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.

MICROBIOLOGIC SPECTRUM AND VISUAL OUTCOMES OF ACUTE-ONSET ENDOPHTHALMITIS UNDERGOING THERAPEUTIC PARS PLANA VITRECTOMY.

PURPOSE: To report the clinical presentation, microbiologic spectrum, and visual outcomes associated with acute-onset infectious endophthalmitis undergoing therapeutic pars plana vitrectomy. METHODS: Multicenter interventional retrospective noncomparative consecutive case series. Billing records were reviewed to identify all charts for patients undergoing pars plana vitrectomy within 14 days of diagnosis of acute-onset infectious endophthalmitis over a 4-year period at 5 large tertiary referral retina practices. Statistical analysis was performed to assess for factors associated with visual outcomes. RESULTS: Seventy patients were identified. The most common clinical setting was postcataract surgery (n = 20). Only 3 patients (4.3%) presented with 20/400 or better visual acuity (VA). Although most of the patients initially underwent vitreous tap and intravitreal antibiotic injection (n = 47, 67.1%), all patients eventually underwent pars plana vitrectomy within 14 days of presentation with 68.5% (48/70) of patients undergoing pars plana vitrectomy within 48 hours of presentation. Positive intraocular cultures were obtained in 56 patients (80%). The most common identified organism was Streptococcus sp (n = 19). Visual acuity at last follow-up was 20/400 or better in 19 patients (27.1%). Three patients underwent evisceration or enucleation (4.3%). Last recorded postoperative VA (mean LogMAR 1.99 ± 0.94, Snellen VA equivalent finger count) improved from presenting VA (mean LogMAR 2.37 ± 0.38, Snellen VA hand motions) (P ≤ 0.001). There was no statistically significant correlation between the underlying etiology or the timing of surgery with this VA outcome. CONCLUSION: Although less than one-third of patients achieved 20/400 or better VA, this VA often improved significantly from presenting VA.

PARS PLANA VITRECTOMY FOR LATE VITREORETINAL SEQUELAE OF INFECTIOUS ENDOPHTHALMITIS: Surgical Management and Outcomes.

PURPOSE: To report the visual acuity outcomes after pars plana vitrectomy for delayed vitreoretinal sequelae of infectious endophthalmitis. All eyes were initially treated with intravitreal antibiotics (Abx). METHODS: Multicenter, retrospective, consecutive case series. RESULTS: Forty-two eyes met the study criteria. The mean follow-up was 48 weeks (SD ± 61.8). Mean interval from Abx to pars plana vitrectomy was 13 weeks (SD ± 14.3, range 2-70). Indications for pars plana vitrectomy included vitreous opacities (VO) (n = 22), epiretinal membrane (n = 9), and retinal detachment (n = 11). LogMAR visual acuity improved from 1.87 (Snellen equivalent: 20/1,482) preoperatively to 1.35 (Snellen equivalent: 20/447) at final evaluation (P < 0.001). LogMAR visual acuity improved significantly for patients with vitreous opacities (P < 0.01) and retinal detachment (P = 0.02) but not for patients with epiretinal membranes (P = 0.08). CONCLUSION: Patients with infectious endophthalmitis can gain vision if they have a pars plana vitrectomy for delayed sequelae such as vitreous opacities or for retinal detachment.

CORRELATION OF SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AND CLINICAL ACTIVITY IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To characterize the features of choroidal neovascularization (CNV) in neovascular age-related macular degeneration with spectral domain optical coherence tomography angiography (OCTA) and to determine whether OCTA can be used to determine clinical activity of CNV. METHODS: Observational, retrospective, consecutive case series. RESULTS: Optical coherence tomography angiography revealed CNV in 28 eyes (62.2%) while 17 eyes (37.8%) did not demonstrate CNV vessels. Choroidal neovascularization was classified as well circumscribed in 12 eyes (42.8%) and poorly circumscribed in 16 eyes (57.2%). Twenty-two eyes with a CNV on OCTA were clinically active, whereas six eyes with visible CNV on OCTA were clinically inactive. Of the 17 eyes that did not have evidence of CNV on OCTA imaging, 14 were clinically inactive and 3 were clinically active. Presence of CNV on OCTA correlated with clinical activity and absence of CNV correlated with inactivity (P < 0.0001). CONCLUSION: Optical coherence tomography angiography is a noninvasive imaging technique that can be used to visualize blood flow comprising CNV. Optical coherence tomography angiography detects CNV vessels in some albeit not all eyes with neovascular age-related macular degeneration. Although the presence or absence of CNV vessels on OCTA highly correlated with clinical activity of CNV, the morphologic appearance of CNV on OCTA did not have significant correlation with clinical activity.

Analysis of the thickness and vascular layers of the choroid in eyes with geographic atrophy using spectral-domain optical coherence tomography.

PURPOSE: To analyze the total choroidal thickness and thickness of the individual vascular layers of the choroid in eyes with geographic atrophy (GA), using spectral-domain optical coherence tomography. METHODS: A cross-sectional retrospective review identified 17 patients with GA (17 eyes) and 14 age-matched healthy subjects (14 eyes), who underwent high-definition raster scanning at New England Eye Center, Boston, MA. Patients were diagnosed with GA based on clinical examination and investigations. Two independent raters evaluated the thickness and vascular layers of the choroid. RESULTS: Mean choroidal thickness was significantly lower in eyes with GA when compared with age-matched healthy eyes (P < 0.0001). Subfoveal choroidal thickness in eyes with GA was significantly less when compared with healthy eyes (158.1 ± 23.65 µm versus 267.5 ± 19.27 µm, P = 0.001). Subfoveal large choroidal vessel layer thickness and medium choroidal vessel layer/choriocapillaris layer thickness were significantly reduced in eyes with GA when compared with healthy eyes (P = 0.001 and P < 0.0001, respectively). CONCLUSION: The choroid is significantly thinner in eyes with GA involving the fovea when compared with healthy eyes. Choroidal thinning in GA involves all its vascular layers. Further studies involving prospective correlation of choroidal vascular changes to the quantitative progression of GA is expected to provide further insight on the choroidal angiopathy associated with GA.

Anaplastic Large-Cell Lymphoma With Vitreous Humor Involvement.

Purpose: To describe a case of T-cell lymphoma with bilateral vitreous involvement. Methods: A case report was reviewed, and a literature review, including search terms such as "anaplastic large-cell lymphoma (ALCL)" and "T-cell lymphoma with ocular involvement", was performed. Results: A 56-year-old man presented with slurred speech, left-sided weakness, and floaters in his right eye. He was found to have an enhancing right frontal lobe mass with biopsy positive for ALCL. The right eye demonstrated 2+ vitreous cell, with a vitreous biopsy consistent with ALCL. His floaters resolved, and the patient was asymptomatic until he developed floaters in his left eye 1½ years later. A subsequent vitreous biopsy revealed recurrence of ALCL in the fellow eye. Conclusions: ALCL is a rare T-cell lymphoma uncommonly reported as having vitreous infiltration.

Subretinal fluid associated with pemigatinib therapy for cholangiocarcinoma; a case report and literature review Pemigatinib-associated subretinal fluid.

PURPOSE: To describe the retinal findings associated with pemigatinib, an oral competitive inhibitor of fibroblast growth factor receptor (FGFR) approved for the treatment of cholangiocarcinoma. METHODS: We present a case report and performed a literature review, revealing only two prior reported cases of pemigatinib-mediated subretinal fluid. RESULTS: A 72-year-old woman presented with transient visual symptoms while on pemigatinib for the treatment of cholangiocarcinoma. Optical coherence tomography (OCT) revealed subfoveal subretinal fluid bilaterally that resolved during a drug holiday, however fluctuated throughout her treatment course. She remained on pemigatinib for ten months without other ocular sequelae. CONCLUSIONS: This is one of the few reported cases of pemigatinib-related retinopathy, which further supports the self-limited and benign nature of subretinal fluid associated with FGFR inhibitors.

BILATERAL SEROUS RETINAL DETACHMENTS IN A PATIENT WITH PREECLAMPSIA WITHOUT HYPERTENSION.

PURPOSE: To report a case of bilateral serous retinal detachments in a patient with preeclampsia without hypertension using multimodal ophthalmic imaging. METHODS: Case report. RESULTS: This case demonstrates the rare presentation of bilateral serous retinal detachment in a patient with preeclampsia without hypertension. Characteristic subretinal fluid was seen on examination and optical coherence tomography. No leakage was noted on fluorescein angiography. Treatment was deferred, and the subretinal fluid resolved within 3 weeks. CONCLUSION: Practitioners should be aware of the rare presentation of serous retinal detachments in preeclampsia, even in the absence of hypertension. Long-term sequelae are uncommon and usually only seen in severe disease. Delivery should be considered once serous retinal detachment develops.

Retinal Pigment Epithelium Aperture Preceding Collapse of Vascular and Avascular Pigment Epithelial Detachments Secondary to AMD.

PURPOSE: To describe retinal pigment epithelium (RPE) aperture preceding the collapse of retinal pigment epithelium detachments (RPED) in eyes with neovascular and non-neovascular age-related macular degeneration (AMD). METHODS: Medical records from five patients with RPE aperture associated with vascular and avascular RPED were reviewed between 2010 and 2021 at the New England Eye Center at Tufts Medical Center. Main outcome measures were analysis of RPE aperture characteristics and temporal course of RPED collapse. RESULTS: RPE apertures were identified in six eyes from five women (mean age of 72.6 years). Two eyes had neovasacular AMD and four eyes had non-neovascular AMD. The RPE aperture initially appeared as a discontinuity at the apex of the RPED without rippling or retraction. Each aperture was associated with hypertransmission of OCT signal into the choroid as well as hyperreflective foci. The mean time between the appearance of the RPE aperture to near complete collapse of the RPED was 9 months. Following RPED collapse, one eye developed choroidal neovascularization, three eyes progressed to geographic atrophy, one eye had recurrence of the RPED, and one eye remained unchanged. CONCLUSION: RPE aperture is a characteristic OCT finding that can be observed in avascular or vascularized RPED secondary to AMD. RPE apertures precede RPED collapse, which are most likely to occur within nine months of RPE aperture detection.

A Deep Learning Model for Automated Segmentation of Geographic Atrophy Imaged Using Swept-Source OCT.

PURPOSE: To present a deep learning algorithm for segmentation of geographic atrophy (GA) using en face swept-source OCT (SS-OCT) images that is accurate and reproducible for the assessment of GA growth over time. DESIGN: Retrospective review of images obtained as part of a prospective natural history study. SUBJECTS: Patients with GA (n = 90), patients with early or intermediate age-related macular degeneration (n = 32), and healthy controls (n = 16). METHODS: An automated algorithm using scan volume data to generate 3 image inputs characterizing the main OCT features of GA-hypertransmission in subretinal pigment epithelium (sub-RPE) slab, regions of RPE loss, and loss of retinal thickness-was trained using 126 images (93 with GA and 33 without GA, from the same number of eyes) using a fivefold cross-validation method and data augmentation techniques. It was tested in an independent set of one hundred eighty 6 × 6-mm2 macular SS-OCT scans consisting of 3 repeated scans of 30 eyes with GA at baseline and follow-up as well as 45 images obtained from 42 eyes without GA. MAIN OUTCOME MEASURES: The GA area, enlargement rate of GA area, square root of GA area, and square root of the enlargement rate of GA area measurements were calculated using the automated algorithm and compared with ground truth calculations performed by 2 manual graders. The repeatability of these measurements was determined using intraclass coefficients (ICCs). RESULTS: There were no significant differences in the GA areas, enlargement rates of GA area, square roots of GA area, and square roots of the enlargement rates of GA area between the graders and the automated algorithm. The algorithm showed high repeatability, with ICCs of 0.99 and 0.94 for the GA area measurements and the enlargement rates of GA area, respectively. The repeatability limit for the GA area measurements made by grader 1, grader 2, and the automated algorithm was 0.28, 0.33, and 0.92 mm2, respectively. CONCLUSIONS: When compared with manual methods, this proposed deep learning-based automated algorithm for GA segmentation using en face SS-OCT images was able to accurately delineate GA and produce reproducible measurements of the enlargement rates of GA.

Ultrahigh Resolution OCT Markers of Normal Aging and Early Age-related Macular Degeneration.

Purpose: Ultrahigh resolution spectral domain-OCT (UHR SD-OCT) enables in vivo visualization of micrometric structural markers which differentially associate with normal aging versus age-related macular degeneration (AMD). This study explores the hypothesis that UHR SD-OCT can detect and quantify sub-retinal pigment epithelium (RPE) deposits in early AMD, separating AMD pathology from normal aging. Design: Prospective cross-sectional study. Participants: A total of 53 nonexudative (dry) AMD eyes from 39 patients, and 63 normal eyes from 39 subjects. Methods: Clinical UHR SD-OCT scans were performed using a high-density protocol. Exemplary high-resolution histology and transmission electron microscopy images were obtained from archive donor eyes. Three trained readers evaluated and labeled outer retina morphological features, including the appearance of a hyporeflective split within the RPE-RPE basal lamina (RPE-BL)-Bruch's membrane (BrM) complex on UHR brightness (B)-scans. A semi-automatic segmentation algorithm measured the thickness of the RPE-BL-BrM split/hyporeflective band. Main Outcome Measures: Qualitative description of outer retinal morphological changes on UHR SD-OCT B-scans; the proportion of the RPE-BL-BrM complex with visible split (%) and the thickness of the resulting hyporeflective band (µm). Results: In young normal eyes, UHR SD-OCT consistently revealed an RPE-BL-BrM split/hyporeflective band. Its visibility and thickness were less in eyes of advanced age. However, the split/hyporeflective band was again visible in early AMD eyes. Both qualitative reading and quantitative thickness measurements showed significantly elevated visibility and thickness of the RPE-BL-BrM split/hyporeflective in early AMD eyes compared to age-matched controls. Conclusions: Our imaging results strongly support the hypothesis that appearance of the RPE-BL-BrM split/hyporeflective band in older subjects is dominated by the BL deposit, an indicator of early AMD well known from histology. Ultrahigh resolution SD-OCT can be used to investigate physiological aging as well as early AMD pathology in clinical imaging studies. Developing quantifiable markers associated with disease pathogenesis and progression can facilitate drug discovery, as well as reduce clinical trial times. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Variants of Uncertain Significance: Twins With Identical Pathogenic Gene Mutations in Retinitis Punctata Albescens.

The authors describe identical twin sisters with similar symptoms, fundus findings, and ophthalmic testing consistent with retinitis punctata albescens (RPA). The pathognomonic white retinal flecks, extensive midperipheral retinal pigment epithelium atrophy, and pigmentary changes demonstrate overlapping phenotypic properties of RPA and other inherited retinal degenerative diseases. Genetic testing confirmed two mutations of the RLBP1 gene: one pathogenic for RPA, and the other a variant of uncertain significance previously reported as a novel RPA mutation in the literature. This report highlights identical phenotypic findings and genetic mutations in twin sisters aiding in further classification of pathogenic mutations associated with RPA. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:450-453.].

Hypervirulent Klebsiella pneumoniae infection in a woman with a CDH1 gene mutation.

The CDH1 gene, which encodes E-cadherin, may be associated with cancer when mutated, but the significance of mutations in the context of infection is unknown. In this report, we describe a case of disseminated hypervirulent Klebsiella pneumoniae infection in a 49 year old Caucasian woman with a documented CDH1 mutation.

Early Experience With Brolucizumab Treatment of Neovascular Age-Related Macular Degeneration.

IMPORTANCE: Outcome data are limited regarding early experience with brolucizumab, the most recently approved anti-vascular endothelial growth factor (VEGF) agent for the treatment of neovascular age-related macular degeneration (nAMD). OBJECTIVE: To report clinical outcomes after intravitreous injection (IVI) of brolucizumab, 6 mg, for nAMD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series conducted at 15 private or academic ophthalmological centers in the United States included all consecutive patients with eyes treated with brolucizumab by 6 retina specialists between October 17, 2019, and April 1, 2020. EXPOSURES: Treatment with brolucizumab IVI, 6 mg. MAIN OUTCOMES AND MEASURES: Change in mean visual acuity (VA) and optical coherence tomography parameters, including mean central subfield thickness and presence or absence of subretinal and/or intraretinal fluid. Secondary outcomes included ocular and systemic safety. RESULTS: A total of 172 eyes from 152 patients (87 women [57.2%]; mean [SD] age, 80.0 [8.0] years) were included. Most eyes (166 [96.5%]) were not treatment naive, and 65.7% of these eyes (109 of 166) were switched from the prior anti-VEGF agent because of persistent fluid detected on optical coherence tomography scans. Study eyes received a mean (SD) of 1.46 (0.62) brolucizumab IVIs. The mean (SD) VA prior to starting brolucizumab was a 64.1 (15.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (Snellen equivalent, 20/50) and was a 63.3 (17.2) ETDRS letter score (Snellen equivalent, 20/63) at the last study evaluation (mean difference, 0.8; 95% CI, -2.7 to 4.3; P = .65). When analyzed by number of brolucizumab IVIs, the presence or absence of fluid prior to starting brolucizumab, or the presence or absence of intraocular inflammation after receiving brolucizumab, there was no difference in mean VA prior to starting brolucizumab compared with after brolucizumab IVIs or at the final study evaluation. The mean (SD) central subfield thickness in all eyes prior to starting brolucizumab was 296.7 (88.0) µm and was 269.8 (66.5) µm at the last study examination (mean difference, 26.9 µm; 95% CI, 9.0-44.7 µm; P = .003). Intraocular inflammation was reported in 14 eyes (8.1%) and was self-limited and resolved without treatment in almost half those eyes (n = 6). One previously reported eye (0.6%) had occlusive retinal vasculitis and severe loss of vision. CONCLUSIONS AND RELEVANCE: In this analysis of brolucizumab IVI for nAMD, VA remained stable, with a reduction in central subfield thickness. Intraocular inflammation events ranged from mild with spontaneous resolution to severe occlusive retinal vasculitis in 1 eye.

SPECTRAL DOMAIN-OPTICAL COHERENCE TOMOGRAPHY FINDINGS OF COMMOTIO RETINAE WITH ASSOCIATED SEROUS RETINAL DETACHMENT.

PURPOSE: To describe the appearance of a serous retinal detachment associated with commotio retinae on spectral domain optical coherence tomography. METHODS: Case report. RESULTS: This case demonstrates the rare presentation of subretinal fluid in commotio retinae. Characteristic outer retinal changes associated with commotio retinae were also seen. Treatment was deferred and the subretinal fluid resolved within 1 week. CONCLUSION: Commotio retinae is rarely associated with a serous retinal detachment. This presentation is important to identify as it can avoid unnecessary workup and treatment.

Progressive left ventricular remodeling, myocyte apoptosis, and protein signaling cascades after myocardial infarction in rabbits.

To determine the temporal changes in oxidative stress, mitogen-activated protein (MAP) kinases and mitochondrial apoptotic proteins, and their relationship to myocyte apoptosis in the remote noninfarcted myocardium after myocardial infarction (MI), rabbits were randomly assigned to either coronary artery ligation to produce MI or sham operation. The animals were sacrificed at 1, 4, 8, or 12 weeks after coronary artery occlusion. Sham rabbits were sacrificed at 12 weeks after surgery. MI rabbits exhibited progressive increases of left ventricular (LV) end-diastolic pressure and end-diastolic dimension, and progressive decreases of LV fractional shortening and dP/dt over 12 weeks. The LV remodeling with LV chamber dilation and LV systolic dysfunction was temporally associated with progressive increases of cardiac oxidative stress as evidenced by decreased myocardial reduced-to-oxidized-glutathione ratio and increased myocardial 8-hydroxydeoxyguanosine and myocyte apoptosis. The ERK and JNK activities were decreased while p38 MAP kinase activity was increased with age of MI. The extent of p38 MAP kinase activation correlated with Bcl-2 phosphorylation. Bcl-2 protein was decreased in both mitochondrial and cytosolic fractions with age of MI. Bax protein was increased in both mitochondrial and cytosolic fractions. Cytochrome c was reduced in mitochondrial fraction and increased in cytosolic fraction in a time-dependent manner after MI. Cleaved caspase 9 and caspase 3 proteins were time-dependently increased after MI. These data suggest that p38 MAP kinase activation is not only time-dependent after MI, but also correlates with oxidative stress, Bcl-2 phosphorylation, and myocyte apoptosis. These changes in the remote noninfarcted myocardium may contribute to LV remodeling and dysfunction after MI.

Optical Coherence Tomography Angiography of Mixed Neovascularizations in Age-Related Macular Degeneration.

PURPOSE: To describe the imaging of mixed neovascular age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). METHODS: Literature review and case series. RESULTS: A review of mixed neovascularization in AMD is discussed, focusing on the different subtypes of neovascularization and the associated characteristics on imaging, including fluorescein angiography, optical coherence tomography, and OCTA. Three cases are presented. CONCLUSION: OCTA is a method of identifying mixed neovascularization in AMD. Neovascular vessels can be seen on en face images of the retina, both below and above the retinal pigment epithelium, corresponding to different types of leakage observed on conventional angiography.