Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients' adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes. METHODS: Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors. RESULTS: Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4 months to 8 years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P = 0.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown. DISCUSSION: Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020216205.

Central Retinal Vein Occlusion after COVID-19 Infection.

INTRODUCTION: Central retinal vein occlusions are not well-known complications of SARS-CoV-2 infection. We describe a case of central retinal vein occlusion secondary to COVID-19, and a review of the literature was performed. HISTORY AND SIGNS: A 47-year-old woman with no underlying ocular or medical condition presented to the hospital complaining about sudden onset of multiple scotomas in her left eye. A COVID-19 infection was confirmed 2 days previously by a PCR test that was performed 2 days after the onset of symptoms. Medical history revealed no risk factors and no oral contraception. Her best-corrected visual acuity was 1.0 in the right eye and 0.04 in the left eye. Clinical exam showed a left relative afferent pupillary defect and a nasally localized papilledema on fundoscopy of the left eye. Multiple dot and blot hemorrhages were also present. Optical coherence tomography revealed cystoid macular edema and paracentral acute middle maculopathy. The results of the fluoresceine angiography were consistent with central retinal vein occlusion. Laboratory workup later revealed an elevated fibrinogen level, corresponding to the COVID-19-induced hypercoagulable state. No other prothrombotic conditions were found. The patient immediately received an intravitreal injection of Lucentis (ranibizumab) after diagnosis. Complete resolution of the retinal hemorrhages and papilledema was observed 1.5 months after treatment and the final visual acuity was 1.25 in the left eye. CONCLUSION: Coagulation abnormalities are frequently observed in infectious diseases such as COVID-19 infection and the resulting prothrombotic state can sometimes lead to retinal vascular complications, including central retinal vein occlusion, irrespective of the presence of other classical risk factors. The consideration of this information could help clinicians establish a prompt diagnosis and therefore appropriate treatment, which could hopefully lead to complete healing of retinal lesions.

[Impact of the French 2020 COVID-19 lockdown on the treatment and follow-up of patients with exudative age-related macular degeneration]. / Impact du confinement français en 2020 sur la prise en charge des patients atteints de dégénérescence maculaire liée à l'âge exsudative.

PURPOSE: To assess the impact of the measures taken during the lockdown period from March 17 to May 11, 2020 on the management of patients with exudative age related macular degeneration treated by intravitreal anti-VEGF injections at the University Hospital of Tours. METHODS: In this retrospective study, patients were included after analysis of the computerized medical records of patients with age related macular degeneration. Those who were treated for exudative age related macular degeneration who received at least 1 intravitreal injection in the 12 months prior and at least one consultation in the 6 months prior to the lockdown period, were included. The initial and final mean visual acuity were compared with a 5 letter non-inferiority margin. A subgroup analysis was performed according to outcomes. The visual acuities immediately after this period were also recorded. RESULTS: In all, 595 eyes of 493 patients were included. The mean initial visual acuity was 59.6 letters, vs. 58.5 for the final visual acuity, i.e. a difference of -1.13 letters with a lower limit of the confidence interval of less than 5. The visual acuity on release from lockdown was comparable to the other 2 measurements. Initial visual acuity and the number of missed treatments were the main factors associated with functional loss. CONCLUSION: Patients' visual acuity during the lockdown period was able to be maintained despite the restrictive measures and limitation of care access in France. The most common cause of substantial visual decline was missed intravitreal injections.

Delaying anti-VEGF therapy during the COVID-19 pandemic: long-term impact on visual outcomes in patients with neovascular age-related macular degeneration.

OBJECTIVES: To evaluate the outcomes of delayed intravitreal injections (IVIs) caused by the outbreak of coronavirus disease 2019 (COVID-19), in patients with neovascular age-related macular degeneration (nAMD). METHODS: nAMD patients with scheduled IVIs between March 1st and April 30th, 2020 were stratified through a risk-based selection into a non-adherent group (NA-group) if they skipped at least one IVI and an adherent group (A-group) if they followed their treatment schedule. During the pandemic visit (v0), if a significant worsening of the disease was detected, a rescue therapy of three-monthly IVIs was performed. Multimodal imaging and best-corrected visual acuity (BCVA) findings were evaluated after 6 months (v6), compared between groups and with the visit prior the lockdown (v-1). RESULTS: Two hundred fifteen patients (132 females, mean age: 81.89 ± 5.98 years) delayed their scheduled IVI while 83 (53 females, mean age: 77.92 ± 6.06 years) adhered to their protocol. For both groups, BCVA at v0 was significantly worse than v-1 (mean 4.15 ± 7.24 ETDRS letters reduction for the NA-group and 3 ± 7.96 for the A-group) but remained stable at v6. The two groups did not significantly differ in BCVA trends after 6 months and neither for development of atrophy nor fibrosis. CONCLUSIONS: A risk-based selection strategy and a rescue therapy may limit the long-term outcomes of an interruption of the treatment protocol in patients with nAMD.

Pathological angiogenesis: mechanisms and therapeutic strategies.

In multicellular organisms, angiogenesis, the formation of new blood vessels from pre-existing ones, is an essential process for growth and development. Different mechanisms such as vasculogenesis, sprouting, intussusceptive, and coalescent angiogenesis, as well as vessel co-option, vasculogenic mimicry and lymphangiogenesis, underlie the formation of new vasculature. In many pathological conditions, such as cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity and SARS-CoV-2(COVID-19), developmental angiogenic processes are recapitulated, but are often done so without the normal feedback mechanisms that regulate the ordinary spatial and temporal patterns of blood vessel formation. Thus, pathological angiogenesis presents new challenges yet new opportunities for the design of vascular-directed therapies. Here, we provide an overview of recent insights into blood vessel development and highlight novel therapeutic strategies that promote or inhibit the process of angiogenesis to stabilize, reverse, or even halt disease progression. In our review, we will also explore several additional aspects (the angiogenic switch, hypoxia, angiocrine signals, endothelial plasticity, vessel normalization, and endothelial cell anergy) that operate in parallel to canonical angiogenesis mechanisms and speculate how these processes may also be targeted with anti-angiogenic or vascular-directed therapies.

Morphovascular changes after anti-VEGF intravitreal injection for a choroidal neovascularization secondary to COVID-19 infection in a pediatric patient.

Choroidal neovascularization (CNV) is a common pathologic lesion that occurs in various chorioretinopathy. Although the incidence of CNV is quite rare in children and adolescents, these lesions have a severe impact on visual acuity and quality of life over patients' lifetime. The management of CNV in pediatric patients is challenging, clear guidelines are limited due to a lack of randomized clinical trials. However, the more promising option is the use of vascular endothelial growth factor (VEGF) inhibitors. We reported a case of recurrent idiopathic choroidal neovascularization in a healthy pediatric patient after COVID 19 infection. Optical coherence tomography angiofraphy (OCTA) showed, in a non invasive way, a choroidal neovascularization at the posterior pole including macula and superior temporal arcade in the right eye, while the left eye was unaffected. In order to inactivate the neovascularization, intravitreal injections of anti-VEGF (Lucentis-Ranibizumab 0.3 mL) were performed in the right eye. Six months after the injections BCVA of the right eye was improved from 0.7 logMAR to 0.2 logMAR. OCT-A examination did not detect any signs of attivation of the preexistent neovascularization. It is reasonable to assert that Anti-VEGF could be the main treatment in case of choroidal neovascularization in young patients after COVID 19 infection due to the high chorioretinal level of VEGF-A described in these diseases.

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.

Controversies and Disparities in the Management of Age-Related Macular Degeneration.

Age-related macular degeneration is a leading cause of blindness in patients aged 50 years and older. Prior to the 21st century, there were no effective treatments for this devastating disease. However, the last 20 years have heralded the development of treatments for both the nonexudative and exudative forms. The invention of AREDS vitamin supplements and anti-VEGF therapies forever changed the treatment of dry and wet age-related macular degeneration, respectively. The rapid adoption and expansion of these vision preserving treatments has created controversy regarding their cost, burden of administration, development, and use of new technologies, genetic considerations, and observed societal disparities. Many of these controversies and disparities persist today and will require further research to resolve.

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.

Inhibition of MMPs supports amoeboid angiogenesis hampering VEGF-targeted therapies via MLC and ERK 1/2 signaling.

BACKGROUND: In the past decades studies on anti-tumoral drugs inhibiting matrix metalloproteinase (MMPs) were disappointing. Recently, we demonstrated that mature endothelial cells (ECs) and endothelial colony forming cells (ECFCs) can switch between invasion modes to cope with challenging environments, performing the "amoeboid angiogenesis" in the absence of proteases activity. METHODS: We first set out to investigate by ELISA if the inhibitors of the main protease family involved in angiogenesis were differently expressed during breast cancer progression. We used Marimastat, a broad-spectrum MMP inhibitor, as a means of inducing amoeboid characteristics and studied VEGF role in amoeboid angiogenesis. Thus, we performed invasion and capillary morphogenesis assay, morphological, cell signaling and in vivo mouse studies. RESULTS: Our data showed that TIMP1, TIMP2, alpha2-antiplasmin, PAI-1 and cystatin increase in breast cancer serum of patients with primary cancer and lymph node positive compared to healthy women. In vitro results revealed that the most high-powered protease inhibitors able to induce amoeboid invasion of ECFCs were TIMP1, 2 and 3. Surprisingly, Marimastat promotes ECFC invasion and tubular formation in vitro and in vivo, inducing amoeboid characteristics. We observed that the combination of Marimastat plus VEGF doesn't boost neither cell invasion nor vessel formation capacity. Moreover, inhibition of VEGF activity with Bevacizumab in the presence of Marimastat confirmed that amoeboid angiogenesis is independent from the stimulus of the main vascular growth factor, VEGF. CONCLUSIONS: We underline the importance to consider the amoeboid mechanism of endothelial and cancer cell invasion, probably responsible for the failure of synthetic metalloproteinase inhibitors as cancer therapy and tumor resistance to VEGF-targeted therapies, to set-up new drugs to be used in cancer therapy.

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.

Efficacy and safety of a new ranibizumab biosimilar CKD-701 using a pro re nata treatment regimen in neovascular age-related macular degeneration: A phase 3 randomized clinical trial.

PURPOSE: This study aimed to establish the efficacy, safety, and immunogenicity equivalence of the proposed biosimilar CKD-701 with the reference ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: A total of 312 participants with active subfoveal choroidal neovascularization were randomly assigned to either the CKD-701 (n = 156) or reference ranibizumab (n = 156) arms. The initial 3-month loading intraocular injections were followed by pro re nata (PRN) dosing for 9 months. The primary outcome was the proportion of patients with less than 15-letters of corrected visual acuity (BCVA) loss at 3 months visit (one month after last loading injection) compared to the baseline time point. The presence of retinal fluid, and changes in BCVA and central retinal thickness (CRT) were assessed as secondary efficacy outcomes. Immunogenicity and safety were evaluated in both treatment arms. RESULTS: In the CKD-701 arm, 143 (97.95%) patients lost <15 letters in the BCVA at 3 months compared to 143 (98.62%) in the reference arm (P = 0.67). The BCVA improved with a mean improvement of +7.0 (CKD-701) and +6.2 (ranibizumab) letters at 3 months (P = 0.43). The least-squares mean (SE) changes in CRT at 3 months from the baseline were -119.3 (12.0) µm and -124.5 (11.9) µm in the CKD-701 and ranibizumab groups, respectively (P = 0.74). The proportion of participants with subretinal or intraretinal fluid at 3, 6, and 12 months was similar between the study arms. The number (SE) of injections were 8.36 (3.13) in the CKD-701 and 8.26 (2.92) in ranibizumab (P = 0.62). The occurrence of adverse events and antidrug antibody in the study arms were also not statistically different. CONCLUSION: CKD-701 is a biosimilar to the reference ranibizumab in terms of efficacy, safety, and immunogenicity for the treatment of patients with nAMD. Moreover, improvement and maintenance of visual outcome were achieved through PRN regimen.

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.

Safety and efficacy of an artificial intelligence-enabled decision tool for treatment decisions in neovascular age-related macular degeneration and an exploration of clinical pathway integration and implementation: protocol for a multi-methods validation study.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) management is one of the largest single-disease contributors to hospital outpatient appointments. Partial automation of nAMD treatment decisions could reduce demands on clinician time. Established artificial intelligence (AI)-enabled retinal imaging analysis tools, could be applied to this use-case, but are not yet validated for it. A primary qualitative investigation of stakeholder perceptions of such an AI-enabled decision tool is also absent. This multi-methods study aims to establish the safety and efficacy of an AI-enabled decision tool for nAMD treatment decisions and understand where on the clinical pathway it could sit and what factors are likely to influence its implementation. METHODS AND ANALYSIS: Single-centre retrospective imaging and clinical data will be collected from nAMD clinic visits at a National Health Service (NHS) teaching hospital ophthalmology service, including judgements of nAMD disease stability or activity made in real-world consultant-led-care. Dataset size will be set by a power calculation using the first 127 randomly sampled eligible clinic visits. An AI-enabled retinal segmentation tool and a rule-based decision tree will independently analyse imaging data to report nAMD stability or activity for each of these clinic visits. Independently, an external reading centre will receive both clinical and imaging data to generate an enhanced reference standard for each clinic visit. The non-inferiority of the relative negative predictive value of AI-enabled reports on disease activity relative to consultant-led-care judgements will then be tested. In parallel, approximately 40 semi-structured interviews will be conducted with key nAMD service stakeholders, including patients. Transcripts will be coded using a theoretical framework and thematic analysis will follow. ETHICS AND DISSEMINATION: NHS Research Ethics Committee and UK Health Research Authority approvals are in place (21/NW/0138). Informed consent is planned for interview participants only. Written and oral dissemination is planned to public, clinical, academic and commercial stakeholders.

Possible Therapeutic Targets from Derivatives of Natural Marine Products Based on PI3K/AKT Dependent Inhibitors in Viral Infection COVID-19.

Natural resources have long played a prominent part in conventional treatments as a parental source due to their multifaceted functions and lesser side effects. The diversity of marine products is a significant source of possible bioactive chemical compounds with a wide range of potential medicinal applications. Marine organisms produce natural compounds and new drugs with unique properties are produced from these compounds. A lot of bioactive compounds with medicinal properties are extracted from marine invertebrates, including Peptides, Alkaloids, Terpenoids, Steroids. Thus, it can be concluded that marine ecosystems are endowed with natural resources that have a wide range of medicinal properties, and it is important to examine the therapeutic and pharmacological capabilities of these molecules. So, finding particular inhibitors of the COVID-19 in natural compounds will be extremely important. Natural ingredients, in this light, could be a valuable resource in the progression of COVID-19 therapeutic options. Controlling the immunological response in COVID-19 patients may be possible by addressing the PI3K/Akt pathway and regulating T cell responses. T cell effector activity can be improved by preventing anti-viral exhaustion by suppressing PI3K and Akt during the early anti-viral response. The diversity of marine life is a significant supply of potentially bioactive chemical compounds with a broad range of medicinal uses. In this study, some biologically active compounds from marine organisms capable of inhibiting PI3K/AKT and the possible therapeutic targets from these compounds in viral infection COVID-19 have been addressed.

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.

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.

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.

Tele-ophthalmology for age-related macular degeneration during the COVID-19 pandemic and beyond.

INTRODUCTION: COVID-19 has disrupted how ophthalmic practice is conducted worldwide. One patient population that may suffer from poor outcomes during the pandemic are those with age-related macular degeneration (AMD). Many practices are performing some form of tele-ophthalmology services for their patients, and guidance is needed on how to maintain continuity of care amongst patients with AMD using tele-ophthalmology. METHODS: A literature search was conducted, ending 1 August 2020, to identify AMD outcomes and telecare management strategies that could be used during the COVID-19 pandemic. RESULTS: 237 total articles were retrieved, 56 of which were included for analysis. Four American Academy of Ophthalmology and Center for Disease Control web resources were also included. DISCUSSION: Risk-stratification models have been developed that let providers readily screen existing patients for their future risk of neovascular AMD (nAMD). When used with at-home monitoring devices to detect nAMD, providers may be able to determine who should be contacted via tele-ophthalmology for screening. Telemedicine triage can be used for new complaints of vision loss to determine who should be referred to a retinal specialist for management of suspected nAMD. To increase access and provider flexibility, smartphone fundus photography images sent to a centralized tele-ophthalmology service can aid in the detection of nAMD. Considerations should also be made for COVID-19 transmission, and tele-ophthalmology can be used to screen patients for the presence of COVID-19 prior to in-person office visits. Tele-ophthalmology has additional utility in connecting with nursing home, rural, and socioeconomically disadvantaged patients in the post-pandemic period.