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Background: Poor surgical outcomes remain a problem in trachoma-endemic countries working to reach elimination thresholds. Methods to improve outcomes could positively impact programmatic success. Methods: This parallel, three-armed clinical trial conducted in Ethiopia randomized individuals with previously unoperated trachomatous trichiasis (TT) to receive surgery utilizing one of three approaches: bilamellar tarsal rotation with a 3 mm incision height (BLTR-3), BLTR with 5 mm incision height (BLTR-5) and posterior lamellar tarsal rotation (PLTR). We followed participants for one year. The primary outcome was post-operative trichiasis (PTT). Secondary outcomes were eyelid contour abnormalities (ECA) and pyogenic granulomata. Findings: We randomized and operated on 4,914 individuals with previously unoperated TT (6,940 eyes). Primary analyses include 6,815 eyes with follow-up. Overall, 1,149 (16.9%) eyes developed PTT. The risk difference for PTT was minimal comparing BLTR-3 and PLTR (adjusted risk difference [aRD] 1.8% (98.3%CI: -0.5–4.2%)), but significantly higher for BLTR-5 surgeries compared to BLTR-3 (aRD: 6.7% (3.9–9.4%)) and PLTR (aRD: 8.6% (5.9–11.3%)). BLTR-5 had the lowest ECA (6.1% versus 9.6% BLTR-3, 11.2% PLTR) and granuloma rates (5.2% versus 6.5% BLTR-3 and 7.5% PLTR). One eyelid operated with PLTR experienced an eyelid margin division; four BLTR-3 and eight BLTR-5 eyelids experienced excessive bleeding. Interpretation: We do not recommend modifying the BLTR incision height of 3 mm. Overall, we did not find a significant difference in PTT between BLTR-3 and PLTR in terms of PTT or ECA. Trial registration: Registration number: NCT03100747; ClinicalTrials.gov Full study protocol available at (https://doi.org/10.15139/S3/QHZXWD) Author summary: Trachomatous trichiasis (TT) surgery is the primary way to manage in-turned eyelashes in trachoma-endemic settings. The goal of this study was to understand what procedure has the best outcomes. We compared three ways of doing TT surgery: bilamellar tarsal rotation (BLTR) surgery with the World Health Organization recommended 3 mm incision height, BLTR with the incision height increased to 5 mm and posterior lamellar tarsal rotation (PLTR). We hypothesized that increasing the BLTR incision height to 5 mm would reduce post-operative trichiasis (PTT) compared with the 3 mm height. On the contrary, this study demonstrates that increasing the incision height of BLTR surgeries does not improve PTT rates. It also suggests that BLTR and PLTR surgeries can have similar outcomes in some settings. Further research is needed to examine the impact of training order on surgery outcomes. The study also investigated whether surgeon performance on a particular procedure depends on the order they were trained. The current study does not suggest that converting BLTR to PLTR surgeons reduces PTT rates. However, given the small number of conversion surgeons in this study, further research is needed to evaluate whether retraining BLTR surgeons is warranted. [ABSTRACT FROM AUTHOR]

BackgroundVertebrate genomes undergo epigenetic reprogramming during development and disease. Emerging evidence suggests that DNA methylation plays a key role in cell fate determination in the retina. Despite extensive studies of the programmed cell death that occurs during retinal development and degeneration, little is known about how DNA methylation might regulate neuronal cell death in the retina.MethodsThe developing chicken retina and the rd1 and rhodopsin-GFP mouse models of retinal degeneration were used to investigate programmed cell death during retinal development and degeneration. Changes in DNA methylation were determined by immunohistochemistry using antibodies against 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC).ResultsPunctate patterns of hypermethylation paralleled patterns of caspase3-dependent apoptotic cell death previously reported to occur during development in the chicken retina. Degenerating rd1 mouse retinas, at time points corresponding to the peak of rod cell death, showed elevated signals for 5mC and 5hmC in photoreceptors throughout the retina, with the most intense staining observed in the peripheral retina. Hypermethylation of photoreceptors in rd1 mice was associated with TUNEL and PAR staining and appeared to be cCaspase3-independent. After peak rod degeneration, during the period of cone death, occasional hypermethylation was observed in the outer nuclear layer.ConclusionThe finding that cell-specific increases of 5mC and 5hmC immunostaining are associated with the death of retinal neurons during both development and degeneration suggests that changes in DNA methylation may play a role in modulating gene expression during the process of retinal degeneration. During retinal development, hypermethylation of retinal neurons associates with classical caspase-dependent apoptosis as well as caspase-3 independent cell death, while hypermethylation in the rd1 mouse photoreceptors is primarily associated with caspase-3 independent programmed cell death. These findings suggest a previously unrecognized role for epigenetic mechanisms in the onset and/or progression of programed cell death in the retina.

Background Postoperative trachomatous trichiasis (PTT) is a challenge for trichiasis surgery programs. Little is known about PTT patients' perceptions regarding outcomes and future disease management. This study aimed to understand the characteristics of PTT patients, how they managed trichiasis and their perceptions of prior surgeries and future surgery uptake. Methods Patients with PTT were identified during an existing trichiasis screening program in Hadiya Zone, Ethiopia. A vision assessment and evaluation of the eyelids were conducted to determine distance vision, presence and severity of trichiasis and eyelid contour abnormalities. A questionnaire was administered to obtain information regarding patients' perceptions of surgery and PTT management approaches. Descriptive statistics were used to characterize PTT and determine associations between PTT severity and patient perceptions. Results Among 404 participants, most were female (79.7%) and aged 40–60 y (62.6%). In total, 514 eyelids had PTT, and nearly half had severe PTT (46.9%). Although >50% of participants were currently epilating to manage their PTT, the majority (82.8%) indicated that they wanted repeat surgery. Most participants indicated that pain persisted despite epilation. The majority (75.1%) indicated satisfaction with their prior surgery and 59.6% indicated that they would recommend surgery to others. Conclusions This study, which included a large proportion of severe PTT cases, indicated that individuals were generally satisfied with prior surgery and would prefer to have surgery again for PTT management. [ABSTRACT FROM AUTHOR]