PREVAIL VII: Cataract Surgery in Ebola Survivors

NCT03309020 | Completed Results

• 2 other identifiers: 99991716717-EI-N167
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cataract

Keywords

OCT; Cataracts; Visual Acuity

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• Comparison of Proportion of Eyes With at Least 20/40 Best Corrected Visual Acuity (BCVA) 12 Months After Cataract Surgery

  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

  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

  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

  Baseline to 12 months (1 year) after cataract surgery

• Impact of Gender on Visual Acuity From Baseline to 12 Months After Surgery

  Baseline to 12 months (1 year) after cataract surgery

Study Arms (2)

Control

ACTIVE COMPARATOR

Control with clinical need for cataract surgery

Procedure: Cataract surgery

EVD Survivors

EXPERIMENTAL

EVD survivors with need for cataract surgery

Procedure: Cataract surgery

Interventions

Cataract surgery PROCEDURE

Cataract surgery and aqueous humor sampling.

Control; EVD Survivors

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

PREVAIL JFK Hospital

Monrovia, Liberia

Location

Related Publications (1)

• Eghrari AO, Shantha JG, Ross RD, Ryn CV, Crozier I, Hayek B, Gradin D, Roberts B, Prakalapakorn SG, Amegashie F, Nishant K, Singh G, Dolo R, Fankhauser J, Burkholder B, Pettitt J, Gross R, Brady T, Dighero-Kemp B, Reilly C, Hensley L, Higgs E, Yeh S, Bishop RJ. Efficacy and Safety Outcomes of Cataract Surgery in Survivors of Ebola Virus Disease: 12-Month Results From the PREVAIL VII Study. Transl Vis Sci Technol. 2021 Jan 25;10(1):32. doi: 10.1167/tvst.10.1.32. eCollection 2021 Jan.

  PMID: 33520427 RESULT

MeSH Terms

Conditions

Cataract

Interventions

Cataract Extraction

Condition Hierarchy (Ancestors)

Lens Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Refractive Surgical Procedures; Ophthalmologic Surgical Procedures; Surgical Procedures, Operative

Results Point of Contact

• Title: Teresa Magone, MD, Principal Investigator, NEI
• Organization: National Institutes of Health

teresa.magonedequadroscosta@nih.gov

301-435-4562

Study Officials

• Teresa M Magone de Quadros Costa, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2017
• First Posted: October 13, 2017
• Study Start: September 21, 2017
• Primary Completion: January 4, 2018
• Study Completion: August 1, 2019
• Last Updated: June 29, 2021
• Results First Posted: June 29, 2021

Record last verified: 2020-08-18

Locations

LI (1)