Search

Background/AimGlaucoma accounts for 8% of global blindness and surgery remains an important treatment. We aimed to determine the impact of adding simulation-based surgical education for glaucoma.MethodsWe designed a randomised controlled, parallel-group trial. Those assessing outcomes were masked to group assignment. Fifty-one trainee ophthalmologists from six university training institutions in sub-Saharan Africa were enrolled by inclusion criteria of having performed no surgical trabeculectomies and were randomised. Those randomised to the control group received no placebo intervention, but received the training intervention after the initial 12-month follow-up period. The intervention was an intense simulation-based surgical training course over 1 week. The primary outcome measure was overall simulation surgical competency at 3 months.ResultsTwenty-five were assigned to the intervention group and 26 to the control group, with 2 dropouts from the intervention group. Forty-nine were included in the final intention-to-treat analysis. Surgical competence at baseline was comparable between the arms. This increased to 30.4 (76.1%) and 9.8 (24.4%) for the intervention and the control group, respectively, 3 months after the training intervention for the intervention group, a difference of 20.6 points (95% CI 18.3 to 22.9, pConclusionThese results support the pursuit of financial, advocacy and research investments to establish simulation surgery training units and courses including instruction, feedback, deliberate practice and reflection with outcome measurement to enable trainee glaucoma surgeons to engage in intense simulation training for glaucoma surgery.Trial registration numberPACTR201803002159198.

Funder: Queen Elizabeth Diamond Jubilee Trust [grant code: ITCRZC6813], Background/objectives: Late presentation of congenital cataract in the developing world has led to poor outcomes such that cataract is the leading cause of childhood blindness. Our hypothesis was that, sensitivity of red-reflex testing is greater than sensitivity of torchlight examination. We aimed to compare sensitivity of new red reflex screening tools and assess the feasibility of Arclight red reflex screening in the community. Subject/methods: We compared the diagnostic accuracy of four different screening tools for cataract and retinoblastoma performed by ophthalmic nurses, using a clinic based enriched sample of 41 positives and 60 negatives. We then conducted a separate feasibility study, training non-specialist community nurses. Following the training, community nurses examined 2827 children

Summary Background Non-facility-based antiretroviral therapy (ART) delivery for people with stable HIV might increase sustainable ART coverage in low-income and middle-income countries. Within the HPTN 071 (PopART) trial, two interventions, home-based delivery (HBD) and adherence clubs (AC), which included groups of 15–30 participants who met at a communal venue, were compared with standard of care (SoC). In this trial we looked at the effectiveness and feasibility of these alternative models of care. Specifically, this trial aimed to assess whether these models of care had similar virological suppression to that of SoC 12 months after enrolment. Methods This was a three-arm, cluster-randomised, non-inferiority trial, done in two urban communities in Lusaka, Zambia included in the HPTN 071 trial. The two communities were split into zones, which were randomly assigned (1:1:1) to the three treatment strategies: 35 zones to the SoC group, 35 zones to the HBD group, and 34 zones to the AC group. ART and adherence support were delivered once every 3 months at home for the HBD group, in groups of 15–30 people in the AC group, or in the clinic for the SoC group. Adults with HIV who were receiving first-line ART for at least 6 months, virally suppressed using national HIV guidelines in the last 12 months, had no other health conditions requiring the clinicians attention, live in the study catchment area, and provided written informed consent, were eligible for inclusion. The primary endpoint was viral suppression at 12 months (with a 6 month final measurement window [ie, 9–15 months]), defined as less than 1000 HIV RNA copies per mL, with a non-inferiority margin of 5%. Findings Between May 5 and Dec 19, 2017, 9900 individuals were screened for inclusion, of whom 2489 (25·1%) participants were enrolled into the trial: 781 (31%) in the SoC group, 852 (34%) in the HBD group, and 856 (34%) in the AC group. A higher proportion of participants had viral load measurements in the primary outcome window in the HBD (581 [61%]of 852 participants) and AC (485 [57%] of 856 participants) groups than in the SoC (390 [50%] of 781 patients) group (p=0·0021). Of the 1096 missing observations, 152 (13·8%) were attributable to either deaths (25 [16%] participants), relocations (37 [24%] participants), or lost to follow-up (90 [59%]); 690 (63·0%) participants had viral load results outside the window period; and 254 (23·2%) did not have a viral load result. The prevalence of viral suppression was estimated to be 98·3% (95% CI 96·6 to 99·7) in the SoC group, 98·7% (97·5 to 99·6) in the HBD group, and 99·2% (98·4 to 99·8) in the AC group. This gave an estimated risk difference of 0·3% (95% CI −1·5 to 2·4) for the HBD group compared with the SoC group and 0·9% (−0·8 to 2·8) for the AC group compared with the SoC group. There was strong evidence (p

Summary: Background: Glaucoma is a major cause of sight loss worldwide, with the highest regional prevalence and incidence reported in Africa. The most common low-cost treatment used to control glaucoma is long-term timolol eye drops. However, low adherence is a major challenge. We aimed to investigate whether selective laser trabeculoplasty (SLT) was superior to timolol eye drops for controlling intraocular pressure (IOP) in patients with open-angle glaucoma. Methods: We did a two-arm, parallel-group, single-masked randomised controlled trial at the Eye Department of Kilimanjaro Christian Medical Centre, Moshi, Tanzania. Eligible participants (aged ≥18 years) had open-angle glaucoma and an IOP above 21 mm Hg, and did not have asthma or a history of glaucoma surgery or laser. Participants were randomly assigned (1:1) to receive 0·5% timolol eye drops to administer twice daily or to receive SLT. The primary outcome was the proportion of eyes from both groups with treatment success, defined as an IOP below or equal to target pressure according to glaucoma severity, at 12 months following randomisation. Re-explanation of eye drop application or a repeat SLT was permitted once. The primary analysis was by modified intention-to-treat, excluding participants lost to follow-up, using logistic regression; generalised estimating equations were used to adjust for the correlation between eyes. This trial was registered with the Pan African Clinical Trials Registry, number PACTR201508001235339. Findings: 840 patients were screened for eligibility, of whom 201 (24%) participants (382 eligible eyes) were enrolled between Aug 31, 2015, and May 12, 2017. 100 (50%) participants (191 eyes) were randomly assigned to the timolol group and 101 (50%; 191 eyes) to the SLT group. After 1 year, 339 (89%) of 382 eyes were analysed. Treatment was successful in 55 (31%) of 176 eyes in the timolol group (16 [29%] of 55 eyes required repeat administration counselling) and in 99 (61%) of 163 eyes in the SLT group (33 [33%] of 99 eyes required repeat SLT; odds ratio 3·37 [95% CI 1·96–5·80]; p

PURPOSE: Epidemiological data is essential for planning; however, all-age population-based surveys are resource intensive. Rapid Assessment of Cataract Surgical Services methodology was developed in India in 1995 and subsequently promoted by the World Health Organisation for use worldwide. The commonly used Rapid Assessment of Avoidable Blindness (RAAB) evolved from this in 2005, constraining surveys to populations aged 50 or more based on the report 'The Epidemiology of Blindness in Nepal' (SEVA, 1988), where 78.7% of blindness occurred in people aged 50+. The purpose of this study is to examine whether more recent total-population-based surveys continue to find a similar proportion of blindness in the population aged 50+. METHODS: A systematic literature review identified all population-based surveys of blindness published 1996-2017. Data extraction was undertaken by two independent researchers and compared. RESULTS: The proportions of blindness (presenting visual acuity (PVA)

Background WHO endorsed the use of epilation as an alternative treatment to surgery for the management of both minor unoperated TT (UTT) and postoperative TT (PTT). However, some trachoma control programmes hesitated to implement epilation citing concerns that it would hamper TT surgical acceptance and result in larger numbers of and stiffer trichiatic eyelashes than the original TT lashes. We investigated the burden and phenotypes of post-epilation trichiatic eyelashes, and willingness to accept surgical management separately in unoperated and postoperative TT cases. Methodology/Principal findings We recruited cases with minor (≤5 eyelashes from the upper eyelid touching the eye or evidence of epilation in, Author summary Trachomatous Trichiasis (TT), the blinding stage of trachoma, ranges from few peripheral eyelashes touching the eye to all eyelashes scratching the cornea. TT is mainly treated with corrective eyelid surgery. However, not all TT cases require surgical correction, and some, particularly, those with few eyelashes decline surgery. Epilation, the repeated removal of eyelashes, is a very common clinical and traditional practice in many trachoma endemic settings. The World Health Organisation recommends that epilation can be offered as an alternative management strategy to surgery for patients with few eyelashes touching the eye or refusing surgery. However, some trachoma control programmes hesitated to implement epilation with the concern that it would hamper surgical acceptance and results in larger numbers of and stiffer eyelashes touching the eye than the original TT eyelashes. In this study, we explored if these concerns are true in epilating minor (≤5 eyelashes from the upper eyelid touching the eye or evidence of epilation in

IntroductionFungal infections of the cornea, fungal keratitis (FK), are challenging to treat. Current topical antifungals are not always effective and are often unavailable, particularly in low-income and middle-income countries where most cases occur. Topical natamycin 5% is usually first-line treatment, however, even when treated intensively, infections may progress to perforation of the eye in around a quarter of cases. Alternative antifungal medications are needed to treat this blinding disease.Chlorhexidine is an antiseptic agent with antibacterial and antifungal properties. Previous pilot studies suggest that topical chlorhexidine 0.2% compares favourably with topical natamycin. Full-scale randomised controlled trials (RCTs) of topical chlorhexidine 0.2% are warranted to answer this question definitively.Methods and analysisWe will test the hypothesis that topical chlorhexidine 0.2% is non-inferior to topical natamycin 5% in a two-arm, single-masked RCT. Participants are adults with FK presenting to a tertiary ophthalmic hospital in Nepal. Baseline assessment includes history, examination, photography, in vivo confocal microscopy and cornea scrapes for microbiology. Participants will be randomised to alternative topical antifungal treatments (topical chlorhexidine 0.2% and topical natamycin 5%; 1:1 ratio, 2–6 random block size). Patients are reviewed at day 2, day 7 (with reculture), day 14, day 21, month 2 and month 3. The primary outcome is the best spectacle corrected visual acuity (BSCVA) at 3 months. Primary analysis (intention to treat) will be by linear regression, with treatment arm and baseline BSCVA prespecified covariates. Secondary outcomes include epithelial healing time, scar/infiltrate size, ulcer depth, hypopyon size, perforation and/or therapeutic penetrating keratoplasty (corneal transplant), positive reculture rate (day 7) and quality of life (EuroQol-5 dimensions, WHO/PBD-VF20, WHOQOL-BREF).Ethics and disseminationThe Nepal Health Research Council, the Nepal Department of Drug Administration and the London School of Hygiene and Tropical Medicine ethics committee have approved the trial. The results will be presented at local and international meetings and submitted to peer-reviewed journals for publication.Trial registration numberISRCTN14332621; pre-results.

Background: Cataract is the commonest cause of childhood blindness in sub Saharan Africa (SSA). The significance of congenital rubella and human cytomegalovirus (HCMV) infection in the etiology is not known. Objectives: We aimed to investigate prevalence of both viruses in cases of congenital cataract and controls. Methods: Lens tissue was collected (from cases), blood and saliva from cases and controls. Using ELISA, we tested blood samples for rubella and cytomegalovirus IgM. Quantitative polymerase chain reaction (qPCR) was also used for detection of the viruses. Results: Cytomegalovirus was detected using qPCR in 72.9% saliva specimens of cases compared to 38.5% of controls (P = 0.0001). Cytomegalovirus IgM was also detected in 10.8% blood specimens of cases and only 1.5% control (P = 0.01). Rubella IgM was detected in 13.8% blood specimens of cases and only 3.1% controls (P = 0.01). In lens aspirates of cases, 12.7% were HCMV positive and 11.1% were rubella positive by qPCR. Cases had lower birth weights (mean = 2.8 kg) than controls (mean = 3.2 kg), independent of viral status (P = 0.004). Conclusions: Although most of the children in the study presented too late to be sure that infection was congenital, our study strongly suggests that HCMV and rubella infection appear important causes of congenital cataract in Tanzania hence virology testing of infantile cataract cases may be useful in assessing effectiveness of immunization programs as they are established throughout SSA.

Background The presence of Chlamydia trachomatis (Ct) DNA at non-ocular sites suggests that these sites may represent plausible routes of Ct transmission in trachoma. However, qPCR cannot discriminate between DNA from viable and non-viable bacteria. Here we use a propodium monoazide based viability PCR to investigate how long Ct remains viable at non-ocular sites under laboratory-controlled conditions. Methods Cultured Ct stocks (strain A2497) were diluted to final concentrations of 1000, 100, 10 and 1 omcB copies/μL and applied to plastic, woven mat, cotton cloth and pig skin. Swabs were then systemically collected from each surface and tested for the presence Ct DNA using qPCR. If Ct DNA was recovered, Ct viability was assessed over time by spiking multiple areas of the same surface type with the same final concentrations. Swabs were collected from each surface at 0, 2, 4, 6, 8 and 24 hours after spiking. Viability PCR was used to determine Ct viability at each timepoint. Results We were able to detect Ct DNA on all surfaces except the woven mat. Total Ct DNA remained detectable and stable over 24 hours for all concentrations applied to plastic, pig skin and cotton cloth. The amount of viable Ct decreased over time. For plastic and skin surfaces, only those where concentrations of 100 or 1000 omcB copies/μL were applied still had viable loads detectable after 24 hours. Cotton cloth showed a more rapid decrease and only those where concentrations of 1000 omcB copies/μL were applied still had viable DNA detectable after 24 hours. Conclusion Plastic, cotton cloth and skin may contribute to transmission of the Ct strains that cause trachoma, by acting as sites where reservoirs of bacteria are deposited and later collected and transferred mechanically into previously uninfected eyes., Author summary Trachoma elimination efforts are hampered by limited understanding of Ct transmission routes. We have recently demonstrated the presence of Ct DNA at non-ocular sites in individuals living in households in Ethiopia where at least one resident had an ocular Ct infection detectable by quantitative PCR (qPCR). Ct DNA was most frequently detected on faces, hands and clothing, being found in such locations in 10–16% of samples tested. However, qPCR cannot discriminate between DNA from viable and non-viable organisms, and potentially misinform our understanding of Ct transmission routes. In this study, we used a propidium monoazide based viability PCR to investigate how long Ct remains viable on non-ocular sites by spiking different surfaces including pig skin, plastic and cotton cloth. These surfaces mimic non-ocular sites previously found to be positive for Ct DNA using standard qPCR. The results of our study show that viable Ct DNA could be recovered from plastic, cotton cloth and skin surfaces for up to 24 hours suggesting that these surfaces a role in ocular Ct transmission.

Background In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set the 90-90-90 targets: that 90% of people living with HIV know their HIV status, that 90% of those who know their HIV-positive status are on antiretroviral therapy (ART), and that 90% of those on treatment are virally suppressed. The aim was to reach these targets by 2020. We assessed the feasibility of achieving the first two targets, and the corresponding 81% ART coverage target, as part of the HIV Prevention Trials Network (HPTN) 071 Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART) community-randomized trial. Methods and findings The study population was individuals aged ≥15 years living in 14 urban and peri-urban “PopART intervention” communities in Zambia and South Africa (SA), with a total population of approximately 600,000 and approximately 15% adult HIV prevalence. Community HIV care providers (CHiPs) delivered the PopART intervention during 2014–2017. This was a combination HIV prevention package including universal home-based HIV testing, referral of HIV-positive individuals to government HIV clinic services that offered universal ART (Arm A) or ART according to national guidelines (Arm B), and revisits to HIV-positive individuals to support linkage to HIV care and retention on ART. The intervention was delivered in 3 “rounds,” each about 15 months long, during which CHiPs visited all households and aimed to contact all individuals aged ≥15 years at least once. In Arm A in Round 3 (R3), 67% (41,332/61,402) of men and 86% (56,345/65,896) of women in Zambia and 56% (17,813/32,095) of men and 71% (24,461/34,514) of women in SA participated in the intervention, among 193,907 residents aged ≥15 years. Following participation, HIV status was known by 90% of men and women in Zambia and by 78% of men and 85% of women in SA. The median time from CHiP referral of HIV-positive individuals to ART initiation was approximately 3 months. By the end of R3, an estimated 95% of HIV-positive women and 85% of HIV-positive men knew their HIV status, and among these individuals, approximately 90% of women and approximately 85% of men were on ART. ART coverage among all HIV-positive individuals was approximately 85% in women and approximately 75% in men, up from about 45% at the start of the study. ART coverage was lowest among men aged 18 to 34 and women aged 15 to 24 years, and among mobile individuals/in-migrants. Findings from Arm B were similar. The main limitations to our study were that estimates of testing and treatment coverage among men relied on considerable extrapolation because, in each round, approximately one-third of men did not participate in the PopART intervention; that our findings are for a service delivery model that was relatively intensive; and that we did not have comparable data from the 7 “standard-of-care” (Arm C) communities. Conclusions Our study showed that very high HIV testing and treatment coverage can be achieved through persistent delivery of universal testing, facilitated linkage to HIV care, and universal treatment services. The ART coverage target of 81% was achieved overall, after 4 years of delivery of the PopART intervention, though important gaps remained among men and young people. Our findings are consistent with previously reported findings from southern and east Africa, extending their generalisability to urban settings with high rates of in-migration and mobility and to Zambia and SA. Trial registration ClinicalTrials.gov NCT01900977., Sian Floyd and co-authors study progress towards goals for population HIV testing and treatment in South Africa and Zambia., Author summary Why was this study done? The HIV Prevention Trials Network (HPTN) 071 Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART) trial aimed to establish whether universal testing and universal treatment for HIV could reduce population-level HIV incidence in a generalised HIV epidemic. In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set targets that, by 2020, 90% of people living with HIV know their HIV status, that 90% of those who know their HIV-positive status are on antiretroviral therapy (ART), and that 90% of those on treatment are virally suppressed (the 90-90-90 targets). We assessed the feasibility of achieving these targets as part of the HPTN 071 (PopART) community-randomised trial. The study population was individuals aged ≥15 years living in 14 urban and peri-urban “PopART” intervention communities in Zambia and the Western Cape of South Africa (SA), with a total population of approximately 600,000 and HIV prevalence of around 15%. What did the researchers do and find? Community HIV care providers (CHiPs) delivered the PopART intervention during 2014–2017 inclusive. This was a combination HIV prevention package including universal home-based HIV testing, referral of HIV-positive individuals to government HIV clinic services that offered universal ART (Arm A, 7 communities) or ART according to national guidelines (Arm B, 7 communities), and revisits to HIV-positive individuals to support linkage to HIV care and retention on ART. High levels of HIV testing and treatment coverage were achieved in communities that received the PopART intervention, especially among women. After 4 years, approximately 95% of HIV-positive women and approximately 85% of HIV-positive men knew their HIV status, up from about 55% at the start of the intervention. Among individuals who knew their HIV-positive status after 4 years, approximately 90% of women and approximately 85% of men were on ART, up from about 80% at the start of the intervention. In the total HIV-positive population—both men and women—the cumulative 90–90 target of 81% ART coverage was met, up from around 45% at the start of the study. Viral suppression among individuals who were taking ART was high, at around 90% in Zambian study communities and around 80%–90% in SA study communities. Testing and treatment coverage increased in each intervention round, but progress was slowed by high rates of mobility and in-migration among both men and women. At the start of a round of intervention, mobile individuals and in-migrants had lower knowledge of HIV-positive status and ART coverage than “stable” residents. Progress was also slowed by the relative difficulty of contacting men at home, which persisted throughout the study. The main remaining gap in coverage against the first and second of the 90-90-90 targets after 4 years of intervention was among men aged 18–34 years and women aged 15–24 years. This reflected fewer prior opportunities for facility-based HIV testing, relatively high HIV incidence compared with HIV prevalence, and relatively high mobility and in-migration rates. Participation in the PopART intervention and uptake of HIV testing were similar to or higher among younger individuals compared with those aged 35–54 years. What do these findings mean? Very high HIV testing and treatment coverage can be achieved through persistent delivery of universal testing, facilitated linkage to HIV care, and universal treatment services. Our findings are consistent with previously reported findings from southern and east Africa, extending their generalisability to urban settings with high rates of in-migration and mobility and to Zambia and SA.

Background Trachoma elimination efforts are hampered by limited understanding of Chlamydia trachomatis (Ct) transmission routes. Here we aimed to detect Ct DNA at non-ocular sites and on eye-seeking flies. Methods A population-based household survey was conducted in Oromia Region, Ethiopia. Ocular and non-ocular (faces, hands, clothing, water containers and sleeping surfaces) swabs were collected from all individuals. Flies were caught from faces of children. Flies, ocular swabs and non-ocular swabs were tested for Ct by quantitative PCR. Results In total, 1220 individuals in 247 households were assessed. Active trachoma (trachomatous inflammation—follicular) and ocular Ct were detected in 10% and 2% of all-ages, and 21% and 3% of 1–9-year-olds, respectively. Ct was detected in 12% (95% CI:8–15%) of tested non-ocular swabs from ocular-positive households, but in none of the non-ocular swabs from ocular-negative households. Ct was detected on 24% (95% CI:18–32%) of flies from ocular-positive households and 3% (95% CI:1–6%) of flies from ocular-negative households. Conclusion Ct DNA was detected on hands, faces and clothing of individuals living in ocular-positive households suggesting that this might be a route of transmission within Ct infected households. In addition, we detected Ct on flies from ocular-positive households and occasionally in ocular-negative households suggesting that flies might be a vector for transmission within and between Ct infected and uninfected households. These potential transmission routes may need to be simultaneously addressed to suppress transmission., Author summary Trachoma elimination efforts are hampered by limited understanding of Ct transmission routes. One previous study demonstrated Ct in nasal secretions, with lower loads than in paired ocular samples. Two other studies reported 15–23% of Musca sorbens caught leaving the faces of Ethiopian children to be PCR-positive for Ct in untreated villages with 30–50% TF prevalence. To date, no published studies have systematically documented the relative frequency of Ct by PCR on non-ocular surfaces and flies. Cross-sectional studies consistently find active trachoma and ocular Ct infection associated with factors such as dirty faces, fly-eye contact, limited water access, crowded living conditions and limited sanitation. In this study, we conducted a population-based household survey in Oromia Region, Ethiopia and test the hypothesis that Ct can be detected at multiple non-ocular sites and on eye-seeking flies. The results of our study show that Ct DNA was only detected on hands, faces and clothing of individuals living in ocular-positive households. In addition, Ct-positive flies were much more likely to be found in ocular-positive households. These findings suggest there may be several plausible ocular Ct transmission routes between people, within and between households, which would need to be simultaneously addressed within communities to suppress transmission.

Eye-to-eye transmission of Chlamydia trachomatis, the causative agent of trachoma, may be plausibly interrupted if faces are kept free of ocular and nasal discharge. Between April and June 2018, 83 children aged 1–9 years with active trachoma were recruited from 62 households and allocated to a face cleaning protocol: face washing with water, face washing with water and soap, or face wiping. Faces were examined for the presence of ocular and nasal discharge, and swabs were taken from faces and hands to test for C. trachomatis at baseline, immediately post protocol, and after 1, 2, and 4 hours (washing protocols). Washing with soap was more effective at removing ocular discharge than either washing with water (89% and 27% of discharge removed, respectively, P = 0.003) or wiping with a hand (42%, P = 0.013). The reduction in prevalence of ocular discharge was sustained for at least four hours. The prevalence of C. trachomatis on face swabs was reduced by all washing protocols. The importance of soap should not be overlooked during facial cleanliness promotion.

BackgroundRecent reports have suggested a significant change in the causes of blindness in children in low-income countries cataract becoming the leading cause. We aimed to investigate the presentations and surgical outcomes in children with cataract operated at different ages in Tanzania.MethodsWe conducted a prospective study of 228 children aged ≤192 months at three tertiary centres, 177 with bilateral cataracts and prospectively followed them for 1-year postsurgery. We collected demographic, surgical, preoperative and postoperative clinical characteristics using the standard childhood cataract surgical assessment questionnaire. Families were encouraged to return for follow-up by phone with travel reimbursement where necessary.ResultsPreoperatively, 76% bilateral children were blind in the better eye. 86% of children were followed up at 1 year and 54% bilateral children achieved visual acuity of 0.48 logMAR or better in the better eye and 5% were blind. 33% of unilateral children achieved visual acuity of 0.48 logMAR or better and 17% were blind. Preoperative blindness (adjusted OR (AOR) 14.65; 95% CI 2.21 to 97.20), preoperative nystagmus/strabismus (AOR 9.22; 95% CI 2.66 to 31.97) and aphakia (AOR, 5.32; 95% CI 1.05 to 26.97) predicted poor visual outcome in bilateral cases. 9% of 342 refracted eyes had initial postoperative cylinder of 1.5 D or more, as did a similar proportion (11%) of 315 eyes refracted 1 year after surgery. Acute fibrinous uveitis occurred in 41 (12%) eyes.ConclusionThree-quarters of children were blind preoperatively whereas over half had good vision 1-year postoperatively. Preoperative blindness, nystagmus/strabismus and aphakia predicted poor visual outcome, suggesting that cataract density determines density of amblyopia.

Purpose: To describe the epidemiology of Microbial Keratitis (MK) in Uganda. Methods: We prospectively recruited patients presenting with MK at two main eye units in Southern Uganda between December 2016 and March 2018. We collected information on clinical history and presentation, microbiology and 3-month outcomes. Poor vision was defined as vision < 6/60). Results: 313 individuals were enrolled. Median age was 47 years (range 18–96) and 174 (56%) were male. Median presentation time was 17 days from onset (IQR 8–32). Trauma was reported by 29% and use of Traditional Eye Medicine by 60%. Majority presented with severe infections (median infiltrate size 5.2 mm); 47% were blind in the affected eye (vision < 3/60). Microbiology was available from 270 cases: 62% were fungal, 7% mixed (bacterial and fungal), 7% bacterial and 24% no organism detected. At 3 months, 30% of the participants were blind in the affected eye, while 9% had lost their eye from the infection. Delayed presentation (overall p = .007) and prior use of Traditional Eye Medicine (aOR 1.58 [95% CI 1.04–2.42], p = .033) were responsible for poor presentation. Predictors of poor vision at 3 months were: baseline vision (aOR 2.98 [95%CI 2.12–4.19], p < .0001), infiltrate size (aOR 1.19 [95%CI 1.03–1.36], p < .020) and perforation at presentation (aOR 9.93 [95% CI 3.70–26.6], p < .0001). Conclusion: The most important outcome predictor was the state of the eye at presentation, facilitated by prior use of Traditional Eye Medicine and delayed presentation. In order to improve outcomes, we need effective early interventions.

All patients with diabetes are at risk of developing diabetic retinopathy (DR), a progressive and potentially blinding condition. Early treatment of DR prevents visual impairment and blindness. The natural history of DR is that it is asymptomatic until the advanced stages, thus annual retinal examination is recommended for early detection. Previous studies show that the uptake of regular retinal examination among people living with diabetes (PLWD) is low. In the Uptake of Retinal Examination in Diabetes (DURE) study, we will investigate the effectiveness of a complex intervention delivered within diabetes support groups to increase uptake of retinal examination. The DURE study will be a two-arm pragmatic cluster randomized clinical trial in Kirinyaga County, Kenya. Diabetes support groups will be randomly assigned to either the intervention or usual care conditions in a 1:1 ratio. The participants will be 700 PLWD who are members of support groups in Kirinyaga. To reduce contamination, the unit of randomization will be the support group. Peer supporters in the intervention arm will receive training to deliver the intervention. The intervention will include monthly group education on DR and individual member reminders to take the eye examination. The effectiveness of this intervention plus usual care will be compared to usual care practices alone. Participant data will be collected at baseline. The primary outcome is the proportion of PLWD who take up the eye examination at six months. Secondary outcomes include the characteristics of participants and peer supporters associated with uptake of eye examination for DR. Intention-to-treat analysis will be used to evaluate the primary and secondary outcomes. Eye care programs need evidence of the effectiveness of peer supporter-led health education to improve attendance to retinal screening for the early detection of DR in an African setting. Given that the intervention combines standardization and flexibility, it has the potential to be adopted in other settings and to inform policies to promote DR screening. Pan African Clinical Trial Registry PACTR201707002430195 , registered 25 July 2017, www.pactr.org

Purpose Glaucoma is a leading cause of blindness in people of African descent. Minimal data is available from African population-based cohort studies. The primary aims of this study were to describe the normative distribution of glaucoma features to enable glaucoma classification and to assess risk factors for those with glaucoma at follow-up among people aged 50 years and above in Kenya. Materials and methods Random cluster sampling with probability proportionate to size was used to select a representative cross-sectional sample of adults aged 50 years and above in 2007 to 2008 in Nakuru District, Kenya. A 6-year follow-up was undertaken in 2013 to 2014. Comprehensive ophthalmic examination included visual acuity, digital retinal photography, visual fields, intraocular pressure, optical coherence tomography, and independent grading of optic nerve images. We report glaucoma features, prevalence and predictors for glaucoma based on the International Society for Geographical & Epidemiological Ophthalmology (ISGEO) criteria. Measures were estimated using a Poisson regression model and including inverse-probability weighting for loss to follow-up. Results At baseline, 4414 participants aged 50 years and above underwent examination. Anterior chamber optical coherence tomography findings: mean anterior chamber angle of 36.6 degrees, mean central corneal thickness of 508.1 μm and a mean anterior chamber depth of 2.67 mm. A total of 2171 participants were examined at follow-up. The vertical cup to disc ratio distribution was 0.7 and 0.8 at the 97.5th and 99.5th percentiles, respectively. A total of 88 (4.3%, 95% confidence interval, 3.5%-5.9%) of participants at follow-up had glaucoma consistent with ISGEO criteria. A relative afferent pupillary defect and raised intraocular pressure were associated with the diagnosis. Conclusions Glaucoma is a public health challenge in low-resource settings. Research into testing and treatment modalities in Africa is needed.

Summary: Background: We re-examined the participants of a clinical trial four years after enrolment to identify which of the two most commonly used eyelid surgery procedures to treat the blinding stage of trachoma (trachomatous trichiasis, TT), the posterior Lamellar Tarsal Rotation (PLTR) and Billamelar Tarsal Rotation (BLTR), gives better results in the long-term. Methods: A randomised, controlled, single masked clinical trial was done in Ethiopia. At baseline, adults (aged >18 years with upper lid unoperated TT were recruited from a community-based screening. Participants were randomly assigned (1:1), to either BLTR or PLTR surgery, stratified by surgeon. At 4 years an independent assessor masked to allocation examined the trial participants’ eyes using the same procedures as for the baseline and earlier follow-ups. The primary outcome was the proportion of individuals who had recurrence (postoperative TT, PTT) at the 4-year examination, or a history of repeat surgery in the 4-year period. The intervention effect was estimated by logistic regression, controlled for surgeon as a fixed effect in the model. The trial is registered with the Pan African Clinical Trials Registry (number PACTR201401000743135). Findings: 1000 participants with TT were enrolled, randomly assigned, and treated (501 in the BLTR group and 499 in the PLTR group) between Feb 13, 2014, and May 31, 2014. At year 4, 943 (94.3%) participants were re-examined (471, PLTR; 472, BLTR) and included in the primary outcome analysis. PTT had developed in 169/943 (17•9%) study eyes, among which 129 (76•3%) had minor trichiasis (≤5 lashes touching the eye). PTT was significantly more frequent at 4-year in the BLTR arm (105/472 [22•2%]) than the PLTR arm (64/471 [13•6%]), adjusted OR 1•82 (95% CI, 1•29–2•56); p = 0•0006, with 8•6% (95%CI 3•8–13•5) risk difference. Interpretation: The PLTR surgical procedure had superior long-term outcomes to the BLTR with significantly lower risk of PTT supporting the current WHO guideline that the PLTR should be the procedure of choice for training new surgeons in the programmatic management of TT. Keywords: Trachoma, Trichiasis, Ethiopia, Surgery, Postoperative, Recurrence

Background: Microbial keratitis (MK) frequently leads to sight-loss, especially when the infection is severe and/or appropriate treatment is delayed. The primary health system as an entry point plays a central role in facilitating and directing patient access to appropriate care. The purpose of this study was to describe the capacity of primary health centres in Uganda in managing MK. Methods: We carried out a rigorous assessment of primary health centres and mid-cadre training schools in South Western Uganda. Through interviews, checklists and a picture quiz, we assessed capacity and knowledge of MK management. In addition, we interviewed the heads of all the mid-cadre training schools to determine the level of eye health training provided in their curricula. Results: In total, 163 health facilities and 16 training schools were enrolled. Of the health facilities, only 6% had an Ophthalmic Clinical Officer. Only 12% of the health workers could make a diagnosis of MK based on the clinical signs in the picture quiz. Although 35% of the facilities had a microscope, none reported doing corneal scraping. None of the facilities had a stock of the recommended first line treatment options for MK (ciprofloxacin and natamycin eye drops). Among the training schools, 15/16 had an eye health component in the curriculum. However, the majority (56%) of tutors had no formal expertise in eye health. In 14/16 schools, students spent an average of two weeks in an eye unit. Conclusions: Knowledge among health workers and capacity of health facilities in diagnosis and management of MK was low. Training for eye health within mid-cadre training schools was inadequate. More is needed to close these gaps in training and capacity.

The putative vector of trachoma, Musca sorbens, prefers to lay its eggs on human faeces on the ground. This study sought to determine whether M. sorbens females were attracted to volatile odours from human faeces in preference to odours from the faeces of other animals, and to determine whether specific volatile semiochemicals mediate selection of the faeces. Traps baited with the faeces of humans and local domestic animals were used to catch flies at two trachoma-endemic locations in The Gambia and one in Ethiopia. At all locations, traps baited with faeces caught more female M. sorbens than control traps baited with soil, and human faeces was the most successful bait compared with soil (mean rate ratios 44.40, 61.40, 10.50 [P, Author summary Musca sorbens, also known as the Bazaar Fly, visits people’s faces to feed on ocular and nasal discharge. While feeding, M. sorbens can transmit Chlamydia trachomatis, the bacterium that causes the infectious eye disease trachoma. Around 1.9 million people worldwide are visually impaired or blind from this disease. Although it is believed that M. sorbens transmits trachoma, very few studies have looked at ways to control this fly. A large-scale trial has shown that control of fly populations with insecticide reduces active trachoma disease prevalence. Odour-baited traps for the suppression of disease vector populations are an attractive option as there is no widespread spraying of insecticide; however, highly attractive baits are critical to their success. Here, we demonstrate that the preference of these flies for breeding in human faeces is probably mediated by odour cues, and we isolate chemicals in the odour of human faeces that cause a response in the antennae of M. sorbens. These compounds may play a role in the specific attractiveness of human faeces to these flies, perhaps by being present in greater amounts or at favourable ratios. These may be developed into a chemical lure for odour-baited trapping to suppress M. sorbens populations.

ObjectiveTo estimate the association between (1) visual impairment (VI) and (2) eye disease and 6-year mortality risk within a cohort of elderly Kenyan people.Design, setting and participantsThe baseline of the Nakuru Posterior Segment Eye Disease Study was formed from a population-based survey of 4318 participants aged ≥50 years, enrolled in 2007–2008. Ophthalmic and anthropometric examinations were undertaken on all participants at baseline, and a questionnaire was administered, including medical and ophthalmic history. Participants were retraced in 2013–2014 for a second examination. Vital status was recorded for all participants through information from community members. Cumulative incidence of mortality, and its relationship with baseline VI and types of eye disease was estimated. Inverse probability weighting was used to adjust for non-participation.Primary outcome measuresCumulative incidence of mortality in relation to VI level at baseline.ResultsOf the baseline sample, 2170 (50%) were re-examined at follow-up and 407 (10%) were known to have died (adjusted risk of 11.9% over 6 years). Compared to those with normal vision (visual acuity (VA) ≥6/12, risk=9.7%), the 6-year mortality risk was higher among people with VI (ConclusionsVisual acuity was related to 6-year mortality risk in this cohort of elderly Kenyan people, potentially because both VI and mortality are related to ageing and risk factors for NCD.

Background The evidence on diagnostic test accuracy (DTA) of diabetic retinopathy (DR) screening utilising photographic studies by non-ophthalmologist personnel in low and middle-income country (LMIC) settings is scarce. We aimed to assess DTA of DR screening using a nonmydriatic hand-held digital camera by trained general physicians in a non-ophthalmic setting. Methods This study is a validation of a screening intervention. We selected 700 people with diabetes (PwDM) > 18 years of age, not previously screened or treated for DR, presenting at a tertiary medical clinic in Sri Lanka. Two-field retinal imaging was used to capture fundus images before and after pupil dilatation, using a hand-held non-mydriatic (Visuscout 100®-Germany) digital retinal camera. The images were captured and graded by two trained, masked independent physician graders. The DTA of different levels of DR was assessed comparing physician’s grading with a retinologist’s clinical examination by mydriatic bio-microscopy, according to a locally adopted guideline. Results Seven hundred eligible PwDM were screened by physician graders. The mean age of participants was 60.8 years (SD ±10.08) and mean duration of DM was 9.9 years (SD ±8.09). Ungradable image proportion in non-mydriatic imaging was 43.4% (either eye-31.3%, both eyes 12.1%). This decreased to 12.8% (either eye-11.6%, both eyes-1.2%) following pupil dilatation. In comparison to detection of any level of DR, a referable level DR (moderate non-proliferative DR and levels above) showed a higher level of DTA. The sensitivity of the defined referable DR was 88.7% (95% CI 81.7–93.8%) for grader 1 (positive predictive value [PPV] 59.1%) and 92.5% (95% CI 86.4–96.5%) for grader 2 (PPV 68%), using mydriatic imaging, after including ungradable images as screen positives. The specificity was 94.9% (95% CI 93.6–96.0%) for grader 1 (negative predictive value [NPV] 99%) and 96.4% (95% CI 95.3–97.3%) for grader 2 (NPV 99.4%). Conclusions The Physicians grading of images from a digital hand-held non-mydriatic camera at a medical clinic, with dilatation of pupil of those who have ungradable images, provides a valid modality to identify referable level of DR. This could be a feasible alternative modality to the existing opportunistic screening to improve the access and coverage. Trial registration Current Controlled Trials ISRCTN47559703. Date of Registration 18th March 2019, Retrospectively registered. Electronic supplementary material The online version of this article (10.1186/s12886-019-1092-3) contains supplementary material, which is available to authorized users.

Background Visual impairment and blindness from diabetic retinopathy (DR), which can be reduced by early screening and treatment, is an emerging public health concern in low-income and middle-income countries (LMICs) owing to the increasing prevalence of diabetes mellitus (DM). However, no systematic screening exists in most LMIC settings. The Western province of Sri Lanka has the highest prevalence of DM (18.6%) in the country. A situational analysis identified a marked gap in DR screening (DRS) and treatment services uptake in this region; only opportunistic screening is practiced currently. Objective The aim of this protocol is to describe the methods of development and validation of a DRS intervention using a hand-held nonmydriatic digital camera by physician graders in a non-ophthalmological setting at a tertiary-level medical clinic to propose a valid and feasible modality to improve uptake. Methods DRS modality was developed after assessing barriers and identifying the most appropriate personnel, methods, and location for screening services, following formative research work. The validation will be conducted in a public sector tertiary care center in the Western province of Sri Lanka. The selected physicians will be trained on capturing and grading images according to a valid locally adopted protocol. Two physicians rated high on training will screen a sample of 506 people with DM at a medical clinic. They will use nonmydriatic and mydriatic 2-field imaging strategy. The validity of the proposed screening procedure will be assessed and compared with the mydriatic indirect biomicroscopic examination by a senior retinologist. Results The validity of screening by physician graders will be analyzed and the sensitivity, specificity, and predictive values (with 95% CIs) calculated by the dilation status and for each grader. The diagnostic accuracy at each level of severity of DR will be assessed to define the most appropriate referable criteria. Data is currently being collected. Conclusions The outcome of this study will be useful for the detection of a defined level of DR at non-ophthalmological setting to filter the people with DM before referral to an eye clinic. This will be helpful to improve the uptake and identify risk groups in advance to prevent sight-threatening DR. Furthermore, evidence from this study will be useful for the implementation of a DRS program in this region and in similar communities. International registered report identifier (irrid) PRR1-10.2196/10900.

TPS2577 Background: Patients diagnosed with malignant high-grade gliomas (WHO grade III-IV) experience significant morbidity and mortality associated with these cancers. While the mainstay of therapy for patients with newly diagnosed high-grade glioma is surgery followed by concurrent chemotherapy and radiation therapy (RT), the outcomes remain very poor. BMX-001 (MnTnBuOE-2-PyP5+) is a metalloporphyrin with differential action in response to radiation therapy and chemotherapy-induced oxidative stress. Early preclinical studies demonstrated BMX-001’s ability to act as a radioprotectant to healthy tissue such as a central nervous white matter and as a radiosensitizer to cancer cells, in particular, human glioblastoma xenografts. We evaluated the safety of BMX-001 in combination with concurrent RT and temozolomide (TMZ) in a phase I study of newly diagnosed high-grade glioma patients, and we found that BMX-001 is safe and well-tolerated in this population. The maximum tolerated dose of BMX-001 during concurrent RT and TMZ was determined to be 28 mg delivered subcutaneously (SC) followed by 16 biweekly SC doses at 14 mg (Peters et al., Neuro-Oncology 2018). Methods: For this multi-site, open-label, phase II study (NCT02655601), we will randomize approximately 160 patients 1:1 to concurrent RT and TMZ with BMX-001 versus concurrent RT and TMZ alone. Key eligibility criteria include newly diagnosed histologically confirmed high-grade glioma (WHO III-IV), 18 ≥ years, and Karnofsky performance status ≥ 70%. The primary endpoint is overall survival. Secondary endpoints include cognitive performance as assessed by standardized cognitive testing, bone marrow protection, safety and tolerability, progression-free survival, overall tumor response rate, and plasma pharmacokinetics. Exploratory endpoints are health-related quality of life (as assessed by Functional Assessment of Cancer Therapy–Brain, Functional Assessment of Cancer Therapy-Cognition, and Functional Assessment of Chronic Illness Therapy-Fatigue), qualitative hair loss, and white matter integrity (as measured by MRI diffusion tensor/susceptibility imaging). Since November 2018, this phase II study has enrolled 64 of 160 high-grade glioma patients at six sites with future sites planned to be implemented. Clinical trial information: NCT02655601 .

There are 466 million people globally with disabling hearing loss, many of whom can benefit from hearing aids. The aim of the study was to assess the impact of providing hearing aids on poverty, mental health, quality of life, and activities, among adults in Guatemala. A nonrandomised before and after study was conducted, with a comparison group to assess for secular trends. Adult cases with bilateral hearing impairment were identified within 150 km of Guatemala City, as well as age- and sex-matched comparison subjects without disabling hearing loss. All participants were interviewed with a semistructured questionnaire, and cases were offered hearing aids. Participants were reinterviewed 6&ndash, 9 months later. We interviewed 135 cases and 89 comparison subjects at baseline and follow-up. At baseline, cases were poorer than comparison subjects with respect to individual income (p = 0.01), household income (p = 0.02), and per capita expenditure (PCE) (p = 0.003). After provision of hearing aids, median household income improved among cases (p = 0.03). In the comparison group, median individual income (p = 0.01) and PCE (p = 0.03) fell between baseline at follow-up. At follow-up, there were also improvements in productive time use, quality of life, and depressive symptoms among cases, but these were less apparent in the comparison group. In conclusion, this study has demonstrated a positive effect of hearing aids in improving quality of life, economic circumstances and mental health among Guatemalan adults.

BackgroundMicrobial keratitis (MK) is a frequent cause of sight loss in sub-Saharan Africa. However, no studies have formally measured its impact on quality of life (QoL) in this context.MethodsAs part of a nested case–control design for risk factors of MK, we recruited patients presenting with MK at two eye units in Southern Uganda between December 2016 and March 2018 and unaffected individuals, individually matched for sex, age and location. QoL was measured using WHO Health-Related and Vision-Related QoL tools (at presentation and 3 months after start of treatment in cases). Mean QoL scores for both groups were compared. Factors associated with QoL among the cases were analysed in a linear regression model.Results215 case-controls pairs were enrolled. The presentation QoL scores for the cases ranged from 20 to 65 points. The lowest QoL was visual symptom domain; mean 20.7 (95% CI 18.8 to 22.7) and the highest was psychosocial domain; mean 65.6 (95% CI 62.5 to 68.8). At 3 months, QoL scores for the patients ranged from 80 to 90 points while scores for the controls ranged from 90 to 100. The mean QoL scores of the cases were lower than controls across all domains. Determinants of QoL among the cases at 3 months included visual acuity at 3 months and history of eye loss.ConclusionMK severely reduces QoL in the acute phase. With treatment and healing, QoL subsequently improves. Despite this improvement, QoL of someone affected by MK (even with normal vision) remains lower than unaffected controls.

Background Cerebral visual impairment (CVI), including perceptual visual dysfunction (PVD), is common in children with cerebral palsy (CP). Inventories of questions relating to practical aspects of visual perception in everyday life, in particular the closed-ended Insight Questions Inventory (IQI), can be used to assess CVI/PVD. Studies linking responses to the inventory with specific visual support strategies, aimed at modifying the child’s environment and/or behaviour to minimize the impact of the CVI/PVD, have been piloted. The IQI and tailored strategies have not been used in an African population, nor have they been tested in a controlled trial. This trial will compare the effectiveness of the IQI and linked visual support strategies versus general supportive treatments on the quality of life of children with CVI/PVD and CP through a randomized controlled trial. Methods/design This is a prospective, double-blind, parallel-arm, randomized controlled trial. The primary outcome is change in quality of life scores between the two arms of the trial at 6 weeks, assessed using the Paediatric Quality of Life Inventory (PedsQL) generic 4.0 and CP 3.0 module. All children will undergo baseline assessment including the Open Questions Inventory, IQI, PedsQL 3.0, PedsQL 4.0 generic, and the Strengths and Difficulties Questionnaire (SDQ). Eligible children with CP aged 4 years to

OBJECTIVE: Congenital talipes equinovarus (CTEV), or clubfoot, is a structural malformation that develops early in gestation. Birth prevalence of clubfoot is reported to vary both between and within low and middle-income countries (LMICs) and this information is needed in order to plan treatment services. This systematic review aims to understand the birth prevalence of clubfoot in LMIC settings. METHODS: Six databases were searched for studies that reported birth prevalence of clubfoot in LMICs. Results were screened and assessed for eligibility using pre-defined criteria. Data on birth prevalence were extracted and weighted pooled estimates were calculated for different regions. Wilcoxon rank-sum test was used to examine changes in birth prevalence over time. Included studies were appraised for their methodological quality, and a narrative synthesis of findings was conducted. RESULTS: 48 studies provided data from 13,962,989 children in 20 countries over 55 years (1960 - 2015). The pooled estimate for clubfoot birth prevalence in LMICs within the Africa region is 1.11 (0.96, 1.26); in the Americas 1.74 (1.69,1.80); in South East Asia (excluding India) 1.21 (0.73, 1.68); in India 1.19 (0.96, 1.42); in Turkey (Europe Region) 2.03 (1.54, 2.53); in Eastern Mediterranean region 1.19 (0.98, 1.40); in West Pacific (excludes China) 0.94 (0.64, 1.24) and in China 0.51 (0.50, 0.53). CONCLUSION: Birth prevalence of clubfoot varies between 0.51 and 2.03/1,000 live births in LMICs. A standardised approach to the study of the epidemiology of clubfoot is required to better understand the variations of clubfoot birth prevalence and identify possible risk factors. This article is protected by copyright. All rights reserved.

Background: Eye care provision is currently insufficient to meet the population&rsquo, s eye health needs in Kenya. Many people remain unnecessarily visually impaired or at risk of becoming so due to treatable or preventable conditions. A lack of access and awareness of services are key barriers, in large part due to their being too few eye care providers in the health system for this unmet need. Methods: A hospital-based, retrospective analysis of patients who attended Kitale eye unit, Trans Nzoia County, Kenya from 1st January 2013 to 31st December 2015. Age and sex standardized hospital attendance rates by residence, age group, and sex were calculated for Trans Nzoia county and each subcounty. The changing trends in attendance rates were estimated by calculating the difference between base year and last year. Incidence rate ratios for attendance for each age-group, sex, and residence were estimated using a multivariable regression model. Results: 20,695 patients from the county were seen in Kitale Eye Unit in 2013, 2014 and 2015. In that period, 8.3% had either uncorrected refractive error, cataracts or glaucoma, the priority VISION2020 diseases, and 61.0% had allergic or other conjunctivitis or normal eyes, which could potentially be managed at primary eye care. During the study period, overall average annual attendance rate increased from 609 to 792 per 100, 000 population, incidence rate ratio (IRR) 1.30 (95% confidence interval (CI) 1.26&ndash, 1.35). Attendance rates increased more in females than males (34.7% vs. 25.1%, respectively), IRR 1.07 (1.04&ndash, 1.10). Attendance rates increased with increasing age, (highest among the elderly compared to the young). We found that in extreme age groups (&gt, 75 years and &lt, 15years) females were less likely to attend than males and there was reduced utilization from those based furthest from the hospital. Conclusion: Specialist eye services are heavily utilized by people with conditions that could be managed at the primary health care level. Barriers to accessing eye services were distance and gender, especially among the most vulnerable groups (young and the elderly). Integration of primary and secondary eye care services could lower barriers to essential eye care services to the population whilst lowering pressure on the limited specialist services by ensuring more appropriate utilization.

Background: Surgery to correct trichiasis is a key component of the World Health Organisation trachoma control strategy, however unfavourable outcomes such as eyelid contour abnormalities (ECA) following surgery are relatively common. This study aimed to understand the transcriptional changes associated with the early development of ECA and the impact of doxycycline, which has anti-inflammatory and anti-fibrotic properties, upon these transcription patterns. Methods: One thousand Ethiopians undergoing trichiasis surgery were enrolled in a randomised controlled trial following informed consent. Equal groups of randomly assigned individuals were orally administered with 100mg/day of doxycycline (n=499) or placebo (n=501) for 28 days. Conjunctival swabs were collected immediately prior to surgery and at one- and six-months post-surgery. 3’ mRNA sequencing was performed on paired baseline and one-month samples from 48 individuals; 12 in each treatment/ECA outcome group. qPCR validation was then performed for 46 genes of interest in 145 individuals who developed ECA at one month and 145 matched controls, using samples from baseline, one and six months. Results: All treatment/outcome groups upregulated genes associated with wound healing pathways at one month relative to baseline, however no individual differences were detected between groups. The summed expression of a highly coexpressed cluster of pro-fibrotic genes was higher in patients that developed ECA in the placebo group relative to controls. qPCR validation revealed that all genes in this cluster and a number of other pro-inflammatory genes were strongly associated with ECA, however these associations were not modulated by trial arm. Conclusions: The development of post-operative ECA is associated with overexpression of pro-inflammatory and pro-fibrotic genes including growth factors, matrix metalloproteinases, collagens and extracellular matrix proteins. There was no evidence that doxycycline modulated the association between gene expression and ECA.

Background: Traditional eye medicine (TEM) is frequently used to treat microbial keratitis (MK) in many parts of Africa. Few reports have suggested that this is associated with a worse outcome. We undertook this large prospective study to determine how TEM use impacts presentation and outcome of MK and to explore reasons why people use TEM for treatment in Uganda. Methods: In a mixed method prospective cohort study, we enrolled patients presenting with MK at the two main eye units in Southern Uganda between December 2016 and March 2018 and collected information on history, TEM use, microbiology and 3-month outcomes. We conducted qualitative interviews with patients, carers traditional healers on reasons why people use TEM. Outcome measures included presenting vision and at 3-months, comparing TEM Users versus Non-Users. A thematic coding framework was deployed to explore reasons for use of TEM. Results: Out of 313 participants enrolled, 188 reported TEM use. TEM Users had a delayed presentation; median presenting time 18 days versus 14 days, p= 0.005; had larger ulcers 5.6 mm versus 4.3 mm p=0.0005; a worse presenting visual acuity median logarithm of the minimum angle of resolution (Log MAR) 1.5 versus 0.6, p=0.005; and, a worse visual acuity at 3 months median Log MAR 0.6 versus 0.2, p=0.010. In a multivariable logistic regression model, distance from the eye hospital and delayed presentation were associated with TEM use. Reasons for TEM use included lack of confidence in conventional medicine, health system breakdown, poverty, fear of the eye hospital, cultural belief in TEM, influence from traditional healers, personal circumstances and ignorance. Conclusion: TEM users had poorer clinical presentation and outcomes. Capacity building of the primary health centres to improve access to eye care and community behavioural change initiatives against TEM use should be encouraged.

IntroductionHigh discontinuation rates of contraceptive methods have been documented in sub-Saharan Africa. However, little is known about gaps within individual episodes of method use, despite their implications for unintended pregnancies. The objective of this mixed methods study was to examine the prevalence of, and explore the factors contributing to, delays in repeat appointments for pills and injectables in Senegal.MethodsFirst, we constructed a longitudinal data set of women’s contraceptive consultations using routine records from 67 facilities in Senegal. Consultations for pills and injectables were classified as on time, delayed or with unknown delay status based on time since previous appointment. We described the prevalence of delayed appointments and used backward stepwise regression to build a mixed-effects model to investigate risk factors for delay. Second, we conducted workshops with family planning (FP) providers, and indepth interviews and focus group discussions with women of reproductive age, to explore factors contributing to delays.ResultsAlmost one-third (30%) of appointments for pills and injectables were delayed, resulting in risk of pregnancy. Previous delay, pill use, lower educational level, higher parity, third and subsequent visits, and Islamic faith were independently predictive of delays (pConclusionDelays in obtaining repeat pills and injections are common among contraceptive users in Senegal, exposing women to unintended pregnancies. Strategies to reduce such delays should move beyond a narrow focus on individual women to consider contraceptive behaviour within the broader socioeconomic and health systems context. In particular, effective interventions addressing low acceptability of contraception and appointment reminder strategies in high illiteracy contexts are needed.

Chronic biofilm formation by Pseudomonas aeruginosa in cystic fibrosis (CF) lungs is a major cause of morbidity and mortality for patients with CF. To gain insights into effectiveness of novel anti-infective therapies, the inhibitory effects of fosfomycin, tobramycin, and a 4:1 (wt/wt) fosfomycin/tobramycin combination (FTI) on Pseudomonas aeruginosa biofilms grown on cultured human CF-derived airway cells (CFBE41o-) were investigated. In preformed biofilms treated for 16 h with antibiotics, P. aeruginosa CFU per mL were reduced 4 log10 units by both FTI and tobramycin at 256 mg L(-1) , while fosfomycin alone had no effect. Importantly, the FTI treatment contained five times less tobramycin than the tobramycin-alone treatment. Inhibition of initial biofilm formation was achieved at 64 mg L(-1) FTI and 16 mg L(-1) tobramycin. Fosfomycin (1024 mg L(-1)) did not inhibit biofilm formation. Cytotoxicity was also determined by measuring lactate dehydrogenase (LDH). Intriguingly, sub-inhibitory concentrations of FTI (16 mg L(-1)) and tobramycin (4 mg L(-1)) and high concentrations of fosfomycin (1024 mg L(-1)) prevented bacterially mediated airway cell toxicity without a corresponding reduction in CFU. Overall, it was observed that FTI and tobramycin demonstrated comparable activity on biofilm formation and disruption. Decreased administration of tobramycin upon treatment with FTI might lead to a decrease in negative side effects of aminoglycosides.

Pregnancy in women with Sickle Cell Disease (SCD) has been linked with an increased incidence of adverse foetal outcomes when compared to women without haemoglobinopathies (HbAA). There's a paucity of data into foetal outcomes for infants born to women with SCD. Customised growth charts have been demonstrated to be better than populationbased growth charts at identifying unhealthy small babies. We analysed the mean birth weight and customised birth weight centiles of infants born to mothers with SCD versus mothers with HbAA genotype, to quantify the risk of having a smaller baby. Birth weight and birth weight centiles were analysed for 88 women with SCD (50 HbSS; 38 HbSC) and 176 controls (HbAA). Statistically significant differences were seen in the mean birth weight (P value = 0.004) and the mean birth weight centiles (P value = 0.016). We conclude that SCD is a risk factor for having a smaller baby.

BACKGROUND: Universal access to Primary Eye Care (PEC) is a key global initiative to reduce and prevent avoidable causes of visual impairment (VI). PEC can address minor eye conditions, simple forms of uncorrected refractive error (URE) and create a referral pathway for specialist eye care, thus offering a potential solution to a lack of eye health specialists in low-income countries. However, there is little information on the population need for PEC, including prevalence of URE in all ages in Sub-Saharan Africa. METHODS: A national survey was conducted of people aged 7 and over in Rwanda in September-December 2016. Participants were selected through two-stage probability proportional to size sampling and compact segment sampling. VI (visual acuity

Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal ‘masculinisation programming window’ (MPW; e15.5–e18.5)’ predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during the MPW ± postnatal testosterone propionate (TP) treatment. To assess penile growth responsiveness, rats were treated with TP in various time windows (late foetal, neonatal through early puberty, puberty onset, or combinations thereof). Phallus length, weight, and morphology, hypospadias and anogenital distance (AGD) were measured in mid-puberty (d25) or adulthood (d90) in males and females, plus serum testosterone in adult males. MPW flutamide exposure reduced adult penile length and induced hypospadias dose-dependently; this was not rescued by postnatal TP treatment. In normal rats, foetal (e14.5–e21.5) TP exposure did not affect male penis size but increased female clitoral size. In males, TP exposure from postnatal d1–24 or at puberty (d15–24), increased penile length at d25, but not ultimately in adulthood. Foetal + postnatal TP (e14–postnatal d24) increased penile size at d25 but reduced it at d90 (due to reduced endogenous testosterone). In females, this treatment caused the biggest increase in adult clitoral size but, unlike in males, phallus size was unaffected by TP during puberty (d15–24). Postnatal TP treatment advanced penile histology at d25 to more resemble adult histology. AGD strongly correlated with final penis length. It is concluded that adult penile size depends critically on androgen action during the MPW but subsequent growth depends on later androgen exposure. Foetal and/or postnatal TP exposure does not increase adult penile size above its ‘predetermined’ length though its growth towards this maximum is advanced by peripubertal TP treatment.

Around $1.6 billion per year is spent financing anti-malaria initiatives, and though malaria morbidity is falling, the impact of annual epidemics remains significant. Whilst malaria risk may increase with climate change, projections are highly uncertain and to sidestep this intractable uncertainty, adaptation efforts should improve societal ability to anticipate and mitigate individual events. Anticipation of climate-related events is made possible by seasonal climate forecasting, from which warnings of anomalous seasonal average temperature and rainfall, months in advance are possible. Seasonal climate hindcasts have been used to drive climate-based models for malaria, showing significant skill for observed malaria incidence. However, the relationship between seasonal average climate and malaria risk remains unquantified. Here we explore this relationship, using a dynamic weather-driven malaria model. We also quantify key uncertainty in the malaria model, by introducing variability in one of the first order uncertainties in model formulation. Results are visualized as location-specific impact surfaces: easily integrated with ensemble seasonal climate forecasts, and intuitively communicating quantified uncertainty. Methods are demonstrated for two epidemic regions, and are not limited to malaria modeling; the visualization method could be applied to any climate impact.

Background: Trachomatous trichiasis (TT) may lead to disability, impeding productive activities, resulting in loss of income. This study was conducted to determine if trichiasis surgery improves participation in productive and leisure activities, and ability to perform activities without difficulty or assistance. Methods: We recruited 1000 adults with trichiasis (cases) and 200 comparison participants, matched to every fifth trichiasis case on age (+/- two years), sex and location. The ‘Stylised Activity List’ tool, developed for the World Bank Living Standard Measurement Survey, was adapted to collect data on activity in the last week (participation in activity, difficulty with activity, requirement of assistance for activity), at baseline and 12 months later. All trichiasis cases received trichiasis surgery at baseline. Random effect logistic regression was used to compare cases and comparison participants. Results: There was strong evidence that trichiasis surgery substantially improves the ability of trichiasis cases to perform all the productive and leisure activities investigated without difficulty, with large increases in processing agricultural products, 21.1% to 87.0% (p Conclusions: Eyelid surgery for TT improves functional capabilities regardless of vision gains. These data lend strong support to the view that TT surgery improves function and contributes to improved household income and wealth.

Glioblastoma multiforme (GBM) is a highly malignant human brain neoplasm with limited therapeutic options. GBMs display a deregulated apoptotic pathway with high levels of the antiapoptotic Bcl-2 family of proteins and overt activity of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Therefore, combined interference of the PI3K pathway and the Bcl-2 family of proteins is a reasonable therapeutic strategy. ABT-263 (Navitoclax), an orally available small-molecule Bcl-2 inhibitor, and GDC-0941, a PI3K inhibitor, were used to treat established glioblastoma and glioblastoma neurosphere cells, alone or in combination. Although GDC-0941 alone had a modest effect on cell viability, treatment with ABT-263 displayed a marked reduction of cell viability and induction of apoptotic cell death. Moreover, combinatorial therapy using ABT-263 and GDC-0941 showed an enhanced effect, with a further decrease in cellular viability. Furthermore, combination treatment abrogated the ability of stem cell–like glioma cells to form neurospheres. ABT-263 and GDC-0941, in combination, resulted in a consistent and significant increase of Annexin V positive cells and loss of mitochondrial membrane potential compared with either monotherapy. The combination treatment led to enhanced cleavage of both initiator and effector caspases. Mechanistically, GDC-0941 depleted pAKT (Serine 473) levels and suppressed Mcl-1 protein levels, lowering the threshold for the cytotoxic actions of ABT-263. GDC-0941 decreased Mcl-1 in a posttranslational manner and significantly decreased the half-life of Mcl-1 protein. Ectopic expression of human Mcl-1 mitigated apoptotic cell death induced by the drug combination. Furthermore, GDC-0941 modulated the phosphorylation status of BAD, thereby further enhancing ABT-263–mediated cell death. Implications: Combination therapy with ABT-263 and GDC-0941 has novel therapeutic potential by specifically targeting aberrantly active, deregulated pathways in GBM, overcoming endogenous resistance to apoptosis. Mol Cancer Res; 12(7); 987–1001. ©2014 AACR.

Macroautophagy is a conserved mechanism for the bulk degradation of proteins and organelles. Pathological studies have implicated defective macroautophagy in neurodegeneration, but physiological functions of macroautophagy in adult neurons remain unclear. Here we show that Atg7, an essential macroautophagy component, regulates dopaminergic axon terminal morphology. Mature Atg7-deficient midbrain dopamine (DA) neurons harbored selectively enlarged axonal terminals. This contrasted with the phenotype of DA neurons deficient in Pten – a key negative regulator of the mTOR kinase signaling pathway and neuron size – that displayed enlarged soma but unaltered axon terminals. Surprisingly, concomitant deficiency of both Atg7 and Pten led to a dramatic enhancement of axon terminal enlargement relative to Atg7 deletion alone. Similar genetic interactions between Atg7 and Pten were observed in the context of DA turnover and DA-dependent locomotor behaviors. These data suggest a model for morphological regulation of mature dopaminergic axon terminals whereby the impact of mTOR pathway is suppressed by macroautophagy., Author Summary Macroautophagy is a major recycling pathway in cells, and its dysfunction is associated with neurological disorders including Alzheimer's disease, Parkinson's disease, and frontotemporal dementia. Here we show that Atg7, an essential component of macroautophagy, regulates mature dopaminergic axon terminal morphology in coordination with the well-described role of the PI3K pathway. Deficiency of Pten, a negative regulator of the PI3K/mTOR pathway, leads primarily to enlarged dopaminergic cell soma but normal-appearing axonal terminals, whereas Atg7 deficiency primarily induces enlarged axonal terminals. Atg7 and Pten double deficiency leads to further axon terminal enlargement, suggesting that Atg7 deficiency unmasks the impact of PI3K/mTOR pathway on mature dopaminergic axon terminals. In addition, we show that Atg7 and Pten coordinately regulate striatal dopamine turnover and dopamine-dependent motor behaviors. Taken together, these data support a novel role for Atg7-dependent macroautophagy in the regulation of dopaminergic axon terminal morphology, in coordination with the PI3K/mTOR pathway.

Dizziness is a common presenting complaint to emergency departments and medical admission units; the key is to differentiate between central and peripheral causes of vertigo. This review focuses on bedside assessment of vertigo and, by looking at patterns of symptoms and signs, provides guidance as to when to suspect a central cause.

Aminoglycoside-resistance mechanisms were characterized in Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients during a recent clinical trial of inhaled tobramycin. Impermeability, in which bacteria have reduced susceptibility to all aminoglycosides, was the predominant mode of resistance in isolates obtained both before and after 6 months of cyclic treatment with tobramycin or placebo administered by aerosol. Enzymatic resistance mechanisms were found in fewer than 10% of resistant isolates. P. aeruginosa from individual patients could be grouped on the basis of genetic relatedness. When enzymatic resistance was involved, all isolates in a group had elevated tobramycin MICs. When impermeability occurred, MICs of a genotypic group varied from susceptible to resistant. These findings suggest that impermeability resistance occurs in only a fraction of the P. aeruginosa population in lungs of persons with CF and that this form of resistance arises by a process involving multiple small changes in MIC.

Becoming a male is ultimately determined by androgen-induced masculinisation. Disorders of this, resulting in hypospadias (abnormal penis development) or cryptorchidism (undescended testes), are common disorders in humans. Together with adult onset disorders (low sperm counts, testis germ cell cancer) hypospadias and cryptorchidism may constitute a testicular dysgenesis syndrome (TDS) in humans, with a proposed common fetal origin that may involve deficiencies in androgen production or action. As animal evidence has shown that anti-androgenic endocrine disruptors (EDs) can induce TDS-like effects, concern has grown regarding their potential involvement in human TDS disorders. We have developed a rat model of TDS, in which we have begun to dissect the fetal mechanisms that underlie TDS disorders. Using another rat model in which androgen action is blocked by the anti-androgen flutamide, we have recently identified a ‘male programming window’, which available evidence suggests occurs also in the human fetus (between ∼8 and 12 week's gestation). Androgens must act within this programming window to set up later correct development of the reproductive tract and genitalia. Surprisingly, androgen-driven (abnormal) masculinisation of females is confined to the same programming window as for normal males. Blocking androgen action only within the programming window induces hypospadias and cryptorchidism and alters penile length in males; these all correlate with reduction in anogenital distance (AGD), which provides a non-invasive, lifelong read-out of androgen exposure in the programming window (but not later in gestation). As AGD is measurable in human newborns/neonates, it may predict adult onset TDS disorders and provide clinically important insights into reproductive tract masculinisation and its disorders. With this new understanding we have also begun to explore the role and timescale of effects of androgens in regulation of penile development and size. We show in the rat, that AGD predicts fetal and adult testis size (and thus sperm production), but the mechanism underlying this is unknown as it is not explained by effects on Sertoli cell number, as androgen regulation of Sertoli cell proliferation extends beyond the ‘male programming window’ (when AGD is determined); this relationship is of potential importance in the context of fetal origins of low sperm counts in humans. These findings strongly support the view that deficient fetal androgen action is a key feature of TDS. We postulate that delayed onset of fetal testosterone production may also be important in TDS. These new findings have considerable implications with regard to the time-window of susceptibility of the fetal male to disruption by EDs.