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Signs of Prior Trachoma Infection among

Trichiasis Surgery Patients without

Trachomatous Scarring

Camille D. Mittendorf

Senior Honors Thesis Health Policy and Management University of North Carolina at Chapel Hill

Spring 2020

Readers:

Emily Gower, PhD

First Reader and Primary Honors Thesis Advisor Department of Epidemiology

Gillings School of Global Public Health University of North Carolina at Chapel Hill

Karl Umble, PhD, MPH Second Reader and Advisor

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Abstract:

Objectives: We seek to determine if trichiasis surgery patients without visible conjunctival

scarring have other signs of prior trachoma. To do this, we will determine the proportion of eyes

in the study cohort with and without visible conjunctival scarring and will characterize and

compare the prevalence of other signs of trachoma that exist in these two groups.

Methods: This study analyzes data from participants’ baseline ocular examinations from the

MTSS trial. We characterize and compare the prevalence and severity of various eyelid

characteristics across a portion of the cohort. We will also cross-tabulate conjunctival scarring

with the five key other signs of trachoma for eyelids with and without conjunctival scarring.

Results: 5,002 people participated in the MTSS trial, and 2,444 eyes had TT in the late phase.

Among these, 51 eyes had no visible conjunctival scarring. Almost half the eyelids without

scarring had some indication of prior TT. The proportion of eyes with conjunctival scarring was

much higher for severe trichiasis than for eyes without conjunctival scarring. Eyes without

conjunctival scarring present with either no signs of Herbert’s Pits or pannus or the mildest

manifestation of both signs. Most eyes without conjunctival scarring do not present with corneal

scarring but approximately 20% of eyes have a corneal scar grade of at least 1. Both eyes with

conjunctival scarring and without conjunctival scarring reported similar proportions of eyes with

lower lid TT.

Discussion: The main finding of this study is that individuals without visible signs of

conjunctival scarring in the field have other signs of trachoma, indicating that their trichiasis is

trachomatous in nature. These eyes are thus eligible for TT surgery and should not be turned

away, and it is thus crucial to consider other signs of trachoma as markers for the disease. These

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Background:

Trachoma is considered a neglected tropical disease and is the “leading infectious cause

of blindness” [1]. As of 2013, 1.2 million people were permanently blinded as a result of the

disease [2]. Numerous risk factors contribute its etiology: areas with endemic trachoma have

populations with low personal and community hygiene typically characterized by poverty,

overcrowding, close contact with active cases, poor sanitation facilities, and inadequate water

availability [1]. Young children are more likely to get this infection because of their close

proximity to others and poor facial cleanliness. However, the advanced stages of trachoma

typically occur in adulthood after people sustain repeated bouts of infections [1].

Trachoma is transmitted through the bacterium, Chlamydia trachomatous, which causes

an infection of the eye [1]. The bacteria is spread through three primary modes of transmission:

direct contact with ocular or nasal discharge from infected persons, exposure to contaminated

inanimate objects (i.e. towels or shawls), and indirect transmission through flies that carry the

bacteria after landing on infected faces [3]. Trachoma distinguishes itself from other eye

infections by its two major phases. The first phase of the disease is the inflammatory stage

wherein active infection and inflammation characterize the eyelid [8]. The inflammatory

response can vary, but when it is severe, it eventually leads to tarsal scarring. Cicatricial

trachoma, which is the second phase of the disease, is demarcated by a structural change in the

eyelid resulting from scarring that causes entropion and trichiasis. During this late phase,

inflammation and infection are less common [8].

(4)

To assess the signs of the disease, the 1987 WHO simplified grading scheme for

trachoma identified five signs to establish grading and diagnostic standardization [8]. The

purpose behind this grading scheme was to measure the impact and disease progression of

trachoma by determining the presence of:

 Active trachoma, which is early onset, severe, and transmissible;

 Cicatricial trachoma, where the disease is well established;

 Corneal scarring, which provides a basis to estimate vision loss [8].

These five signs delineate these stages of the disease and include tarsal follicles, inflammatory

thickening, tarsal scarring, trichiasis, and corneal opacity. The first stage of the disease

progression and the grading scheme is trachomatous inflammation – follicular (TF), which is

characterized by the presence of five or more follicles in the upper tarsal conjunctiva [8].

Trachomatous inflammation – intense (TI) is the second stage of active trachoma and involves

inflammatory thickening of the tarsal conjunctiva that conceals more than half of the normal

deep tarsal vessels [8]. Trachomatous scarring (TS) is the third stage and is characterized by

scarring—visible white bands or lines—in the tarsal conjunctiva that exemplifies the late phase

of trachoma [8]. The fourth stage is trachomatous trichiasis (TT), which occurs when at least one

eyelash touches the eyeball as a result of the eyelid turning inwards [8]. TT is indicative of the

severe structural transformation that corresponds with the late phase of the disease. Lastly, the

simplified grading scheme assesses corneal opacity (CO) as a measure of visual impairment,

which is easily visible opacity that covers the pupil or where the pupil margin is blurred [8].

These four signs (TF, TI, TS, TT) are mutually exclusive and are graded as present or not present

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Signs and Structural Change in the Cicatricial Phase

This study focuses on signs that appear in the late phase of trachoma. Active infection

creates an inflammatory response in the conjunctiva [1]. As it is easy to transmit the bacteria,

individuals in trachoma-endemic areas can get multiple reinfections, although infection is less

likely to occur in adults. In the cicatricial phase, repeated infections can lead to tarsal

conjunctival scarring in the underside of the eyelid, where white bands of scarring appear [1].

Eventually, this scarring causes a distortion of the eyelid wherein the eyelid turns inwards,

causing the eyelashes to point down towards the eye. When the eyelashes touch the eye, this

condition is known as TT and produces intense pain, globe discomfort, and visual impairment or

blindness [1]. Individuals cope with TT in two ways. The first is through eyelash epilation,

which is the self-management technique of plucking eyelashes to provide pain relief [5].

Although epilation can provide temporary relief, the more effective solution to treat trichiasis is

TT surgery [14]. An individual with one eyelash angled in such a way that it touches the eye

should be considered for this surgery.

Other Signs of Trachoma and TT Severity

Aside from conjunctival scarring and trichiasis, other signs of trachoma appear in

individuals that are also indicative of the disease. In this study, we will examine five of these

signs: Herbert’s pits, pannus, corneal scarring, lower eyelid trachomatous trichiasis, and prior

surgery.

Herbert’s pits are “corneal manifestations of trachoma” [9]. These are grayish, marginal

pits or depressions in the upper part of the cornea that form along the cornea’s perimeter [9].

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by the “scleral, episcleral and corneal bundles which were destroyed due to the formation of the

trachomatous nodules” that did not grow back when the eye recovered from active trachoma

[12]. Herbert’s pits are unique signs of the disease.

Pannus is superficial corneal vascularization where the limbus and cornea become

vascularized due to the growth of blood vessels across the eye [10]. Researchers postulated that

pannus could form earlier in the trachomatous disease process than conjunctival scarring, stating

that the “late appearance of scars compared to pannus would indeed suggest that this mechanism

is entirely different from that of pannus formation or even the mechanism of Herbert’s pits” [11].

This presents the idea that these three signs are mutually exclusive from one another, and thus,

the manifestation of one does not necessarily affect the manifestation of another. In some

individuals, Herbert’s pits and pannus might be the only sign that they ever had trachoma in the

first place [9].

Corneal scarring is synonymous to corneal opacity and is a late sign of trachoma. It

typically occurs after the eyelashes have abraded the cornea and caused trauma to it. Corneal

scarring is measured by the extent to which the cornea is obscured by visible opacity. Lower

eyelid TT, a fourth sign of trachoma, occurs when the eyelashes of the lower lid mirror the

mechanism of upper lid TT and start to rotate inwards. Although this occurs more rarely, there

are only two types of lower lid TT, and one of them is trachomatous. Thus, this sign is a potential

marker that an eyelid with trichiasis does have TT. We also considered prior TT surgery as a sign

of trachoma because if an individual had surgery in the past, in at least one eye, this would

indicate that they had prior TT.

Although it is not viewed as a separate sign of trachoma, we believe it is important to

(7)

eye’s TT severity is an assessment not made in the field but by the study team. This variable is

determined by considering a combination of two factors: the number of eyelashes touching the

globe and the amount of epilation.

Global Strategy to Eradicate Trachoma

In 1996, the WHO Alliance for the Global Elimination of Trachoma by 2020 (GET 2020)

was formed to promote efforts to eliminate trachoma as a public health issue through the SAFE

strategy and global cooperation and collaboration [3]. The SAFE initiative is an effective

package approach to trachoma elimination where S stands for surgery for trachomatous

trichiasis; A is antibiotics to clear infection; F is facial cleanliness to prevent transmission; and E

is environmental improvement to address risk factors such as improving water and sanitation

conditions [3].

Currently, 2.5 million people need surgery to manage their TT [4] [6]. The “ultimate

intervention goal” or global target for eliminating trachoma includes bringing the prevalence of

TT in endemic areas to less than 0.2% in people aged 15 years and above or less than 1 case for

every 1000 individuals of any age in a district [3] [7]. Great strides were made by members of

the WHO alliance in the fifteen years following its inception [1], including great expansion in the

number of TT surgeries performed. The largest number of surgeries conducted occurred in 2016

[3]. Out of all TT surgeries that year, 71% were done in Ethiopia [3], which is the country with

the greatest burden of trachoma [1]. As of 2019, eight countries had successfully eliminated

trachoma as a public health problem, and five countries claimed meeting the prevalence targets

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Problem

In current discussions around managing TT and assessing the TT backlog, some experts

believe that people with trichiasis should not get surgery if they do not present with visible

conjunctival scarring as assessed by field graders or they should not be included in the TT

backlog count. However, we believe an individual can still have TT even if they do not have

visible scarring because they could present with other visible signs trachoma, such as those

mentioned of above. Some research indicates that some of these signs could develop differently

from conjunctival scarring [11]. We postulate that in trachoma-endemic communities, among

individuals with trichiasis but without visible tarsal conjunctival scarring, their trichiasis is likely

trachomatous in nature, and this can be demonstrated by assessing them for other signs of prior

trachomatous infections.

To evaluate this hypothesis, there is a need to determine how common other signs of

trachoma are in patients with trichiasis who present without visible conjunctival scarring.

Concluding this would invalidate the proposed argument, which currently poses a risk to those

who seek surgery for TT but do not have visible conjunctival scarring in the field. If these

individuals are excluded from surgery, it is possible that a significant proportion of people would

be unjustifiably excluded from the TT backlog count and would not benefit from a surgery that

can provide pain relief and minimize their risk for blindness. Additionally, this proposed

argument could, in the long term, hinder a country from truly eliminating trachoma as a public

health problem by minimizing the magnitude of its trachoma backlog and enabling it to

prematurely claim attainment of the WHO ultimate intervention goal [3] [7]. Ultimately, this

impact could lead to a backsliding of the global progress that has already been made to eradicate

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Research Aim

To address the proposed argument in the field, we seek to determine if trichiasis surgery

patients without visible conjunctival scarring have other signs of prior trachoma. We hope to

achieve this by determining the proportion of eyes in the study cohort with and without visible

conjunctival scarring. Secondly, we will characterize and compare the prevalence of other signs

of trachoma that exist in both groups.

Methods:

This cross-sectional study is an extension of the MTSS trial (Maximizing Trachomatous

Trichiasis Surgery Success trial), which is an ongoing randomized controlled trial in Ethiopia.

The MTSS trial is led by a consortium of researchers from the University of North Carolina at

Chapel Hill, Johns Hopkins School of Medicine, and Orbis International Ethiopia. The aim of

this larger study is to compare post-operative surgical outcomes across three TT surgeries.

Study population and Participant Recruitment

Recruitment for the MTSS trial spanned April 2017 to May 2019 during which 6,900

eyes were enrolled in the study. To recruit participants for the trial, the study was promoted in

two ways: community-based TT case finders and community announcements. After a brief

training on identifying TT cases, community-based case finders were asked to visit all the

households in their neighborhood to locate eligible individuals with TT. The identified

individuals were asked to assemble at a location in the community on the designated day of the

(10)

to make announcements in public places, such as assemblies and local markets, advertising the

details for community-based screening and the upcoming surgery day.

On surgery day (Day 0), a TT surgeon inspected all individuals presenting with suspected

TT. Individuals deemed eligible for TT surgery were transported to the surgical site, where

medical examiners inspected all cases for operable TT. All operable TT individuals met with a

study team member to confirm study eligibility, review the study requirements, and determine

the individual’s interest in participation. Eligibility criteria included having at least one eyelid

with trichiasis that did not have prior TT surgery, being at least eighteen years of age, and being

able to comply with the study requirements for the duration of the study. All eligible and willing

individuals met with a consent specialist to provide appropriate consent in the individual’s native

language. After consent and enrollment, each participant was randomly assigned to one of three

surgery protocols at the time of surgery and underwent a baseline ocular exam prior to surgery.

Data Collection and Data Sources

This study analyzes data from participants’ baseline ocular examinations. Although we

characterize the prevalence of various eyelid characteristics across the entire study cohort (n =

5,002 individuals), we specifically focus on baseline ocular examinations conducted from

August 2018 to April 2019 when the questionnaire included assessments for all of the signs of

trachoma under investigation. The exam was completed for both eyes on the same day as study

enrollment, prior to surgery, with the intended purpose of describing characteristics of both

eyelids, regardless if only one eye had surgery. Data were inputted into an electronic repository.

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WHO validated grading schemes for trachoma. These data are found in the Clinical MTSS Trial

Dataset.

Statistical Analysis

Data from the baseline ocular exams were aggregated into an excel file, and we

performed all quantitative data analyses in RStudio. We divided the dataset into two phases, an

early study phase and a late study, where the cutoff date was August 15, 2018. Prior to this date,

the baseline ocular exam did not contain all questions relating to the variables under

investigation. In order to examine our hypothesis, we had to limit our analysis to the subset of

data where all variables for the signs of trachoma under investigation were collected.

After this initial step, we assessed the person-level characteristics (Table 1) and eye-level

characteristics (Table 2) to determine whether our subset was similar to the entire study cohort.

We provide the counts and proportions for both tables. Person-level characteristics concerned the

demographics of the study cohort, and eye-level characteristics examined specific trichiatic

and/or trachomatous characteristics that could differ between one eye and the other.

Additionally, for the eye-level characteristics, we divided each phase into two groups: eyes with

conjunctival scarring and eyes without conjunctival scarring. The purpose of this was to assess

differences in the prevalence of eyelid characteristics between both groups. This analysis also

enabled us to analyze any differences in the severity of eyelid characteristics between those with

and without conjunctival scarring.

Examining specific variables that were collected in the late phase of the study, the final

step of our analysis was to cross tabulate conjunctival scarring with the five key other signs of

(12)

signs that each eye presented with and then determining the total number of eyes that had zero or

more signs. Our goal was to understand how the prevalence of these unique signs of trachoma

differed between eyes with and without conjunctival scarring. We further cross tabulated

conjunctival scarring with trichiasis severity to explore their association.

Results:

Baseline Person-Level Characteristics

A total of 10,004 eyes (n = 5002 individuals) were included. Table 1 presents the

person-level characteristics across the early and late phase of the study, showing that approximately

three quarters of the study cohort was female for both phases, and most of the participants fell in

the 40-59 age group.

Table 1: Person-Level Characteristics for the MTSS Study Cohort*

Total Study Population

Early Surgery Period

Late Surgery Period

Number of participants 5002 3227 1775

Age n % n % n %

18-39 937 18.7 499 15.5 438 24.7

40-59 2350 47.0 1531 47.4 819 46.1

60+ 1715 34.3 1197 37.1 518 29.2

Gender

Male 1221 24.4 823 25.5 398 22.4

Female 3781 75.6 2404 74.5 1377 77.6

*All eyes from study cohort are included because these eligible participants have TT in at least one or both eyes.

Baseline Prevalence for Eye-Level Characteristics Across the Early and Late Study Phases

Data for the early and late phase of the study are presented to determine whether there

was a difference in eyelid characteristics between both groups (Table 2 in appendix). The cohort

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of eyes that were determined to have TT at baseline received surgery to correct for trachomatous

trichiasis.

Of the eyes with TT, a majority of them (n=4387, 58.7% of the combined total; n=2993,

63.7% of the early phase; n=1394, 50.2% of the late phase) had 1-4 lashes that were touching the

globe on the surgery visit day. A larger proportion of eyes had ten or more lashes touching the

globe in the late study period compared to the early study period (19.3% vs. 9.1%). All eyes

without TT did not have any lashes touching the globe.

In both the early and late study phases, the majority of people did not epilate (n=5345,

71.5% of the combined total; n=3527, 75.1% of the early phase; n=1818, 65.5% of the late

phase). A greater proportion of eyes in the late study period than the early study period (10.2%

vs. 4.2%) had eyes where 1/3 of the lashes or less were epilated.

Amongst eyes with TT, more eyes in the early phase of the study had mild trichiasis than

in the late phase (53.3% of eyes in the early phase vs. 36.9% of eyes in the late phase), where

most eyes had severe trichiasis (44.4% of eyes in the late phase vs. 29.1% of eyes in the early

phase). It is unclear why people in the early phase of the study present with milder forms of

trichiasis. One of the reasons could be that this group had milder conjunctival scarring, but we

cannot ascertain this because conjunctival scar data was not collected at the point of the study.

Conjunctivalization of the eyelid margin, which characterizes the extent to which the

eyelid margin has rotated inwards, tends to correlate with TT severity. In both phases of the

study, a large majority of eyes had the most severe grade for conjunctivalization (n=6838, 92.7%

of the combined total; n=4560, 98.2% of the early phase; n=2278, 83.4% of the late phase)

(14)

eyes without TT, a large proportion of eyes presented with the highest severity grade for

conjunctivalization, suggesting that they might be at an early stage of late trachoma.

Among eyes with TT, a relatively equal proportion of eyes had never had prior surgery

across both phases (n=7331, 99.0% of the combined total; n=4600, 99.2% of eyes form the early

phase; n=2731, 98.6% of eyes from the late phase). For the few eyes that did have prior surgery

(n=74, 1.0% of the combined total; n=35, 0.8% of eyes from the early phase; n=39, 1.4% of eyes

from the late phase), their other eye did not have prior surgery, which is why they were included

in the study. For eyes without TT, none had prior surgery (n=42, 100% of the combined total),

which means that they never had TT, even in the past.

In the early phase of the study for both the group with and without TT, there are no data

on conjunctival scarring because this data was not yet collected prior to the cutoff date (August

15, 2018). Looking at the data from the late phase, 61% of eyes with TT had severe conjunctival

scarring of the upper eyelid, and only 2% of eyes with TT had no easily visible conjunctival

scarring. This suggests that in this trachoma-endemic area, a minority of eyes present with

trichiasis without having any visible signs of scarring. The was also seen in eyes without TT

although a smaller proportion of eyes (34.8%) had severe conjunctival scarring of the upper

eyelid and the smallest proportion of eyes (12.7%) had no conjunctival scarring. This highlights

the possibility that even in eyes without TT, they might still have trachoma that has not yet

evolved to a point where trichiasis occurs.

Among eyes with TT, there is a discrepancy between the early and late phase of the study

in that 82% of eyes did not have any corneal scarring in the early phase, whereas only 22% of

eyes had no corneal scarring in the late phase of the study. In contrast, the largest proportion of

(15)

although there could be an association between TT severity and corneal scarring where the more

severe the trichiasis, the more likely corneal scarring will be present and/or severe. This would

posit that TT severity was lower in the early study group than the late study group. A similar

finding is observed in the group without TT. For those with reported data, most eyes had no

corneal scarring in the early phase whereas a larger proportion of eyes had a corneal scar grade

of 1 in the late phase. Alternatively, perhaps trauma from another disease mechanism caused the

corneal scarring. It is important to note that for the vast majority of eyes without TT, data was

not collected on their degree of corneal scarring perhaps because this was not collected after their

TT determination was made. Additionally, data on corneal scarring was a variable for which data

was collected after the start of the study. Thus, some eyes simply do not have any reported data.

For eyes with TT, impaired vision was very common (n=2945, 39.8% of the combined

total), followed by those with normal vision (n=2744, 37.1% of the combined total), then eyes

that were deemed blind (n=1704, 23.0% of the combined total). Among eyes without TT, most

eyes had normal visual acuity across both phases (n=1065, 44.1% of the combined total),

followed by impaired vision (n=879, 36.4% of the combined total), then blind eyes (n=470,

19.5% of the combined total). Since trichiasis leads to worsened visual acuity and a considerable

number of eyes without TT have impaired vision, a plausible explanation is that these eyes are at

an earlier stage of trachoma, had prior TT surgery, or other trauma or risk factors impacted their

vision.

Only 176 eyes (2.4%) had lower lid TT among eyes with TT, and 38 eyes (1.6%) had

lower lid TT among eyes without TT. Thus, it is possible for eyes to only present with lower lid

TT and not upper lid TT or to present with both upper and lower lid TT. Findings were

(16)

Data for the presence of Herbert’s pits was collected starting August 15, 2018, so only

eyes in the latter half of the study have reported data. For those with TT, 51% of eyes do not

have any sign of Herbert’s pits and 34% of eyes have 1 to 3 typical Herbert’s pits. Fewer eyes

have more extreme manifestations of Herbert’s pits. In the group of eyes without TT, signs of

Herbert’s pits are also observed, with 21% of eyes showing 1 to 3 typical Herbert’s pits.

However, Herbert’s pits were less common in eyes without TT.

Focusing on eyes with TT, 68% of eyes did not have pannus and 20% of eyes had

between 0 and 2 mm vessel extension. The proportion of those with pannus decreased as pannus

severity increased. Similarly, in eyes without TT, roughly 87% had no pannus, and 10% had

pannus extension between 0 and 2 mm.

Conjunctival Scarring and the Severity for Five Signs of Trachoma

Further examining the presence of other signs of trachoma in eyes with TT, we compared

the group with conjunctival scarring to the group without conjunctival scarring (Table 3 in

appendix). The “total number of signs” variable summarizes the number of eyes that present with

zero or more of the signs of trachoma under investigation after August 15, 2018. Separating eyes

into those with conjunctival scarring and those without, we can see the total number of signs that

eyes had at baseline although this measure does not reflect the severity of their presentations.

Across the group that presented with conjunctival scarring, 43% had one of the signs of trachoma

under investigation, and 30% of eyes had two signs. Only 9% of eyes had no other signs of

trachoma. Of those without conjunctival scarring, 59% of eyes presented with at least one other

sign of trachoma. This signifies that over half of these eyes have some indication of prior

(17)

nature and thus requires TT surgery. This affirms that other signs of trachoma could be present

even if the main marker, conjunctival scarring, is not. For both groups, the proportion of eyes

decreased as the number of total signs increased. In addition, neither group had eyes that

displayed all five signs of trachoma under investigation.

0 1 2 3 4 5

0% 20% 40% 60% 80% 100%

Total Number of Signs of Trachoma

No Conjunctival Scarring Yes Conjunctival Scarring

Total Number of Signs of Trachoma

P e rc e n ta g e o f St u d y C o h or t

Figure 1: Total Number of Signs of Trachoma between Eyes with Conjunctival Scarring and Eyes without Conjunctival Scarring

The proportion of eyes with conjunctival scarring decreases as the severity of Herbert’s

pits increases. On the other hand, eyes without conjunctival scarring present with either no signs

of Herbert’s pits (57%) or 1 to 3 typical characteristics of the sign (43%), which is the mildest

manifestation of the sign. No eyes without visible conjunctival scarring have a higher severity

grade for Herbert’s pits, suggesting that only milder forms of the sign will present in these eyes.

Despite only presenting in a milder form, eyes without conjunctival scarring that have visible

Herbert’s pits have evidence that their trichiasis is trachomatous in nature and consequently

(18)

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Entir e up

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ncirc led 0% 40% 80%

Herbert’s pits

No Conjunctival Scarring Yes Conjunctival Scarring

Herbert’s pits Grade

P e rc e n ta ge o f S tu d y C o h o rt

Figure 2: The Severity of Herbert’s Pits between Eyes with Conjunctival Scarring and Eyes without Conjunctival Scarring

Similarly, the proportion of eyes with conjunctival scarring decreases as the severity of

pannus increases. A larger proportion of eyes (72%) have no evidence of pannus, and only 19%

of eyes have pannus between 0 and 2 mm in size. Among eyes without conjunctival scarring,

86% do not present with any signs of pannus, and 12% show pannus between 0 and 2 mm. These

findings purport that pannus is rare in both groups but that a majority of eyes with pannus have a

milder form of it for both groups. Pannus also seems to occur in some eyes regardless of the

presence of conjunctival scarring, emphasizing that the trichiasis in some eyes without

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0 mm extension >0 - <2.0 mm

extension 2.0- <4.0 mm extension 4.0 - <6.0 mm extension 6.0 mm or more extension 0%

20% 40% 60% 80% 100%

Pannus Extension

No Conjunctival Scarring Yes Conjunctival Scarring

Pannus Grade

P

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rc

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ta

g

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St

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C

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Figure 3: The Severity of Pannus between Eyes with Conjunctival Scarring and Eyes without Conjunctival Scarring

In terms of corneal scarring, most eyes with conjunctival scarring (60%) have a corneal

scar grade of 1, and the frequency of eyes drops considerably as the corneal scar grade increases.

However, 6% of eyes have a corneal scar grade of 4. For eyes without conjunctival scarring,

most eyes do not present with significant corneal scarring although approximately 25% of eyes

have a corneal scar grade of at least 1. Additionally, it is possible that those with less severe

corneal scarring have less severe trichiasis and less severe conjunctival scarring because the

(20)

0 1 2a 2b 2c 2d 3 4 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Corneal Scarring

No Conjunctival Scarring Yes Conjunctival Scarring

Corneal Scarring Grade

P e rc e n ta g e o f St u d y C o h o rt

Figure 4: The Severity of Corneal Scarring between Eyes with Conjunctival Scarring and Eyes without Conjunctival Scarring

Both eyes with conjunctival scarring and without conjunctival scarring reported similar

proportions of eyes with lower lid TT (Table 3; 4% in the group without conjunctival scarring vs.

3% in the group with conjunctival scarring). These strikingly similar findings between both

groups could suggest that lower lid TT has the same prevalence in eyes with and without

conjunctival scarring, signifying that lower lid TT—albeit rare—could be used as an indicator of

trichiasis that is trachomatous in nature, as it is part of the inflammatory trachoma disease

process.

Almost no one in both groups had prior surgery (Table 3; 0% of eyes without

conjunctival scarring vs. 1% of eyes with conjunctival scarring). As a result, prior surgery is

likely not an effective measure to use when considering the diagnosis of TT in eyes that did not

present with conjunctival scarring as so few individuals had prior surgery. These findings do

report that eyes with conjunctival scarring that did have prior surgery (n=27), and therefore had

(21)

suggest that the eyes in the group without conjunctival scarring had TT in the past that received

treatment. With such a small sample of eyes without conjunctival scarring, it cannot be inferred

whether prior surgery should be used as a marker to assess if their trichiasis is trachomatous. It is

important to mention that if these eyes did have prior surgery, this is evidence that they had TT

in the past that received treatment. Correspondingly, their trichiasis is likely trachomatous in

nature because it is possible for trichiasis to return even having had surgery because the

trachoma disease process is still impacting the eye [14].

Lastly, we also looked at differences in trichiasis severity in eyes with and without

conjunctival scarring. Almost two times the proportion of eyes without conjunctival scarring

presented with milder forms of trichiasis compared to the proportion of eyes with conjunctival

scarring. In contrast, the proportion of eyes with conjunctival scarring with severe trichiasis was

almost twice the proportion of eyes without conjunctival scarring. This proposes that eyes

without visible conjunctival scarring are at earlier stages of the disease where scarring is not yet

visible and the disease progression has not yet shown the same magnitude the structural

transformation that leads to more serious trichiasis.

None Mild Moderate Severe

0% 20% 40% 60% 80% 100%

Trichiasis Severity

No Conjunctival Scarring Yes Conjunctival Scarring

Trichiasis Severity Grade

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Figure 5: Trichiasis Severity between Eyes with Conjunctival Scarring and Eyes without Conjunctival Scarring

Discussion:

Public Health and Policy Implications

The main implication of this study is that individuals without visible signs of conjunctival

scarring in the field have other signs of trachoma that suggest that their trichiasis is trachomatous

in nature, as evidenced by Herbert’s pits, pannus, corneal scarring, and lower lid TT in eyes

without visible scarring. This stresses that it is possible to have trichiasis that is trachomatous

without presenting with visible conjunctival scarring. It is thus imperative to consider other signs

of trachoma as markers for the disease in determining whether trichiasis is trachomatous.

Presenting with any number of these other signs in addition to trichiasis suggests that an

individual has TT, are eligible for TT surgery, and should not be turned away.

Refusing surgery to patients who present with these other signs of trachoma and no

visible conjunctival scarring compromises efforts to eliminate trachoma as a public health

problem. These individuals escape the scrutiny of meeting global intervention targets, such as

those stipulated under the SAFE strategy, and risk a country underreporting the number of TT

cases it seeks to treat. As a result, it jeopardizes the global efforts that have been made in

eliminating trachoma and a country’s programmatic decision-making in adequately addressing

the prevalence of TT in its borders.

Rather than turning people away from surgery for not presenting with conjunctival

scarring and reducing the magnitude of the problem, it is important to advocate for the continued

expansion of TT surgery. Governments in countries with trachoma should maintain or expand

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enhancing screening procedures to screen for other signs of trachoma and ensure that those who

do not have scarring do not get excluded from surgery. In this way, surgery campaigns will be

more effective at catching all those with clinical TT who would have otherwise gone untreated

for trichiasis if their TT was only determined by the extent of their conjunctival scarring.

Ultimately, the goal behind this recommendation is to better strive for the WHO ultimate

intervention goal and continue the progress that has been made in eliminating trachoma.

Relationship Between Trichiasis Severity and Conjunctival Scarring

The nature of the relationship between trichiasis severity and conjunctival scarring is

predicated on the phase of the trachoma disease process. Per the findings, eyes without visible

conjunctival scarring presented with milder trichiasis. On the other hand, while some eyes with

visible conjunctival scarring presented more severe trichiasis, others were still mild. This

suggests that eyes without scarring may be at an early stage of the cicatricial phase of trachoma

because the scarring has only started the structural inward rotation of the eyelid. In contrast, eyes

with visible conjunctival scarring are further along in the cicatricial phase. Visibly worse

conjunctival scarring indicates greater structural change, which may be indicative of TT that has

progressed more. Consequently, these eyes with conjunctival scarring will more often have

severe trichiasis.

Context Constraints with Field Workers

A supporting argument for looking at other signs of trachoma when determining the

nature of the trichiasis is that field workers have an inherently harder time identifying the minor

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not detect conjunctival scarring in the field even though it would be observed by specialized

experts in a clinical setting. Minor signs of conjunctival scarring might be too difficult or

obscured to observe in the field given the context and resource constraints that field workers

face. With many patients to address, field workers are limited by the time they can spend

assessing the signs of trachoma, increasing the risk of missing small or hidden indications of

scarring. Field workers are further limited by the tools at their disposal. Unlike expert clinicians

who can observe magnified images of the eye, field workers are less able to detect these signs

without the use of specialized equipment. Lastly, field workers do not receive the same training

that expert ophthalmologists have and thus may not have an acute skillset to perceive the

nuanced signs of conjunctival scarring. This reinforces the need to also consider the other signs

of trachoma in the field—not only conjunctival scarring—to confirm the trachomatous nature of

the trichiasis.

Limitations

The primary limitation of this study is that not all variables were collected from the start

of the MTSS trial. This forced us to exclude many individuals from the dataset and only consider

data after August 15, 2018, which was the first date where all variables for the other signs of

trachoma were collected and reported. For example, data on the conjunctival scar variable was

not collected until August 15, 2018. A ramification of this is that it restricted our sample size and

resulted in a low number of individuals that presented with eyes without conjunctival scarring in

the late phase of the study. This low sample size may impact the ability of the findings to be

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Future Research

This study is significant because it supports the argument that other signs should be

evaluated alongside conjunctival scarring when determining whether trichiasis is trachomatous in

nature. Any eye with trichiasis that presents with any number of these signs of trachoma likely

has clinical TT. These signs—such as Herbert’s pits, pannus, and lower lid TT—should thus be

considered as markers for the disease, as they are part of the disease manifestation.

Although our findings show that eyes without conjunctival scarring presenting with these

other signs of trachoma have clinical TT, a fraction of eyes without conjunctival scarring (Table

3) presented with no other signs of trachoma. Additionally, for each of the other signs of

trachoma under investigation, a large proportion of eyes without conjunctival scarring still did

not present with the sign. In both of these cases, it would be paramount to research the signs of

trachoma that appear in the opposite eye, as it could provide evidence for the presence and state

of the disease process in an individual. It is possible that signs might not present themselves in

one eye but could be visible in the other. Exploring eyelid characteristics in the opposite eye

provides an opportunity to better grasp the various markers of trachoma and the nature of

trachoma.

Acknowledgements:

Completing this project would not have been possible without the assistance and support of the

following people:

Emily Gower, PhD, who provided me with incredible mentorship and guidance as I developed

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trachoma research, and after I switched thesis topics, she was most willing to help me develop a

new research question and project.

Alison Singer, PhD, who provided me with invaluable support and assistance on framing the

data analysis for this project.

Karl Umble, PhD, MPH, who went above and beyond with being the best thesis program

coordinator and second reader. I am forever grateful for Dr. Umble and for his investment in the

success of my thesis experience and in my future.

References:

[1] “WHO Alliance for the Global Elimination of Blinding Trachoma by the Year 2020 Progress Report on Elimination of Trachoma, 2013.” Weekly Epidemiological Record, vol. 89, no. 39, Sept. 2014, pp. 421–28, https://www.who.int/wer/2013/wer8939.pdf.

[2] Pascolini, Donatella, and Silvio Paolo Mariotti. “Global Estimates of Visual Impairment: 2010.” British Journal of Ophthalmology, vol. 96, no. 5, May 2012, pp. 614–18, https://bjo-bmj-com.libproxy.lib.unc.edu/content/96/5/614.

[3] “WHO Alliance for the Global Elimination of Trachoma by 2020: Progress Report on Elimination of Trachoma, 2014–2016.” Weekly Epidemiological Record, vol. 92, no. 26, June 2017, pp. 359–368,

https://apps.who.int/iris/bitstream/handle/10665/255778/WER9226.pdf;jsessionid=61FA749D51 5EC0DE711083961D9B5E63?sequence=1.

[4] “WHO Alliance for the Global Elimination of Trachoma by 2020: Progress Report on Elimination of Trachoma, 2018.” Weekly Epidemiological Record, vol. 94, no. 29, July 2019, pp. 317–328, https://apps.who.int/iris/bitstream/handle/10665/325910/WER9429-en-fr.pdf? ua=1.

[5] International Coalition for Trachoma Control. Global Scientific Meeting on Trachomatous Trichiasis: Meeting Discussions, Conclusions & Suggested Research. International Coalition for Trachoma Control, 2012,

http://www.kcco.net/wp-content/uploads/2017/08/ictc_tt_surgery_report_2012_english.pdf. [6] “Key Trachoma Facts and Statistics.” International Coalition for Trachoma Control, International Coalition for Trachoma Control, 2019,

http://www.trachomacoalition.org/trachomastatistics.

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[9] “Herbert's Peripheral Pits.” The British journal of ophthalmology vol. 15,7 (1931): 411-2. doi:10.1136/bjo.15.7.411

[10] ZSCHEILE, F.PAUL. “Herbert’s pits.” Arch Ophthalmol, vol. 73, no. 6, 1965, pp. 827–828, doi:https://doi.org/10.1001/archopht.1965.00970030829014.

[11] Dawson, C. R., et al. “Limbal Disease in Trachoma and Other Ocular Chlamydial Infections: Risk Factors for Corneal Vascularisation.” Eye, vol. 3, Mar. 1989, pp. 204–09, doi:doi:10.1038/eye.1989.29.

[12] Busacca, Archimede. “On the Structure of Herbert’s pits.” The British Journal of Opthalmology, vol. 19, no. 1, Jan. 1935, pp. 26–31,

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC511760/pdf/brjopthal00801-0045.pdf.

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Table 2: Eye-Level Characteristics for Study Cohort*

Early Surgery Period Late Surgery Period Total Study Population Eyes that

have TT Eyes that donot have TT Eyes thathave TT Eyes that donot have TT Eyes thathave TT Eyes that donot have TT

Number 4678 1699 2747 721 7425 2420

Number of eyes

that had surgery n (%) n (%) n (%) n (%) n (%) n (%)

No 293 (6.3) 1699 (100.0) 178 (6.5) 721 (100.0) 471 (6.3) 2420 (100.0) Yes 4385 (93.7) 0 (0.0) 2569 (93.5) 0 (0.0) 6954 (93.7) 0 (0.0) Total number of

lashes touching the globe

0 273 (5.8) 1709 (100.0) 267 (9.6) 734 (100.0) 540 (7.2) 2443 (100.0) 1,4 2993 (63.7) 0 (0.0) 1394 (50.2) 0 (0.0) 4387 (58.7) 0 (0.0) 5,9 1005 (21.4) 0 (0.0) 579 (20.9) 0 (0.0) 1584 (21.2) 0 (0.0) 10,inf 427 (9.1) 0 (0.0) 535 (19.3) 0 (0.0) 962 (12.9) 0 (0.0) Epilation

None 3527 (75.1) 1709 (100.0) 1818 (65.5) 734 (100.0) 5345 (71.5) 2443 (100.0) <1/3 196 (4.2) 0 (0.0) 282 (10.2) 0 (0.0) 478 (6.4) 0 (0.0) 1/3-2/3 165 (3.5) 0 (0.0) 137 (4.9) 0 (0.0) 302 (4.0) 0 (0.0) >2/3 809 (17.2) 0 (0.0) 538 (19.4) 0 (0.0) 1347 (18.0) 0 (0.0) Trichiasis severity

None 0 (0.0) 1709 (100.0) 0 (0.0) 734 (100.0) 0 (0.0) 2443 (100.0) Mild 2504 (53.3) 0 (0.0) 1024 (36.9) 0 (0.0) 3528 (47.2) 0 (0.0) Moderate 827 (17.6) 0 (0.0) 520 (18.7) 0 (0.0) 1347 (18.0) 0 (0.0) Severe 1368 (29.1) 0 (0.0) 1231 (44.4) 0 (0.0) 2599 (34.8) 0 (0.0) Conjunctivalization

(CM) grade

0 1 (0.0) 0 (0.0) 0 (0.0) 6 (0.8) 1 (0.0) 6 (0.8)

1 16 (0.3) 1 (5.6) 62 (2.3) 65 (8.9) 78 (1.1) 66 (8.8)

2 68 (1.5) 3 (16.7) 390 (14.3) 138 (18.8) 458 (6.2) 141 (18.8) 3 4560 (98.2) 14 (77.8) 2278 (83.4) 524 (71.5) 6838 (92.7) 538 (71.6) Prior Surgery

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Conjunctival Scar Grade

No scarring -- -- 51 (2.1) 83 (12.7) 51 (2.1) 83 (12.7)

Mild -- -- 279 (11.4) 161 (24.7) 279 (11.4) 161 (24.7)

Moderate -- -- 618 (25.3) 182 (27.9) 618 (25.3) 182 (27.9)

Severe -- -- 1496 (61.2) 227 (34.8) 1496 (61.2) 227 (34.8)

Corneal Scar (CO) Grade

0 3825 (82.4) 15 (71.4) 617 (22.4) 293 (40.7) 4442 (60.0) 308 (41.6) 1 575 (12.4) 6 (28.6) 1618 (58.7) 386 (53.6) 2193 (29.6) 392 (52.9) 2a 86 (1.9) 0 (0.0) 201 (7.3) 17 (2.4) 287 (3.9) 17 (2.3)

2b 50 (1.1) 0 (0.0) 52 (1.9) 5 (0.7) 102 (1.4) 5 (0.7)

2c 59 (1.3) 0 (0.0) 190 (6.9) 4 (0.6) 249 (3.4) 4 (0.5)

2d 23 (0.5) 0 (0.0) 51 (1.8) 10 (1.4) 74 (1.0) 10 (1.3)

3 21 (0.5) 0 (0.0) 27 (1.0) 3 (0.4) 48 (0.6) 3 (0.4)

4 5 (0.1) 0 (0.0) 2 (0.1) 2 (0.3) 7 (0.1) 2 (0.3)

Distance Visual Acuity

Normal 1723 (37.2) 711 (42.2) 1021 (36.9) 354 (48.5) 2744 (37.1) 1065 (44.1) Impaired 1826 (39.5) 612 (36.3) 1119 (40.5) 267 (36.6) 2945 (39.8) 879 (36.4)

Blind 1078 (23.3) 361 (21.4) 626 (22.6) 109 (14.9) 1704 (23.0) 470 (19.5) Lower Eyelid TT

no 4588 (98.0) 1691 (98.9) 2687 (97.0) 713 (97.1) 7275 (97.6) 2404 (98.4) yes 93 (2.0) 18 (1.1) 83 (3.0) 21 (2.9) 176 (2.4) 39 (1.6) Herbert’s pits

None -- -- 1414 (51.2) 555 (76.4) 1414 (51.2) 555 (76.4)

1-3 typical -- -- 947 (34.3) 153 (21.1) 947 (34.3) 153 (21.1)

>3, upper lunular

not involved -- -- 373 (13.5) 17 (2.3) 373 (13.5) 17 (2.3)

Entire upper

lunular involved -- -- 18 (0.7) 0 (0.0) 18 (0.7) 0 (0.0)

Cornea encircled -- -- 9 (0.3) 1 (0.1) 9 (0.3) 1 (0.1)

Pannus

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extension 2.0- <4.0 mm extension

-- -- 185 (6.7) 7 (1.0) 185 (6.7) 7 (1.0)

4.0 - <6.0 mm extension

-- -- 81 (2.9) 5 (0.7) 81 (2.9) 5 (0.7)

6.0 mm or more extension

--

--56 (2.0) 1 (0.1) 56 (2.0) 1 (0.1)

*All eyes from the cohort are included and are divided in eyes that had TT and eyes that did not have TT across the early and late phase of the study.

Table 3 - Trachomatous Scarring and Graded Severity of Five Other Signs of Trachoma*

No Conjunctival Scarring Yes Conjunctival Scarring

Number 51 2393

Total Number of Other Signs n (%) n (%)

0 21 (41) 226 (9)

1 19 (37) 1045 (44)

2 8 (16) 734 (31)

3 3 (6) 369 (15)

4 0 (0) 19 (1)

5 0 (0) 0 (0)

Trichiasis Severity

None 0 (0) 0 (0)

Mild 35 (69) 916 (38)

Moderate 5 (10) 478 (20)

Severe 11 (22) 999 (42)

Herbert’s pits

None 29 (57) 1305 (55)

1-3 typical 22 (43) 789 (33)

>3, upper lunular not involved 0 (0) 279 (12)

Entire upper lunular involved 0 (0) 12 (1)

Cornea encircled 0 (0) 0 (0)

Pannus

0 mm extension 44 (86) 1719 (72)

>0 - <2.0 mm extension 6 (12) 458 (19)

2.0- <4.0 mm extension 0 (0) 130 (5)

4.0 - <6.0 mm extension 1 (2) 59 (2)

6.0 mm or more extension 0 (0) 27 (1)

Corneal Scar (CO) Grade

0 38 (75) 553 (23)

1 11 (22) 1434 (60)

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2c 1 (2) 153 (6)

2d 1 (2) 37 (2)

3 0 (0) 18 (1)

4 0 (0) 1 (0)

Lower Lid Trachomatous Trichiasis

no 49 (96) 2317 (97)

yes 2 (4) 72 (3)

Prior TT Surgery

no 51 (100) 2363 (99)

yes 0 (0) 27 (1)

Figure

Updating...

Related subjects :