Long-Term Decrease in Intraocular Pressure in Survivors of Ebola Virus Disease in the Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) III Study.

Objective: Survivors of Ebola virus disease (EVD) experience decreased intraocular pressure (IOP) relative to unaffected close contacts during the first year of convalescence. Whether this effect persists over time and its relationship to intraocular pathology are unclear. We sought to determine whether IOP remained lower in survivors of EVD over 4 years of follow-up and to identify associated risk factors. Design: Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) III is a 5-year, longitudinal cohort study of survivors of EVD and their close contacts and is a collaboration between the Liberian Ministry of Health and the United States National Institutes of Health. Participants: Participants who enrolled in PREVAIL III at John F. Kennedy Medical Center in Liberia, West Africa from June 2015 to March 2016 who underwent comprehensive ophthalmic evaluation annually for 5 consecutive visits. Methods: Intraocular pressure was measured at each visit by a handheld rebound tonometer using sterile tips. Comparisons are made between antibody-positive survivors and antibody-negative close contacts. Main Outcome Measures: Intraocular pressure, measured in mmHg, at each study visit. Results: Of 565 antibody-positive survivors and 644 antibody-negative close contacts enrolled in the study at baseline, the majority of participants returned annually, with 383 (67.8%) and 407 (63.2%) participants, respectively, presenting for the final study visit at a median of 60 months after symptom onset. A sustained, relative decrease in IOP was observed in survivors relative to close contacts, with mean difference of -0.72 mmHg (95% confidence interval [CI] -1.18 to -0.27) at the final study visit. This difference remained constant throughout the study period (P = 0.4 for interaction over time). Among survivors, physical examination findings of vitreous cell and OCT findings of vitreous opacities both demonstrated a significant association with decreased IOP at baseline (P < 0.05 for both). After adjusting for such factors, the difference throughout the follow-up (-0.93 mmHg, 95% CI, -1.23 to -0.63) remained significant. Conclusions: Survivors of EVD experienced a sustained decrease in IOP relative to close contacts over a 5-year period after EVD. The results highlight the importance of considering long-term sequelae of emerging infectious diseases within a population. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Efficacy and Safety Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease: 12-Month Results From the PREVAIL VII Study.

Purpose: In survivors of Ebola virus disease (EVD), intraocular viral persistence raises questions about the timing and safety of cataract surgery. To the best of our knowledge, this is the first controlled study evaluating Ebola virus persistence and cataract surgery safety and outcomes in EVD survivors. Methods: Seropositive EVD survivors and seronegative controls with vision worse than 20/40 from cataract and without active intraocular inflammation were enrolled. Aqueous humor from survivors was tested with reverse transcription-polymerase chain reaction for Ebola viral RNA. Participants underwent manual small-incision cataract surgery and 1 year of follow-up examinations. Results: Twenty-two eyes of 22 survivors and 12 eyes of eight controls underwent cataract surgery. All of the aqueous samples tested negative for Ebola viral RNA. Median visual acuity improved from 20/200 at baseline to 20/25 at 1 year in survivors and from count fingers to 20/50 in controls (overall, P < 0.001; between groups, P = 0.07). After a 1-month course of topical corticosteroids, 55% of survivors and 67% of controls demonstrated at least 1+ anterior chamber cell. Twelve months after surgery, optical coherence tomography revealed a median increase in macular central subfield thickness of 42 µm compared with baseline (overall, P = 0.029; between groups, P = 0.995). Conclusions: EVD survivors and controls demonstrated significant visual improvement from cataract surgery. The persistence of intraocular inflammation highlights the importance of follow-up. The absence of detectable intraocular Ebola viral RNA provides guidance regarding the safety of eye surgery in Ebola survivors. Translational Relevance: These findings demonstrate the safety and efficacy of cataract surgery in Ebola survivors and will inform ocular surgery guidelines in this population.

Characterization of Ebola Virus-Associated Eye Disease.

Importance: Survivors of Ebola virus disease (EVD) may experience ocular sequelae. Comparison with antibody-negative individuals from the local population is required to characterize the disease. Objective: To assess features of ophthalmic disease specific to EVD. Design, Setting, and Participants: This baseline cross-sectional analysis of survivors of EVD and their close contacts was conducted within PREVAIL III, a 5-year, longitudinal cohort study. Participants who enrolled at John F. Kennedy Medical Center in Liberia, West Africa from June 2015 to March 2016 were included in this analysis. Close contacts were defined as household members or sex partners of survivors of EVD. Data were analyzed from July 2016 to July 2020. Exposures: All participants, both survivors and close contacts, underwent testing of IgG antibody levels against Ebola virus surface glycoprotein. Main Outcomes and Measures: Ocular symptoms, anterior and posterior ophthalmologic examination findings, and optical coherence tomography images were compared between antibody-positive survivors and antibody-negative close contacts. Results: A total of 564 antibody-positive survivors (320 [56.7%] female; mean [SD] age, 30.3 [14.0] years) and 635 antibody-negative close contacts (347 [54.6%] female; mean [SD] age, 25.8 [15.5] years) were enrolled in this study. Survivors were more likely to demonstrate color vision deficit (28.9% vs 19.0%, odds ratio [OR], 1.6; 95% CI, 1.2-2.1) and lower intraocular pressure (12.4 vs 13.5 mm Hg; mean difference, -1.2 mm Hg; 95% CI, -1.6 to -0.8 mm Hg) compared with close contacts. Dilated fundus examination revealed a higher percentage of vitreous cells (7.8% vs 0.5%; OR, 16.6; 95% CI, 5.0-55.2) and macular scars (4.6% vs 1.6%; OR, 2.8; 95% CI, 1.4-5.5) in survivors than in close contacts. Uveitis was present in 26.4% of survivors and 12.1% of close contacts (OR, 2.4; 95% CI, 1.8-3.2). Among all participants with uveitis, survivors were more likely than close contacts to have intermediate uveitis (34.2% vs 6.5% of all cases; OR, 7.8; 95% CI, 3.1-19.7) and had thicker mean central subfield thickness on optical coherence tomography (222 vs 212 µm; mean difference, 14.4 µm; 95% CI, 1.9-26.9 µm). Conclusions and Relevance: In this cross-sectional study, survivors of EVD had a distinct spectrum of ocular and neuro-ophthalmologic findings compared with close contacts that potentially require medical and surgical treatment.

Development of a screening eye clinic for Ebola virus disease survivors: Lessons learned and rapid implementation at ELWA Hospital in Monrovia, Liberia 2015.

BACKGROUND: In the wake of the West African Ebola virus disease (EVD) outbreak of 2014-2016, thousands of EVD survivors began to manifest a constellation of systemic and ophthalmic sequelae. Besides systemic arthralgias, myalgias, and abdominal pain, patients were developing uveitis, a spectrum of inflammatory eye disease leading to eye pain, redness, and vision loss. To investigate this emerging eye disease, resources and equipment were needed to promptly evaluate this sight-threatening condition, particularly given our identification of Ebola virus in the ocular fluid of an EVD survivor during disease convalescence. METHODOLOGY/PRINCIPAL FINDINGS: A collaborative effort involving ophthalmologists, infectious disease specialists, eye care nurses, and physician leadership at Eternal Love Winning Africa (ELWA) Hospital in Liberia led to the development of a unique screening eye clinic for EVD survivors to screen, treat, and refer patients for more definitive care. Medications, resources, and equipment were procured from a variety of sources including discount websites, donations, purchasing with humanitarian discounts, and limited retail to develop a screening eye clinic and rapidly perform detailed ophthalmologic exams. Findings were documented in 96 EVD survivors to inform public health officials and eye care providers of the emerging disease process. Personal protective equipment was tailored to the environment and implications of EBOV persistence within intraocular fluid. CONCLUSIONS/SIGNIFICANCE: A screening eye clinic was feasible and effective for the rapid screening, care, and referral of EVD survivors with uveitis and retinal disease. Patients were screened promptly for an initial assessment of the disease process, which has informed other efforts within West Africa related to immediate patient care needs and our collective understanding of EVD sequelae. Further attention is needed to understand the pathogensis and treatment of ophthalmic sequelae given recent EVD outbreaks in West Africa and ongoing outbreak within Democratic Republic of Congo.