An interventional study of Cataract surgery in Cataract, sponsored by National Eye Institute (NEI). Completed at 1 site in Liberia. Open to participants aged 14 Years and older. Per ClinicalTrials.gov, last updated 2021-06-29.
Sponsored by National Eye Institute (NEI) · Not applicable, Interventional, and Treatment
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.
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.
To be eligible, the following inclusion criteria must be met, where applicable.
Participant must be either:
EXCLUSION CRITERIA:
A participant is not eligible if any of the following exclusion criteria are present.
Control with clinical need for cataract surgery
Procedure: Cataract surgery
EVD survivors with need for cataract surgery
Procedure: Cataract surgery
Cataract surgery and aqueous humor sampling.
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.
Time frame: 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
Time frame: 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
Time frame: 3 months after cataract surgery
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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: One week prior to cataract surgery
| Milestone | Control | EVD Survivors |
|---|---|---|
| Started | 12 | 25 |
| Underwent cataract surgery | 10 | 24 |
| Completed | 9 | 24 |
| Not completed | 3 | 1 |
| Withdrew: Death | 1 | 0 |
| Withdrew: Did not undergo surgery | 2 | 1 |
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.
| Participants | EVD Survivors |
|---|---|
| Proportion of EVD Survivors With Evidence of Persistence of Ebola Viral RNA in Ocular Tissue | 0 |
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
| AC cell grade | Control | EVD Survivors |
|---|---|---|
| Comparison of the Amount of Intraocular Inflammation Between EVD Survivors and Controls at 1 Month Following Cataract Surgery | .67 ± .49 | .64 ± .66 |
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
| AC cell grade | Control | EVD Survivors |
|---|---|---|
| Comparison of the Amount of Intraocular Inflammation Between EVD Survivors and Controls at 3 Months Following Cataract Surgery | .5 ± 1.17 | .82 ± 1.01 |
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.
| eyes | Control | EVD Survivors |
|---|---|---|
| Comparison of Proportion of Eyes With at Least 20/40 Best Corrected Visual Acuity (BCVA) 12 Months After Cataract Surgery | 5 | 18 |
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
| eyes | Control | EVD Survivors |
|---|---|---|
| Baseline | 0 | 0 |
| Month 1 | 0 | 0 |
| Month 3 | 1 | 3 |
| Month 6 | 0 | 1 |
| Month 9 | 1 | 2 |
| Month 12 | 2 | 2 |
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
| µm | Control | EVD Survivors |
|---|---|---|
| Baseline | 203 (182 to 204) | 209 (184 to 244.5) |
| Month 1 | 222 (217.5 to 260) | 224 (211 to 269.5) |
| Month 3 | 227 (196.8 to 260.2) | 216 (188 to 253) |
| Month 6 | 226.5 (209.5 to 234.8) | 234 (203 to 258) |
| Month 9 | 240 (227.8 to 258.2) | 238 (214 to 254.5) |
| Month 12 | 244 (221.5 to 264.5) | 231 (212.5 to 245.5) |
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
| µm | Control | EVD Survivors |
|---|---|---|
| Baseline | 203 (182 to 204) | 218 (190.2 to 244) |
| Month 1 | 222 (217.5 to 260) | 224 (211 to 269.5) |
| Month 3 | 223 (196.5 to 248) | 214 (183.5 to 224) |
| Month 6 | 220 (207 to 234) | 229 (202.8 to 251.2) |
| Month 9 | 240 (225.5 to 253) | 238 (211 to 254) |
| Month 12 | 242 (211 to 248) | 231 (216 to 244) |
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.
| visual acuity (20/x) | All Participants |
|---|---|
| Baseline | 800 (100 to 4000) |
| Month 1 | 40 (25 to 50) |
| Month 12 | 32 (25 to 50) |
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
| lines of improvement | All Participants |
|---|---|
| Impact of Gender on Improvement in the Number of Lines Read on an ETDRS Eye Chart From Baseline to 12 Months After Surgery | 8.06 (4.01 to 20.97) |
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.
| visual acuity (20/x) | All Participants |
|---|---|
| Baseline | 800 (100 to 4000) |
| Month 1 | 40 (25 to 50) |
| Month 12 | 32 (25 to 50) |
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
| lines of improvement | All Participants |
|---|---|
| Impact of Age on Improvement in the Number of Lines Read on an ETDRS Eye Chart From Baseline to 12 Months After Surgery | 8.06 (4.01 to 20.97) |
Participants undergo aqueous fluid (aqueous humor) sampling to assess for the presence of Ebola virus RNA via RT-PCR using the GeneXpert assay.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
Collected over Participants are monitored during all study visits, with the last visit being 12 (+/- 1.5) months from the day of surgery.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Control | 1/8 (12.5%) | 1/8 (12.5%) | 0/8 (0%) |
| EVD Survivors | 0/22 (0%) | 2/22 (9.1%) | 0/22 (0%) |
| Event | Control | EVD Survivors |
|---|---|---|
| Subluxed intraocular lensEye disorders | 1/8 | 1/22 |
| Retinal detachmentEye disorders | 1/8 | 0/22 |
| Surgery on the fellow eyeEye disorders | 0/8 | 1/22 |
| Age, Continuous(years) | Control | EVD Survivors | Total |
|---|---|---|---|
| Median | 56 (40 to 63.8) | 62 (40 to 68) | 59 (40 to 68) |
| Sex: Female, Male(Participants) | Control | EVD Survivors | Total |
|---|---|---|---|
| Female | 6 | 14 | 20 |
| Male | 6 | 11 | 17 |
| Race and Ethnicity Not Collected(Participants) | Control | EVD Survivors | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(participants) | Control | EVD Survivors | Total |
|---|---|---|---|
| Liberia | 12 | 25 | 37 |
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