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: We aimed to determine the incidence of blepharoptosis following intravitreal anti-vascular endothelial growth factor (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 (ICD-10) was used to identify patients with exudative age-related macular degeneration (AMD) and those who developed ptosis following intravitreal injections. Patients with nonexudative AMD who did not receive intravitreal injections served as control. The outcomes were the incidence of ptosis in the injection group compared to the non-injection group and incidence of ptosis in patients whose injections were performed with an eyelid speculum as compared to those whose injections were performed without specula. RESULTS: We recruited 1,100 exudative AMD patients who received at least one intravitreal anti-VEGF injection and 2,258 nonexudative AMD patients who had not received an injection. In the injection group, 18 out of 1100 patients (1.6%) developed ptosis, compared to 52 out of 2258 patients (2.3%) in the non-injection group (p=0.25). Within the injection group, ptosis was mostly bilateral, diagnosed on average 22.4 months following the initial injection, and following more than a one-year injection-free period. 11 out of 537 patients (2.0%) injected without a speculum developed ptosis, compared to 8 out of 444 patients (1.8%) injected with a speculum (p= 0.82). 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.

TECHNIQUE FOR REMOVAL OF A GANCICLOVIR IMPLANT DISLOCATED IN THE VITREOUS CAVITY.

PURPOSE: To report a technique to remove a dislocated ganciclovir implant in the vitreous cavity. METHODS: Retrospective case series. Two patients with dislocated ganciclovir implants in the vitreous cavity. RESULTS: A 6-mm pars plana incision was made; the soft tip was used to elevate the implant behind the intraocular lens and then 0.12-mm forceps were used to externalize the implant. The implant was successfully removed in both patients. CONCLUSION: Removal of a dislocated ganciclovir implant with its encasing strut can be effectively retrieved using a bimanual approach.

Improving model fairness in image-based computer-aided diagnosis.

Deep learning has become a popular tool for computer-aided diagnosis using medical images, sometimes matching or exceeding the performance of clinicians. However, these models can also reflect and amplify human bias, potentially resulting inaccurate missed diagnoses. Despite this concern, the problem of improving model fairness in medical image classification by deep learning has yet to be fully studied. To address this issue, we propose an algorithm that leverages the marginal pairwise equal opportunity to reduce bias in medical image classification. Our evaluations across four tasks using four independent large-scale cohorts demonstrate that our proposed algorithm not only improves fairness in individual and intersectional subgroups but also maintains overall performance. Specifically, the relative change in pairwise fairness difference between our proposed model and the baseline model was reduced by over 35%, while the relative change in AUC value was typically within 1%. By reducing the bias generated by deep learning models, our proposed approach can potentially alleviate concerns about the fairness and reliability of image-based computer-aided diagnosis.

Facilitating deep learning through preprocessing of optical coherence tomography images.

BACKGROUND: While deep learning has delivered promising results in the field of ophthalmology, the hurdle to complete a deep learning study is high. In this study, we aim to facilitate small scale model trainings by exploring the role of preprocessing to reduce computational burden and accelerate learning. METHODS: A small subset of a previously published dataset containing optical coherence tomography images of choroidal neovascularization, drusen, diabetic macula edema, and normal macula was modified using Fourier transformation and bandpass filter, producing high frequency images, original images, and low frequency images. Each set of images was trained with the same model, and their performances were compared. RESULTS: Compared to that with the original image dataset, the model trained with the high frequency image dataset achieved an improved final performance and reached maximum performance much earlier (in fewer epochs). The model trained with low frequency images did not achieve a meaningful performance. CONCLUSION: Appropriate preprocessing of training images can accelerate the training process and can potentially facilitate modeling using artificial intelligence when limited by sample size or computational power.

Primary and secondary focal choroidal excavation morphologic phenotypes, associated ocular disorders and prognostic implications.

AIMS: To characterise and classify the morphological, clinical and tomographic characteristics of focal choroidal excavation (FCE) lesions to determine their prognostic implications. METHODS: 36 eyes with FCE (32 patients) underwent multimodal imaging, including spectral domain optical coherence tomography and fundus autofluorescence. FCE lesions were classified into three subtypes: (1) type 1: myopic (central choroidal thickness: <100 µm), (2) type 2: suspected congenital (central choroidal thickness: 100-200 µm, without associated chorioretinal pathology) and (3) type 3: secondary or acquired (central choroidal thickness: >200 µm, with associated chorioretinal pathology). RESULTS: 80.6% of eyes were followed longitudinally (26.8±18.8 months). There were 9 type 1 FCEs (myopic), 8 type 2 FCEs (U-shaped, congenital) and 19 type 3 FCEs (V-shaped, secondary). Type 2 FCEs trended towards larger maximum widths (p=0.0563). Type 3 FCEs were associated with central serous chorioretinopathy or pachyvessels (47.4%), but were also seen in pattern dystrophy, geographic atrophy, inactive choroiditis, torpedo maculopathy and adult-onset vitelliform dystrophy. Choroidal neovascular membranes (CNVMs) were more prevalent in type 3 FCE (41.2% compared with 11.1% for type 1 FCE, p=0.251, and 0% for type 2 FCE, p=0.043). CONCLUSIONS: The FCE types, stratified by central choroidal thickness, demonstrated distinct morphological characteristics and associated findings. The classification scheme held prognostic implications as type 3 FCE with V shapes were associated with other chorioretinal conditions and were more likely to develop CNVM.

NOVEL MFRP MUTATION WITH NANOPHTHALMOS, OPTIC DISK DRUSEN, AND PERIPHERAL RETINOSCHISIS IMAGED WITH ULTRA-WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To describe with multimodal imaging including the use of ultra-widefield optical coherence tomography imaging a distinct phenotype of autosomal recessive nanophthalmos associated with a novel mutation of the MFRP gene (membrane-type frizzled-related protein). METHODS: Case report of a single patient followed by the Weill Cornell Medicine Department of Ophthalmology Retina and Glaucoma Services, and review of the relevant literature. RESULTS: A patient with a novel homozygous mutation in the MFRP gene (c.472C>T) presented with nanophthalmos, optic disk drusen, foveal hypoplasia, and extensive peripheral retinoschisis, which was revealed to be multilevel retinoschisis on ultra-widefield optical coherence tomography. Unlike other reported cases, the findings associated with this novel mutation did not include foveoschisis or clinically obvious retinitis pigmentosa. The patient underwent prophylactic peripheral laser iridotomy in both eyes. CONCLUSION: Here, we present a patient with nanophthalmos, optic disk drusen, and foveal hypoplasia associated with extensive peripheral retinoschisis imaged by ultra-widefield optical coherence tomography, but not foveal retinoschisis or prominent retinitis pigmentosa. The findings may expand the clinical spectrum of MFRP -associated nanophthalmos.

Advancements in ocular gene therapy delivery: vectors and subretinal, intravitreal, and suprachoroidal techniques.

INTRODUCTION: Ocular gene therapy represents fertile ground for rapid innovation, with ever-expanding therapeutic strategies, molecular targets, and indications. AREAS COVERED: Potential indications for ocular gene therapy have classically focused on inherited retinal disease (IRD) but more recently include acquired retinal diseases, such as neovascular age-related macular degeneration, geographic atrophy, and diabetic retinopathy. Ocular gene therapy strategies have proliferated recently, and include gene augmentation, gene inactivation, gene editing, RNA modulation, and gene-independent gene augmentation. Viral vector therapeutic constructs include adeno-associated virus and lentivirus and continue to evolve through directed evolution and rationale design. Ocular gene therapy administration techniques have expanded beyond pars plana vitrectomy with subretinal injection to intravitreal injection and suprachoroidal injection. EXPERT OPINION: The success of treatment for IRD, paired with the promise of clinical research in acquired retinal diseases and in administration techniques, has raised the possibility of in-office gene therapy for common retinal disorders within the next 5 to 10 years.

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.

Quantitative Modeling of Ultra-Widefield Choroidal Indocyanine Green Angiography in Systemic Vascular Diseases.

BACKGROUND AND OBJECTIVE: To evaluate quantitative measurements of choroidal vasculature as obtained via ultra-widefield indocyanine green angiography (ICGA) in patients with systemic vascular diseases. PATIENTS AND METHODS: Retrospective chart review and image analysis of 38 eyes from 21 patients with ICGA as part of routine retinal care. Images were binarized with lines drawn at specific antero-posterior landmarks. The vessel density and mean vessel caliber were measured along these lines and correlated with systemic vascular disease status. RESULTS: Unlike those with other systemic vascular diseases, patients with obstructive sleep apnea (OSA) were found to have increased choroidal vascular density and vessel caliber in all measurements of the peripheral choroid compared with those patients without (P < .05 for all measurements). CONCLUSIONS: Patients with OSA may have increased vascular density secondary to increased choroidal vessel caliber. Further work is needed to validate the modeling and confirm the association. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:281-287.].

Choroidal Neovascularization and Macular Hemorrhage: Real-World Experience During the New York City COVID-19 Lockdown.

Purpose: This work reviews ocular, systemic, and demographic factors contributing to presentation of choroidal neovascular membrane (CNVM)-associated macular hemorrhage after the New York City coronavirus disease 2019 (COVID-19) lockdown. Methods: A retrospective, consecutive case series was conducted of all established patients presenting with macular hemorrhage between March 22, 2020, and August 10, 2020. Results: Fourteen patients (mean age 82.2 years) were evaluated. Ten patients had active CNVMs, 1 had an inactive lesion that was last injected 2 years prior, and 3 had new conversions from nonexudative age-related macular degeneration. In the actively treated CNVM group there was a delay in expected follow-up from 50.4 days to 125 days. Eight patients with previously active CNVM (73%) had a history of prior macular hemorrhage. Eight patients (57%) were on some form of antiplatelet or anticoagulation therapy. Twelve patients (86%) had COVID-19-specific risk factors besides age, and all but 1 patient (93%) delayed care without discussion with a physician. Ten patients (71%) had more than 1 week of symptoms prior to presentation. Twelve patients (86%) had signs of CNVM on prior optical coherence tomography. Conclusions: Adequate documentation of potential risks for hemorrhage (particularly prior hemorrhage or presence of subclinical type 1 CNVM), as well as COVID-19-specific risk factors, would aid triage of clinic appointments in future lockdowns. High-risk patients would likely benefit from direct physician communication discussing their individual risk profiles to alleviate anxiety over clinic visits and communicate their risk of severe vision loss.

Feasibility and Clinical Utility of Ultra-Widefield-Navigated Swept-Source Optical Coherence Tomography Imaging.

Purpose: This work aims to evaluate the clinical utility and feasibility of a novel scanning laser ophthalmoscope-based navigated ultra-widefield swept-source optical coherence tomography (UWF SS-OCT) imaging system. Methods: A retrospective, single-center, consecutive case series evaluated patients between September 2019 and October 2020 with UWF SS-OCT (modified Optos P200TxE, Optos PLC) as part of routine retinal care. The logistics of image acquisition, interpretability of images captured, nature of the peripheral abnormality, and clinical utility in management decisions were recorded. Results: Eighty-two eyes from 72 patients were included. Patients were aged 59.4 ± 17.1 years (range, 8-87 years). During imaging, 4.4 series of images were obtained in 4.1 minutes, with 86.4% of the image series deemed to be diagnostic of the peripheral pathology on blinded image review. The most common pathologic findings were chorioretinal scars (18 eyes). In 31 (38%) eyes, these images were meaningful in supporting clinical decision-making with definitive findings. Diagnoses imaged included retinal detachment combined with retinoschisis, retinal hole with overlying vitreous traction and subretinal fluid, vitreous inflammation overlying a peripheral scar, Coats disease, and peripheral retinal traction in sickle cell retinopathy. Conclusions: Navigated UWF SS-OCT imaging was clinically practical and provided high-quality characterization of peripheral retinal lesions for all eyes. Images directly contributed to management plans, including laser, injection or surgical treatment, for a clinically meaningful set of patients (38%). Future studies are needed to further assess the value of this imaging modality and its role in diagnosing, monitoring, and treating peripheral lesions.

Case Report: Glaucoma in an Infant With Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness that occurs due to incomplete development of retinal blood vessels in preterm infants. Glaucoma is an ocular comorbidity in some patients with ROP, and it may be associated with immature anterior chamber development, ROP itself, or the treatment for ROP. There have been a few reports of narrow-angle glaucoma after laser treatment for ROP. In this case report, we describe the course of a female infant born at 24 weeks and 5 days of gestational age with treatment-requiring ROP treated with laser photocoagulation who subsequently developed very elevated intraocular pressure and shallow anterior chambers without pupillary block. The patient required bilateral ab externo trabeculotomy for elevated intraocular pressure, which normalized after the procedure. The patient has remained stable at the last follow-up at 51 weeks postmenstrual age. Differing from previous glaucoma presentations in this setting, we illustrate a case of elevated intraocular pressure and anterior chamber narrowing after laser therapy without pupillary block or synechiae. The possible multifactorial etiology of glaucoma in this patient, including incomplete angle development, ischemia, and laser treatment, highlight the need for glaucoma screening in patients with ROP, both in the short and long term.

Scleral-Sutured Intraocular Lens Dislocations Secondary to Eyelet Fractures.

OBJECTIVE: To report clinical features and visual outcomes following eyelet fractures of scleral-sutured enVista MX60 (Bausch + Lomb) intraocular lenses (IOL). DESIGN: Retrospective, multi-center, multi-surgeon, observational case series. METHODS: Study Population: Patients with scleral-sutured enVista MX60 IOLs that experienced either an intraoperative or post-operative eyelet fracture associated with dislocation or subluxation. PROCEDURES: All records were reviewed for patients with a dislocated or subluxed scleral-sutured enVista MX60 IOL. Clinical features and outcomes were gathered. Main Outcome Measures: Clinical setting, surgical technique, complications, and visual acuity. RESULTS: A total of 25 scleral-sutured enVista MX60 IOLs displacements secondary to eyelet fractures in 23 eyes of 23 patients were included. There were 20 IOLs that sustained a postoperative fracture and 5 IOLs that sustained an intraoperative fracture. Of the postoperative fractures, 7 were dislocated and 13 were subluxed. Gore-Tex was the suture of choice for 19 of the postoperative fractures and all 5 of the intraoperative fractures, and Prolene was used for 1 postoperative fracture. The mean time until postoperative fracture was 96 ± 125 days, and the median time was 61 (IQR 48-144) days. Of the postoperative fractures, new MX60s were sutured in 10 patients, and 2 of them experienced repeat displacements due to a new eyelet fracture. In the intraoperative fracture group, new MX60s were sutured in 4 patients and an Akreos AO60 lens was placed in the 5th patient. The mean preoperative best-corrected logMAR visual acuity for all patients improved from 1.2 ± 0.8 (20/317 Snellen equivalent) to 0.5 ± 0.5 (20/63 Snellen equivalent) at most recent follow-up after lens replacement. CONCLUSIONS: Scleral-sutured MX60 intraocular lenses can experience intraoperative or postoperative eyelet fractures, resulting in lens subluxation or dislocation. Surgeons should be aware of this complication when evaluating secondary intraocular lens options.

Drug-induced maculopathy.

PURPOSE OF REVIEW: The purpose of this article is to provide an overview of drug-induced maculopathies including their clinical presentations, diagnostic findings, and treatment options. With the increasing pace of development and arrival of drugs to the market, this review aims to inform retina specialists of relevant side effects that may be encountered in a clinical practice setting. RECENT FINDINGS: The major themes visited in this article focus on relevant findings of drugs that cause pigmentary and crystalline maculopathy, photoreceptor dysfunction, cystoid macular edema, central serous choroidopathy, uveitis, and vascular damage. SUMMARY: The current review reports updated findings and discusses the pathophysiologic mechanisms, presentations, and treatments of drug-induced maculopathies.