Pseudophakia as a surprising protective factor in neovascular age-related macular degeneration.

PURPOSE: To assess the impact of lens status on macular function among patients treated for neovascular age-related macular degeneration (nvAMD) in whom scheduled intravitreal injections were delayed. METHODS: We reviewed demographic and clinical data as well as macular optical coherence tomographic images of 34 patients (48 eyes) who did not follow their injection schedule during the first wave of COVID-19 in Israel. Functional worsening was defined as a loss of at least 0.1 in decimal best-corrected visual acuity (BCVA). Morphological worsening was defined as new or increased subretinal/intraretinal fluid or a new hemorrhage. OCT indices of quality were used as a measure for cataract density and progression. RESULTS: Pseudophakia was associated with a better functional outcome than phakic status: there was a loss of 0.06±0.12 vs. 0.15±0.10 decimal BCVA in the pseudophakic and phakic eyes, respectively (P=.001). A similar trend was observed for morphological changes over the same period: there was an increase in macular thickness of 9±26% vs.12±40%, respectively (P=0.79). During the first wave of COVID-19, the index of OCT quality remained stable for phakic eyes (26±3.6 before the first wave of COVID-19, 26±2.9 afterward; P=1) and pseudophakic eyes (30±2.4 before the first wave of COVID-19, 30±2.6 afterward; P=1). CONCLUSION: Pseudophakic eyes with nvAMD that missed their scheduled intravitreal injections experienced fewer morphological and functional complications than phakic eyes with nvAMD.

Intravitreal application of epidermal growth factor in non-exudative age-related macular degeneration.

PURPOSE: To assess the safety of intravitreally applied epidermal growth factor (EGF). METHODS: The clinical interventional, prospective, single-centre, case series study included patients with age-related macular degeneration-related geographic atrophy (GA), in whom the eye with the worse best-corrected visual acuity (BCVA) underwent a single, or repeated, intravitreal injection of EGF (0.75 µg in 50 µL). At baseline and afterwards, the eyes underwent ophthalmological examinations. RESULTS: The study included seven patients (mean age:70.0±12.2 years (range: 54-86 years), with five patients receiving a single injection and two patients receiving two intravitreal injections in an interval of 4 weeks. Mean duration of follow-up was 97±97 days (median:35 days; range: 7-240 days). Mean BCVA was lower at baseline than at study end (1.41±0.44 logMAR vs 0.97±0.12 logMAR; p=0.03). Mean size of the GA lesions did not differ significantly between baseline and study end (29 212±22 887 pixels vs 29 300±22 905 pixels; p=0.59) nor did the mean perimetric mean defect (-10.3±5.9 dB vs 12.0±8.8 dB; p=0.35) or the electroretinographical b-wave amplitude (44.53±31.7 µV vs 64.5±25.5 µV; p=0.12). After a second injection 4 weeks after the first injection, one of two patients developed a cystoid macular oedema in association with an induced incomplete posterior vitreous detachment. It persisted for 3 weeks. Visual acuity in this eye improved from 1.0 logMAR at baseline to 0.80 logMAR at study end. CONCLUSIONS: Except for one eye with temporary, self-resolving cystoid macular oedema, single and repeated intravitreal applications of EGF (0.75 µg) in patients with GA did not lead to intraocular inflammations or any observed intraocular side effect. TRIAL REGISTRATION NUMBER: ISRCTN12733334.

Diagnostic accuracy of current machine learning classifiers for age-related macular degeneration: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The objective of this study was to systematically review and meta-analyze the diagnostic accuracy of current machine learning classifiers for age-related macular degeneration (AMD). Artificial intelligence diagnostic algorithms can automatically detect and diagnose AMD through training data from large sets of fundus or OCT images. The use of AI algorithms is a powerful tool, and it is a method of obtaining a cost-effective, simple, and fast diagnosis of AMD. METHODS: MEDLINE, EMBASE, CINAHL, and ProQuest Dissertations and Theses were searched systematically and thoroughly. Conferences held through Association for Research in Vision and Ophthalmology, American Academy of Ophthalmology, and Canadian Society of Ophthalmology were searched. Studies were screened using Covidence software and data on sensitivity, specificity and area under curve were extracted from the included studies. STATA 15.0 was used to conduct the meta-analysis. RESULTS: Our search strategy identified 307 records from online databases and 174 records from gray literature. Total of 13 records, 64,798 subjects (and 612,429 images), were used for the quantitative analysis. The pooled estimate for sensitivity was 0.918 [95% CI: 0.678, 0.98] and specificity was 0.888 [95% CI: 0.578, 0.98] for AMD screening using machine learning classifiers. The relative odds of a positive screen test in AMD cases were 89.74 [95% CI: 3.05-2641.59] times more likely than a negative screen test in non-AMD cases. The positive likelihood ratio was 8.22 [95% CI: 1.52-44.48] and the negative likelihood ratio was 0.09 [95% CI: 0.02-0.52]. CONCLUSION: The included studies show promising results for the diagnostic accuracy of the machine learning classifiers for AMD and its implementation in clinical settings.

Association of Ocular Adverse Events With Inactivated COVID-19 Vaccination in Patients in Abu Dhabi.

Importance: As vaccinations against COVID-19 continue, potential ocular adverse events should be reported in detail to increase awareness among the medical community, although typically, a causal relationship cannot be established definitively. Objective: To describe ocular adverse events that occur soon after receiving an inactivated COVID-19 vaccination (Sinopharm). Design, Setting, and Participants: This case series took place from September 2020 to January 2021 at Cleveland Clinic Abu Dhabi, a tertiary referral center. Patients who reported ocular adverse events and presented within 15 days from the first of 2 doses of an inactivated COVID-19 vaccine were analyzed. Main Outcomes and Measures: Each patient underwent Snellen best-corrected visual acuity that was then converted to logMAR, applanation tonometry, and biomicroscopic examination with indirect ophthalmoscopy. Color fundus photography was obtained with a conventional 9-field fundus photography camera or with a widefield fundus photography system. Optical coherence tomography and optical coherence tomographic angiography images were obtained. Sex, race, age, and clinical data were self-reported. Results: Nine eyes of 7 patients (3 male individuals) presenting with ocular complaints following COVID-19 vaccine were included in the study. The mean (SD) age was 41.4 (9.3) years (range, 30-55 years); the mean best-corrected visual acuity was 0.23 logMAR (range, 0-1 logMAR; approximate Snellen equivalent, 20/32). The mean time of ocular adverse event manifestations was 5.2 days (range, 1-10 days). One patient was diagnosed with episcleritis, 2 with anterior scleritis, 2 with acute macular neuroretinopathy, 1 with paracentral acute middle maculopathy, and 1 with subretinal fluid. Conclusions and Relevance: In this case series study of 7 patients, the timing of transient and ocular complications 5.2 days after vaccination with an inactivated COVID-19 vaccine supported an association with the ocular findings, but a causal relationship cannot be established from this study design.

A Case of Post-COVID-19-Associated Paracentral Acute Middle Maculopathy and Giant Cell Arteritis-Like Vasculitis.

ABSTRACT: A 47-year-old man with a history of COVID-19 infection 2 months before presentation, presented with a scotoma of the paracentral visual field of the right eye. After thorough testing and evaluation, a diagnosis of paracentral acute middle maculopathy (PAMM) was established. Two months later, the patient developed temporal headache and jaw claudication. High-dose steroids were initiated, and workup for giant cell arteritis (GCA) was undertaken. The patient experienced resolution of the symptoms within 24 hours of steroid initiation. ESR, CRP, and temporal artery biopsy results were normal, although all were obtained more than 2 weeks after steroid initiation. To the best of our knowledge, our patient represents the first individual to date to potentially implicate COVID-19 in both small and large vessel vasculitis in the ophthalmic setting.

A Smart Mobile Application to Monitor Visual Function in Diabetic Retinopathy and Age-Related Macular Degeneration: The CLEAR Study.

PURPOSE: The purpose of this study was to determine if a mobile application, the Checkup Vision Assessment System, could reliably monitor visual acuity (VA) and metamorphopsia remotely versus standard VA reference tests in the clinic. With the current COVID-19 pandemic, an even greater need for remote monitoring exists. Mobile tools enhance the ability to monitor patients virtually by enabling remote monitoring of VA and Amsler grid findings. DESIGN: Prospective, multicenter reliability analysis. METHODS: Participants: Patients (N = 108) with near corrected VA better than 20/200 and a diagnosis of age-related macular degeneration, diabetic retinopathy, or healthy patients without retinal disease (best-corrected visual acuity [BCVA] of 20/32 or better). INTERVENTION: participants were tested using the Checkup, reference VA, and Amsler tests, with the order of testing (Checkup or reference) randomized. Patients monitored their vision using Checkup at least twice a week at home between office visits. Main outcome measurements were near corrected VA and Amsler grid test results. RESULTS: Agreement was strong between Checkup and reference tests for VA (r = 0.86) and Amsler grid (sensitivity: 93%; specificity: 92%). Home versus clinic testing showed excellent agreement (r = 0.96). Patients reported successful home use. There were no serious adverse events or discontinuations. Patients rated the usability of Checkup to be excellent. CONCLUSIONS: There was good agreement between Checkup and in-clinic test results for VA and Amsler grid. The low variance of Checkup testing, agreement between in-clinic and home results, and excellent usability support Checkup as a reliable method for monitoring retinal pathology in clinic and home settings.

COVID-19 Morbidity and Severity in Patients With Age-Related Macular Degeneration: A Korean Nationwide Cohort Study.

PURPOSE: To determine the potential association between age-related macular degeneration (AMD), a representative chronic age-related degenerative disease of the retina associated with inflammation and aging, and susceptibility to SARS-CoV-2 infection and severe COVID-19 outcomes. DESIGN: Nationwide cohort study with propensity-score matching. METHODS: A population-based nationwide cohort in Korea was examined. Data were obtained from the Health Insurance Review & Assessment Service of Korea, including all patients aged ≥40 years who underwent SARS-CoV-2 testing in South Korea between January 1, 2020 and May 15, 2020 (excluding self-referral). The primary outcome was SARS-CoV-2 test positivity and the secondary outcome was severe clinical outcome of COVID-19. RESULTS: The unmatched cohort consisted of 135,435 patients who were tested for SARS-CoV-2: 4531 patients (3.3%) tested positive for SARS-CoV-2 and 5493 (4.1%) had AMD. After propensity score matching, exudative AMD was associated with an increased likelihood of susceptibility to SARS-CoV-2 infection (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.03-2.25), and a considerably greater risk of severe clinical outcomes of COVID-19 (aOR, 2.26; 95% CI, 1.02-5.26), but not any AMD and non-exudative AMD. CONCLUSIONS: In a Korean nationwide cohort, data suggest that clinicians should be aware of the greater risk of susceptibility to severe clinical outcomes of COVID-19 in patients with exudative AMD. These findings provide an improved understanding of the relationship between the pathogenesis of COVID-19 and chronic neurological disorders.

Patient Perceptions of SARS-CoV-2 Exposure Risk and Association With Continuity of Ophthalmic Care.

Importance: Patient perceptions regarding the risks of obtaining in-person ophthalmic care during the coronavirus disease 2019 (COVID-19) pandemic may affect adherence to recommended treatment plans and influence visual outcomes. A deeper understanding of patient perspectives will inform strategies to optimize adherence with vision-preserving therapies. Objective: To evaluate perceptions of COVID-19 exposure risk and their association with appointment attendance among patients at high risk of both reversible and irreversible vision loss from lapses in care. Design, Setting, and Participants: This survey study included a nonvalidated telephone survey designed in April and May of 2020 and a retrospective medical record review conducted in parallel with survey administration from May 22 to August 18, 2020. Participants were recruited from 2 tertiary eye care centers (Emory Eye Center in Atlanta, Georgia, and W.K. Kellogg Eye Center in Ann Arbor, Michigan). The study included a random sample of patients with diagnoses of exudative age-related macular degeneration (AMD) or diabetic retinopathy (DR) who received an intravitreal injection between January 6 and March 13, 2020, and were scheduled for a second injection between March 13 and May 6, 2020. Main Outcomes and Measures: Association between perceptions regarding COVID-19 risks and loss to follow-up. Results: Of 1004 eligible patients, 423 (42%) were successfully contacted, and 348 (82%) agreed to participate (participants' mean [SD] age, 75 [12] years; 195 women [56%]; 287 White [82%] patients). Respondents had a mean (SD) of 2.7 (1.1) comorbidities associated with severe COVID-19, and 77 (22%) knew someone with COVID-19. Of all respondents, 163 (47%) were very concerned or moderately concerned about vision loss from missed treatments during the pandemic. Although 208 (60%) believed the COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exposure at the eye clinic was extremely unlikely or unlikely, 49 (14%) believed it was extremely likely or likely. Seventy-eight participants (22%) were lost to follow-up. Concern regarding COVID-19 exposure during clinic visits (odds ratio [OR], 3.9; 95% CI, 1.8-8.4) and diagnosis of DR (vs AMD) (OR, 8.130; 95% CI, 3.367-20.408) were associated with an increase in likelihood of loss to follow-up. Conclusions and Relevance: Among patients at high risk for vision loss from lapses in care, many expressed concerns regarding the effect of the pandemic on their ability to receive timely care. Survey results suggest that fear of SARS-CoV-2 exposure was associated with a roughly 4-fold increase in the odds of patient loss to follow-up. These results support the potential importance of clearly conveying infection-control measures.

Effects of the COVID-19 pandemic on neovascular age-related macular degeneration and response to delayed Anti-VEGF treatment.

OBJECTIVES: To investigate the effects of the COVID-19 pandemic on the treatment course of neovascular age-related macular degeneration (nAMD) patients who received anti-VEGF injection therapy with real-life data. METHODS: This retrospective study consisted of 116 eyes of 106 patients. Ophthalmic examination, assessment of best-corrected visual acuity (BCVA), optical coherence tomography (OCT) findings and data of last two visits before restrictions (V-2 and V-1) and the first visit (V0) after the release of national lockdown and subsequent visits (V1 and Vlast) were recorded. The lockdown period was determined by the time interval between March 11 and June 1, 2020. MAIN RESULTS: The injection interval before V-1 was significantly longer than the interval after V0 (2.56±0.9 vs. 2.14±0.8 months, P=0.02). While the median central macular thickness (CMT) was significantly increased at V0 compared to V-1 [274(132-711) vs. 238(136-628), P<0.001], the median CMT was significantly lower at V1 compared to V0 [256 (136-591) vs. 274(132-711), P=0.003]. The median BCVA was 0.67(0.1-1.1) logMAR at V-1 and significantly worsened to 0.78 (0.1-1.2) logMAR at V0 (P=0.003). Although the median BCVA improved to 0.69 logMAR (0.1-1.2) at Vlast, the difference did not reach statistical significance compared to V0 (P=0.08). CONCLUSION: Treatment delay due to the COVID-19 pandemic cause progression of nAMD and visual impairment. To plan more frequent anti-VEGF treatments and visits may be an appropriate approach until the disease stabilizes. However, it should be kept in mind that despite the improvement in OCT findings, the desired success in VA could not be achieved in the short term.

Digital Technology for AMD Management in the Post-COVID-19 New Normal.

PURPOSE: The COVID-19 pandemic has put strain on healthcare systems and the availability and allocation of healthcare manpower, resources and infrastructure. With immediate priorities to protect the health and safety of both patients and healthcare service providers, ophthalmologists globally were advised to defer nonurgent cases, while at the same time managing sight-threatening conditions such as neovascular Age-related Macular Degeneration (AMD). The management of AMD patients both from a monitoring and treatment perspective presents a particular challenge for ophthalmologists. This review looks at how these pressures have encouraged the acceptance and speed of adoption of digitalization. DESIGN AND METHODS: A literature review was conducted on the use of digital technology during COVID-19 pandemic, and on the transformation of medicine, ophthalmology and AMD screening through digitalization. RESULTS: In the management of AMD, the implementation of artificial intelligence and "virtual clinics" have provided assistance in screening, diagnosis, monitoring of the progression and the treatment of AMD. In addition, hardware and software developments in home monitoring devices has assisted in self-monitoring approaches. CONCLUSIONS: Digitalization strategies and developments are currently ongoing and underway to ensure early detection, stability and visual improvement in patients suffering from AMD in this COVID-19 era. This may set a precedence for the post COVID-19 new normal where digital platforms may be routine, standard and expected in healthcare delivery.