key: cord-0721251-cpxovqjp
authors: Patel, Samir N.; Tang, Peter H.; Storey, Philip P.; Wolfe, Jeremy D.; Fein, Jordana; Shah, Sumit P.; Chen, Eric; Abbey, Ashkan; Ferrone, Philip J.; Shah, Chirag P.; Liang, Michelle C.; Stem, Maxwell S.; Khan, M. Ali; Yonekawa, Yoshihiro; Garg, Sunir J.
title: The influence of universal face mask use on endophthalmitis risk after intravitreal anti-VEGF injections during the COVID-19 pandemic
date: 2021-05-18
journal: Ophthalmology
DOI: 10.1016/j.ophtha.2021.05.010
sha: a237e6dbb847ffaba85ee67ddec4abae89337cad
doc_id: 721251
cord_uid: cpxovqjp

OBJECTIVE: 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 COVID-19 pandemic. This study evaluates the impact of physician, ancillary staff, and patient face mask use on rates and outcomes of post-injection endophthalmitis. DESIGN: Retrospective, multicenter, comparative cohort study PARTICIPANTS: Eyes receiving intravitreal anti-VEGF injections from 10/1/2019 to 7/31/2020 at twelve centers from the United States of America. INTERVENTION: 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. RESULTS: Of 505,968 intravitreal injections from 110,547 eyes administered, 85 of 294,514 (0.0289%; 1 in 3,464 injections) cases of presumed endophthalmitis occurred in the “no face mask” group, and 45 of 211,454 (0.0213%; 1 in 4,699) cases occurred in the “universal face mask” group (odds ratio [OR], 0.74; 95%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 to 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 to one (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 logMAR visual acuity at endophthalmitis presentation was 2.04 [∼20/2200] for “no face mask” group compared to 1.65 [∼20/900] for the “universal face mask” group (p=0.022), although no difference was observed three months after treatment (p=0.764). CONCLUSION: 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 following presentation, there was no difference in visual acuity between the groups.

Prior studies involving simulated intravitreal injections suggest that face mask 118 use by physicians may reduce bacterial dispersion associated with speech. 9, 10 In 119 contrast, one study of 483,622 intravitreal injections found that physician face mask use 120 did not influence the overall risk of PIE compared to a "no talking" policy, though it may 121 reduce oral flora-associated endophthalmitis. 11 It is unknown how patient face mask use 122 or a combination of physician, ancillary staff, and patient face mask use alters post-123 injection endophthalmitis risk. Recently, experimental investigations have suggested 124 that patient face mask use during intravitreal injections may direct bacterial dispersion 125 and expiratory airflow toward the eye, which could potentially increase the risk of PIE. 12-126 14 Despite these findings, it is unclear if these changes in face mask protocols alters the 127 clinical risk of PIE. This lack of data is particularly relevant given the routine use of face 128 mask for patients and ophthalmologists during intravitreal injections. 15 The purpose of 129 this study is to evaluate the rates and outcomes of post-injection endophthalmitis with a 130 J o u r n a l P r e -p r o o f universal face mask policy compared to no face mask use by physicians, ancillary staff, 131 and patients. 132 133

This retrospective, multicenter, comparative cohort study received approval from 135 the institutional review board at Wills Eye Hospital. Data were collected in accordance 136

with Health Insurance Portability and Accountability Act of 1996 guidelines, and the 137 study conformed to the tenets of the Declaration of Helsinki. 138

Across all participating centers, patients who developed endophthalmitis 140 following anti-VEGF injections were identified through billing and clinical records. The 141 total number of intravitreal injections, type of anti-VEGF injection used, gender, and age 142 were obtained from each center. De-identified endophthalmitis data included date of 143 causative injection; face mask use; date of endophthalmitis treatment; best available 144 visual acuity (VA) based on the better of pinhole testing or habitual correction before 145 causative injection, at time of tap and antibiotic injection and/or vitrectomy, at 3 months 146 post-procedure, and at last follow-up; and microbial culture results. Face mask policies 147 for each participating center including dates of physician face mask use, patient face 148 mask use, and taping of face masks were obtained. 149

All patients diagnosed with presumed PIE following an intravitreal injection of 151 bevacizumab, ranibizumab, or aflibercept were included in this study. Patients who 152 J o u r n a l P r e -p r o o f underwent treatment with intravitreal brolucizumab or intravitreal steroids (triamcinolone 153 or dexamethasone intravitreal implant) were excluded. Dates of inclusion were October 154 1, 2019 to July 31, 2020. Cases of endophthalmitis were defined by the decision of the 155 treating physician to inject intravitreal antibiotics, either during a tap and inject 156 procedure or during pars plana vitrectomy. Culture-positive endophthalmitis was defined 157 as any patient with bacterial growth on culture from a vitreous or anterior chamber tap. The primary outcome for this study was the rate of presumed acute-onset 196 bacterial endophthalmitis following intravitreal injection in the "universal face mask" 197 group compared to the "no face mask" group. The secondary outcomes included rate of 198 J o u r n a l P r e -p r o o f UNIVERSAL FACE MASKING AND ENDOPHTHALMITIS RISK Page 9 of 20 culture-positive endophthalmitis, rate of oral-flora endophthalmitis, visual acuity, and 199 microbial spectrum of culture-positive cases. Snellen VA was converted to logarithm of 200 the minimum angle of resolution (logMAR) equivalent for the purpose of statistical 201 analysis as established by prior studies. 16, 17 Univariate relationships between the 202 groups were evaluated without adjustment for other covariates using Pearson's Chi-203 squared test or Fisher's exact test for categorical variables and two sample t-test, 204

Mann-Whitney U test, or analysis of variance with a Tukey's honest significant 205 difference post-hoc test for continuous variables. Statistical significance was considered 206

to be a 2-sided P value < 0.05. All data were analyzed using statistical software (IBM 207 Patients were followed for an average of 6.2 months (range, 6 days -12.0 261 months) after endophthalmitis treatment, and mean (SD) follow up for patients in the "no 262 face mask" group was 8.3 (2.9) months compared to 2.70 (1.3) months for the 263 "universal face mask" group (P < 0.001). 264

Of the 116 endophthalmitis cases sent for culture, 78 of 85 (92%) were from the 265 "no face mask" group, and 38 of 45 (84%) were from the "universal face mask" group (P 266 = 0.239). Forty-three of 78 (55%) microbiologic specimens in the "no face mask" group 267 J o u r n a l P r e -p r o o f were anterior chamber aspirates compared to 23 of 38 (61%) from the "universal face 268 mask" group (P = 0.58). In the "universal face mask" group, 9 of 38 (24%) cases were 269 culture-positive compared to 27 of 78 (35%) endophthalmitis cases in the "no face 270 mask" group (P = 0.379). Endophthalmitis cases in the "universal face mask" group 271

were oral flora-associated in 1/38 (3%) cases compared to 3/78 (4%) cases for the "no 272 face mask" group (P > 0.99). between the "universal face mask" group and "no face mask" group based on drug type 284 (Table 2) . Prior studies have suggested that physician face mask use may reduce bacterial 320 dispersion associated with speech in simulated scenarios; 9,10 however, no differences 321 were observed in a recent clinical study. 11 With regard to patient face mask use, 322

previous studies have suggested that patient face mask use during intravitreal injections 323 may direct air, and subsequently bacteria, toward the treatment eye. 12,13 These findings 324 may suggest that, under certain scenarios, patient face mask use may paradoxically 325 increase the risk for PIE. However, it is unknown if these alterations in expiratory airflow 326 and possibly bacterial dispersion around an intravitreal injection site alters the risk of 327 PIE in a clinical setting. In this study, we found that, at a minimum, there was no 328 increased risk of PIE with a universal face mask policy that included physician, staff, 329 and patient face mask use. 330 A particular concern for increased expiratory airflow directed towards the eye 331 with patient face mask use is the increased risk for oral flora-associated 332 endophthalmitis. Indeed, prior studies have suggested that securing the superior portion 333 of a patient's face mask with tape may reduce bacterial dispersion or air particles 334 J o u r n a l P r e -p r o o f toward the eye. 13,14 At 3 of 12 centers involved in our study, adhesive tape was used to 335 secure the entire top portion of the patient's face mask such that 18,602 of 211,454 336 (9%) of injections in the "universal face mask" group were administered with this policy. 337

Our findings suggest no difference in endophthalmitis risk with this additional measure. 338

However, no cases of oral flora endophthalmitis were observed in this subgroup. Given 339 the devastating visual prognosis of oral flora-associated endophthalmitis, taping the 340 superior portion of a patient's face mask may still be a clinically relevant prophylaxis 341 measure; however, our study was underpowered to specifically address this question. 342

Economic considerations for universal face masking should also be considered. 343

If presumed endophthalmitis risk is reduced from 0.0289% in the "no face mask" group 344 to 0.0213% in the "universal face mask" group, then approximately 13,158 patients 345 would need to be treated with a universal face mask policy to avoid one additional case 346 of endophthalmitis and prevent a visual decline from 20/70 at causative injection to 347 20/200 at three months following treatment. Furthermore, with regard to potential vision 348 benefit for endophthalmitis cases, visual outcomes following endophthalmitis were 349 similar in the "universal face mask" group compared to the "no face mask" group. 350

Although visual acuity at the time of the causative injection was similar between the two 351 groups, eyes in the "no face mask" group were more likely to present with worse visual 352 acuity at the time of endophthalmitis presentation. This may be driven by the increased 353 number of culture-positive endophthalmitis cases, which had worse outcomes; however, 354 visual outcomes at three months following treatment were similar between the two 355 groups. 356 J o u r n a l P r e -p r o o f Overall endophthalmitis risk was higher with intravitreal aflibercept compared to 357 intravitreal ranibizumab or intravitreal bevacizumab. Prior studies have reported an 358 increased risk of sterile intraocular inflammation after intravitreal aflibercept injection 359 though no clustered spikes were reported during the study period. 18, 19 The authors' 360 standard practice is to have a low threshold to administer intravitreal antibiotics 361 whenever the treating physicians believe that a case could represent infectious 362 endophthalmitis. However, any patient only treated with topical steroids without 363 additional interventions was excluded from this study. Furthermore, during the study 364 period, there was a transition to aflibercept prefilled syringes from medication vials, 365 which could alter the risk of infection. Indeed, prior studies have suggested that prefilled 366 syringe use may decrease endophthalmitis risk by reducing handling of the medication 367 in preparation for treatment. 5,20 368

Limitations of this study are inherent in its retrospective nature, and include 369 inconsistent data entry, potential missing data, heterogeneity of injection preferences 370 amongst physicians, and inconsistency in laboratory testing. Although we report a 371 multicenter study of PIE with over 500,000 intravitreal injections, our findings may still 372 be limited by sample size, particularly when evaluating the role of taping the top of face 373 masks as well as changes to the rate of oral flora-associated endophthalmitis. The low 374 incidence of oral flora-associated endophthalmitis necessitates a study with over 2.2 375 million injections to be sufficiently powered, and the inability to confirm microbiologic 376 flora limits the use of large-scale insurance claims databases or clinical registries. 377 Table 1 . Rates of endophthalmitis after intravitreal anti-vascular endothelial growth factor injection in the "no face mask" group compared to "universal face mask" group. J o u r n a l P r e -p r o o f Table 3 . Visual acuity outcomes for endophthalmitis after intravitreal anti-vascular endothelial group factor injection in the "universal face mask" group vs. "no face mask" group Universal face mask group ( In a retrospective, multicenter study of 505,968 intravitreal anti-VEGF injections, universal face masking did not alter the risk of presumed endophthalmitis but was associated with a reduced rate of culture-positive endophthalmitis.

452 Functional status and quality of life measurement among ophthalmic patients

Novel method for analyzing snellen visual 455 acuity measurements

Aflibercept-related sterile intraocular 457 inflammation outcomes

Postmarketing analysis of aflibercept-459 related sterile intraocular inflammation

Association of acute endophthalmitis 461 with intravitreal injections of corticosteroids or anti-vascular growth factor agents 462 in a nationwide study in france

Predictors of endophthalmitis after intravitreal 464 injection: A multivariable analysis based on injection protocol and povidone 465 iodine strength

Another limitation is the lack of a standardized protocol for intravitreal injections 378 across institutions with physicians individually determining injection protocols including 379 the potential use of viscous lidocaine gel, which may alter the risk of endophthalmitis. 21 380However, there was no change to the unique protocols of each clinical site during the 381 study period with the exception of the face mask policy. Furthermore, there was no 382 standardization among the different institutions with regard to the type of face mask 383 worn by patients and physicians. It is possible that the risk of PIE may be altered by 384 different types of face masks (surgical, cloth, N95). Another limitation is that this study 385 did not adjust for intercorrelation of multiple injections from the same eye or same 386 patient. It is possible that intercorrelation of multiple injections administered in the same 387 eye may alter the incidence of endophthalmitis. 388Lastly, it is possible that other factors could have contributed to the decreased 389 risk of endophthalmitis observed in our study. For example, with coronavirus 390 restrictions, it is possible that additional infectious control precautions such as room 391 sterilization, air filtration, and more strict observance to sterile technique, in addition to 392 universal face masking, may have influenced the risk of endophthalmitis. While these 393 limitations are inherent in retrospective studies, our findings reflect real-world 394 experiences and represent the environment in which many physicians currently operate. 395Although some studies suggest that patient face mask use may direct 396 oropharyngeal air flow towards the treatment eye leading to an increased risk of PIE, 397 our large, multicenter, retrospective study suggests that universal face mask use during