Trachoma
Conditions
Keywords
Trachoma, trichiasis, bilamellar tarsal rotation procedure
Brief summary
Trachoma, an ocular infection caused by C. trachomatis, is the second leading infectious cause of blindness worldwide. Years of repeated infection with C. trachomatis cause the eyelid to scar and contract and ultimately to rotate inward such that the eyelashes rub against the eyeball and abrade the cornea (trichiasis). The World Health Organization (WHO) has endorsed a multi-faceted strategy to combat trachoma which includes surgery to repair lids distorted by trachoma (trichiasis) in imminent danger of vision loss. Current evidence suggests that long-term success rates of trichiasis surgery are less than optimal due to variation in surgical technique. Previous research by this study team has demonstrated that shorter incisions have a higher rate of trichiasis recurrence. In addition, observations by this team's oculoplastic surgeon have led to the hypothesis that granuloma formation and lid contour abnormalities may result from current surgical practices. The objective of this study is to compare outcomes of trichiasis surgeries performed with the newly developed trachomatous trichiasis (TT) clamp versus surgeries following standard technique (bilamellar tarsal rotation procedure or BLTR).
Detailed description
Field observations in 2005 by this study's PI and oculoplastic surgeon revealed some significant departures from current trichiasis surgery procedure (bilamellar tarsal rotation procedure or BTRP), as described in the WHO manual, Trichiasis Surgery for Trachoma-the Bilamellar Tarsal Rotation Procedure. These procedural departures were felt to contribute to adverse outcomes, including trichiasis recurrence, granuloma formation and lid contour abnormalities. This study team developed a new surgical tool, the TT clamp, to help improve surgical outcomes following BLTR. A randomized, single-masked clinical trial will be implemented in the Mtwara region in Tanzania. Study participants will be randomized on a 1:1 basis to surgery with the TT clamp or to surgery with standard BLTR equipment. All surgeries will take place at surgical centers in Mtwara and Lindi over an 8-month period. Baseline assessment for severity of trichiasis and other predictors of surgical failure will be carried out prior to surgery. Follow-up is planned at 2 weeks (for suture removal), 6 weeks, 12 months, and 24 months post-surgery. At each follow-up visit participants will be assessed for evidence of unfavorable outcomes, including trichiasis recurrence, granuloma formation, and lid contour abnormalities. All outcomes will be assessed clinically by a trained observer who is masked to intervention status.
Interventions
DEVICETT Clamp
trichiasis surgery performed with TT clamp
PROCEDUREStandard BLTR Technique
bilamellar tarsal rotation procedure in trichiasis surgery
Sponsors
Bill and Melinda Gates Foundation
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Presence of upper lid trichiasis: defined by at least one eyelash touching the globe of the eye or evidence of epilation * No previous report of trichiasis surgery in at least one eye with trichiasis: * eyes with prior surgery are already at high risk due to the prior surgery, and their inclusion may decrease our ability to clearly evaluate our primary outcome * if unilateral surgery has been performed previously, only the eye without prior history of surgery will be in the study, even if both eyes require surgery * Age 18 or older (in order to provide consent as an adult): the vast majority of trichiasis patients are aged 18 or older * At time of enrollment, subjects must state their intention to remain in the area for two years to facilitate study follow-up
Exclusion criteria
* Absence of upper lid trichiasis * Prior trichiasis surgery on both eyes * Age 18 or younger * Subjects who are transiently in the area
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Eyelids With Presence of Recurrent Trichiasis | 2 years | Trichiasis: 1 or more eyelashes touching globe in primary position |
| Number of Eyelids With Pyogenic Granuloma | 2 years | A pyogenic granuloma was defined as a sessile growth of 2 mm or more in diameter on the tarsal conjunctiva. |
| Number of Eyelids Experiencing an Unfavorable Outcome | 2 years | At least 1 unfavorable outcome, including mild, moderate, or severe trichiasis; granuloma; or mild, moderate, or severe eyelid contour abnormality |
| Number of Eyelids With Normal or Mild Eyelid Contour Abnormalities vs Moderate or Severe Eyelid Contour Abnormalities | 2 years | Eyelid contour abnormalities (ECA) were graded by photographs of the eyes. In the primary outcome measure, normal eyes and mild eyelid contour abnormalities are considered together, and moderate or severe eyelid contour abnormalities are considered together. ECA severity is defined as follows: Mild: Vertical deviation from the natural contour \< 1 mm in height (less than half the pupil height in daylight) and affecting \< 1/3 of horizontal eyelid length; Moderate: Vertical deviation from the natural contour 1-2 mm in height (about the pupil height in daylight) or affecting 1/3-2/3 of horizontal eyelid length; Severe: Vertical deviation from the natural contour \> 2 mm in height (more than the pupil height in daylight) or a defect \> 2/3 of the horizontal eyelid length |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Eyelids With Mild, Moderate, Severe, or no Eyelid Contour Abnormality | 2 years | Eyelid contour abnormalities (ECA) were graded by photographs of the eyes. ECA severity is defined as follows: Mild: Vertical deviation from the natural contour \< 1 mm in height (less than half the pupil height in daylight) and affecting \< 1/3 of horizontal eyelid length; Moderate: Vertical deviation from the natural contour 1-2 mm in height (about the pupil height in daylight) or affecting 1/3-2/3 of horizontal eyelid length; Severe: Vertical deviation from the natural contour \> 2 mm in height (more than the pupil height in daylight) or a defect \> 2/3 of the horizontal eyelid length |
| Number of Eyelids With Normal, Mild, Moderate, or Severe Trachomatous Trichiasis | 2 Years | Trichiasis is generally defined as 1 or more eyelashes touching globe in primary position. Classifications of trichiasis severity are as follows: Mild: 1-4 Eyelashes touching globe, no epilation OR 1-10 Eyelashes epilated, no eyelashes touching globe; Moderate: 5-9 Eyelashes touching globe, no epilation OR 1-4 Eyelashes touching globe and 1-10 eyelashes epilated; Severe: 5-9 Eyelashes touching globe and 1-10 eyelashes epilated OR 10 Eyelashes touching globe, regardless of epilation status OR 11-20 Eyelashes epilated, regardless of eyelashes touching globe OR Entire eyelid epilated, regardless of eyelashes touching globe |
Countries
United States
Participant flow
Recruitment details
Community-level eye screenings were conducted to identify all trichiasis cases in the community. Patients were scheduled for surgery. On the day of surgery they were invited to join the study if they were eligible.
Pre-assignment details
963 individuals assigned to Trachomatous Trichiasis (TT) clamp, 6 did not participate. 3 refused surgery, 2 ineligible because of lower eyelid trichiasis only, 1 participant did not present for surgery. 964 individuals assigned to Standard, 4 did not participate. 2 refused surgery, 2 ineligible because of lower eyelid trichiasis only.
Participants by arm
| Arm | Count |
|---|---|
| Standard Instrumentation Eyelids operated with standard BLTR instrumentation | 960 |
| TT Clamp Eyelids operated with the TT clamp instead of standard BLTR instrumentation. The TT clamp replaces the 2 hemostats and lid plate | 957 |
| Total | 1,917 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 2 |
Baseline characteristics
| Characteristic | Standard Instrumentation | TT Clamp | Total |
|---|---|---|---|
| Age, Continuous | 55.6 years STANDARD_DEVIATION 13.1 | 54.9 years STANDARD_DEVIATION 13.5 | 55.2 years STANDARD_DEVIATION 13.3 |
| Region of Enrollment Tanzania | 960 participants | 957 participants | 1917 participants |
| Sex/Gender, Customized Female | 722 participants | 705 participants | 1427 participants |
| Sex/Gender, Customized Male | 238 participants | 252 participants | 490 participants |
| Trichiasis mild | 347 eyelids | 303 eyelids | 650 eyelids |
| Trichiasis moderate | 453 eyelids | 423 eyelids | 876 eyelids |
| Trichiasis severe | 874 eyelids | 945 eyelids | 1819 eyelids |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 960 | 12 / 957 |
| serious Total, serious adverse events | 0 / 960 | 0 / 957 |
Outcome results
Primary
Number of Eyelids Experiencing an Unfavorable Outcome
At least 1 unfavorable outcome, including mild, moderate, or severe trichiasis; granuloma; or mild, moderate, or severe eyelid contour abnormality
Time frame: 2 years
Population: Of the original 1771 eyelids assigned to TT clamp, 1 participant (2 eyelids) was excluded from TT Clamp analysis because participant died before follow-up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TT Clamp | Number of Eyelids Experiencing an Unfavorable Outcome | Any unfavorable outcome | 1017 eyelids |
| TT Clamp | Number of Eyelids Experiencing an Unfavorable Outcome | Normal | 652 eyelids |
| Standard BLTR Technique | Number of Eyelids Experiencing an Unfavorable Outcome | Any unfavorable outcome | 1055 eyelids |
| Standard BLTR Technique | Number of Eyelids Experiencing an Unfavorable Outcome | Normal | 619 eyelids |
95% CI: [0.66, 1.18]
Primary
Number of Eyelids With Normal or Mild Eyelid Contour Abnormalities vs Moderate or Severe Eyelid Contour Abnormalities
Eyelid contour abnormalities (ECA) were graded by photographs of the eyes. In the primary outcome measure, normal eyes and mild eyelid contour abnormalities are considered together, and moderate or severe eyelid contour abnormalities are considered together. ECA severity is defined as follows: Mild: Vertical deviation from the natural contour \< 1 mm in height (less than half the pupil height in daylight) and affecting \< 1/3 of horizontal eyelid length; Moderate: Vertical deviation from the natural contour 1-2 mm in height (about the pupil height in daylight) or affecting 1/3-2/3 of horizontal eyelid length; Severe: Vertical deviation from the natural contour \> 2 mm in height (more than the pupil height in daylight) or a defect \> 2/3 of the horizontal eyelid length
Time frame: 2 years
Population: Of the original 1771 eyelids assigned to TT clamp, 1 participant (2 eyelids) was excluded from TT Clamp analysis because participant died before follow-up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TT Clamp | Number of Eyelids With Normal or Mild Eyelid Contour Abnormalities vs Moderate or Severe Eyelid Contour Abnormalities | No/Mild ECA | 1549 eyelids |
| TT Clamp | Number of Eyelids With Normal or Mild Eyelid Contour Abnormalities vs Moderate or Severe Eyelid Contour Abnormalities | Moderate/Severe ECA | 120 eyelids |
| Standard BLTR Technique | Number of Eyelids With Normal or Mild Eyelid Contour Abnormalities vs Moderate or Severe Eyelid Contour Abnormalities | Moderate/Severe ECA | 174 eyelids |
| Standard BLTR Technique | Number of Eyelids With Normal or Mild Eyelid Contour Abnormalities vs Moderate or Severe Eyelid Contour Abnormalities | No/Mild ECA | 1500 eyelids |
95% CI: [0.44, 0.98]
Primary
Number of Eyelids With Presence of Recurrent Trichiasis
Trichiasis: 1 or more eyelashes touching globe in primary position
Time frame: 2 years
Population: Of the 1671 eyes initially assigned to TT Clamp, 1 participant (2 eyelids) was excluded from TT Clamp analysis because participant died before follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TT Clamp | Number of Eyelids With Presence of Recurrent Trichiasis | Normal | 948 eyelids |
| TT Clamp | Number of Eyelids With Presence of Recurrent Trichiasis | TT Recurrence | 721 eyelids |
| Standard BLTR Technique | Number of Eyelids With Presence of Recurrent Trichiasis | Normal | 1062 eyelids |
| Standard BLTR Technique | Number of Eyelids With Presence of Recurrent Trichiasis | TT Recurrence | 612 eyelids |
95% CI: [0.96, 1.93]
Primary
Number of Eyelids With Pyogenic Granuloma
A pyogenic granuloma was defined as a sessile growth of 2 mm or more in diameter on the tarsal conjunctiva.
Time frame: 2 years
Population: Of the original 1771 eyelids assigned to TT clamp, 1 participant (2 eyelids) was excluded from TT Clamp analysis because participant died before follow-up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TT Clamp | Number of Eyelids With Pyogenic Granuloma | Normal | 1388 eyelids |
| TT Clamp | Number of Eyelids With Pyogenic Granuloma | Granuloma | 281 eyelids |
| Standard BLTR Technique | Number of Eyelids With Pyogenic Granuloma | Granuloma | 375 eyelids |
| Standard BLTR Technique | Number of Eyelids With Pyogenic Granuloma | Normal | 1299 eyelids |
95% CI: [0.46, 0.98]
Secondary
Number of Eyelids With Mild, Moderate, Severe, or no Eyelid Contour Abnormality
Eyelid contour abnormalities (ECA) were graded by photographs of the eyes. ECA severity is defined as follows: Mild: Vertical deviation from the natural contour \< 1 mm in height (less than half the pupil height in daylight) and affecting \< 1/3 of horizontal eyelid length; Moderate: Vertical deviation from the natural contour 1-2 mm in height (about the pupil height in daylight) or affecting 1/3-2/3 of horizontal eyelid length; Severe: Vertical deviation from the natural contour \> 2 mm in height (more than the pupil height in daylight) or a defect \> 2/3 of the horizontal eyelid length
Time frame: 2 years
Population: Of the 1771 participants originally assigned to TT Clamp, 1 participant (2 eyelids) was excluded from TT Clamp analysis because participant died before follow-up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TT Clamp | Number of Eyelids With Mild, Moderate, Severe, or no Eyelid Contour Abnormality | Normal | 1397 eyelids |
| TT Clamp | Number of Eyelids With Mild, Moderate, Severe, or no Eyelid Contour Abnormality | Mild ECA | 152 eyelids |
| TT Clamp | Number of Eyelids With Mild, Moderate, Severe, or no Eyelid Contour Abnormality | Moderate ECA | 89 eyelids |
| TT Clamp | Number of Eyelids With Mild, Moderate, Severe, or no Eyelid Contour Abnormality | Severe ECA | 31 eyelids |
| Standard BLTR Technique | Number of Eyelids With Mild, Moderate, Severe, or no Eyelid Contour Abnormality | Severe ECA | 43 eyelids |
| Standard BLTR Technique | Number of Eyelids With Mild, Moderate, Severe, or no Eyelid Contour Abnormality | Normal | 1278 eyelids |
| Standard BLTR Technique | Number of Eyelids With Mild, Moderate, Severe, or no Eyelid Contour Abnormality | Moderate ECA | 131 eyelids |
| Standard BLTR Technique | Number of Eyelids With Mild, Moderate, Severe, or no Eyelid Contour Abnormality | Mild ECA | 222 eyelids |
Comparison: Mild ECA compared with Normal95% CI: [0.42, 0.97]
Comparison: Moderate ECA compared with Normal95% CI: [0.39, 1.01]
Comparison: Severe ECA compared with Normal95% CI: [0.35, 1.1]
Secondary
Number of Eyelids With Normal, Mild, Moderate, or Severe Trachomatous Trichiasis
Trichiasis is generally defined as 1 or more eyelashes touching globe in primary position. Classifications of trichiasis severity are as follows: Mild: 1-4 Eyelashes touching globe, no epilation OR 1-10 Eyelashes epilated, no eyelashes touching globe; Moderate: 5-9 Eyelashes touching globe, no epilation OR 1-4 Eyelashes touching globe and 1-10 eyelashes epilated; Severe: 5-9 Eyelashes touching globe and 1-10 eyelashes epilated OR 10 Eyelashes touching globe, regardless of epilation status OR 11-20 Eyelashes epilated, regardless of eyelashes touching globe OR Entire eyelid epilated, regardless of eyelashes touching globe
Time frame: 2 Years
Population: Of the 1669 TT eyelids and 1674 BLTR eyelids included in the initial analysis, 13 eyes (4 in the TT clamp group, 9 in the BLTR group) without TT at 1 year underwent operation between years 1 and 2. They are not included in the data for severity of recurrence because we do not know the TT severity.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TT Clamp | Number of Eyelids With Normal, Mild, Moderate, or Severe Trachomatous Trichiasis | Normal | 948 eyelids |
| TT Clamp | Number of Eyelids With Normal, Mild, Moderate, or Severe Trachomatous Trichiasis | Moderate TT Recurrence | 121 eyelids |
| TT Clamp | Number of Eyelids With Normal, Mild, Moderate, or Severe Trachomatous Trichiasis | Severe TT Recurrence | 120 eyelids |
| TT Clamp | Number of Eyelids With Normal, Mild, Moderate, or Severe Trachomatous Trichiasis | Mild TT Recurrence | 476 eyelids |
| Standard BLTR Technique | Number of Eyelids With Normal, Mild, Moderate, or Severe Trachomatous Trichiasis | Severe TT Recurrence | 100 eyelids |
| Standard BLTR Technique | Number of Eyelids With Normal, Mild, Moderate, or Severe Trachomatous Trichiasis | Normal | 1062 eyelids |
| Standard BLTR Technique | Number of Eyelids With Normal, Mild, Moderate, or Severe Trachomatous Trichiasis | Mild TT Recurrence | 417 eyelids |
| Standard BLTR Technique | Number of Eyelids With Normal, Mild, Moderate, or Severe Trachomatous Trichiasis | Moderate TT Recurrence | 86 eyelids |
95% CI: [0.97, 1.53]