INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR PHARMACEUTICAL UTILIZATION AND FINANCIAL IMPACT IN A VALUE-BASED CARE PROGRAM.

PURPOSE: To investigate trends and the potential impact of the COVID-19 pandemic on the utilization of intravitreal antivascular endothelial growth factor (anti-VEGF) pharmaceuticals in an accountable care organization (ACO). METHODS: We retrospectively analyzed the Centers for Medicare and Medicaid Services beneficiary claims for all patients in the Houston Methodist Coordinated Care ACO registry during the years 2018, 2019, and 2020. RESULTS: Across the 3 years studied, a mean of 708 patients received anti-VEGF injections per year. The percentage of patients who received anti-VEGF injections decreased in each sequential year, with a steeper decline during the COVID-19 pandemic in the year 2020 (decrease by 0.4% from 2019 to 2020, P < 0.001; decrease by 0.2% from 2018 to 2019, P = 0.1453). The percentage of patients receiving bevacizumab of the total number of patients receiving any anti-VEGF treatment decreased (bevacizumab decreased by 6% from 2019 to 2020, P = 0.0174; decreased by 7% from 2018 to 2019, P = 0.0074). The COVID-19 pandemic did not seem to correlate with a change in the distribution of the specific anti-VEGF injection used. CONCLUSION: Despite the lower price which may correlate with value-based care, bevacizumab was the least used anti-VEGF treatment. COVID-19 correlated with a larger decrease in the utilization of all three anti-VEGF drugs.

Bilateral radiation retinopathy 17 years following radiotherapy for nasopharyngeal carcinoma: A diagnostic and therapeutic challenge during COVID-19 lockdown.

A 40-year-old male presented with reduced vision in the right eye for one week. He had a history of nasopharyngeal carcinoma for which 34-Gy radiation was administered. The best-corrected visual acuity (BCVA) was 20/40 in the right eye and 20/20 in the left eye. Anterior segment examination suggested a bilateral early posterior subcapsular cataract. Fundoscopy revealed bilateral localized telangiectasia and macular edema in the right eye. Diagnosis of bilateral extremely delayed onset radiation retinopathy with right eye macular edema was made. Three doses of intravitreal bevacizumab injection were administered in the right eye. The patient was lost to follow-up due to COVID-19 and presented with recurrence.

Central Retinal Vein Occlusion After Discontinuation of Rivaroxaban Therapy in a Young Patient with COVID-19 Pulmonary Embolism: A Case Report.

BACKGROUND We present the report of the first case, to the best of our knowledge, of central retinal vein occlusion (CRVO) that occurred 3 days after anticoagulation discontinuation in a patient with a history of pulmonary embolism in the course of COVID-19. CASE REPORT A previously healthy 38-year-old man was hospitalized in April 2021 with severe COVID-19 pneumonia, complicated by segmental and subsegmental pulmonary embolism. The patient was treated with a concurrent combination of remdesivir, dexamethasone, therapeutic enoxaparin, ceftriaxone, passive oxygen therapy, and convalescent plasma therapy, which led to pulmonary improvement. The treatment with therapeutic enoxaparin (80 mg/0.8 mL twice a day) was continued for 1 month after discharge, followed by 15 mg of rivaroxaban twice a day for 3 weeks and 20 mg of rivaroxaban once a day for 11 weeks. Within 3 days after rivaroxaban discontinuation, the patient experienced a decrease in visual acuity in his right eye, to the level of 5/25. Nonischemic CRVO with cystoid macular edema was diagnosed and an intravitreal injection of ranibizumab was performed. Common identifiable factors contributing to CRVO were excluded, and the treatment with prophylactic enoxaparin was initiated. Two weeks later, macular edema decreased significantly and visual acuity improved to 20/20. The treatment with enoxaparin was discontinued. CONCLUSIONS Rebound hypercoagulability after discontinuation of rivaroxaban therapy can manifest as CRVO in a young patient with a history of COVID-19 pulmonary embolism. It was successfully treated with an intravitreal injection of ranibizumab.

Candida Albicans Sub-Retinal Abscess following COVID-19.

A 42-year-old male post-renal transplantation presented with sudden diminution of vision in the left eye. The right eye was lost following a failed vitreoretinal surgery 5 years ago. The patient had been hospitalized 4 months prior for coronavirus disease 2019 infection with a good recovery. The presenting visual acuity was 20/600 in the right eye and 20/250 in the left eye. Fundus examination revealed a sub-macular sub-retinal abscess in the left eye. Sub-retinal aspiration of the abscess revealed Candida albicans. The patient was managed with repeated intravitreal amphotericin B injections, following which the abscess resolved with scarring and vision improving to 20/60.

Drop in well-being of ARMD patients under treatment with anti-VEGF injections during the COVID-19 pandemic.

PURPOSE: Patients with age-related macular degeneration (ARMD) are required to follow a treatment protocol that requires regular follow-ups. The COVID-19 pandemic has created an additional burden for patients with ARMD under treatment with anti-vascular endothelial growth factor (anti-VEGF) injections, since patients face a congestion of the health system and closing of the outpatient services. This study examines the impact of the uncertainty regarding patients' treatment on their sense of well-being. METHODS: This is a longitudinal cohort study of eighty patients who were followed during the year following the outbreak of the COVID pandemic. Patients reported their sense of well-being with the WHO-5 questionnaire and their perception and fears for the impact of the pandemic on their ongoing ARMD treatment. RESULTS: There was a significant drop in mental well-being during the pandemic that paralleled the self-reported impact of the pandemic on ARMD treatment. Patients who reported a higher impact of COVID-19 on their treatment had experienced a higher drop in mental wellbeing compared to those who hadn't, with female gender being an additional risk factor. Objective measurements of visual acuity did not factor in the drop of sense of well-being. CONCLUSIONS: The high initial level of uncertainty regarding ARMD patients' long-term course was further exacerbated when exposed to additional uncertainties during the pandemic regarding their standard of care. Planning ahead for continuation of services and close contact with patients during similar health emergencies is of paramount importance.

Retinal vascular occlusion and SARS-CoV-2 vaccination.

PURPOSE: To assess the clinical and retinal imaging features of patients in whom retinal vascular occlusion (VO) had developed in temporal associations with COVID-19 vaccination. METHODS: In this retrospective case series, all consecutive adult patients with new onset VO within 6 weeks of vaccination against COVID-19 were included in the study between May 1 and October 31, 2021. All patients had a systemic medical health assessment, full ophthalmic evaluation, and complete fundus imaging. RESULTS: Fifteen eyes of VO (14 patients) after COVID-19 vaccinations were identified. The median time between vaccination and symptoms onset was 14 days (range 7-42 days). The mean best-corrected visual acuity (BCVA) was 20/55 with a range of 20/20 to 20/200. Eleven of 15 eyes (73.3%) had visual acuity improvement after intravitreal treatment at 60-90 days (range, 45-105 days) from the presentation. Four of 5 cases without systemic risk factors for VO had a mean BCVA > 20/32 at presentation and > 20/25 at the latest evaluation. Between May 1 and October 31, 2021, a temporal association was found between the 15 reported cases and COVID-19 vaccination out of a total of 29 VO (p = 0.05). The incidence of VO was higher in the considered period compared to the equivalent 6-month period in 2019 (1.17% vs 0.52%, respectively; p = 0.0134). CONCLUSIONS: Retinal vascular occlusion with different grades of severity are reported in temporal association with COVID-19 vaccination. The exact pathogenic mechanism needs to be further studied. No certain causal relationship can be established from this case series.

The negative impact of COVID-19 pandemic on age-related macular degeneration patients treated with intravitreal bevacizumab injections.

PURPOSE: COVID-19 emerged in the end of 2019 and was declared a worldwide pandemic shortly after. Social distancing and lockdowns resulted in lower compliance in intravitreal injections and office visits. We aimed to assess clinical outcomes among patients who missed these visits compared to those who arrived as planned. METHODS: Patients who missed or were late to office visits or intravitreal injections were defined as non-adherent and were compared to adherent patients. Our main outcomes were the need for subsequent injections, mean change in best-corrected visual acuity (BCVA), and central macular thickness (CMT). RESULTS: This study included 77 patients (24 adherent and 53 non-adherent). The mean BCVA remained stable during the study period for the adherent group (p = 0.159) and worsened in the non-adherent group (p < 0.001). Changes in CMT and maximum thickness were not significant for either group. A higher proportion of patients in the non-adherent group needed subsequent intravitreal injections (49% vs 20%, p = 0.014). CONCLUSION: The findings demonstrate the negative implications of the COVID-19 pandemic and the effect of deferring bevacizumab injections among individuals with age-related macular degeneration. This emphasizes the importance of a scheduled follow-up, also during a pandemic.

Results of the treatment of patients with exudative AMD during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVE: The SARS-CoV-2 pandemic has caused chaos in all health systems on the planet. It has been difficult to cope with COVID 19, but also to maintain the activity in other specialties. In ophthalmology, the scientific societies recommended providing urgent care, including the intravitreal treatment of patients with active neovascular age-related macular degeneration (AMD), since a delay in treatment implies a potential loss of visual acuity (VA). The main objective of this study was to measure the impact of the coronavirus lockdown on the activity and visual results in patients with neovascular AMD in Area 3 of Madrid. MATERIAL AND METHOD: A retrospective observational study was conducted of all patients with neovascular AMD who attended a consultation and/or received intravitreal treatment in the 3 months before the lockdown. RESULTS: In the 3 months before the lockdown, 144 patients with neovascular AMD were treated, of whom only 51 attended a consultation during the lockdown and, at 6 months after it, only 117 patients had resumed their follow-up. Mean VA before the lockdown was 58.0 ±â€¯23.7 letters and was statistically significantly reduced to 53.0 ±â€¯27.1 letters at 6 months after the lockdown. We also observed a significant decrease in the number of visits during the lockdown, despite the security measures implemented. CONCLUSIONS: Our study shows that patients with neovascular AMD have had a statistically significant decrease in VA due to the lockdown. A VA of almost 58 letters was reduced to 53 at 6 months after the lockdown. The percentage of patients who lost 15 or more letters doubled. We observed a 63.3% loss of temporary follow-up during the lockdown and a 14.58% loss of permanent follow-up at 6 months after the lockdown.

Estimating excess visual loss from neovascular age-related macular degeneration in the UK during the COVID-19 pandemic: a retrospective clinical audit and simulation model.

OBJECTIVES: To report the reduction in new neovascular age-related macular degeneration (nAMD) referrals during the COVID-19 pandemic and estimate the impact of delayed treatment on visual outcomes at 1 year. DESIGN: Retrospective clinical audit and simulation model. SETTING: Multiple UK National Health Service (NHS) ophthalmology centres. PARTICIPANTS: Data on the reduction in new nAMD referrals were obtained from four NHS Trusts comparing April 2020 with April 2019. To estimate the potential impact on 1-year visual outcomes, a stratified bootstrap simulation model was developed drawing on an electronic medical records dataset of 20 825 nAMD eyes from 27 NHS Trusts. MAIN OUTCOME MEASURES: Simulated mean visual acuity and proportions of eyes with vision ≤6/60, ≤6/24 and ≥6/12 at 1 year under four hypothetical scenarios: 0-month, 3-month, 6-month and 9-month treatment delays. Estimated additional number of eyes with vision ≤6/60 at 1 year nationally. RESULTS: The number of nAMD referrals dropped on average by 72% (range 65%-87%). Simulated 1-year visual outcomes for 1000 nAMD eyes with a 3-month treatment delay suggested an increase in the proportion of eyes with vision ≤6/60 from 15.5% (13.2%-17.9%) to 23.3% (20.7%-25.9%), and a decrease in the proportion of eyes with vision ≥6/12 (driving vision) from 35.1% (32.1%-38.1%) to 26.4% (23.8%-29.2%). Outcomes worsened incrementally with longer modelled delays. Assuming nAMD referrals are reduced to this level for 1 month nationally, these simulated results suggest an additional 186-365 eyes with vision ≤6/60 at 1 year. CONCLUSIONS: We report a large decrease in nAMD referrals during the COVID-19 lockdown and provide an important public health message regarding the risk of delayed treatment. As a conservative estimate, a treatment delay of 3 months could lead to a >50% relative increase in the number of eyes with vision ≤6/60 and 25% relative decrease in the number of eyes with driving vision at 1 year.

Profile of patients receiving intravitreal anti-vascular endothelial growth factor injections during COVID-19-related lockdown.

PURPOSE: The aim of this study was to analyze the impact on vision due to delay in presentation of patients requiring intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, consequent to COVID-19-related travel restrictions. METHODS: Data were collected retrospectively of patients who received anti-VEGF injections during four months of the COVID-19 pandemic. Visual acuities, indication for treatment were noted along with basic demographic characteristics. RESULTS: Data were analyzed for 303 eyes of 263 patients. The indication for treatment was age-related macular degeneration (AMD) in 60 eyes (19.8%), while 162 eyes (53.5%) had Diabetic Macular Edema, 71 eyes (23.4%) had Retinal Vein Occlusion and 10 eyes (3.3%) had other diagnosis. The visual acuity in the treatment naïve eyes (Group A, n = 168) was significantly worse (P <0.001) than those who presented for retreatment (Group B, n = 135). In Group B, there was a significant decline in vision for the entire cohort (P = 0.009) and those with AMD (P = 0.036). Those in Group B presented at a mean interval of 19.1 ± 10.6 (range, 4-64) weeks for retreatment. CONCLUSION: The COVID-19 pandemic has led to a delay in patients receiving anti-VEGF injections. The visual acuity is worse in both treatment naïve as well as those requiring retreatment. This could have long-term impact on vision of patients requiring this vision preserving treatment.

Anti-VEGF intravitreal injections in the era of COVID-19: responding to different levels of epidemic pressure.

PURPOSE: Following the first wave of the COVID-19 pandemic in early 2020, the easing of strict measures to reduce its spread has led to a resurgence of cases in many countries at both the national and local level. This article addresses how guidance for ophthalmologists on managing patients with retinal disease receiving intravitreal injections of anti-vascular endothelial growth factor (VEGF) during the pandemic should be adapted to the local epidemic pressure, with more or less stringent measures implemented according to the ebb and flow of the pandemic. METHODS: The Vision Academy's membership of international retinal disease experts analyzed guidance for anti-VEGF intravitreal injections during the COVID-19 pandemic and graded the recommendations according to three levels of increasing epidemic pressure. The revised recommendations were discussed, refined, and voted on by the 14-member Vision Academy Steering Committee for consensus. RESULTS: Protocols to minimize the exposure of patients and healthcare staff to COVID-19, including use of personal protective equipment, physical distancing, and hygiene measures, should be routinely implemented and intensified according to local infection rates and pressure on the hospital/clinic or healthcare system. In areas with many COVID-19-positive clusters, additional measures including pre-screening of patients, postponement of non-urgent appointments, and simplification of complex intravitreal anti-VEGF regimens should be considered. Treatment prioritization for those at greatest risk of irreversible vision loss should be implemented in areas where COVID-19 cases are increasing exponentially and healthcare resources are strained. CONCLUSION: Consistency in monitoring of local infection rates and adjustment of clinical practice accordingly will be required as we move forward through the COVID-19 era. Ophthalmologists must continue to carefully weigh the risk-benefits to minimize the exposure of patients and healthcare staff to COVID-19, ensure that patients receive sight-saving treatment, and avoid the potential long-term impact of prolonged treatment postponement.

HIGHLIGHTS OF ADVANCES IN MEDICAL RETINA FROM THE VIRTUAL WORLD OPHTHALMOLOGY CONGRESS 2020.

The World Ophthalmology Congress (WOC) is one of the largest international ophthalmology conferences, taking place every two years. The event this year was the first of its kind, held as a virtual summit due to the Covid-19 pandemic. There were over 2000 talks from world experts, a virtual industry exhibition including free papers, e-posters, live symposia and presentations. Medical retina is a subspecialty in which exciting and innovative advances in research were presented. The topics covered included the use of Conbercept for Polypoidal Choroidal Vasculopathy, Faricimab in Diabetic Macular Oedema and neovascular Age Related Macular Degeneration (nAMD), Brolucizumab, Aflibercept and Port Delivery Systems in nAMD, amongst many others. Medical retina continues to be a rapidly advancing field within ophthalmology with new research findings having great implications for treatment burden and service delivery. This report summaries the highlights of advances within the medical retina subspecialty from free papers in WOC 2020.

Intravitreal injections of anti-VEGF agents during COVID-19 pandemic: clinical audit from Tanta University Hospital.

BACKGROUND: The aims of this study were to provide real-life data about the effect of COVID-19 pandemic on the practice of anti-VEGF injections and to evaluate the safety of the modifications in the injection protocol imposed during the ongoing pandemic on the anatomical and functional outcome of patients. METHODS: All patients attending Tanta University hospital for receiving intravitreal anti-VEGF injections were screened. Patients who were previously deferred according to a modified protocol implemented in the hospital in response to the pandemic or who demonstrated deviation from it were included for further analysis. RESULTS: During the audit period, 83 patients attending for anti-VEGF injections were screened, of whom 40 met the abovementioned criteria and were included for analysis. In the deferred subgroup (11 eyes), predeferral mean values of logMAR best corrected visual acuity (BCVA) and central retinal subfield thickness (CST) were 1 ± 0.23 and 444.57 ± 200.1 µm, respectively. There was no significant change when the patients returned for their deferred injections, with the mean BCVA and CST values being 0.8 ± 0.22 and 413.71 ± 237.7 µm, respectively (p = 0.27 and p = 0.12). Moreover, 29 patients encountered a disturbed injection schedule, particularly skipping their injection appointments due to infection fear as found in 18 patients. CONCLUSION: The COVID-19 pandemic has imposed pressing challenges in maintaining essential health care while ensuring the prevention of spread of infection. Although the modified injection protocol confirmed to be safe for patients, the pandemic caused deflection from the optimum practice in the form of successive skipping of appointments and delays in the processing of patient injection schedules.

Extended intervals for wet AMD patients with high retreatment needs: informing the risk during COVID-19, data from real-world evidence.

BACKGROUND/OBJECTIVE: Some clinicians may be forced to temporarily extend treatment intervals in neovascular age-related macular degeneration (nAMD) eyes with frequent retreatments to reduce the number of visits during the COVID-19 pandemic. To provide an indication of what these outcomes may be, we studied eyes with active lesions with unplanned treatment interval extensions before the pandemic occurred. METHODS: We compared eyes with active disease despite ≤6 weekly injections whose next injection was extended to ≥7 weeks and those whose intervals were not extended. We identified 1559 (16%) of 9602 eyes from the Fight Retinal Blindness! (FRB!) registry (2013 and 2018) that fit this criteria. Eyes were further stratified into four groups by the mean interval over the following 6 months: (1) ≤6 weeks (81%), (2) 7-9 weeks (9%), (3) 10-12 weeks (5%) and (4) >12 weeks (5%). RESULTS: There was a significant loss in VA in eyes extended to >12 weeks compared to the non-extended group (adjusted VA change, mean (95% CI): ≤6 weeks, 0.4 (-1.5 to 2.2), versus >12 weeks, -4.7 (-7.4 to -2.1), letters, p = 0.03 and a threefold increase in relative risk of losing ≥15 letters (absolute risk (14% versus 4%, p < 0.01)). CONCLUSION: Mean VA remained stable for 6 months in eyes requiring frequent treatment despite retreatment interval extension up to 10-12 weeks. There was a significant short-term risk to vision when retreatment interval was extended beyond 12 weeks, hence extensions to this level should be considered cautiously. These data may be useful for physicians who are considering reducing visits to mitigate the risk of COVID-19.

Retinal vein occlusion in COVID-19: A novel entity.

Coronavirus disease 2019 (COVID-19) is a form of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been declared a pandemic by the World Health Organization (WHO). Ocular manifestations related to COVID-19 are uncommon with conjunctivitis being reported in a few cases. We report a unique case of vasculitic retinal vein occlusion (RVO) secondary to COVID-19 in a 52-year-old patient who presented with the diminution of vision in the left eye 10 days after he tested positive for SARS-CoV-2. All investigations for vasculitis were negative. This case supports the mechanism of thrombo-inflammatory state secondary to the "cytokine-storm" as the pathogenesis for systemic manifestations of COVID-19.

Intravitreal injections during COVID-19 outbreak: Real-world experience from an Italian tertiary referral center.

We report our experience during COVID-19 outbreak for intravitreal injections in patients with maculopathy. We proposed a treatment priority levels and timings; the "High" priority level includes all monocular patients; the "Moderate" is assigned to all patients with an active macular neovascularization; the patients affected by diabetic macular edema or retinal vein occlusion belong to the "Low" class. This organization allowed us to treat the most urgent patients although the injections performed had a 91.7% drop compared to the same period of 2019.

Impact of COVID-19 on outpatient visits and intravitreal treatments in a referral retina unit: let's be ready for a plausible "rebound effect".

PURPOSE: To quantify the shrinking in outpatient and intravitreal injections' volumes in a tertiary referral retina unit secondary to virus causing coronavirus disease 2019 (COVID-19). METHODS: In this retrospective cross-sectional study, we reviewed the charts of all patients who had a visit at a medical retina referral center during the Italian quarantine (from 9th of March 2020 to 3rd of May 2020). Number and characteristics of these data were compared with data from the same period in 2019 (from 9th of March 2019 to 3rd of May 2019). RESULTS: In the 2019 study period, there were 303 patients attending clinic (150 males, 153 females). In the 2020 study period, patients decreased to 75 (48 males, 27 females; P = 0.022 comparing gender prevalence between the two periods) with an overall reduction of 75.2%. Mean ± SD age was 71.4 ± 14.3 years (range 25-93 years) in the 2019 study period and 66.7 ± 13.1 years (range 32-91 years) in the 2020 study period (P = 0.005). The largest drop in outpatient volume was recorded in AMD patients (- 79.9%). Regarding the intravitreal treatments, there were 1252 injections in the 2019 period and 583 injections in the 2020 period (- 53.6% in injections). The drop in intravitreal treatments was larger in patients with posterior uveitis, retinal vein occlusion, and diabetes (- 85.7%, - 61.9%, and - 59.6%, respectively). CONCLUSION: The volume of outpatient visits and intravitreal injections declined during the COVID-19 quarantine. The short- and long-term impacts are that routine in-person visits and intravitreal injections are expected to increase after the quarantine and, even more, after the pandemic.

Proof-of-concept calculations to determine the health-adjusted life-year trade-off between intravitreal anti-VEGF injections and transmission of COVID-19.

BACKGROUND: Clinical ophthalmological guidelines encourage the assessment of potential benefits and harms when deciding whether to perform elective ophthalmology procedures during the COVID-19 pandemic, in order to minimize the risk of disease transmission. METHOD: We performed probability calculations to estimate COVID-19 infection status and likelihood of disease transmission among neovascular age-related macular degeneration patients and health-care workers during anti-VEGF procedures, at various community prevalence levels of COVID-19. We then applied the expected burden of COVID-19 illness and death expressed through health-adjusted life-years (HALYs) lost. We compared these results to the expected disease burden of severe visual impairment if sight protecting anti-VEGF injections were not performed. RESULTS: Our calculations suggest a wide range of contexts where the benefits of treatment to prevent progression to severe visual impairment or blindness are greater than the expected harms to the patient and immediate health care team due to COVID-19. For example, with appropriate protective equipment the benefits of treatment outweigh harms when the chance of progression to severe visual impairment is >0.044% for all scenarios where COVID-19 prevalence was 1/1000, even when the attack rate in the clinical setting is very high (5-43%). CONCLUSION: Unless COVID-19 prevalence is very high, the reduced disease burden from avoiding visual impairment outweighs the expected HALYs lost from COVID-19 transmission. This finding is driven by the fact that HALYs lost when someone suffers severe visual impairment for 5 years are equivalent to nearly 400 moderate cases of infectious disease lasting 2 weeks each.