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.

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.

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.

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.

Corneal hysteresis and anterior segment optical coherence tomography anatomical parameters in primary angle closure suspects.

IMPORTANCE: Corneal hysteresis (CH) is a dynamic marker of structural and functional changes in the cornea associated with intraocular pressure (IOP) and central corneal thickness, but its utility in assessing primary angle closure suspects (PACS) has not been fully elucidated. BACKGROUND: This study assesses if anterior segment measurements correlate with CH in PACS patients. DESIGN: IRB-approved retrospective review of imaging and records at a university practice. PARTICIPANTS: Sixty-three eyes from 37 patients diagnosed as PACS, without other ocular pathology. METHODS: Every eye underwent measurements including: ocular response analyzer (ORA), anterior segment optical coherence tomography (OCT) and a clinical evaluation. ORA measurements were correlated with other anatomic parameters using a mixed effects multivariable linear regression framework. MAIN OUTCOME MEASURES: ORA measurements included: CH, corneal resistance factor, Goldmann IOP (IOPg ) and corneal compensated IOP (IOPcc ). Anterior segment OCT measurements included: central corneal thickness (CCTOCT ), nasal and temporal peripheral corneal thicknesses (PCT1 and PCT2), anterior chamber depth (ACD), nasal angle to temporal angle distance (ATA) and temporal and nasal angle measurements. Clinical measurements included: central corneal thickness via pachymetry, IOP measured by Goldmann applanation, axial length by A-scan ultrasound and spherical equivalent. RESULTS: CH was negatively correlated with IOPcc, and ACD CH was positively correlated with CCTOCT , CCTp , CRF, PCT1 and PCT2. Females were found to have lower CH. In multivariable regression controlling for gender, CCT, PCT, IOP and ACD, no correlation was seen between CH and anatomic measurements. CONCLUSIONS AND RELEVANCE: CH values in PACS do not correlate with anterior segment anatomy.

Pneumocephalus and Sixth Nerve Palsy after Epidural Steroid Injection: Case Report and Review of the Literature.

BACKGROUND: Pneumocephalus has been described as an unintended outcome after epidural injections. However, oculomotor palsy from pneumocephalus after epidural injection is very rare. CASE REPORT: We report a case of pneumocephalus-induced sixth nerve palsies and diplopia in an 87-year-old woman after epidural steroid injection. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Pneumocephalus-induced oculomotor palsy is a rare complication after epidural injection, a commonly performed medical procedure. Knowledge of this presentation will help emergency physicians distinguish between this entity and other causes of neurologic deficits.

Case-matched comparison of vitrectomy, peripheral retinal endolaser, and endocyclophotocoagulation versus standard care in neovascular glaucoma.

PURPOSE: To evaluate the efficacy of combination pars plana vitrectomy, endoscopic peripheral panretinal photocoagulation, and endocyclophotocoagulation (ECP) as compared with standard care in patients with neovascular glaucoma. METHODS: This age-matched case-controlled retrospective series of 54 eyes compared the clinical outcomes between a consecutive series of combination pars plana vitrectomy/panretinal photocoagulation/ECP (n = 27) versus the current standard of care (n = 27) for patients with neovascular glaucoma. "Standard" treatments for patients with neovascular glaucoma include panretinal photocoagulation, intravitreal bevacizumab, filtration surgery, pars plana vitrectomy, and Ahmed valve placement. RESULTS: After 1 year, mean intraocular pressure reduced from 40.7 ± 12.40 mmHg preoperatively to 12.3 ± 4.84 mmHg (P < 0.001) in the ECP group and from 34.7 ± 12.38 mmHg to 23.2 ± 12.34 mmHg in the control group (P = 0.002). Compared with controls, the mean drop in intraocular pressure in the ECP group was significantly greater at all postoperative visits. Logarithm of the minimal angle of resolution visual acuity outcomes were similar in both groups. There were 2 cases (7.4%) of postoperative phthisis bulbi in each group. CONCLUSION: Endoscopic pars plana vitrectomy, panretinal photocoagulation, and ECP seem to control intraocular pressure to a greater extent than standard glaucoma treatments in patients with neovascular glaucoma. In this aged-matched comparative case series, there was no significant difference between the two treatments' effects on visual acuity.

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.

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.

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.

Harnessing the power of longitudinal medical imaging for eye disease prognosis using Transformer-based sequence modeling.

Deep learning has enabled breakthroughs in automated diagnosis from medical imaging, with many successful applications in ophthalmology. However, standard medical image classification approaches only assess disease presence at the time of acquisition, neglecting the common clinical setting of longitudinal imaging. For slow, progressive eye diseases like age-related macular degeneration (AMD) and primary open-angle glaucoma (POAG), patients undergo repeated imaging over time to track disease progression and forecasting the future risk of developing a disease is critical to properly plan treatment. Our proposed Longitudinal Transformer for Survival Analysis (LTSA) enables dynamic disease prognosis from longitudinal medical imaging, modeling the time to disease from sequences of fundus photography images captured over long, irregular time periods. Using longitudinal imaging data from the Age-Related Eye Disease Study (AREDS) and Ocular Hypertension Treatment Study (OHTS), LTSA significantly outperformed a single-image baseline in 19/20 head-to-head comparisons on late AMD prognosis and 18/20 comparisons on POAG prognosis. A temporal attention analysis also suggested that, while the most recent image is typically the most influential, prior imaging still provides additional prognostic value.

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.

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.

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.

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.

Morphologic differences in epiretinal membranes on ocular coherence tomography as a predictive factor for surgical outcome.

PURPOSE: To evaluate whether morphologic differences in idiopathic epiretinal membranes seen on optical coherence tomography may help predict surgical outcomes. METHODS: Seventy-five eyes of 74 patients who underwent primary pars plana vitrectomy with membrane peeling were retrospectively reviewed. Outcome measures included visual acuity, macular contour on optical coherence tomography, central macular thickness, and reoperation rate. RESULTS: According to the preoperative macular contour, 75 eyes were categorized into 4 types: 42 eyes were included in the diffuse (DIF) type, 12 in the cystoid macular edema (CME) type, 14 in the pseudolamellar hole (PLH) type, and 7 in the vitreomacular traction (VMT) type. Surgical procedure significantly improved vision in all types except for the PLH type (DIF, P < 0.0001; CME, P = 0.0378; PLH, P = 0.838; and VMT, P = 0.0273). There was a significant relationship between pre- and postoperative macular contour. All preoperative VMT showed normal contour on postoperative optical coherence tomography but had the highest reoperation rate. CONCLUSION: Surgical intervention for the PLH-type epiretinal membrane was not associated with the visual improvement seen in other epiretinal membrane types, and the VMT type had the highest reoperation rate. Future studies should evaluate the potential benefit of internal limiting membrane peeling with or without short-term gas tamponade in these cases.

A retrospective analysis of triple combination therapy with intravitreal bevacizumab, posterior sub-tenon's triamcinolone acetonide, and low-fluence verteporfin photodynamic therapy in patients with neovascular age-related macular degeneration.

PURPOSE: To assess the efficacy of triple combination therapy (TCT) including bevacizumab (BEV), low-fluence photodynamic therapy, and posterior sub-Tenon's triamcinolone acetonide in patients with wet age-related macular degeneration. METHODS: This institutional review board-approved retrospective consecutive case series included 31 eyes treated for wet age-related macular degeneration with TCT at the Beth Israel Deaconess Medical Center between June 2004 and November 2008. Outcome measures included visual acuity, retinal thickness as measured by optical coherence tomography, time to retreatment, and complications. RESULTS: Triple combination therapy eyes showed significant 3-month and 6-month improvement in visual acuity of 0.140 ± 0.273 logarithm of the minimum angle of resolution and 0.182 ± 0.383 logarithm of the minimum angle of resolution after treatment, respectively (P = 0.0219 and 0.0470, respectively). Central retinal thickness significantly improved at 3 months (-123.8 ± 102.7 µm), 6 months (-87.7 ± 99.8 µm), and 12 months (-101.6 ± 103.3 µm) on optical coherence tomography. Half of eyes that underwent TCT required retreatment by the conclusion of their follow-up, and eyes that underwent TCT had a 1-year Kaplan-Meier survival rate of 62.1 ± 10.8%. CONCLUSION: Triple combination therapy (TCT) appears to effectively improve visual acuity and decrease retinal thickness often without need for subsequent retreatment within the first year of follow-up. Further investigation of TCT in prospective trials is warranted.

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.].

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.