12/103) of patients with a referrable screening result followed up compared to 35.5% of patients under the AI Workflow (N=99/279; χ2df=2 = 36.70, p < 0.00000001). Conclusion: Ophthalmology follow-up after a positive DR screening result is approximately three-fold higher under the AI Workflow than either the Human Workflow or AI-Human Hybrid Workflow. Improved follow-up behavior may be due to the decreased time to screening result.

Ophthalmology at the Forefront of Big Data Integration in Medicine: Insights from the IRIS Registry Database.

Ophthalmology stands at the vanguard of incorporating big data into medicine, as exemplified by the integration of The Intelligent Research in Sight (IRIS) Registry. This synergy cultivates patient-centered care, demonstrates real world efficacy and safety data for new therapies, and facilitates comprehensive population health insights. By evaluating the creation and utilization of the world's largest specialty clinical data registry, we underscore the transformative capacity of data-driven medical paradigms, current shortcomings, and future directions. We aim to provide a scaffold for other specialties to adopt big data integration into medicine.

Risk of Stroke, Myocardial Infarction, and Death After Retinal Artery Occlusion.

Importance: Patients with retinal artery occlusions (RAOs) are recommended to have emergent stroke workup, although the true risk of death and subsequent vascular events post-RAO is not clear. Objective: To determine short-term and long-term rates of stroke, myocardial infarction (MI), and death in patients after RAO compared with a control cohort. Design, Setting, and Participants: This retrospective cohort study used aggregated electronic health records from January 1, 2003, through April 14, 2023, from TriNetX, a network with data from more than 111 million patients. Patients with RAO and a cataract control group were identified and matched for age, sex, race, and comorbidities, including hypertension, diabetes, hyperlipidemia, and smoking status. Patients were excluded if they had a stroke or MI within 2 years before the diagnosis of RAO or cataract. Exposure: International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis code for RAO or age-related cataract. Main Outcomes and Measures: Rate of death, stroke, and MI at 2 weeks, 30 days, 1 year, 5 years, and 10 years after RAO compared with matched controls. Results: There were a total of 34 874 patients with at least 1 year of follow-up in the RAO cohort. The mean (SD) age at the RAO event was 66 (15.2) years. The rate of death after RAO diagnosis was higher than after cataract diagnosis at 2 weeks (0.14% vs 0.06%; relative risk [RR], 2.45; 95% CI, 1.46-4.12; risk difference [RD], 0.08%; 95% CI, 0.04%-0.13%; P < .001), 30 days (0.29% vs 0.14%; RR, 2.10; 95% CI, 1.49-2.97; RD, 0.15%; 95% CI, 0.08%-0.22%; P < .001), 1 year (3.51% vs 1.99%; RR, 1.78; 95% CI, 1.61-1.94; RD, 1.41%; 95% CI, 1.17%-1.66%; P < .001), 5 years (22.74% vs 17.82%; RR, 1.28; 95% CI, 1.23-1.33; RD, 4.93%; 95% CI, 4.17%-5.68%; P < .001), and 10 years (57.86% vs 55.38%; RR, 1.05; 95% CI, 1.02-1.07; RD, 2.47%; 95% CI, 1.25%-3.69%; P < .001). Risk of stroke after RAO was higher at 2 weeks (1.72% vs 0.08%; RR, 21.43; 95% CI, 14.67-31.29; RD, 1.64%; 95% CI, 1.50%-1.78%; P < .001), 30 days (2.48% vs 0.18%; RR, 14.18; 95% CI, 10.94-18.48; RD, 2.31%; 95% CI, 2.14%-2.47%; P < .001), 1 year (5.89% vs 1.13%; RR, 5.20; 95% CI, 4.67-5.79; RD, 4.64%; 95% CI, 4.37%-4.91%; P < .001), 5 years (10.85% vs 4.86%; RR, 2.24; 95% CI, 2.09-2.40; RD, 6.00%; 95% CI, 5.50%-6.50%; P < .001), and 10 years (14.59% vs 9.18%; RR, 1.59; 95% CI, 1.48-1.70; RD, 5.41%; 95% CI, 4.62%-6.21%; P < .001). Risk of MI after RAO was higher at 2 weeks (0.16% vs 0.06%; RR, 3.00; 95% CI, 1.79-5.04; RD, 0.11%; 95% CI, 0.06%-0.16%; P < .001), 30 days (0.27% vs 0.10%; RR, 2.61; 95% CI, 1.78-3.83; RD, 0.17%; 95% CI, 0.10%-0.23%; P < .001), 1 year (1.66% vs 0.97%; RR, 1.72; 95% CI, 1.51-1.97; RD, 0.59%; 95% CI, 0.42%-0.76%; P < .001), 5 years (6.06% vs 5.00%; RR, 1.21; 95% CI, 1.12-1.31; RD, 1.07%; 95% CI, 0.64%-1.50%; P < .001), and 10 years (10.55% vs 9.43%; RR, 1.12; 95% CI, 1.04-1.21; RD, 1.13%; 95% CI, 0.39%-1.87%; P = .003). Conclusions and Relevance: This study showed an increased risk of death, stroke, and MI in patients with RAO at both short-term and long-term intervals after RAO compared with a matched control population diagnosed with cataract. These findings suggest a potential need for multidisciplinary evaluation and long-term systemic follow-up of patients post-RAO.

Retinal Vasculitis Associated With Dermatomyositis Treated With Intravenous Steroids.

Purpose: This work aims to present treatment and long-term follow-up of a 31-year-old woman with dermatomyositis who presented with hemorrhagic retinal vasculitis and macular edema. Methods: A retrospective case report is presented. Results: A 31-year-old woman with dermatomyositis treated with systemic immunosuppression was evaluated for acute, reduced vision. Best-corrected visual acuity was hand motion in the right eye and 20/200 in the left eye. Fundus examination revealed diffuse intraretinal hemorrhages, cotton-wool spots, and vascular sheathing with a frosted branch angiitis-like appearance. Optical coherence tomography revealed significant macular edema and subretinal fluid that quickly resolved after admission and treatment with intravenous steroids. Multimodal imaging at 7-year follow-up disclosed long-term sequelae including peripheral nonperfusion and retinal neovascularization. Conclusions: When vasculitis associated with dermatomyositis is treated aggressively with intravenous steroids at initial presentation, good visual acuity outcomes can be achieved, but long-term consequences of retinal nonperfusion and neovascularization persist.

Effects of Dietary Soy Protein Isolate Versus Isoflavones Alone on Poststroke Skilled Ladder Rung Walking and Cortical mRNA Expression Differ in Adult Male Rats.

Dietary soy protein isolate (SPI) and the isoflavones daidzein and genistein have been shown to provide neuroprotection from stroke. However, the mechanisms remain uncertain. We sought to determine whether the addition of isoflavones to a diet containing caseinate (CAS) as the protein source would induce behavioral neuroprotection similar to that seen previously in rats fed SPI. Furthermore, we aimed to characterize the baseline and poststroke expression of mRNAs involved in pathways previously published as perhaps mediating soy-based neuroprotection from stroke and other markers of neuronal plasticity, oxidative stress, and inflammation. Adult male rats were fed a semipurified diet containing (1) sodium caseinate (CAS), (2) CAS plus daidzein and genistein (CAS+ISO), or (3) SPI for 2 weeks. A subset of rats was euthanized, and tissue was collected for quantitative real-time PCR (qPCR). Remaining rats underwent a middle cerebral artery occlusion to induce a stroke. Samples for qPCR were collected on day 3 poststroke. Rats fed SPI made fewer errors on the skilled ladder rung walking task after stroke compared to rats fed CAS (P < .05). Rats fed CAS+ISO were not different from rats fed CAS or SPI. Significant effects of diet were found at day 0 for Syp, Pparg, and Ywhae and at day 3 for Rtn4 expression. We concluded that the benefits of SPI are not solely attributable to daidzein and genistein.

Bilateral infectious scleritis from Histoplasma capsulatum in an immunosuppressed uveitis patient.

PURPOSE: To describe a case of bilateral infectious scleritis secondary to Histoplasma capsulatum in the setting of a locally and systemically immunosuppressed patient. OBSERVATIONS: A 45-year-old man with HLA-B27 associated ankylosing spondylitis and anterior uveitis on systemic secokinumab, underwent bilateral cataract extraction which required extensive peri-operative steroids, including intravitreal triamcinolone, topical prednisolone, and oral prednisone. Six weeks after cataract surgery, the patient presented with mild eye irritation and was found to have bilateral subconjunctival purulence and necrosis. Histoplasma capsulatum was identified on fungal cultures and confirmed by DNA probe. The patient was treated with fortified amphotericin drops and oral itraconazole with complete resolution of scleritis. CONCLUSION AND IMPORTANCE: H. capsulatum is a rare cause of infectious scleritis that must be considered in our immunosuppressed and post-surgical patients.

Differences in activation of intracellular signaling in primary human retinal endothelial cells between isoforms of VEGFA 165.

Purpose: There are reports that a b-isoform of vascular endothelial growth factor-A 165 (VEGFA165b) is predominant in normal human vitreous, switching to the a-isoform (VEGFA165a) in the vitreous of some diseased eyes. Although these isoforms appear to have a different ability to activate the VEGF receptor 2 (VEGFR2) in various endothelial cells, the nature of their ability to activate intracellular signaling pathways is not fully characterized, especially in retinal endothelial cells. We determined their activation potential for two key intracellular signaling pathways (MAPK, AKT) over complete dose-response curves and compared potential effects on the expression of several VEGFA165 target genes in primary human retinal microvascular endothelial cells (HRMECs). Methods: To determine full dose-response curves for the activation of MAPK (ERK1/2), AKT, and VEGFR2, direct in-cell western assays were developed using primary HRMECs. Potential differences in dose-response effects on gene expression markers related to endothelial cell and leukocyte adhesion (ICAM1, VCAM1, and SELE) and tight junctions (CLDN5 and OCLN) were tested with quantitative PCR. Results: Activation dose-response analysis revealed much stronger activation of MAPK, AKT, and VEGFR2 by the a-isoform at lower doses. MAPK activation in primary HRMECs displayed a sigmoidal dose-response to a range of VEGFA 165 a concentrations spanning 10-250 pM, which shifted higher into the 100-5,000 pM range with VEGFA 165 b. Similar maximum activation of MAPK was achieved by both isoforms at high concentrations. Maximum activation of AKT by VEGFA 165 b was only half of the maximum activation from VEGFA 165 a. At a lower intermediate dose, where VEGFA 165 a activated intracellular signaling stronger than VEGFA 165 b, the changes in VEGFA target gene expression were generally greater with VEGFA 165 a. Conclusions: In primary HRMECs, VEGFA 165 a could maximally activate MAPK and AKT at lower concentrations where VEGFA 165 b had relatively little effect. The timing for maximum activation of MAPK was similar for the isoforms, which is different from that reported for non-retinal endothelial cells. Although differences in VEGFA 165 a and VEGFA 165 b are limited to the sequence of their six C-terminal six amino acids, this results in a large difference in their ability to activate at least two key intracellular signaling pathways and VEGF-target gene expression in primary human retinal endothelial cells.

Uveal Metastasis: Clinical Features and Survival Outcome of 2214 Tumors in 1111 Patients Based on Primary Tumor Origin.

PURPOSE: The purpose of this study is to evaluate patients with uveal metastasis based on primary tumor site. METHODS: Retrospective analysis from Wills Eye Hospital, Philadelphia, PA, USA, for uveal metastasis clinical features and outcomes based on the primary tumor site. RESULTS: There were 2214 uveal metastases diagnosed in 1111 consecutive patients. The demographics included mean age of 60 years (median 61 years), Caucasian race (88%), and female gender (64%). The tumor was unilateral (82%) and primary site was established before uveal metastasis (67%). The primary tumor originated in the breast (37%), lung (26%), kidney (4%), gastrointestinal (GI) tract (4%), cutaneous melanoma (2%), lung carcinoid (2%), prostate (2%), thyroid (1%), pancreas (1%), other sites (3%), and unknown (16%). Comparative analysis of the 5 most common primary sites (breast, lung, kidney, GI tract, and cutaneous melanoma), revealed metastasis at mean age (57, 62, 66, 61, 59 years), as unilateral tumor (74%, 86%, 85%, 93%, 85%), with mean number of metastasis/eye (1.9, 1.7, 1.0, 1.1, 2.0), and in females (99%, 46%, 26%, 25%, 30%). Choroidal metastases measured mean base (9.3, 10.2, 9.1, 11.0, 7.3 mm), mean thickness (2.4, 3.6, 4.4, 4.0, 2.9 mm), and demonstrated predominant color yellow (94%, 91%, 56%, 97%, 36%). Of the 769 patients with documented follow-up, mean patient survival was poor (22.2, 11.5, 8.6, 12.4, 11.4 months) and Kaplan-Meier analysis revealed 3-year survival (33%, 19%, 0%, 14%, 21%) and 5-year survival (24%, 13%, 0%, 14%, 21%). The worst survival was found in patients with pancreatic metastasis (mean 4.2 months) and best survival with lung carcinoid (92% at 5 years). CONCLUSION: In a tertiary referral service, uveal metastasis originates from cancer in the breast, lung, kidney, GI tract, cutaneous melanoma, or others. Overall prognosis is poor with 5-year survival at 23% and worst survival with pancreatic metastasis whereas best survival with lung carcinoid metastasis.

Clinical Features Differentiating Benign From Malignant Conjunctival Tumors in Children.

IMPORTANCE: Conjunctival tumors in children are usually benign and rarely malignant. OBJECTIVE: To evaluate clinical features of conjunctival tumors in children by comparing benign tumors with their malignant counterparts. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series reviewed 806 cases of conjunctival tumor in children (aged <21 years) who were evaluated at a tertiary referral center between November 1, 1975, and July 1, 2015. This study included 262 children who were part of a published review. MAIN OUTCOMES AND MEASURES: Features of benign and malignant tumors were compared. Data were collected on patient demographics, tumor features, and specific diagnoses to determine findings related to each tumor. RESULTS: Among the 806 patients with conjunctival tumor, the top 5 diagnoses included nevus (492 [61%]), benign reactive lymphoid hyperplasia (BRLH) (38 [5%]), nodular conjunctivitis (31 [4%]), dermoid (30 [4%]), and primary acquired melanosis (27 [3%]). Overall, conjunctival tumors were benign (779 [97%]) or malignant (27 [3%]), including melanoma (18 [2.2%]) and lymphoma (9 [1.1%]). The mean age at detection was 11 years for benign tumors and 14 years for malignant tumors (P = .005), with mean difference of 3 years (95% CI, 1.2-4.6). The relative frequency of any malignancy (per all conjunctival tumors) by age bracket (0-5 years, >5-10 years, >10-15 years, and >15-<21 years) was 1%, 2%, 3%, and 7%, respectively. A comparison between nevus and melanoma found differences with melanoma in the 10 to 15 years age bracket (29% vs 61%; difference of 32% [95% CI, 10%-55%]; P = .006), mean tumor thickness (1.1 mm vs 1.5 mm; difference of 0.4 mm [95% CI, -0.29 mm to 1.12 mm]; P = .04), tumor base of 10 mm or greater (relative risk [RR] = 4.92; 95% CI, 1.73-13.97; P = .003), tumor hemorrhage (RR = 25.30; 95% CI, 11.91-53.78; P < .001), and lack of intrinsic cysts (RR = 5.06; 95% CI, 1.84-13.98; P = .002). A comparison between BRLH and lymphoma revealed lymphoma with a larger base (RR = 5.16; 95% CI, 1.19- 22.19; P = .002) and diffuse location (RR = 16.50; 95% CI, 4.31-63.22; P < .001) and inferior (RR = 12.38; 95% CI, 2.88-53.16; P < .001) or superior vs nasal (RR = 8.25; 95% CI, 1.56-43.51; P = .01). The small cohort of malignant lesions precluded determining if these features were independent of one another. CONCLUSIONS AND RELEVANCE: These data, from an ocular tertiary referral center, suggest that conjunctival tumors in children are nearly always benign. The few malignant tumors included melanoma and lymphoma. Melanoma, compared with nevus, was associated with older children (aged >10-15 years) with larger tumor, hemorrhage, and lack of cyst. Lymphoma, compared with BRLH, was associated with larger size and diffuse involvement.

Conjunctival Tumors in 5002 Cases. Comparative Analysis of Benign Versus Malignant Counterparts. The 2016 James D. Allen Lecture.

PURPOSE: To evaluate frequency of conjunctival tumors in all ages and compare benign vs malignant counterparts. DESIGN: Retrospective series. METHODS: setting: Tertiary referral center. STUDY POPULATION: Total of 5002 patients. OBSERVATION: Clinical features. MAIN OUTCOME MEASURE: Differentiation of benign from malignant counterparts. RESULTS: The tumor was benign (52%), premalignant (18%), or malignant (30%). Malignant tumors included melanoma (12%), squamous cell carcinoma (SCC) (9%), lymphoma (7%), and others. Comparison of primary acquired melanosis vs melanoma revealed melanoma with greater median patient age (54 vs 61 years, P < .0001), male sex (35% vs 49%, P < .0001), location in fornix (2% vs 6%, P = .0016) and tarsus (1% vs 4%, P = .0018), larger median basal diameter (6 vs 8 mm, P < .0001) and thickness (<1 vs 1 mm, P < .0001), and intralesional cysts (0% vs 7%, P < .0001), feeder vessels (10% vs 48%, P < .0001), intrinsic vessels (4% vs 33%, P < .0001), and hemorrhage (<1% vs 3%, P = .0001). Comparison of conjunctival intraepithelial neoplasia (CIN) vs SCC revealed SCC with greater diffuse involvement (1% vs 8%, P < .0001) and larger median basal diameter (7 vs 8 mm, P < .0001) and thickness (1 mm vs 2 mm, P < .0001). Comparison of benign reactive lymphoid hyperplasia vs lymphoma revealed lymphoma with greater median patient age (50 vs 61 years, P < .0001), fornix location (32% vs 54%, P < .0001), larger median basal diameter (10 vs 20 mm, P < .0001), and less involvement of nasal region (50% vs 23%, P < .0001). CONCLUSION: In an ocular oncology practice, conjunctival tumors are benign (52%), premalignant (18%), or malignant (30%). Malignant tumors tend to occur in older patients and demonstrate greater basal diameter and thickness, compared with benign counterparts.

Conjunctival fibrous histiocytoma in an 8-year-old boy.

An 8-year-old healthy boy underwent surgery for excision of a painless, enlarging vascularized conjunctival tumor. Histopathology disclosed a mass comprised of interweaving spindle cells and scattered histiocytes in a fibrous matrix, consistent with benign fibrous histiocytoma. This rare tumor can resemble several conditions, including scleritis/episcleritis, inflamed pterygium, juvenile xanthogranuloma, foreign body granuloma, solitary fibrous tumor, amelanotic melanoma, and squamous cell carcinoma.

Subcutaneous daidzein administration enhances recovery of skilled ladder rung walking performance following stroke in rats.

Stroke is a devastating event which can result in permanent disability. Due to the lack of treatments available for use after stroke, compounds which work to limit cell loss, reduce behavioral deficits, and enhance recovery of function are needed. The isoflavone daidzein has been demonstrated to be neuroprotective when fed to rats beginning prior to stroke. Herein, we tested whether subcutaneous delivery of daidzein beginning at the time of stroke reduced injury and/or enhanced functional recovery over 14 days after stroke. Baseline performance on the skilled ladder rung walking task was recorded immediately before stroke (Day 0). Rats then underwent a unilateral permanent middle cerebral artery occlusion and received a subcutaneous minipump containing either daidzein dissolved in vehicle or vehicle alone. Performance on the skilled ladder rung walking task was recorded again on Day +3, Day +7, and Day +14 post-stroke. Rats were then euthanized and brains were collected for lesion volume analysis. The numbers of slight and deep forelimb slips on the task were recorded for 3 trials for each rat per day. Rats treated with daidzein exhibited fewer deep slips over the course of the experiment than rats which received only vehicle (p<0.05). No difference was detected in total forelimb slips or slight slips (p>0.05). Lesion volume was not different between groups (p>0.05). No differences were found in weight between groups during the study (p>0.05).