Adverse Events Associated With 3 Vitrectomy Platforms Reported to the US FDA MAUDE Database.

Purpose: To identify and describe adverse events (AEs) observed with real-world use of the following 3 vitrectomy platforms: Constellation (Alcon), Enhancing Visual Acuity (EVA, Dutch Ophthalmic Research Center), and Stellaris (Bausch + Lomb). Methods: All reports submitted to the US Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database between January 2010 and November 2021 that were associated with the 3 vitrectomy platforms were analyzed. Each report was reviewed for AEs or consequences and the type of complication noted. Duplicates and reports with an inadequate narrative to categorize the event were excluded. A descriptive analysis was performed for the prevalence of device-specific issues within each platform. Results: The analysis included 2534 reports (1738 Constellation, 117 EVA, 679 Stellaris). Overall, the most commonly reported complications involved the vitrectomy probe (n = 957 [37.8%]) and the central processing unit (n = 368 [14.5%]). Differences in the distribution of AEs among the platforms were noted, with vitrectomy probe issues being the most reported events for the Constellation and Stellaris and infusion issues for the EVA. Infusion issues most frequently led to reports of patient harm with the Constellation (31/1738 [1.8%]) and EVA (7/116 [6.0%]), while issues with the vitrectomy probe were reported with the Stellaris (11/679 [1.6%]). Conclusions: An analysis of real-world data in the MAUDE database highlighted the spectrum of device-specific AEs of greatest relevance to surgical practice. Familiarity with potential device complications will help minimize harm to patients.

PREVALENCE OF DIDANOSINE-RELATED RETINAL TOXICITY AT AN URBAN ACADEMIC CENTER AS DIAGNOSED WITH ULTRA-WIDEFIELD IMAGING.

PURPOSE: Antiretroviral therapy has revolutionized HIV treatment with didanosine (DDI) as a pioneering drug. However, DDI has been associated with retinal toxicity, characterized by peripheral chorioretinal degeneration with macular sparing. Despite its clinical recognition, the prevalence and risk factors for didanosine-induced retinopathy are not well described. METHODS: This retrospective case series analyzed 127 DDI-treated patients at Weill Cornell Medicine Department of Ophthalmology. Inclusion criteria included at least 6 months of DDI use and available ultra-widefield imaging. Patients were categorized as affected or unaffected based on retinal imaging assessed by two reviewers. The affected group was further divided into "probable" or "possible" retinopathy. Patient demographics, DDI usage characteristics, and imaging findings were analyzed with statistical comparisons drawn between affected and unaffected cohorts. RESULTS: Of the 127 patients, 9 (7%) showed signs of didanosine-induced retinal toxicity. On average, the affected group was older compared with the unaffected group (65.1 vs. 56.5 years, P = 0.025), with lower BMI (23.2 vs. 27.4, P = 0.04), and older at the start of the treatment (51.6 vs. 40.8 years, P = 0.026). Mild phenotypes with peripheral pigmentary changes were also identified using ultra-widefield imaging. CONCLUSION: This pioneering academic study highlighted a notable prevalence of DDI-induced retinal toxicity. Statistical analysis demonstrated age, BMI, and age at treatment initiation as potential risk factors. Ultra-widefield autofluorescence emerged as a valuable tool in detecting and delineating findings. Follow-up studies are needed to determine the necessity of regular screening for individuals on or with a history of didanosine use.

Prevalence of Age-Related Macular Degeneration in Patients with Chronic Exposure to P2X7R Inhibitors.

PURPOSE: P2X7 receptor (P2X7R) is a purinergic cation channel whose activation has been linked with age-related macular degeneration (ARMD). Several nucleoside reverse transcriptase inhibitors, zidovudine (AZT), lamivudine (3TC) and abacavir (ABC), have been shown to inhibit P2X7R and improve outcomes in animal models of ARMD. Our aim is to investigate the association between chronic AZT, 3TC, and ABC therapy and ARMD in a clinical setting. METHODS: This is a retrospective cohort study comparing 445 patients with HIV and confirmed usage of AZT, 3TC, and ABC against 200 patients with HIV without usage of AZT, 3TC, and ABC and 445 non-HIV infected patients. Fundus examination and spectral domain optical coherence tomography (SD-ODT) were used to measure prevalence of early-intermediate stage ARMD, geographic atrophy, and exudative ARMD. RESULTS: There was no statistically significant difference in the prevalence of early-intermediate stage ARMD between the HIV infected patients with a history of AZT, 3TC, and ABC use and the HIV infected patients without AZT, 3TC, and ABC use (p = 0.887). There was also no statistically significant difference in the prevalence of geographical atrophy (p = 0.062) and exudative AMD (p > 0.999) between the HIV infected patients with a history of AZT, 3TC, and ABC use and non-HIV infected patients. CONCLUSION: We did not find an effect of P2X7R inhibiting antiretrovirals usage on early-intermediate stage ARMD, geographical atrophy, or exudative ARMD. Studies with larger cohort and more rigorous medication history are needed to assess the effects on geographical atrophy or exudative ARMD.

Incidence of Blepharoptosis Following Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To determine the incidence of blepharoptosis after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and compare the rates of blepharoptosis between patients injected with an eyelid speculum and those injected without a speculum. DESIGN: Retrospective cohort study. METHODS: International Classification of Diseases, Tenth Revision (ICD-10), codes were used to identify patients with exudative age-related macular degeneration (AMD) and those who developed ptosis after intravitreal injections. Patients with nonexudative AMD who did not receive intravitreal injections served as controls. The outcomes were the incidence of ptosis in the injection group compared to the noninjection group and incidence of ptosis in patients whose injections were performed with an eyelid speculum as compared to those whose injections were performed without a speculum. RESULTS: We recruited 1100 exudative AMD patients who received at least 1 intravitreal anti-VEGF injection and 2258 nonexudative AMD patients who had not received an injection. In the injection group, 18 of 1100 patients (1.6%) developed ptosis, compared with 52 of 2258 patients (2.3%) in the noninjection group (P = .25). Within the injection group, ptosis was mostly bilateral, diagnosed on average 22.4 months after the initial injection, and after more than a 1-year injection-free period. Eleven of 537 patients (2.0%) injected without a speculum developed ptosis, compared with 8 of 444 patients (1.8%) injected with a speculum (P = .82). CONCLUSIONS: No statistically significant differences in incidence rates of ptosis were observed. In this analysis, neither intravitreal anti-VEGF injections nor speculum use during injections appears to increase the risk of ptosis.

Implementation of a Teleophthalmology Screening Program for Diabetic Retinopathy in New York City.

Purpose: To examine the implementation of a teleophthalmology program for diabetic retinopathy (DR) screening at a metropolitan hospital system and identify the challenges that the clinical teams encountered using the program. Methods: The study was conducted in 2 parts. The first was a pilot retrospective chart review of 300 consecutive patients screened for DR by the teleophthalmology screening program. The baseline variables, DR capture rate and staging, and continuity of care for those diagnosed with DR were analyzed. The second was a web-based survey identifying the barriers encountered by 36 physicians and clinical staff as they participated in the teleophthalmology screening program. Results: Part 1: Of the patients evaluated, 57 (19.0%) were diagnosed with DR; 42 (73.7%) had mild nonproliferative DR (NPDR), 7 (12.3%) had moderate NPDR, none had severe NPDR, and 8 (14.0%) had PDR. Thirty-one patients (54.4%) with retinopathy diagnoses were referred for an in-person follow-up at the clinic while the rest continued monitoring via the program. Of this subset, 22 (71.0%) completed the follow-up visit. Part 2: The survey respondents comprised 28 physicians (77.8%), 6 licensed nurse practitioners (16.7%), and 2 medical assistants (5.6%). Twenty-two providers (71.0%) preferred initiating referrals for in-person annual examinations over teleophthalmology screening referrals. The most common barriers described were related to workflow interruption, time constraints, and staff shortages. Conclusions: The teleophthalmology DR screening program allowed identification of early or absent DR at clinics in an urban setting (New York City). The findings suggest areas for targeted improvement in the screening program to better complement internal referral practices' workflows.

EVALUATING ULTRA-WIDEFIELD IMAGING UTILITY IN THE DETECTION OF TREATMENT-REQUIRING PERIPHERAL RETINAL TEARS AND HOLES.

PURPOSE: To determine the utility of ultra-widefield (UWF) imaging in detecting pathologic peripheral retinal tears and holes. METHODS: This was a retrospective, observational study. One-hundred ninety-eight eyes of 198 patients diagnosed with acute posterior vitreous detachment were included. Eyes were divided into two groups: 89 eyes with peripheral retinal holes and tears treated with laser retinopexy (treatment group) and 109 control eyes. Patients underwent UWF imaging and indirect ophthalmoscopy with scleral depression. UWF images from both groups were reviewed by two blinded graders and then compared with funduscopic examination and medical records. RESULTS: UWF imaging identified 60 of the 89 eyes (sensitivity of 67.4%) found to have treatment-requiring peripheral retinal lesions and 107 of the 109 control eyes (specificity of 98.2%).The distribution of misses based on octant location did reach statistical significance ( P = 0.004). Lesions anterior to the equator were more likely to be missed (21/41 eyes, 51.2%) compared with those located posterior to the equator (4/20 eyes, 25.0%) and at the equator (4/28, 14.3%), P = 0.002. The combined discordance rate between graders in the entire cohort was 12.1% (24/198 eyes) yielding an interrater agreement of 87.9%. CONCLUSION: UWF imaging showed a moderate sensitivity and high specificity in detecting treatment-requiring retinal tears and holes, with high interrater agreement. Given there is only a moderate sensitivity in identifying treatment-requiring retinal tears and holes, UWF imaging can assist with clinical examination, but a 360-degree scleral depressed examination should remain the gold standard.

Heads-Up Three-Dimensional Viewing Systems in Vitreoretinal Surgery: An Updated Perspective.

Three-Dimensional (3D) heads-up visualization systems have significantly advanced vitreoretinal surgery, providing enhanced detail and improved ergonomics. This review discusses the application of 3D systems in vitreoretinal surgery, their use in various procedures, their combination with other imaging modalities, and the role of this technology in medical education and telementoring. Furthermore, the review highlights the benefits of 3D systems, such as improved ergonomics, reduced phototoxicity, enhanced depth of field, and the use of color filters. Potential challenges, including the learning curve and additional costs, are also addressed. The review concludes by exploring promising future applications, including teleophthalmology for remote assistance and specialist availability expansion, virtual reality integration for global clinical education, and the combination of remotely robotic-guided surgery with artificial intelligence for precise, efficient surgical procedures. This comprehensive review offers insights into the current state and future potential of 3D heads-up visualization systems in vitreoretinal surgery, underscoring the transformative impact of this technology on ophthalmology.

Multilayered macular hemorrhages as an unusual complication of transorbital neuroendoscopic surgery.

Purpose: To report a case of multilayered intraocular hemorrhage at the posterior pole as a complication of transorbital neuroendoscopic surgery. Observations: Our patient underwent an uncomplicated endoscopic transorbital resection of a left sphenoid wing meningioma. In the immediate post-operative period, the patient reported blurred vision of her left eye, and dilated fundus examination demonstrated multilayered hemorrhages at the posterior pole. No intracranial hemorrhage was identified on post-operative imaging. Due to persistent subnormal visual acuity and non-clearing hemorrhage over several weeks of follow-up, a pars plana vitrectomy with peeling of the internal limiting membrane was performed to clear the hemorrhagic component obscuring the macula. Conclusions and Importance: We report the first case of multilayered intraocular hemorrhages at the posterior pole, mimicking Terson syndrome, in the absence of intracranial hemorrhage or elevated intracranial pressure as a complication of transorbital surgery.

Automated Retinal Layer Segmentation in CLN2-Associated Disease: Commercially Available Software Characterizing a Progressive Maculopathy.

Purpose: CLN2-associated disease is a hereditary, fatal lysosomal storage disorder characterized by progressive brain and retinal deterioration. Here, we characterize the inner and outer retinal degeneration using automated segmentation software in optical coherence tomography scans, providing an objective, quantifiable metric for monitoring subtle changes previously identified with a validated disease classification scale (the Weill Cornell Batten Scale). Methods: This study is a retrospective, single-center cohort review of images from examinations under anesthesia in treatment-naïve patients with CLN2-associated disease. Automated segmentation software was used to delineate retinal nerve fiber, ganglion cell layer (GCL), and outer nuclear layer (ONL) thickness measurements in the fovea, parafovea, and perifovea based on age groups (months): 30 to 38, 39 to 45, 46 to 52, 53 to 59, 60 to 66, and 67 or older. Results: Twenty-seven eyes from 14 patients were included, with 8 serial images yielding 36 interpretable optical coherence tomography scans. There was a significant difference in parafoveal ONL thickness between 39 to 45 and 46 to 52 months of age (P = 0.032) not seen in other regions or retinal layers. Perifoveal ONL demonstrated a difference in thickness between the 60 to 66 and greater than 67 months age cohorts (P = 0.047). There was strong symmetry between eyes, and high segmentation repeatability. Conclusions: Parafoveal ONL thickness represents a sensitive, early age indicator of CLN2-associated degeneration. Outer retinal degeneration is apparent at younger ages than inner retinal changes though in treatment-naïve patients all retinal layers showed significant differences between 60 to 66 and more than 67 months of age. Translational Relevance: This study establishes sensitive, quantitative biomarkers for assessing retinal degeneration in a large cohort natural history study in anticipation of future clinical trials.

Ocular Outcomes after Treatment of Cytomegalovirus Retinitis Using Adoptive Immunotherapy with Cytomegalovirus-Specific Cytotoxic T Lymphocytes.

PURPOSE: To describe ocular outcomes in eyes with cytomegalovirus (CMV) retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic Tlymphocytes (CMV-specific CTLs). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with active CMV retinitis evaluated at a tertiary care academic center. METHODS: Treatment of CMV retinitis with standard-of-care therapy (systemic or intravitreal antivirals) or CMV-specific CTLs (with or without concurrent standard-of-care therapies). MAIN OUTCOME MEASURES: The electronic medical record was reviewed to determine baseline characteristics, treatment course, and ocular outcomes, including best-corrected visual acuity (BCVA), treatments administered (CMV-specific CTLs, systemic antivirals, intravitreal antivirals), resolution of CMV retinitis, any occurrence of immune recovery uveitis, cystoid macular edema, retinal detachment, or a combination thereof. RESULTS: Seven patients (3 of whom had bilateral disease [n = 10 eyes]) were treated with CMV-specific CTLs, whereas 20 patients (6 of whom had bilateral disease [n = 26 eyes]) received standard-of-care treatment. Indications for CMV-specific CTL therapy included persistent or progressive CMV retinitis (71.4% of patients); CMV UL54 or UL97 antiviral resistance mutations (42.9%); side effects or toxicity from antiviral agents (57.1%); patient intolerance to longstanding, frequent antiviral therapy for persistent retinitis (28.6%); or a combination thereof. Two patients (28.6%; 4 eyes [40%]) received CMV-specific CTL therapy without concurrent systemic or intravitreal antiviral therapy for active CMV retinitis, whereas 5 patients (71.4%; 6 eyes [60%]) continued to receive concurrent antiviral therapies. Resolution of CMV retinitis was achieved in 9 eyes (90%) treated with CMV-specific CTLs, with BCVA stabilizing (4 eyes [40%]) or improving (4 eyes [40%]) in 80% of eyes over an average follow-up of 33.4 months. Rates of immune recovery uveitis, new-onset cystoid macular edema, and retinal detachment were 0%, 10% (1 eye), and 20% (2 eyes), respectively. These outcomes compared favorably with a nonrandomized cohort of eyes treated with standard-of-care therapy alone, despite potentially worse baseline characteristics. CONCLUSIONS: CMV-specific CTL therapy may represent a novel monotherapy or adjunctive therapy, or both, for CMV retinitis, especially in eyes that are resistant, refractory, or intolerant of standard-of-care antiviral therapies. More generally, adoptive cell transfer and adoptive immunotherapy may have a role in refractory CMV retinitis. Larger prospective, randomized trials are necessary.

ROLE OF OPTICAL COHERENCE TOMOGRAPHY FOR PREDICTING POSTOPERATIVE VISUAL OUTCOMES AFTER REPAIR OF MACULA-OFF RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To identify any prognostic associations between preoperative optical coherence tomography findings and postoperative visual outcomes in patients with macula-off rhegmatogenous retinal detachment. METHODS: A retrospective, single-center study of patients diagnosed with macula-off rhegmatogenous retinal detachment whom underwent surgical reattachment from 2012 to 2017. Optical coherence tomography images were analyzed by two retina surgeons. Outcome measures included "good" final vision (best-corrected visual acuity of 20/40 or better), "poor" final vision (best-corrected visual acuity of 20/200 or worse), and change in vision (worsened, improved, and improved ≥15 letters) at most recent follow-up. P values were calculated using t tests, analysis of variance, Wilcoxon rank-sum, or Kruskall-Wallis test. RESULTS: A total of 49 eyes were included. There was a significant difference in the mean preoperative central retinal thickness between patients who had good final vision and patients who did not (96 µm vs. 161 µm, P = 0.048). In addition, a worse preoperative best-corrected visual acuity and greater subretinal fluid height were associated with vision improvement (P < 0.001). Those with persistent ellipsoid zone disruption postoperatively were less likely to have good final vision (odds ratio = 0.217, 95% confidence interval: 0.057-0.828). CONCLUSION: A lower mean preoperative central retinal thickness is associated with good visual prognosis. Eyes with ellipsoid zone disruption postoperatively were less likely to have good final vision. Future studies should include a larger cohort of patients and more optical coherence tomography variables to address the inconsistencies in the current literature.