Patient Perspective on the Monitoring of Their Wet Age-Related Macular Degeneration during Coronavirus Disease 2019: A Retrospective Study.

Background and Objectives: The purpose was to provide the patients' perspective on the monitoring of their wet age-related macular degeneration (wet AMD) during coronavirus disease 2019 (COVID-19) and the importance of telemedicine. Materials and Methods: Wet AMD patients that underwent intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in two Swiss ophthalmology clinics, completed two questionnaires after the first confinement due to COVID-19 in Switzerland. The first evaluated their views concerning their adherence to scheduled injections during the confinement, and the application of telemedicine in the future. The second, adapted from the National Eye Institute Visual Function Questionnaire-25, assessed their opinions on visual function change during confinement. Results: From a total of 130 patients, 8.5% responded they did not respect their assigned schedule (group 1) while 91.5% responded they did (group 2). A total of 78.7% of group 2 considered treatment reception as more relevant compared to the risk of COVID-19 contraction. During the pre-lockdown period, group 2 patients required more help from others than group 1 patients (p = 0.02). In the possibility of another lockdown, 36.3% of group 1 and 8.7% of group 2 would choose telemedicine to monitor their wet AMD (p = 0.02), 54.5% and 86.9% would rather visit the clinic (p = 0.02), while 9.0% and 4.3% would cancel their appointment, respectively. It was found that 70% of group 1 and 33.6% of group 2 would prefer to use the telemedicine services than visiting a telemedicine centre (p = 0.04). Conclusions: During circumstances similar to the COVID-19 confinement, most patients would prefer to visit the clinic. Group 1 would prefer wet AMD monitoring via telemedicine at a higher rate than group 2.

Outcome of Patients Treated by Intravitreal Injections During the COVID-19 Lockdown: An Institutional Experience.

PURPOSE: To determine the loss of follow-up ratio and reasons during the COVID-19 lockdown in patients with retinal diseases treated by anti-vascular endothelial growth factor intravitreal injections and to report the visual outcome and rate of complications of these patients 1 year after the end of the lockdown. METHODS: This is a prospective descriptive cohort study (NCT04395859) conducted at the Rothschild Foundation Hospital - Paris between April 2020 and May 2021. Patients with retinal diseases treated by repeated intravitreal anti-VEGF injections (IVI) since before October 2019 were included. They filled-out a questionnaire and were followed up during a period of 1 year. RESULTS: During the COVID-19 lockdown 198 eyes (82.5%) of 157 patients (82.6%) received their injections in a timely manner (group 1) while 42 eyes (17.5%) of 33 patients (17.4%) had their injections delayed or missed (group 2). No statistically significant difference was found between group 1 and group 2 when comparing the change of mean best corrected distance visual acuity (BCVA) between month 12 and inclusion (p = 0.6) and the rate of ocular complications. The most frequent reasons for missing scheduled injections are appointments cancellation by the hospital (12 patients, 36%), fear of virus exposure during transportation (7 patients, 21%) or at the hospital (5 patients, 15%). Eighty-four percent (130/157 patients) of patients who attended their appointment were satisfied by the protective measures used in the hospital. CONCLUSION: COVID-19 lockdown did not seem to negatively affect the 1-year outcome of patients with retinal diseases treated by anti-VEGF IVIs who missed their scheduled injections. The BCVA and rate of complications at 1 year did not differ whether patients missed their scheduled injections or not. Maintaining IVIs during lockdown periods and educating patients about the risks of missing injections are pivotal in improving prognosis of retinal diseases.

Effects of COVID-19 on Intravitreal Injection Clinic After Lockdown.

Purpose: To examine the return of patients to intravitreal injection clinic after the COVID-19 lockdown. Patients and Methods: The electronic medical records of all patients who received intravitreal injections at a tertiary care Veterans Health Administration (VHA) clinic 14 weeks post-lockdown (5/9/20-8/13/20) in Los Angeles County were reviewed. Reference groups included injection patients during the 7-week COVID-19 lockdown (3/19/20-5/8/20) and a 7-week pre-pandemic period in 2019 (3/19/19-5/8/19). Clinic volume was compared using a one-way ANOVA. Demographic data, medical and psychiatric co-morbidities, injection diagnoses, visual acuities, and clinic volumes were compared between the 3 periods using a generalized estimating equation multivariate analysis. Results: The post-lockdown period group averaged 25.1 visits per week, compared with 12.3/week during lockdown and 25.4/week pre-COVID in intravitreal injection clinic. In the post-lockdown period, the VHA injection clinic returned closer to the pre-lockdown volume compared to the VHA comprehensive clinic (98.9% vs 57.4%, p < 0.001). Post-lockdown, COPD patients and organ transplant patients were less likely to receive injections compared to 2019 (OR 0.76 p = 0.008, OR 1.37 p < 0.0001, respectively). Patients with a diagnosis of cancer increased in proportion between the pre-pandemic and the post-lockdown periods (OR 1.31, p = 0.007). No differences were found, according to psychiatric co-morbidities. After lockdown, the proportion of patients receiving injections for diabetic macular edema (DME) increased (OR 1.11, p = 0.01). Conclusion: Injection volume returned to pre-pandemic levels immediately after lockdown ended. However, patients with high-risk comorbidities did not return to intravitreal injection clinic post-lockdown. These results can inform medical organizations, which groups may need increased safety measures and targeted outreach to address their ophthalmic needs.

Consecutive central and branch retinal vein occlusions in the same eye of a young healthy COVID-19 patient: A unique case report.

Purpose: To report a case of consecutive central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) in the same eye correlated with coronavirus disease (COVID-19) of the otherwise healthy patient. Observations: A 39-year-old woman with the diagnosis of COVID-19 infection for two weeks presented with a nonischemic central retinal vein occlusion (CRVO) in her right eye. The patient was on low-dose aspirin for anticoagulant prophylaxis (100 mg/day) for a week when the CRVO occurred. She had no history of any systemic risk factors for retinal vein occlusion (RVO) and her systemic evaluation failed to identify an etiology for her unilateral CRVO. While she was on monthly follow-up with no additional treatment, she experienced sudden visual acuity decrease in the same eye four months after the first RVO incident and one month after the cessation of aspirin intake. Her best corrected visual acuity (BCVA) was decreased from 20/25+ to 20/63. Her fundoscopic examination revealed increased intraretinal hemorrhages, dilated tortuous veins in the upper hemifield and macular edema. The central macular thickness measurement by optic coherence tomography was increased from 234 µm to 700 µm. The patient refused to undergo a fundus fluorescein angiography. After the diagnosis of the branch retinal vein occlusion with cystoid macular edema was done, the aspirin prophylaxis was restarted, and she received three intravitreal antivascular endothelial growth factor one month apart for her macular edema. Her BCVA improved to 20/20, and macular edema disappeared without any recurrence during the 6-month follow-up. Conclusions and importance: To the best of our knowledge, this unique case is the first report of consecutive RVOs in the same eye of a healthy young patient associated with COVID-19. As our case report demonstrated, close follow-up and timely initiation of appropriate treatment could give rise to complete resolution of RVO.

Impact of the COVID-19 pandemic on visual outcomes of diabetic macular edema patients at a tertiary care veterans affairs center.

Purpose: There are limited studies on factors that impacted retina clinic patient outcomes during the COVID-19 pandemic. We aimed to evaluate visual and anatomic outcomes in patients with diabetic macular edema (DME) requiring anti-VEGF injections at the veterans' affairs tertiary care eye clinic in Houston, TX. Methods: Patient volume from April 2020 was compared to that of April 2019 to determine attendance changes. To evaluate outcomes, we reviewed patients with DME who had scheduled appointments during April 2020. We tracked changes in central foveal thickness (CFT) and Snellen visual acuity (VA) measurements. Patient outcomes were classified as poor (defined as worsening VA or CFT at follow-up) or good (no worsening of either at follow-up). Regression analysis identified characteristics associated with poor outcomes. Results: To prevent the spread of COVID-19, patients were called to reschedule clinic appointments. Attendance frequency decreased from 523 patients in April 2019 to 246 patients in April 2020. 134 patients met inclusion criteria (mean age of 64.7 ± 8.8 years). 19/134 of patients were seen on schedule, 89/134 had delayed appointments (average follow-up interval of 115.2 ± 50.0 days), and 26/134 were lost to follow-up. Patients with delayed appointments had higher odds of poor outcome at follow-up compared to patients seen on schedule (OR = 4.03, 95% CI: 1.14-16.92, p = 0.04). Patient's baseline visual acuity, macular thickness, comorbidities, and diabetic retinopathy severity, and demographics did not affect visual outcome at follow-up. Conclusions: On average, patients were rescheduled to a visit 2.4 months later than their usual visit. Over half these patients experienced worsening of vision or edema. This demonstrates that lapses in care result in worsening of DME. However, there is no clear association between baseline characteristics and risk of disease progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01049-5.

The importance of monitoring wet age-related macular degeneration patients during Coronavirus disease 19 pandemic: A retrospective study of assessment of functional and structural outcomes.

OBJECTIVES: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the gold standard treatment for wet age-related macular degeneration (wet AMD). Coronavirus disease 2019 (COVID-19) has led to the cancellation of many scheduled intravitreal anti-VEGF injection visits. We compared the functional and structural visual outcomes of wet AMD patients who did not adhere to their planned intervals (group 1) with those who did (group 2). METHODS: Wet AMD patients of Swiss Visio Montchoisi and RétinElysée were included. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) changes between their first visit after the end of the first national lockdown in Switzerland (27 April 2020, first post-lockdown visit) and their last visit before the beginning of the first national lockdown in Switzerland (13 March 2020, last pre-lockdown visit) were assessed. The BCVA outcome was defined as unfavorable when there was a loss of≥5 ETDRS letters in the first post-lockdown visit compared to the BCVA at last pre-lockdown visit. The OCT outcome was defined as unfavorable when there was an increase in at least one of the parameters, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment (PED), at the first post-lockdown visit compared to the last pre-lockdown visit. MAIN RESULTS: Group 1 (89 patients, 109 eyes) had a 13.41% greater rate of unfavorable BCVA outcomes and a 38.27% greater rate of unfavorable OCT outcomes than group 2 (96 patients, 122 eyes) (P=0.04, P<0.0001, respectively). Multivariate analysis showed that the more the patients deviated from their programmed injections and the higher the BCVA pre-lockdown, the higher the rate of unfavorable BCVA outcomes (P=0.03 and P=0.02, respectively). OCT outcomes were not a predictive factor for an unfavorable BCVA outcome. CONCLUSIONS: The cancellation of many intravitreal anti-VEGF injection appointments resulted in worse functional and structural outcomes in wet AMD patients. The COVID-19 pandemic led many patients to refrain from their routine intravitreal anti-VEGF injection appointments, allowing us to analyze the role of designated intervals in the treatment of wet AMD. During any future lockdown due to COVID-19 or similar circumstances, continuity of care for wet AMD patients should be maintained.

Long-term impact of delayed follow-up due to COVID-19 lockdown on patients with neovascular age-related macular degeneration.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic in 2020 outpatient care of neovascular age-related macular degeneration (nAMD) patients was severely reduced due to lockdown. Missed visits are known to be detrimental to patients in need of continued anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVIs). The purpose of the study was to assess the effect of a month-long pause of regular visits and anti-VEGF IVIs in nAMD patients. METHODS: A retrospective study was performed. Patients were treated in a pro re nata ("as needed") scheme. Distance (logMAR) and near (logRAD) visual acuity (VA), optical coherence tomography, delay between planned and actual visit date and the indication for IVI were assessed for 3 continous visits in the 6 months before lockdown (V-3, -2, -1) and the 2 visits after lockdown (V0, V + 1). For analysis of long-term impact, records for visits 1 years before and after lockdown (V-3, V + 2) were gathered. RESULTS: We included 166 patients (120 female, 46 male) with a median (range) age of 80.88 (59.8-99.36) years. Compared to V-1, distance VA was significantly worse at both V0 (0.27 ± 0.21 vs 0.31 ± 0.23 logMAR, p < 0.001) and V + 1 (0.27 ± 0.21 vs 0.30 ± 0.23 logMAR, p = 0.021). Near VA was significantly worse at both V0 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.037) and V + 1 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.02). Visit delay (VD) at V0 was significantly longer than at V + 1 (30.81 ± 20.44 vs 2.02 ± 6.79 days, p < 0.0001). Linear regression analysis showed a significant association between visit delay and a reduction of near VA between V-1 and V + 1 (p = 0.0223). There was a significant loss of distance VA (p = 0.02) in the year after the lockdown period (n = 125) compared to the year before. Loss of reading acuity was not significantly increased (p = 0.3). One year post lockdown, there was no correlation between VA change and visit delay after lockdown (p > 0.05). CONCLUSIONS: In nAMD patients whose visits and treatment were paused for a month during the first wave of the COVID-19 pandemic, we found a loss of VA immediately after lockdown, which persisted during follow-up despite re-established anti-VEGF treatment. In the short term, length of delay was predictive for loss of reading VA. The comparison of development of VA during the year before and after the lockdown showed a progression of nAMD related VA loss which may have been accelerated by the disruption of regular visits and treatment. TRIAL REGISTRATION: This article does not report the outcome of a health care intervention. This retrospective study was therefore not registered in a clinical trials database.

Ranibizumab port delivery system in neovascular age-related macular degeneration.

Ranibizumab has proven its efficacy in various retinal diseases and particularly in neovascular age-related macular degeneration (nAMD). The number of injections and the frequent follow-up visits has been burdensome to patients particularly during the COVID era. Ranibizumab port delivery system (RPDS) seems to be a boon in prolonging the action of the drug without the need for frequent injections and follow-up visits. This review article highlights the dosage, adverse effects, and visual outcome associated with various trials of RPDS. For this article, we conducted a PubMed search and review of literature on nAMD, the incidence of AMD, anti-vascular endothelial growth factor (anti-VEGF) agents, RPDS, phase-1 trial of RPDS, phase-2 (LADDER trial) of RPDS, phase-3 (ARCHWAY trial) of RPDS, PORTAL trial of RPDS, results of phase-1 trial of RPDS, results of phase-2 (LADDER) trial of RPDS, and results of phase-3 (ARCHWAY) trial of RPDS.

Real-Time Diabetic Retinopathy Severity Score Level versus Ultra-Widefield Leakage Index-Guided Management of Diabetic Retinopathy: Two-Year Outcomes from the Randomized PRIME Trial.

The prospective PRIME trial applied real-time, objective imaging biomarkers to determine individualized retreatment needs with intravitreal aflibercept injections (IAI) among eyes with diabetic retinopathy (DR). 40 eyes with nonproliferative or proliferative DR without diabetic macular edema received monthly IAI until a DR severity scale (DRSS) level improvement of ≥2 steps was achieved. Eyes were randomized 1:1 to DRSS- or PLI- guided management. At the final 2-year visit, DRSS level was stable or improved compared to baseline in all eyes, and mean PLI decreased by 11% (p = 0.73) and 23.6% (p = 0.25) in the DRSS- and PLI-guided arms. In both arms, the percent of pro re nata (PRN) visits requiring IAI was significantly higher in year 2 versus 1 (p < 0.0001). The percent of PRN visits receiving IAI during year 1 was significantly correlated with the percent of PRN visits with IAI during year 2 (p < 0.0001). Through week 104, 77.4% of instances of DRSS level worsening in the DRSS-guided arm were preceded by or occurred alongside an increase of PLI. Overall, consistent IAI re-treatment interval requirements were observed longitudinally among individual patients. Additionally, PLI increases appeared to precede DRSS level worsening, highlighting PLI as a valuable biomarker in the management of DR.

Evaluation of a calculation model to estimate the impact of the COVID-19 pandemic lockdown on visual acuity in neovascular AMD.

PURPOSE: A model was calculated during the first Austrian coronavirus disease-2019 (COVID-19) pandemic lockdown to estimate the effect of a short-term treatment interruption due to healthcare restrictions on visual acuity (VA) in neovascular age-related macular degeneration (nAMD). The model was compared to the real-life outcomes before treatment re-started. METHODS: Retrospective data-collection of 142 eyes in 142 patients receiving repeated intravitreal injections with anti-VEGF at a retina unit in Vienna in a personalized pro-re-nata regimen prior to the COVID-19 associated lockdown, when treatment was deferred between March 16 and May 4, 2020. During the lockdown, the preliminary data was integrated into pre-existing formulae based on the natural course of the disease in untreated eyes in the long term. Patients were re-scheduled and treated after gradually opening operating rooms. The calculation model was compared to the effective VA change. RESULTS: The model calculated an overall VA loss of 3.5 ± 0.8 letters early treatment diabetes retinopathy study (ETDRS) (p < 0.001 [95% CI:3.3;3.6]) on average compared to 2.5 ± 6 letters ETDRS (p < 0.001 [95% CI:1.5;3.5]) as measured with a mean treatment delay of 61 ± 14 days after previously scheduled appointments. The total difference between the model exercise and the real-life outcomes accounted for 1 ± 5.9 letters ETDRS (p = 0.051 [95% CI: 0.1;1.9]). CONCLUSION: The herein presented calculation model might not be suitable to estimate the effective VA loss correctly over time, although untreated eyes and eyes under therapy show similarities after short-term treatment interruption. However, this study demonstrated the potentially negative impact of the COVID-19 pandemic lockdown on patients compromised by nAMD.

The Impact of Non-Ophthalmic Factors on Intravitreal Injections During the COVID-19 Lockdown.

PURPOSE: Early on in the COVID-19 pandemic, it was difficult to know what factors would affect patient and physician decision-making regarding ophthalmic care utilization. The purpose of this study is to investigate the effect of non-ophthalmic factors on patient decision-making to receive intravitreal injections during the COVID-19 lockdown. PATIENTS AND METHODS: Data on patients who had intravitreal injection appointments at a tertiary care Veterans Health Administration clinic during a seven-week period (March 19, 2020-May 8, 2020) of the COVID-19 outbreak in Los Angeles County were collected and compared to patients who had intravitreal injection appointments during the same time period in 2019. Demographic characteristics, injection diagnoses, visual acuities, body mass indices, co-morbidities, and psychiatric conditions of patients and clinic volumes were tabulated and compared between the two time periods. RESULTS: There were 86 patients in the injection clinic in 2020 compared to 176 patients in 2019. The mean age and gender of patients in the injection clinic did not differ between 2019 and 2020. Compared to 2019, the number of patients who identified as Hispanic or Latino remained nearly the same, but the number of patients who identified as White, Black, or Asian or Pacific Islander decreased by nearly half. In 2020, a greater proportion of patients came to the injection clinic for neovascular age-related macular degeneration (56.5% vs 39.3%, p=0.017), but a decreased proportion of patients diagnosed with a heart condition (OR 0.57, 95% CI 0.33, 0.96), chronic obstructive pulmonary disease (OR 0.43, 95% CI 0.21, 0.91), or asthma (OR 0.09, 95% CI 0.01, 0.70) came to the injection clinic. CONCLUSION: The COVID-19 pandemic was associated with behavioral changes in eyecare utilization influenced by race and systemic co-morbidities. These data can be used to design and implement strategies to address disparities in essential ophthalmic care among vulnerable populations.

The Effect of Treatment Discontinuation During the COVID-19 Pandemic on Visual Acuity in Exudative Neovascular Age-Related Macular Degeneration: 1-Year Results.

INTRODUCTION: To evaluate the effect of a 9-week treatment deferral due to healthcare restrictions caused by Austria's first governmental lockdown associated with the coronavirus disease 2019 (COVID-19) pandemic on visual acuity (VA) in eyes compromised by exudative neovascular age-related macular degeneration (nAMD) after 1 year. METHODS: Retrospective data collection of 98 eyes (98 patients) with a treatment discontinuation at a tertiary eye care center (Clinic Landstraße, Vienna Healthcare Group, Austria) between March 16 and May 4, 2020. Prior to the lockdown, patients received multiple intravitreal injections (IVI) of anti-vascular endothelial growth factor with a personalized treatment interval for 3 years on average and at least three IVI after the lockdown. RESULTS: When the treatment interval doubled to 117.6 ± 31.4 days in spring 2020, patients lost 2.2 ± 4.6 ETDRS letters (p = 0.002) on average before reinitiating therapy. In total, 4.1 ± 8.1 letters (p < 0.0001) were lost despite continuous individual re-treatment over the course of the next year. In a univariate analysis, the extended interval time remained statistically significant (p < 0.0001), indicating a larger VA reduction within intervals with increasing interval time in days. CONCLUSION: The short-term treatment interruption had a persistent negative impact on the VA course of eyes under therapy after 1 year. Continuous therapy independent of the underlying treatment regimen remains of utmost importance in exudative nAMD. Our data should create awareness to regulators regarding future decisions despite the global pandemic.

Age-related macular degeneration (AMD) is the leading cause of legal blindness in developed countries. Wet AMD refers to the existence of new vessel growth in the macular, the part of the retina with the highest concentration of photoreceptors and hence the best visual acuity. The gold standard therapy of wet AMD consists of repeated injections of an antibody against new vessel formation into the eye to stabilize the disease. The sudden break of a treatment regimen for an individual person has never been investigated as it is ethically not acceptable. The coronavirus disease 2019 (COVID-19) pandemic and its associated lockdown led to an emerging situation in spring, 2020. We were forced by governmental restrictions to minimize contact with the most vulnerable patient cohort­the elderly. As an initial consequence, the Medical Retina Unit of Department of Ophthalmology (Clinic Landstraße, Vienna Healthcare Group, Austria) postponed appointments of patients with only one eye afflicted by wet AMD. This study examined the effect of a short-term treatment deferral caused by the first national COVID-19 lockdown in eyes of patients with ongoing therapy of wet AMD in Austria. The break led to a persistent visual loss despite re-treatment, which was still evident after 1 year. Our findings provide further support for an adequate and permanent therapy of wet AMD and regard intravitreal injections as urgent standard of care. It should be taken into consideration by authorities in future pandemic planning.

Short-Term Effects of COVID-19-Related Deferral of Intravitreal Injection Visits.

PURPOSE: To determine secondary effects of the mandated COVID-19 pandemic closure period for elective treatment on non-elective, injection-based retina care and outcomes. PATIENTS AND METHODS: In this cross-sectional, retrospective analysis of a single-provider outpatient clinic across multiple satellites, consecutive patients returning for intravitreal injections (IVIs) of anti-vascular endothelial growth factor or corticosteroids were identified as "delayed" or "undelayed" during a six-week study interval during the COVID-19 pandemic that closely following a mandated period of prohibited elective encounters. A "delayed" encounter was defined as having a follow-up interval exceeding 33% of the recommended cycle. Patients seen for IVIs during the corresponding six-week interval a year previously were identified for study as pre-COVID-19 controls. Main outcome measures included best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) assessment based on findings of intraretinal or subretinal fluid consistent with new or recurrent neovascular events. RESULTS: The study included 183 eyes of 144 patients who underwent IVI-based care from June 18, 2020, through August 7, 2020, compared to 193 eyes of 154 patients injected during the corresponding interval 1 year before. There were 62 eyes of 46 patients seen in the study period later than scheduled (among 144 patients of 183 eyes in total), which represented a larger proportion of delayed patients compared to the previous year (31.9% vs. 14.9%, p<0.0005). Considering the patterns from the control group, the attributed delay due to COVID-19 was 15.0% of patients. The delayed return eyes had a greater decline in BCVA (3 letters), higher rates of worsened OCT results (48%), and prompted reduction in previously prescribed injection intervals (p<0.02). CONCLUSION: The unintended consequence of delayed care of patients on established care regimens should be anticipated, and mitigate strategies considered if similar restrictions are mandated in the future.