PREVAIL VII: Cataract Surgery in Ebola Survivors

Study Overview
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Brief Summary
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Objective: Zaire ebolavirus is a single-stranded RNA virus associated with high morbidity and mortality. The most recent epidemic of Ebola virus disease (EVD) in West Africa resulted in over 11,000 deaths and disabling sequelae among survivors, among which eye complications are highly represented. Chronic intraocular inflammation and viral persistence may result in posterior synechiae and cataract formation, resulting in loss of visual acuity and requiring surgical intervention to resolve. Approximately one out of ten Ebola survivors present with cataract, most of whom will require intraocular surgery during their lifetime, and many of whom require intervention in the near future to regain quality of life. For survivors who are blind from cataract, cataract extraction is necessary to restore visual function, allow reintegration into society and facilitate performance of activities of daily living. However, surgical parameters among Ebola survivors are unknown, including whether Ebola viral RNA persists in aqueous humor, whether additional anti-inflammatory medication is needed, and the expected degree of improvement in visual function. Moreover, sites of viral persistence are unknown, and it is unclear if lens tissues removed during cataract surgery may harbor virus in Ebola-affected eyes. We propose following EVD survivors and control subjects undergoing cataract surgery to determine visual outcomes among Ebola survivors and explore detection of the presence of virus in lens tissues. The data will inform both future surgical intervention and aid in the understanding of the pathophysiology of Ebola-associated eye disease. Study Population: Up to 60 Ebola survivors and up to 60 controls will be enrolled. The accrual ceiling is 120 participants. Design: This is a prospective, natural history study to evaluate the persistence of Ebola viral RNA in the eyes of Ebola survivors and assess the response to cataract surgery in survivors as compared to controls. EVD survivors will first undergo assessment of aqueous humor for the presence of viral RNA. Survivors testing negative for viral RNA and control subjects will undergo clinically indicated cataract surgery. Subjects will be evaluated 1 day, 1 week, 1 month, and 3, 6, 9 and 12 months after surgery for safety and visual outcome assessments, and more often as clinically indicated. Outcome Measures: The primary outcomes are: 1) the proportion of EVD survivors with evidence of persistence of Ebola viral RNA in ocular tissue and 2) the comparison of amount of intraocular inflammation, as measured by average grade of anterior chamber cell by SUN criteria, between EVD survivors and controls at 1 month and 3 months following cataract surgery. Secondary outcomes include: 1) the proportion of survivors with at least 20/40 best corrected visual acuity (BCVA) after cataract surgery, relative to controls; 2) impact of the covariates age and gender on viral persistence and cataract outcomes; 3) post-operative optical coherence tomography results in EVD survivors.

Detailed Description
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Objective: Zaire ebolavirus is a single-stranded RNA virus associated with high morbidity and mortality. The most recent epidemic of Ebola virus disease (EVD) in West Africa resulted in over 11,000 deaths and disabling sequelae among survivors, among which eye complications are highly represented. Chronic intraocular inflammation and viral persistence may result in posterior synechiae and cataract formation, resulting in loss of visual acuity and requiring surgical intervention to resolve. Approximately one out of ten Ebola survivors present with cataract, most of whom will require intraocular surgery during their lifetime, and many of whom require intervention in the near future to regain quality of life. For survivors who are blind from cataract, cataract extraction is necessary to restore visual function, allow reintegration into society and facilitate performance of activities of daily living. However, surgical parameters among Ebola survivors are unknown, including whether Ebola viral RNA persists in aqueous humor, whether additional anti-inflammatory medication is needed, and the expected degree of improvement in visual function. Moreover, sites of viral persistence are unknown, and it is unclear if lens tissues removed during cataract surgery may harbor virus in Ebola-affected eyes. We propose following EVD survivors and control subjects undergoing cataract surgery to determine visual outcomes among Ebola survivors and explore detection of the presence of virus in lens tissues. The data will inform both future surgical intervention and aid in the understanding of the pathophysiology of Ebola-associated eye disease. Study Population: Up to 60 Ebola survivors and up to 60 controls will be enrolled. The accrual ceiling is 120 participants. Design: This is a prospective, natural history study to evaluate the persistence of Ebola viral RNA in the eyes of Ebola survivors and assess the response to cataract surgery in survivors as compared to controls. EVD survivors will first undergo assessment of aqueous humor for the presence of viral RNA. Survivors testing negative for viral RNA and control subjects will undergo clinically indicated cataract surgery. Subjects will be evaluated 1 day, 1 week, 1 month, and 3, 6, 9 and 12 months after surgery for safety and visual outcome assessments, and more often as clinically indicated. Outcome Measures: The primary outcomes are: 1) the proportion of EVD survivors with evidence of persistence of Ebola viral RNA in ocular tissue and 2) the comparison of amount of intraocular inflammation, as measured by average grade of anterior chamber cell by SUN criteria, between EVD survivors and controls at 1 month and 3 months following cataract surgery. Secondary outcomes include: 1) the proportion of survivors with at least 20/40 best corrected visual acuity (BCVA) after cataract surgery, relative to controls; 2) impact the of covariates, age and gender on viral persistence and cataract outcomes; 3) post-operative optical coherence tomography results in EVD survivors.

Official Title
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PREVAIL VII: Persistence of Ebola Virus in Ocular Tissues and Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease

Conditions
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Cataract

Intervention / Treatment
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* Procedure: Cataract surgery


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: To be eligible, the following inclusion criteria must be met, where applicable. Participant must be 14 years of age or older. Participant must be able to understand and sign an informed consent or have a parent/legal guardian do so if they are minor children or a legally authorized representative to provide consent for adults without consent capacity. Participant must be either: an Ebola virus disease (EVD) seropositive survivor or seropositive control OR an EVD seronegative survivor or seronegative control (Serology confirmation is available for PREVAIL participants and will be conducted for non-PREVAIL participants.). Participant must have visually significant cataract(s) consistent with level of visual deficit. Participant must have corrected visual acuity worse than 20/40 in affected eye and vision loss believed to be primarily the result of the cataract. Any woman and persons of childbearing potential age have a negative pregnancy test at screening and must be willing to undergo pregnancy testing prior to the cataract surgery. EXCLUSION CRITERIA: A participant is not eligible if any of the following exclusion criteria are present. Concurrent life-threatening illness or other condition that compromises a participant's ability to safely undergo surgery, as determined by the surgical and medical team, including any condition that prevents the participant from lying down supine or remaining still, such as severe lung disease, or a known life-threatening, untreated or unstable cardiac or pulmonary condition. Active uveitis at time of surgery or within the past three months, if documented. Participant is pregnant, as surgery is elective and no adequate data regarding the use of postoperative topical antibiotic-steroid combination drops exists in pregnant women. Any condition that poses a risk to the participant having a safe surgical or post-operative experience, including known inability or unwillingness to follow up for the full duration of the protocol.

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Control with clinical need for cataract surgery | Procedure: Cataract surgery<br>* Cataract surgery and aqueous humor sampling.<br>|
| Experimental: EVD Survivors<br>EVD survivors with need for cataract surgery | Procedure: Cataract surgery<br>* Cataract surgery and aqueous humor sampling.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of EVD Survivors With Evidence of Persistence of Ebola Viral RNA in Ocular Tissue | Participants undergo aqueous fluid (aqueous humor) sampling to assess for the presence of Ebola virus RNA via RT-PCR using the GeneXpert assay. The study was intended to include analysis of lens tissue to explore detection of the presence of virus in lens tissue in EVD survivors; however, the collected lens tissue samples were damaged during storage and transport. Therefore, the lens samples were unable to yield any reportable data. | One week prior to cataract surgery | 
| Comparison of the Amount of Intraocular Inflammation Between EVD Survivors and Controls at 1 Month Following Cataract Surgery | The amount of intraocular inflammation is measured by the average grade of anterior chamber (AC) cell per Standardization of Uveitis Nomenclature (SUN) criteria. AC cell grading, with higher grades indicating a worse outcome: Grade 0 -- 0-5 cells per 1 mm x 1 mm high-powered field; Grade 1 -- 6-15 cells per 1 mm x 1 mm high-powered field; Grade 2 -- 16-25 cells per 1 mm x 1 mm high-powered field; Grade 3 -- 26-50 cells per 1 mm x 1 mm high-powered field; Grade 4 -- > 50 cells per 1 mm x 1 mm high-powered field | 1 month after cataract surgery | 
| Comparison of the Amount of Intraocular Inflammation Between EVD Survivors and Controls at 3 Months Following Cataract Surgery | The amount of intraocular inflammation is measured by the average grade of anterior chamber cell per Standardization of Uveitis Nomenclature (SUN) criteria. AC cell grading, with higher grades indicating a worse outcome: Grade 0 -- 0-5 cells per 1 mm x 1 mm high-powered field; Grade 1 -- 6-15 cells per 1 mm x 1 mm high-powered field; Grade 2 -- 16-25 cells per 1 mm x 1 mm high-powered field; Grade 3 -- 26-50 cells per 1 mm x 1 mm high-powered field; Grade 4 -- > 50 cells per 1 mm x 1 mm high-powered field | 3 months after cataract surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Proportion of Eyes With at Least 20/40 Best Corrected Visual Acuity (BCVA) 12 Months After Cataract Surgery | Comparison of proportion with at least 20/40 best corrected visual acuity (BCVA) after cataract surgery 12 months in survivors vs controls. Best corrected visual acuity was measured using the Tumbling-E Early Treatment Diabetic Retinopathy Study (ETDRS) protocol vision chart. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. | 12 months (1 year) after cataract surgery | 
| Comparison of Intraretinal Fluid Cysts Between EVD Survivors and Controls From Baseline to 12 Months After Cataract Surgery | Optical coherence tomography (OCT) imaging of the retina and optic nerve was used to identify the presence of intraretinal fluid cysts in EVD survivors vs. controls from baseline to 12 months after surgery | Baseline to 12 months (1 year) after cataract surgery | 
| Comparison of Central Subfield Thickness (CST) Between EVD Survivors and Controls From Baseline to 12 Months After Cataract Surgery | Optical coherence tomography (OCT) imaging of the retina and optic nerve was used to measure macular central subfield thickness (CST) in µm in EVD survivors vs. controls from baseline to 12 months after cataract surgery | Baseline to 12 months (1 year) after cataract surgery | 
| Comparison of Central Subfield Thickness (CST) Between EVD Survivors and Controls, Excluding Cases of Intraretinal Fluid Cysts, From Baseline to 12 Months After Cataract Surgery | Optical coherence tomography (OCT) imaging of the retina and optic nerve was used to measure central subfield thickness (CST) in µm in EVD survivors vs. controls, excluding cases of intraretinal fluid cysts, from baseline to 12 months after cataract surgery | Baseline to 12 months (1 year) after cataract surgery | 
| Impact of Gender on Visual Acuity From Baseline to 12 Months After Surgery | Visual acuity (20/x) was measured using the Tumbling-E Early Treatment Diabetic Retinopathy Study (ETDRS) protocol vision chart. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. | Baseline to 12 months (1 year) after cataract surgery | 
| Impact of Gender on Improvement in the Number of Lines Read on an ETDRS Eye Chart From Baseline to 12 Months After Surgery | Visual acuity was measured using the Tumbling-E Early Treatment Diabetic Retinopathy Study (ETDRS) protocol vision chart. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. Number of lines improvement equals the number of lines read at 12 months post cataract surgery minus the number of lines read at baseline | Baseline to 12 months (1 year) after cataract surgery | 
| Impact of Age on Visual Acuity From Baseline to 12 Months After Surgery | Age was age at enrollment in years. Visual acuity (20/x) was measured using the Tumbling-E Early Treatment Diabetic Retinopathy Study (ETDRS) protocol vision chart. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. | Baseline to 12 months (1 year) after cataract surgery | 
| Impact of Age on Improvement in the Number of Lines Read on an ETDRS Eye Chart From Baseline to 12 Months After Surgery | Age was age at enrollment in years. Visual acuity was measured using the Tumbling-E Early Treatment Diabetic Retinopathy Study (ETDRS) protocol vision chart. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. Number of lines improvement equals the number of lines read at 12 months post cataract surgery minus the number of lines read at baseline | Baseline to 12 months (1 year) after cataract surgery | 
| Impact of Gender on Viral Persistence One Week Prior to Cataract Surgery | Participants undergo aqueous fluid (aqueous humor) sampling to assess for the presence of Ebola virus RNA via RT-PCR using the GeneXpert assay. | One week prior to cataract surgery | 
| Impact of Age on Viral Persistence One Week Prior to Cataract Surgery | Age was age at enrollment in years. Participants undergo aqueous fluid (aqueous humor) sampling to assess for the presence of Ebola virus RNA via RT-PCR using the GeneXpert assay. | One week prior to cataract surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OCT, Cataracts, Visual Acuity