Conjunctival blue nevus in a child - Case report and review of literature.

Purpose: To report a rare case of a conjunctival blue nevus in a child. Observations: A 10-year-old girl underwent an excisional biopsy for an atypical growing melanocytic conjunctival lesion. The diagnosis of a conjunctival blue nevus was confirmed on histopathology. We describe the histopathology and the anterior segment optical coherence tomography features of a blue nevus in a 10-year-old child along with a review of literature. Conclusion and importance: Conjunctival blue nevus is rare and has rarely been reported in a child. Multimodal imaging may help document lesion progression. This condition should remain in the differential for a growing, pigmented conjunctival lesion.

Ophthalmic Immune-Related Adverse Events and Association with Survival: Results from a Real-World Database.

PURPOSE: Assessing immune-related ocular toxicities from immune checkpoint inhibitors (ICIs) is crucial, though rare. This study, utilizing real-world data, examines the occurrence of ophthalmic immune-related adverse events (irAEs) after ICI treatment and their impact on overall survival. DESIGN: A retrospective cohort study METHODS: Data were obtained from TriNetX, an aggregated electronic health records database. Patients who developed ophthalmic irAEs within 1 year after the first instance of ICI therapy were included. Participants with defined ocular toxicities 6 months before ICI treatment were excluded. Subjects were paired with controls using propensity scores derived from demographics and cancer type. A Cox proportional hazard model was used to determine hazard ratios. A Kaplan-Meier survival function was evaluated with the log-rank test based on the development of ophthalmic irAEs in a 12-month landmark analysis. RESULTS: A cohort of 41,020 patients comprising 57.4% males with a mean age of 65.2±11.9 years was included. The five most prevalent ophthalmic irAEs in this cohort were dry eye syndrome (2%), conjunctivitis (0.87%), blepharitis (0.51%), anterior uveitis (0.39%), and keratitis (0.38%). Dry eye syndrome was the most common irAE among all ICI classes. Subjects taking CTLA-4 inhibitor plus PD-1 inhibitor and CTLA-4 inhibitors had higher rates of anterior uveitis (1.39% and 1.29%, respectively) than PD-1 inhibitors (0.27%) and PD-L1 inhibitors (0.14%) within 1 year after taking ICI. After a 12-month landmark analysis, there was a significant decreased chance of survival for the following categories: any ophthalmic irAE (HR, 1.37; 95% CI, 1.20-1.56; P < 0.0001), neuro-ophthalmic irAE (HR, 1.53; 95% CI, 1.09-2.14; P = 0.0124), and cornea and ocular surface irAE (HR, 1.34; 95% CI, 1.15-1.56; P < 0.0001). CONCLUSIONS: Ophthalmic irAEs involving the anterior segment are more frequent than the posterior segment, regardless of ICI class. Ophthalmic irAEs may also portend decreased survival. This insight could help guide clinicians aggressively manage irAEs and allow patients to continue ICI therapy despite having ocular issues.

Impact of Obstructive Sleep Apnea on Diabetic Retinopathy Progression and Systemic Complications.

PURPOSE: Evaluate the risk of diabetic retinopathy progression and systemic vascular events, including death, in patients with non-proliferative diabetic retinopathy (NPDR) with obstructive sleep apnea (OSA). DESIGN: Retrospective cohort study. METHODS: Electronic chart query using TriNetX (Cambridge, MA, USA), an electronic health records network comprising data from over 124 million patients. Patients with NPDR with and without OSA were identified. Patients were excluded if they had history of proliferative disease (PDR), diabetic macular edema (DME), or prior ocular intervention (intravitreal injection, laser, or pars plana vitrectomy). Propensity score matching was performed to control for baseline demographics and comorbidities. Rate of progressing to vision threatening complications (VTCs), need for ocular intervention, and systemic events was measured at 1, 3, and 5 years. RESULTS: 11,931 patients in each group were analyzed after propensity score matching. There was elevated risk of PDR in the OSA cohort at 1 (RR: 1.34, P<0.001), 3 (RR: 1.31, P<0.001), and 5 years (RR: 1.28, P<0.001). There was elevated risk of DME in the OSA group at all time points: 1 (RR: 1.31, P<0.001), 3 (RR: 1.19, P<0.001), and 5 years (RR: 1.18, P<0.001). With respect to ocular interventions, there was an increased risk of intravitreal injection in OSA patients at 1 (RR: 1.59, P<0.001), 3 (RR: 1.58, P<0.001), and 5 years (RR: 1.54, P<0.001), and similar trends were noted with laser photocoagulation, but not vitrectomy. Regarding systemic events, NPDR patients with OSA had a greater risk of stroke (1 year RR: 1.80, P<0.001; 3 year RR: 1.56, P<0.001; 5 year RR: 1.49, P<0.001), myocardial infarction (1 year RR: 1.51, P<0.001; 3 year RR: 1.46, P<0.001; 5 year RR: 1.43, P<0.001), and death (1 year RR: 1.31, P<0.001; 3 year RR: 1.19, P<0.001; 5 year RR: 1.15, P<0.001). CONCLUSIONS: There is an increased rate of DR progression to VTCs, need for ocular intervention, and systemic complications, including death, for patients with OSA. We emphasize the need for improved screening measures of patients with NPDR and potential OSA.

Risk of ocular neovascular conversion and systemic bleeding complications in patients with AMD on DOACs or Warfarin.

PURPOSE: Conversion to neovascular disease in patients with non-neovascular age-related macular degeneration (AMD) initiated on direct oral anticoagulants (DOAC) compared to matched patients treated with warfarin. DESIGN: Retrospective cohort study. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: The study included 20,300 patients and 13,387 patients with non-neovascular AMD initiated on DOACs or warfarin, respectively, before propensity score matching (PSM). METHODS, INTERVENTION, OR TESTING: TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with non-neovascular AMD stratified by treatment with DOACs or warfarin with at least six months of follow-up. Propensity score matching was performed to control for baseline demographics and medical comorbidities. MAIN OUTCOME MEASURES: Relative risk (RR) of developing neovascular AMD, macular hemorrhage (MH), vitreous hemorrhage (VH), and requiring an ocular intervention (intravitreal anti-vascular endothelial growth factor (VEGF) therapy or pars plana vitrectomy (PPV)) within six months and one year. Patients with chronic atrial fibrillation (AF) on anticoagulation were separately evaluated for the same measures within 5 years after initiating therapy. RESULTS: Treatment with warfarin was associated with higher risk of developing neovascular AMD at six months (RR,1.24, 95% CI, 1.12 - 1.39; P<.001) and one year (RR, 1.26, 95% CI, 1.14 - 1.40; P<.001) when compared to matched patients treated with DOACs. There was an increased risk of requiring intravitreal anti-VEGF therapy (6 months: RR, 1.30; 95% CI, 1.13-1.49; P<.001; 1 year: RR, 1.31, 95% CI, 0.72 - 2.05; P<.001) and PPV (6 months: RR, 1.16; 95% CI, 1.16-3.94; P = .01; 1 year: RR, 2.29, 95% CI, 1.30 - 4.05; P=.003). Among patients with AMD and AF treated with warfarin, there was an increased risk of ocular complications (neovascular AMD: RR, 1.25; 95% CI, 1.14-1.38; P<.001; MH: RR, 1.86; 95% CI, 1.47-2.35; P<.001; VH: RR, 2.22; 95% CI, 1.51-3.26; P<.001) and need for intravitreal anti-VEGF therapy (RR, 1.34; 95% CI, 1.18-1.52; P<.001) over an extended 5-year period. There was no significant difference in the development of major systemic hemorrhagic events between the two cohorts over five years. CONCLUSIONS: Patients with non-neovascular AMD treated with warfarin were more likely to develop neovascular disease and require ocular intervention for hemorrhagic complications when compared to matched patients initiated on DOACs.

Initial Therapy of Panretinal Photocoagulation vs Anti-VEGF Injection for Proliferative Diabetic Retinopathy.

Importance: While combined treatment of anti-vascular endothelial growth factor (VEGF) injections plus panretinal photocoagulation (PRP) is a common approach for treating proliferative diabetic retinopathy (PDR) in the clinical practice setting, large randomized clinical trials typically use monotherapy. Subsequently, information is limited as to whether the order of treatment when combining PRP and anti-VEGF injections for PDR affects outcomes. Objective: To compare outcomes of patients with PDR treated with PRP and subsequent anti-VEGF injections with outcomes of matched patients treated with anti-VEGF injections and subsequent PRP. Design, Setting, and Participants: This retrospective cohort study used data from January 2003 to January 2024 in the TriNetX aggregated electronic health records network, with data analysis performed in January 2024. Patients with PDR treated with PRP and anti-VEGF injections were eligible for inclusion. Exposures: Patients with new PDR diagnoses stratified by therapy with PRP and subsequent anti-VEGF injections or anti-VEGF injections and subsequent PRP. Main Outcomes and Measures: The primary outcome was the need for pars plana vitrectomy (PPV), defined by Current Procedural Terminology codes 67040 or 67113. The secondary outcome included incidence of PPV, vitreous hemorrhage (VH), or tractional retinal detachment (TRD). Relative risk ratios, relative risk differences, and 95% CIs were all calculated for univariate comparison of the cohorts and the development of primary outcomes after matching. Results: Before propensity score matching (PSM), which controlled for baseline demographic characteristics and medical comorbidities, 2167 patients with PDR treated with PRP first and subsequent anti-VEGF injections and 1549 patients with PDR treated with anti-VEGF injections and subsequent PRP were included. Post-PSM, mean (SD) participant age was 63.0 (13.1) years in cohort 1 (PRP and subsequent anti-VEGF injection) and 63.0 (12.4) years in cohort 2 (anti-VEGF injection and subsequent PRP). Of 1377 total participants in each cohort, 641 patients (46.6%) and 663 patients (48.1%) in cohorts 1 and 2 were female, respectively. Treatment with PRP first and subsequent anti-VEGF injection was associated with higher rates of PPV at 5 years compared with patients treated with anti-VEGF injection and subsequent PRP (relative risk [RR], 1.88; 95% CI, 1.55-2.27; risk difference [RD], 8.93%; 95% CI, 6.31%-11.55%; P < .001), with similar associations at 6 months, 1 year, and 3 years. Treatment with PRP and subsequent anti-VEGF injection was associated with higher rates of VH at 5 years (RR, 1.40; 95% CI, 1.09-1.80; RD, 6.47%; 95% CI, 1.66%-11.29%; P < .001) and TRD at 5 years (RR, 1.85; 95% CI, 1.35-2.53; RD, 4.31%; 95% CI, 2.10%-6.52%; P < .001), with similar findings at 6 months, 1 year, and 3 years compared with patients treated with anti-VEGF injection and subsequent PRP. Conclusions and Relevance: In this retrospective cohort study, findings suggest that patients with PDR treated with PRP first then subsequent anti-VEGF injection are more likely to undergo PPV for VH and TRD compared with matched patients treated with anti-VEGF agents first, then PRP. These findings support the need for further investigations to determine if the order of PRP and anti-VEGF injections should be considered when treating patients with PDR.

15-Gene Expression Profile and PRAME as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1).

PURPOSEValidated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and PRAME RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/PRAME classifier.MATERIALS AND METHODSThis study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers. Test results for 15-GEP (class 1 or class 2) and PRAME expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS).RESULTS15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. PRAME status was negative in 1,106 (70.1%) and positive in 471 (29.9%) patients. Five-year MFS was 95.6% (95% CI, 93.9 to 97.4) for class 1/PRAME(-), 80.6% (95% CI, 73.9 to 87.9) for class 1/PRAME(+), 58.3% (95% CI, 51.1 to 66.4) for class 2/PRAME(-), and 44.8% (95% CI, 37.9 to 52.8) for class 2/PRAME(+). By multivariable Cox proportional hazards analysis, 15-GEP was the most important independent predictor of MFS (hazard ratio [HR], 5.95 [95% CI, 4.43 to 7.99]; P < .001), followed by PRAME status (HR, 1.82 [95% CI, 1.42 to 2.33]; P < .001). The only clinical variable demonstrating additional prognostic value was tumor diameter.CONCLUSIONIn the largest prospective multicenter prognostic biomarker study performed to date in UM to our knowledge, the COOG2 study validated the superior prognostic accuracy of the integrated 15-GEP/PRAME classifier over 15-GEP alone and clinical prognostic variables. Tumor diameter was found to be the only clinical variable to provide additional prognostic information. This prognostic classifier provides an advanced resource for risk-adjusted metastatic surveillance and adjuvant trial stratification in patients with UM.

Endogenous Fusarium Endophthalmitis after Bone Marrow Transplant: A Case Report and Literature Review.

PURPOSE: We aim to present a case of disseminated fusariosis that occurred in the setting of immunosuppression and presented with bilateral endogenous endophthalmitis, along with a literature review of Fusarium endophthalmitis, highlighting management strategies. OBSERVATION: A 70-year-old male with acute myeloid leukemia who had recently undergone a bone marrow transplant noted bilateral floaters and decreased vision. He was found to have bilateral Fusarium endophthalmitis, with subsequent evidence of fungemia and fusariosis in his skin and joints. Despite aggressive local and systemic treatment, he succumbed to the disease. Endophthalmitis was initially stabilized with pars plana vitrectomy and intravitreal amphotericin and voriconazole until the patient transitioned to comfort measures. A review of 31 cases demonstrates that outcomes are poor and that the disease must be treated aggressively, often both systemically and surgically. CONCLUSION: This case highlights the recalcitrance of Fusarium bacteremia and Fusarium endophthalmitis.

Using Electronic Health Record Data to Determine the Safety of Aqueous Humor Liquid Biopsies for Molecular Analyses.

Purpose: Knowing the surgical safety of anterior chamber liquid biopsies will support the increased use of proteomics and other molecular analyses to better understand disease mechanisms and therapeutic responses in patients and clinical trials. Manual review of operative notes from different surgeons and procedures in electronic health records (EHRs) is cumbersome, but free-text software tools could facilitate efficient searches. Design: Retrospective case series. Participants: A total of 1418 aqueous humor liquid biopsies from patients undergoing intraocular surgery. Methods: Free-text EHR searches were performed using the Stanford Research Repository cohort discovery tool to identify complications associated with anterior chamber paracentesis and subsequent endophthalmitis. Complications of the surgery unrelated to the biopsy were not reviewed. Main Outcome Measures: Biopsy-associated intraoperative complications and endophthalmitis. Results: A total of 1418 aqueous humor liquid biopsies were performed by 17 experienced surgeons. EHR free-text searches were 100% error-free for surgical complications, >99% for endophthalmitis (<1% false positive), and >93.6% for anesthesia type, requiring manual review for only a limited number of cases. More than 85% of cases were performed under local anesthesia without ocular muscle akinesia. Although the most common indication was cataract (50.1%), other diagnoses included glaucoma, diabetic retinopathy, uveitis, age-related macular degeneration, endophthalmitis, retinitis pigmentosa, and uveal melanoma. A 50- to 100-µL sample was collected in all cases using either a 30-gauge needle or a blunt cannula via a paracentesis. The median follow-up was >7 months. There was only one minor complication (0.07%) identified: a case of a small tear in Descemet membrane without long-term sequelae. No other complications occurred, including other corneal injuries, lens or iris trauma, hyphema, or suprachoroidal hemorrhage. There was no case of postoperative endophthalmitis. Conclusions: Anterior chamber liquid biopsy during intraocular surgery is a safe procedure and may be considered for large-scale collection of aqueous humor samples for molecular analyses. Free-text EHR searches are an efficient approach to reviewing intraoperative procedures. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Sensitivity of Magnetic Resonance Imaging in Detection of Choroidal Metastases.

Introduction: The objective of this study was to determine the sensitivity of brain magnetic resonance imaging (MRI) in the detection of choroidal metastasis (CM) from systemic primary cancers. Methods: A retrospective chart review identified patients with clinically confirmed CM seen on the Oncology Service (Byers Eye Institute) between January 2018 and March 2022. Patients had an MRI brain and/or orbits performed within 3 months of CM diagnosis. Evaluation of CM detection by MRI was then divided into two parts: an initial "standard read," where determination of CM detection was based solely on the original radiology report, to reflect real-world performance, and a subsequent "dedicated read," for which a board-certified neuroradiologist, blinded to the laterality and location of the CM, reevaluated the studies to provide an objective "gold standard" interpretation regarding the radiographic detection of CM. Results: The study included 42 eyes of 40 patients with confirmed CM. On standard read, MRI detection of CM occurred in 21 of 42 eyes (50%), with no significant difference between MRI brain and orbit protocols (p = 0.249). Features associated with improved detection were increased tumor basal diameter (p < 0.001) and ultrasonographic tumor thickness (p = 0.003). On dedicated read, MRI detection of CM improved to 26 of 33 eyes (76%; limited to eyes with full complement of pre- and post-gadolinium sequences). Post-gadolinium 3D fluid-attenuated inversion recovery (FLAIR) sequence with fat suppression was the most sensitive (88%) for CM detection. 42% and 58% of lesions were visualized using conventional pre-gadolinium T1- and T2-weighted imaging, respectively. Conclusions: MRI sensitivity to detect CM improved from 50% to 76% with focused reinterpretation. Increased utilization of the post-gadolinium 3D FLAIR sequence and increased ocular scrutiny in cancer patients undergoing brain imaging may facilitate earlier diagnosis of CM.

Progression to Pars Plana Vitrectomy in Patients With Proliferative Diabetic Retinopathy.

Importance: The Diabetic Retinopathy Clinical Research Network Protocol S suggested that vitrectomy for vitreous hemorrhage (VH) or tractional retinal detachment (TRD) was more common among eyes assigned initially to panretinal photocoagulation (PRP) vs anti-vascular endothelial growth factor (anti-VEGF) for proliferative diabetic retinopathy (PDR). These clinical implications warrant further evaluation in the clinical practice setting. Objective: To explore outcomes of PDR treated with PRP monotherapy compared with matched patients treated with anti-VEGF monotherapy. Design, Setting, and Participants: Retrospective cohort study using an aggregated electronic health records research network. Patients with PDR who received PRP or anti-VEGF monotherapy between January and September 2023 were included before propensity score matching. Patients were excluded with 6 or fewer months' follow-up after monotherapy or with a combination of PRP and anti-VEGF. Data were analyzed in September 2023. Exposures: Patients with new PDR diagnoses stratified by monotherapy with PRP or anti-VEGF agents using Current Procedural Terminology code. Main Outcome Measures: Incidence of pars plana vitrectomy (PPV), VH, or TRD. Results: Among 6020 patients (PRP cohort: mean [SD] age, 64.8 [13.4]; 6424 [50.88%] female; 3562 [28.21%] Black, 6180 [48.95%] White, and 2716 [21.51%] unknown race; anti-VEGF cohort: mean [SD] age, 66.1 [13.2]; 5399 [50.52%] male; 2859 [26.75%] Black, 5377 [50.31%] White, and 2382 [22.29%] unknown race) who received treatment, PRP monotherapy was associated with higher rates of PPV when compared with patients treated with anti-VEGF monotherapy at 5 years (RR, 1.18; 95% CI, 1.05-1.36; RD, 1.37%; 95% CI, 0.39%-2.37%; P < .001), with similar associations at 1 and 3 years. PRP monotherapy was associated with higher rates of VH at 5 years (relative risk [RR], 1.72; 95% CI, 1.52-1.95; risk difference [RD], 7.05; 95% CI, 5.41%-8.69%; P < .001) and higher rates of TRD at 5 years (RR, 2.76; 95% CI, 2.26-3.37; RD, 4.25%; 95% CI, 3.45%-5.05%; P < .001), with similar magnitudes of associations at 6 months, 1 year, and 3 years, when compared with patients treated with anti-VEGF monotherapy. Conclusions and Relevance: These findings support the hypothesis that patients with PDR treated with PRP monotherapy are more likely to develop VH, TRD, and undergo PPV when compared with matched patients treated with anti-VEGF monotherapy. However, given the wide range in relative risk, confounding factors may account for some of the association between PRP vs anti-VEGF monotherapy and outcomes evaluated.

Impact of GLP-1 Agonists and SGLT-2 Inhibitors on Diabetic Retinopathy Progression: An Aggregated Electronic Health Record Data Study.

PURPOSE: To examine the effects of glucagon-like peptide-1 receptor (GLP-1) agonists compared to SGLT-2 inhibitors on diabetic retinopathy. DESIGN: Retrospective clinical cohort study using TriNetX, a federated electronic health records network comprising multiple healthcare organizations. METHODS: Patients with an International Classification of Diseases, Tenth Revision (ICD-10) code of nonproliferative diabetic retinopathy (PDR) and monotherapy treatment, excluding insulin, with GLP-1 agonists or SGLT-2 inhibitors. Patients with a history of PDR prior to initiation of treatment were excluded. The rate of progression to PDR and rate of development of diabetic macular edema (DME) were compared between patients on GLP-1 agonists compared to those on SGLT-2 inhibitors. The groups were propensity score matched for age, gender, ethnicity, race, type of diabetes, and severity of PDR. Main outcomes included rate and relative risk (RR) of progression to PDR and risk of DME in the GLP-1 agonist group versus the SGLT-2 inhibitor group. RESULTS: A total of 6481 patients were identified in the GLP-1 cohort and the SGLT-2 inhibitor cohort after propensity score matching. At 1 and 3 years after initiation of therapy, a higher rate of progression of PDR was noted (RR: 1.26, CI 1.04-1.51, P = .017 at 1 year, RR: 1.284, CI 1.1-1.499, P = .002 at 3 years) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. There was a higher rate of DME noted at 3 months (RR: 1.192, CI 1.059-1.276, P = .002), 6 months (RR: 1.22, CI 1.13-1.32, P < .001), 1 year (RR: 1.24, CI 1.15-1.33, P < .001), and at 3 years (RR: 1.29, CI 1.21-1.38, P < .001) in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor cohort. CONCLUSIONS: A higher rate of progression of PDR and risk of new-onset DME was observed in patients on monotherapy with GLP-1 agonists compared to those on SGLT-2 inhibitors. It is important for clinicians to be aware of these potential effects and to consider the current retinopathy status when initiating treatment with newer hypoglycemic agents to ensure these patients are appropriately monitored for developing potential vision-threatening complications.

Association of Ocular Manifestations of Marfan Syndrome With Cardiovascular Complications.

PURPOSE: To evaluate associations between ocular manifestations of Marfan syndrome and cardiovascular complications. DESIGN: Retrospective cohort study. METHODS: The TriNetX Analytics platform, a federated health research network of aggregated deidentified electronic health record data of more than 119 million patients, was used to identify patients diagnosed with Marfan syndrome. Univariate logistic regression models were used to evaluate the association of ocular manifestations of Marfan syndrome (such as retinal tears/detachment, lens dislocation, and myopia), with cardiovascular comorbidities. Additional sensitivity analyses were performed using propensity matching. Odds ratios and 95% CIs were calculated for incidence of cardiovascular comorbidities (including aortic dissection, valvular disease, and arrhythmias) following diagnosis of Marfan syndrome. RESULTS: A total of 19,105 patients were identified who were diagnosed with Marfan disease without ocular manifestations, and an additional 3887 Marfan patients with ocular comorbidities. Patients who were diagnosed with ocular disease included 883 with ectopic lens, 417 with retinal tear or detachment, 683 with aphakia, 534 with pseudophakia, and 2465 with myopia. Patients with any ocular manifestations of Marfan were significantly more likely to be diagnosed with all cardiovascular comorbidities modeled including aortic aneurysm and dissection (OR 2.035; P < .0001), mitral valve prolapse (OR 2.725; P < .0001), tricuspid valve disorders (OR 2.142; P < .0001), cardiac arrhythmias (OR 1.836; P < .0001), and all cardiovascular outcomes combined (OR 2.194; P < .0001). CONCLUSIONS: In a large and diverse cohort of patients with Marfan syndrome, ocular manifestations of the disorder appear strongly associated with cardiovascular comorbidities.

Association of Cutaneous Keloids, Hypertrophic Scarring, and Fibrosis with Risk of Postoperative Proliferative Vitreoretinopathy.

PURPOSE: To assess an association between cutaneous keloids, hypertrophic scarring, and fibrosis (KHF) and risk of postoperative proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD) repair. DESIGN: Retrospective, population-based cohort study. PARTICIPANTS: Patients aged ≥ 18 years who underwent initial retinal detachment (RD) repair with pars plana vitrectomy with or without scleral buckle (SB) (Current Procedural Terminology [CPT] 67108), pneumatic retinopexy (67110), and primary SB (67107) from January 1, 2003, to March 1, 2023. METHODS: A de-identified electronic health record database through TriNetX, a global health research network, was used to analyze patients. Patients were queried for International Classification of Diseases, 10th Revision (ICD-10) codes L91.0 (hypertrophic scar) and L90.5 (scar conditions and fibrosis of skin). Frequency of subsequent diagnosis of PVR (H35.2) and CPT codes for secondary surgery including complex RD repair (67113) were determined. Patients with proliferative diabetic retinopathy (PDR) (ICD-10 H10.35/H11.35) were excluded. Descriptive statistics (Z-test) and propensity score matching (PSM) were used to match for age, sex, and race. MAIN OUTCOME MEASURES: Prevalence of H35.2 and CPT 67113 within 180 days after RRD repair in the KHF cohort versus the non-KHF cohort. RESULTS: Among patients with CPT 67108, 1061 in each cohort (KHF and non-KHF) were analyzed after PSM. The mean (standard deviation) age was 60.7 (15.2) years. Within 180 days, 10.1% of patients in the KHF cohort and 3.4% in the non-KHF cohort had a diagnosis of PVR (H35.2) (P < 0.001, odds ratio [OR], 3.2; 95% confidence interval [CI], 2.13-4.71). A total of 8.3% of patients in the KHF cohort and 5.4% of patients in the non-KHF cohort underwent complex RD repair (CPT 67113) (P = 0.008; OR, 3.2; 95% CI, 1.13-2.25). When including all RD repair types (CPT 67108, 67110, 67107), the rate of PVR diagnosis was still significantly greater in the KHF cohort than in the non-KHF cohort (9.0% vs 4.2%, P < 0.01; OR, 2.28; 95% CI, 1.64-3.16). CONCLUSIONS: A dermatologic history of KHF may be a risk factor for PVR after RD repair. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Liquid Biopsy Proteomics in Ophthalmology.

Minimally invasive liquid biopsies from the eye capture locally enriched fluids that contain thousands of proteins from highly specialized ocular cell types, presenting a promising alternative to solid tissue biopsies. The advantages of liquid biopsies include sampling the eye without causing irreversible functional damage, potentially better reflecting tissue heterogeneity, collecting samples in an outpatient setting, monitoring therapeutic response with sequential sampling, and even allowing examination of disease mechanisms at the cell level in living humans, an approach that we refer to as TEMPO (Tracing Expression of Multiple Protein Origins). Liquid biopsy proteomics has the potential to transform molecular diagnostics and prognostics and to assess disease mechanisms and personalized therapeutic strategies in individual patients. This review addresses opportunities, challenges, and future directions of high-resolution liquid biopsy proteomics in ophthalmology, with particular emphasis on the large-scale collection of high-quality samples, cutting edge proteomics technology, and artificial intelligence-supported data analysis.

Risk of Stroke, Myocardial Infarction, Deep Vein Thrombosis, Pulmonary Embolism, and Death After Retinal Vein Occlusion.

PURPOSE: To examine rates of stroke, myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolism (PE), and death in patients after retinal vein occlusion (RVO) compared to controls. DESIGN: Retrospective cohort study. METHODS: An aggregated electronic health records research network, TriNetX, was used to identify patients with diagnosis of RVO and a control group of patients with cataract. Patients were excluded if they had history of stroke, MI, DVT, or PE within 2 years of diagnosis of RVO or cataract. Propensity score matching was performed to control for baseline demographics and medical comorbidities. Main outcomes included relative risk (RR) of death, stroke, MI, DVT, and PE after RVO compared to those in matched controls. RESULTS: A total of 45,304 patients were included in each cohort. There was elevated risk of death in the RVO cohort compared to the control cohort at 1 year (RR = 1.30, P < .01), 5 years (RR = 1.22, P < .01), and 10 years (RR = 1.08, P < .01). There was elevated risk of stroke at 1 year (RR = 1.61, P < .01), 5 years (RR = 1.31, P < .01), and 10 years (RR = 1.18, P < .01). There was elevated risk of MI at 1 year (RR = 1.26, P < .01) and 5 years (RR = 1.13, P < .01), but not at 10 years (RR = 1.06, P = .12). There was mildly elevated risk of DVT at 1 year (RR = 1.65, P < .01) but not at 5 years (RR = 0.94, P = .94) or 10 years (RR = 1.05, P = .37). There was no elevated risk of PE at 1 year (RR = 0.98, P = 0.80), 5 years (RR = 0.95, P = .42), or 10 years (RR = 0.85, P =.40). CONCLUSIONS: There is an increased rate of death, stroke, and MI after RVO compared to those in matched controls. We emphasize the need for long-term systemic evaluation after RVO.

Cross-Platform Identification and Validation of Uveal Melanoma Vitreous Protein Biomarkers.

Purpose: The purpose of this study was to profile protein expression liquid vitreous biopsies from patients with uveal melanoma (UM) using mass spectrometry to identify prognostic biomarkers, signaling pathways, and therapeutic targets. Methods: Vitreous biopsies were collected from two cohorts in a pilot study: comparative control eyes with epiretinal membranes (ERM; n = 3) and test eyes with UM (n = 8). Samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Identified proteins were compared to data from a targeted multiplex ELISA proteomics platform. Results: A total of 69 significantly elevated proteins were detected in the UM vitreous, including LYVE-1. LC-MS/MS identified 62 significantly upregulated proteins in UM vitreous that were not previously identified by ELISA. Analysis of differential protein expression by tumor molecular classification (gene expression profiling [GEP] and preferentially expressed antigen in melanoma [PRAME]) further identified proteins that correlated with these classifications. Patients with high-risk GEP tumors displayed elevated vitreous expression of HGFR (fold-change [FC] = 2.66E + 03, P value = 0.003) and PYGL (FC = 1.02E + 04, P = 1.72E-08). Patients with PRAME positive tumors displayed elevated vitreous expression of ENPP-2 (FC = 3.21, P = 0.04), NEO1 (FC = 2.65E + 03, P = 0.002), and LRP1 (FC = 5.59E + 02, P value = 0.01). IGF regulatory effectors were highly represented (P value = 1.74E-16). Cross-platform analysis validated seven proteins identified by ELISA and LC-MS/MS. Conclusions: Proteomic analysis of liquid biopsies may provide prognostic information supporting gene expression of tumor biopsies. The use of multiple protein detection platforms in the same patient samples increases the sensitivity of candidate biomarker detection and allows for precise characterization of the vitreous proteome.

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.