A model to quantify the influence of treatment patterns and optimize outcomes in nAMD.

Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that often leads to severe and permanent vision loss. Early initiation of anti-vascular endothelial growth factor (anti-VEGF) therapy has been shown to preserve vision in nAMD patients. Concurrently, treatment outcomes in real-world are inferior to those reported in clinical trials. The most likely reasons observed are fewer treatment-intensity in routine clinical practice than in clinical trials. The other possibility could be the delay in starting treatment and the re-treatment interval. Although a negative impact of aforementioned parameters seems obvious, quantitative impact measures remain elusive in a real-world setting due to a lack of an 'optimal treatment' control group. To overcome this shortcoming, we developed, validated, and applied a model to assess and quantify the impact of anti-VEGF administration variables on visual acuity development in a prospective nAMD patient cohort. The model was further applied to probe the impact of the COVID-19 pandemic on visual progressions in nAMD patients. The presented model paves the way to systematically explore and evaluate realistic interventions in the current treatment paradigm, that can be adopted in routine clinical care.

The Influence of Universal Face Mask Use on Endophthalmitis Risk after Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: Routine use of face masks for patients and physicians during intravitreal anti-vascular endothelial growth factor (VEGF) injections has increased with the emergence of the coronavirus disease 2019 pandemic. This study evaluates the impact of universal face mask use on rates and outcomes of post-injection endophthalmitis (PIE). DESIGN: Retrospective, multicenter, comparative cohort study. PARTICIPANTS: Eyes receiving intravitreal anti-VEGF injections from October 1, 2019, to July 31, 2020, at 12 centers. METHODS: Cases were divided into a "no face mask" group if no face masks were worn by the physician or patient during intravitreal injections or a "universal face mask" group if face masks were worn by the physician, ancillary staff, and patient during intravitreal injections. MAIN OUTCOME MEASURES: Rate of endophthalmitis, microbial spectrum, and visual acuity (VA). RESULTS: Of 505 968 intravitreal injections administered in 110 547 eyes, 85 of 294 514 (0.0289%; 1 in 3464 injections) cases of presumed endophthalmitis occurred in the "no face mask" group, and 45 of 211 454 (0.0213%; 1 in 4699) cases occurred in the "universal face mask" group (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.51-1.18; P = 0.097). In the "no face mask" group, there were 27 cases (0.0092%; 1 in 10 908 injections) of culture-positive endophthalmitis compared with 9 cases (0.004%; 1 in 23 494) in the "universal face mask" group (OR, 0.46; 95% CI, 0.22-0.99; P = 0.041). Three cases of oral flora-associated endophthalmitis occurred in the "no face mask" group (0.001%; 1 in 98 171 injections) compared with 1 (0.0005%; 1 in 211 454) in the "universal face mask" group (P = 0.645). Patients presented a mean (range) 4.9 (1-30) days after the causative injection, and mean logarithm of the minimum angle of resolution (logMAR) VA at endophthalmitis presentation was 2.04 (~20/2200) for "no face mask" group compared with 1.65 (~20/900) for the "universal face mask" group (P = 0.022), although no difference was observed 3 months after treatment (P = 0.764). CONCLUSIONS: In a large, multicenter, retrospective study, physician and patient face mask use during intravitreal anti-VEGF injections did not alter the risk of presumed acute-onset bacterial endophthalmitis, but there was a reduced rate of culture-positive endophthalmitis. Three months after presentation, there was no difference in VA between the groups.

FACE MASK CONTAMINATION DURING COVID-19 PANDEMIA. A STUDY ON PATIENTS RECEIVING INTRAVITREAL INJECTIONS.

PURPOSE: To investigate the bacterial growth in the surgical face masks used by patients who received intravitreal injections and study the effect of povidone-iodine on the periocular area (PA) of masks. METHODS: Forty patients who attended for intravitreal injections were divided in those with less (<4 hours) and more (>4 hours) than 4 hours of mask use. Each group was divided depending on the application or not of povidone-iodine in the PA of the mask. Bacterial load was studied on PA and mouth area samples. RESULTS: The bacterial load in the PA was higher in the >4 hours group compared with the <4 hours group (13.2 vs. 48.75 colony-forming units/µL; P = 0.03). The contamination in the PA significantly decreased after applying povidone-iodine in the >4 hours group (P = 0.01). The use or not of povidone-iodine was strongly correlated to a positive culture (OR = 9.0, P = 0.00. CI 1.63-49.44). CONCLUSION: Surgical face masks worn for more than 4 hours present higher contamination in the PA than those with less use. Bacterial load in the PA is reduced with povidone-iodine on masks used for more than 4 hours. This contamination should be considered in the asepsis protocol of intravitreal injections.

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.

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.

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.

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.

The Effect of Delay in Care among Patients Requiring Intravitreal Injections.

PURPOSE: To examine the effect of delay in care on visual acuity (VA) in patients requiring intravitreal injections (IVIs). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients 18 years of age or older with diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), or both; neovascular age-related macular degeneration (nAMD); or retinal vein occlusion (RVO) scheduled to see a retina specialist during the mandated lockdown period (March 14 - May 4, 2020 [the coronavirus disease 2019 period]) and who had received an IVI in the 12 weeks prior. METHODS: Chart review was performed and demographics, diagnoses, procedures, and VA were recorded. MAIN OUTCOME MEASURES: VA in patients who completed, canceled, and no-showed for the scheduled visit. RESULTS: Of the 1041 total patients, 620 (60%) completed the scheduled visit, whereas 376 (36%) canceled and 45 (4%) no-showed. In patients who missed the visit, the average delay in care was 5.34 weeks. In those who missed a visit, VA was assessed at the subsequent visit. Patients who canceled a visit were older, and patients who no-showed had lower baseline vision (mean Early Treatment Diabetic Retinopathy Study letters ± standard error [SE]: no-show, 53.27 ± 3.21 letters; canceled, 60.79 ± 1.11 letters; and completed, 62.81 ± 0.84 letters; P = 0.0101) and were more likely to have DME, PDR, or both (no-show, 13 patients [29%]; canceled, 56 patients [16%]; completed, 81 patients [13%]; P = 0.0456). Patients who missed a visit lost vision as compared with the patients who completed one (no-show, -5.024 ± 1.88 letters; canceled, -1.633 ± 0.65 letters; completed, 0.373 ± 0.50 letters; P = 0.0028). Patients with DME, PDR, or both (-3.48 ± 1.95 letters vs. 2.71 ± 1.75 letters; P = 0.0203), with RVO (-3.22 ± 1.41 letters vs. 0.95 ± 1.23 letters; P = 0.0230), and, to lesser degree, with nAMD (-1.23 ± 0.70 letters vs. -0.24 ± 0.56 letters; P = 0.2679) lost vision compared with patients with same diagnoses who completed the scheduled visit. CONCLUSIONS: In patients requiring IVIs, a delay in care of 5.34 weeks resulted in vision loss. It was seen in all patients, but was more prominent in patients with DME, PDR or both and RVO. Further studies are necessary to examine whether these vision changes persist over a longer duration.

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.

The Impact of Physician Face Mask Use on Endophthalmitis After Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To evaluate the effect of physician face mask use on rates and outcomes of postinjection endophthalmitis. DESIGN: Retrospective, comparative cohort study. METHODS: Setting: Single-center. StudyPopulation: Eyes receiving intravitreal anti-vascular endothelial growth factor injections from July 1, 2013, to September 1, 2019. INTERVENTION: Cases were divided into "Face Mask" group if face masks were worn by the physician during intravitreal injections or "No Talking" group if no face mask was worn but a no-talking policy was observed during intravitreal injections. MainOutcomeMeasures: Rate of endophthalmitis, visual acuity, and microbial spectrum. RESULTS: Of 483,622 intravitreal injections administered, 168 out of 453,460 (0.0371%) cases of endophthalmitis occurred in the No Talking group, and 9 out of 30,162 (0.0298%) cases occurred in the Face Mask group (odds ratio, 0.81; 95% confidence interval, 0.41-1.57; P = .527). Sixteen cases of oral flora-associated endophthalmitis were found in the No Talking group (1 in 28,341 injections), compared to none in the Face Mask group (P = .302). Mean logMAR visual acuity at presentation in cases that developed culture-positive endophthalmitis was significantly worse in the No Talking group compared to the Face Mask group (17.1 lines lost from baseline acuity vs 13.4 lines lost; P = .031), though no difference was observed at 6 months after treatment (P = .479). CONCLUSION: Physician face mask use did not influence the risk of postinjection endophthalmitis compared to a no-talking policy. However, no cases of oral flora-associated endophthalmitis occurred in the Face Mask group. Future studies are warranted to assess the role of face mask use to reduce endophthalmitis risk, particularly attributable to oral flora.