Background
Trachoma is the leading infectious cause of blindness worldwide. It is caused by particular strains of the intracellular bacterium
Chlamydia trachomatis, believed to be transmitted through infected eye and nose secretions carried on fingers, fomites and eye-seeking flies [
1,
2]. Repeated infection leads to scarring of the tarsal conjunctiva, which can then lead to trichiasis (eyelashes touching the eyeball) [
3]. Left untreated, trachomatous trichiasis can result in the formation of corneal opacities, which irreversibly impair vision [
4].
Surgery is an integral part of the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, Environmental improvement) advocated by World Health Organization (WHO) for elimination of trachoma as a public health problem [
5]. Surgery for trichiasis aims to re-position the eyelid margin by externally rotating it so that eyelashes no longer touch the eyeball. Not all cases of trichiasis are due to trachoma and not all cases of trachomatous trichiasis involve entropion; other management approaches may be preferable when correction of entropion is not indicated. When appropriately performed, apart from preserving vision, surgery has also been shown to enhance patient comfort due to decreases in pain and photophobia, and resolution of corneal swelling [
6]. Surgery substantially increases quality of life for individuals with trichiasis, even if vision itself does not improve [
7]. However, for surgery to be effective in preventing trachoma-related blindness and to encourage other trichiasis patients to consent to an operation, there must be good long-term surgical outcomes with a low incidence of post-operative trichiasis.
WHO’s third global scientific meeting on trachoma [
8], convened in 2010, recommended that national trachoma programmes should report the incidence of post-operative trichiasis, and target a cumulative post-operative trichiasis incidence of ≤10% at one-year post-surgery. However, several studies report incidence estimates that are considerably higher than this [
9]. There are only limited operational data on the incidence of post-operative trichiasis published from settings where trachoma elimination programmes are active [
9].
Generating an evidence-based understanding of the magnitude and determinants of post-operative trichiasis would help inform discussions on current outcome targets and strategies to improve surgery outcomes for trichiasis. This review aims to partially fill this gap by consolidating data on incidence of post-operative trichiasis and other poor outcomes of trichiasis surgery from observational and interventional studies conducted in Africa.
Methods
Ethical approval
The protocol was approved by the University of Cape Town Faculty of Health Sciences’ Human Research Ethics Committee (076/2018) and deemed by the WHO Ethics Review Committee to not require full formal ethics review (0003034). The protocol was registered on PROSPERO: CRD42018085253.
Search strategy
We undertook a systematic search of PubMed, Academic Search Premier, Africa-Wide Information, CINAHL and Health Source Nursing through EBSCOhost, Web of Science [all databases], and the Cochrane Central Register of Controlled Trials, including material published up to and including the month of May 2018. In addition, Google Scholar and the reference lists of relevant reviews and all eligible papers were searched to cross-check for studies not already identified. Websites of organizations identified in published studies were searched for pertinent grey literature. No language limitations were applied in these searches.
The full search strategy is provided as a supplemental file.
Study selection
Two reviewers (GM, PC) independently screened the titles and abstracts of the articles found to determine their potential eligibility for inclusion. The full texts of potentially eligible studies were obtained. Selection for inclusion into the review was conducted by the two reviewers working independently. Any disagreements regarding inclusion of studies were resolved by discussion or by consulting the third reviewer (AWS).
Included studies met the following criteria: 1) conducted within Africa; 2) measured post-operative trichiasis (defined as the presence of one or more eyelashes touching the eyeball or evidence of epilation of in-turned eyelashes after surgery) as an outcome; 3) included participants aged ≥15 years with previously unoperated trachomatous trichiasis in at least one eye within either [a] an interventional or [b] observational study.
Editorial articles, reviews, expert opinion pieces, conference papers and meeting abstracts were excluded, as were studies conducted outside Africa, studies that did not have a surgical intervention, and those that did not measure or report post-operative trichiasis as an outcome. Any studies published before 1990 were also excluded.
We divided studies into two groups - observational and interventional studies - with the expectation that surgeons operating in the latter were more likely to be highly selected and re-trained before the study than those in the former. It should be noted however, that some interventional studies included in this review did not report criteria-based selection or re-training of surgeons before the intervention.
Qualitative assessment of studies
The methodological quality of the papers included in this review was assessed using a slight adaptation of the Joanna Briggs Institute critical appraisal checklist for prevalence studies [
10]. Critical appraisal was conducted by two reviewers independently, with disagreements resolved through discussion or by consulting the third reviewer.
Assessment of heterogeneity
Studies included in this systematic review were checked for heterogeneity by examining their characteristics (study design, population, follow up period, etc.) and risk of bias. Statistical heterogeneity was assessed using I
2 and Chi [
2] tests. Heterogeneity was considered as significant if the I
2 was above 50%.
Data synthesis
The studies included in this review were varied in terms of design, interventions, follow up period and outcomes. As a result, there was high statistical heterogeneity which precluded pooling of data for the outcomes (I
2 > =95%). RevMan 5.3 software [
11] was used for all quantitative data analyses in this review.
For the intervention studies, treatment effects were measured by calculating odds ratios for the different interventions and 95% confidence interval for these. Dichotomous data from these studies are presented in forest plots without a summary estimate, and as a narrative summary. For observational studies, data are presented as a percentage of those who developed the outcome of interest out of the total number of study participants.
Discussion
Our systematic review suggests that there is a huge disparity between policy and practice with respect to the incidence of post-operative trichiasis in Africa. WHO recommends that national trachoma programmes strive to achieve ≤10% post-operative trichiasis by 1 year after surgery [
8], but in the eight studies we identified that had one-year data, only one had an incidence of post-operative trichiasis ≤ 10% [
19]. This suggests that there is a need to put in place or strengthen existing measures to improve the proportion of patients achieving satisfactory outcomes. A logical approach would be for national trachoma programmes to establish and implement policies and systems to follow up patients, assess surgical outcomes and maximize the performance of individual surgeons through post-surgical audits with provision of additional support, where needed.
BLTR and PLTR are currently the most commonly used procedures, with evidence presented elsewhere suggesting that they produce better outcomes than other techniques [
13,
23,
24]. Only one recent study [
25] has directly compared the two. Additional research is warranted to confirm the apparent superiority of PLTR [
49].
Our study has clear weaknesses for estimating the rate and determinants of success in trichiasis surgery programs; these should be acknowledged before further conclusions are drawn. We did not collect program-level data, but rather collated reported post-operative trichiasis incidence estimates from the literature, with referenced papers derived from the experience of academically supported settings over three decades. The contemporary incidence of bad outcomes when surgery was being routinely performed in unselected program delivery environments could easily have been higher (or lower) than noted, and there are too few data points and too many potential explanatory variables to try to infer possible changes in incidence over time.
Data on the phenotype of post-operative trichiasis were generally not published; the potential implications for vision of having one or two peripheral trichiatic eyelashes are likely to be considerably less than those of large numbers of central trichiatic eyelashes. It is also important to note that most studies included in this review were conducted before publication of the International Coalition for Trachoma Control’s training and supervision guidelines [
50,
51], and before mannequin-based surgical simulation training [
52] became available. These measures are likely (though formally unproven) to improve the outcomes of trichiasis surgery.
How else could success rates be optimized? A large randomized controlled trial in Ethiopia suggested that a single dose of peri-operative azithromycin was associated with a 33% reduction in post-operative trichiasis by 3 years after surgery, compared with topical tetracycline prescribed for 6 weeks [
19‐
21]. These data differ from a smaller clinical trial comparing peri-operative oral azithromycin with two post-surgical weeks of topical tetracycline conducted in The Gambia [
15], where no significant difference in outcomes was observed. One important difference between those two trials was the absence of trial-specific training and standardization of surgeons in the Gambian study, which might have resulted in a higher incidence of post-operative trichiasis; significant variability between surgeons was noted, with incidence of post-operative trichiasis ranging by surgeon from 0 to 83%. The Ethiopian study [
19] used surgeons who had been trained and certified by the study team prior to the start of the trial. One interpretation of this combination of findings would be that, though azithromycin might have a protective effect against post-operative trichiasis, it cannot overcome shortfalls in training, standardization and supervision of surgeons. Other differences between the two environments might also, or alternatively, be responsible. The mechanism for azithromycin having an impact, if it does, is not necessarily clear: it could potentially relate to either the anti-inflammatory or anti-infective action of the macrolide.
In another randomized controlled trial conducted in Ethiopia [
17], there was no evidence that use of absorbable sutures was associated with a lower incidence of post-operative trichiasis at 1 year after surgery compared to the use of silk (although absorbable sutures were found to reduce the incidence of granulomata) [
16,
17]. Despite careful standardisation, there was significant variability in outcomes between different surgeons in this trial. To protect patients, operator-dependent factors, including dexterity, handedness, visual acuity, rigor of training and certification, supervision and motivation, must always be considered possible contributors to the occurrence of post-operative trichiasis. The tendency noted in the current review for post-operative trichiasis incidence to be lower in interventional than in observational studies was most marked for interventional studies where surgeons were re-trained prior to initiation of the study, reinforcing the (perhaps expected) point that greater skill levels drive better results.
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