Confronting the human papillomavirus-HIV intersection: Cervical cytology implications for Kenyan women living with HIV.

Background: High-risk human papillomavirus (HR-HPV) is the primary cause of cervical cancer, leading to over 311 000 global deaths, mainly in low- and middle-income countries. Kenyan women living with HIV (WLHIV) face a disproportionate burden of HR-HPV. Objectives: We determined the prevalence of HR-HPV infections and their association with cervical cytology findings among Kenyan WLHIV. Method: We conducted a cross-sectional study among WLHIV attending the HIV care and treatment clinic at the Kenyatta National Hospital (KNH), Kenya's national referral hospital. Study nurses collected a cervical sample with a cytobrush for HR-HPV genotyping using Gene Xpert® assays and HPV Genotypes 14 Real-TM Quant V67-100FRT. Bivariate analysis explored the associations. Results: We enrolled 647 WLHIV (mean age of 42.8 years), with 97.2% on antiretroviral therapy (ART) and 79% with a suppressed viral load (< 50 copies/mL plasma). The prevalence of any and vaccine-preventable HR-HPV was 34.6% and 29.4%, respectively, with HPV 52 being the most common genotype (13.4%). Among WLHIV with HR-HPV infections, 21.4% had abnormal cervical cytology. Women with multiple HR-HPV infections were more likely to have abnormal cytology compared to those with single HR-HPV infections (34.9 vs 9.3%, adjusted odds ratio [aOR] = 6.2, 95% confidence interval [CI]: 2.7-14.1, P = 0.001). Women with HR-HPV infection (single or multiple) were more likely to be on the second-line ART regimen compared to those without HR-HPV infections (53.1% vs 46.7%, aOR = 2.3, 95% CI: 1.3-4.1, P = 0.005). Conclusion: Among WLHIV at KNH, abnormal cytology was common and more frequent among women with multiple HR-HPV infections.

The Impact of Simulation-Based Trabeculectomy Training on Resident Core Surgical Skill Competency.

PRCIS: Simulation-based surgical education shows a positive, immediate, and sustained impact on core surgical skill competency in trabeculectomy among resident ophthalmologists in training. PURPOSE: To measure the impact of trabeculectomy, surgical simulation training on core surgical skill competency in resident ophthalmologists. MATERIALS AND METHODS: This is a post hoc analysis of the GLAucoma Simulated Surgery trial, which is a multicenter, multinational randomized controlled trial. Resident ophthalmologists from 6 training centers in sub-Saharan Africa (in Kenya, Uganda, Tanzania, Zimbabwe, and South Africa) were recruited according to the inclusion criteria of having performed zero surgical trabeculectomies and assisted in <5. Participants were randomly assigned to intervention and control arms using allocation concealment. The intervention was a 1-week intensive trabeculectomy surgical simulation course. Outcome measures were mean surgical competency scores in 8 key trabeculectomy surgical skills (scleral incision, scleral flap, releasable suturing, conjunctival suturing, sclerostomy, tissue handling, fluidity, and speed), using a validated scoring tool. RESULTS: Forty-nine residents were included in the intention-to-treat analysis. Baseline characteristics were balanced between arms. Median baseline surgical competency scores were 2.88/16 [interquartile range (IQR): 1.75-4.17] and 3.25/16 (IQR: 1.83-4.75) in the intervention and control arms, respectively. At primary intervention, median scores increased to 11.67/16 (IQR: 9.58-12.63) and this effect was maintained at 3 months and 1 year ( P =0.0001). Maximum competency scores at primary intervention were achieved in the core trabeculectomy skills of releasable suturing (n=17, 74%), scleral flap formation (n=16, 70%), and scleral incision (n=15, 65%) compared with scores at baseline. CONCLUSIONS: This study demonstrates the positive impact of intensive simulation-based surgical education on core trabeculectomy skill development. The rapid and sustained effect of resident skill acquisition pose strong arguments for its formal integration into ophthalmic surgical education.

Simulation-based surgical education for glaucoma versus conventional training alone: the GLAucoma Simulated Surgery (GLASS) trial. A multicentre, multicountry, randomised controlled, investigator-masked educational intervention efficacy trial in Kenya, South Africa, Tanzania, Uganda and Zimbabwe.

BACKGROUND/AIM: Glaucoma 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. METHODS: We 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. RESULTS: Twenty-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, p<0.001). At 1 year, the mean surgical competency score of the intervention arm participants was 28.6 (71.5%), compared with 11.6 (29.0%) for the control (difference 17.0, 95% CI 14.8 to 19.4, p<0.001). CONCLUSION: These 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 NUMBER: PACTR201803002159198.

How can we improve the quality of cataract services for all? A global scoping review.

BACKGROUND: Cataract is a leading cause of blindness and vision impairment globally. Cataract surgery is one of the most frequently performed operations worldwide, but good quality services are not universally available. This scoping review aims to summarise the nature and extent of published literature on interventions to improve the quality of services for age-related cataract globally. METHODS: We used the dimensions of quality adopted by WHO-effectiveness, safety, people-centredness, timeliness, equity, integration and efficiency-to which we added planetary health. On 17 November 2019, we searched MEDLINE, Embase and Global Health for manuscripts published since 1990, without language or geographic restrictions. We included studies that reported quality-relevant interventions and excluded studies focused on technical aspects of surgery or that only involved children (younger than 18 years). Screening of titles/abstracts, full-text review and data extraction were performed by two reviewers independently. Studies were grouped thematically and results synthesised narratively. RESULTS: Most of the 143 included studies were undertaken in high-income countries (n = 93, 65%); 29 intervention groups were identified, most commonly preoperative education (n = 17, 12%) and pain/anxiety management (n = 16, 11%). Efficiency was the quality element most often assessed (n = 58, 41%) followed by people-centredness (n = 40, 28%), while integration (n = 4) and timeliness (n = 3) were infrequently reported, and no study reported outcomes related to planetary health. CONCLUSION: Evidence on interventions to improve quality of cataract services shows unequal regional distribution. There is an urgent need for more evidence relevant to low- and middle-income countries as well as across all quality elements, including planetary health.

Experiences and Perceptions of Ophthalmic Simulation-Based Surgical Education in Sub-Saharan Africa.

BACKGROUND: Simulation-based surgical education (SBSE) can positively impact trainee surgical competence. However, a detailed qualitative study of the role of simulation in ophthalmic surgical education has not previously been conducted. OBJECTIVE: To explore the experiences of trainee ophthalmologists and ophthalmic surgeon educators' use of simulation, and the perceived challenges in surgical training. METHODS: A multi-center, multi-country qualitative study was conducted between October 2017 and August 2020. Trainee ophthalmologists from six training centers in sub-Saharan Africa (SSA) (in Kenya, Uganda, Tanzania, Zimbabwe and South Africa) participated in semi-structured interviews, before and after an intense simulation training course in intraocular surgery. Semi-structured interviews were also conducted with experienced ophthalmic surgeon educators. Interviews were anonymized, recorded, transcribed and coded. An inductive, bottom-up, constant comparative method was used for thematic analysis. RESULTS: Twenty-seven trainee ophthalmologists and 12 ophthalmic surgeon educators were included in the study and interviewed. The benefits and challenges of conventional surgical teaching, attributes of surgical educators, value of simulation in training and barriers to implementing ophthalmic surgical simulation were identified as major themes. Almost all trainees and trainers reported patient safety, a calm environment, the possibility of repetitive practice, and facilitation of reflective learning as beneficial aspects of ophthalmic SBSE. Perceived barriers in surgical training included a lack of surgical cases, poor supervision and limited simulation facilities. CONCLUSIONS: Simulation is perceived as an important and valuable model for education amongst trainees and ophthalmic surgeon educators in SSA. Advocating for the expansion and integration of educationally robust simulation surgical skills centers may improve the delivery of ophthalmic surgical education throughout SSA.

Ophthalmology training in sub-Saharan Africa: a scoping review.

Sub-Saharan Africa is home to 12% of the global population, and 4.3 million are blind and over 15 million are visually impaired. There are only 2.5 ophthalmologists per million people in SSA. Training of ophthalmologists is critical. We designed a systematic literature review protocol, searched MEDLINE Ovid and Embase OVID on 1 August 2019 and limited these searches to the year 2000 onwards. We also searched Google Scholar and websites of ophthalmic institutions for additional information. We include a total of 49 references in this review and used a narrative approach to synthesise the results. There are 56 training institutions for ophthalmologists in eleven Anglophone, eleven Francophone, and two Lusophone SSA countries. The median duration of ophthalmology training programmes was 4 years. Most curricula have been regionally standardised. National, regional and international collaborations are a key feature to ophthalmology training in more than half of ophthalmology training programmes. There is a drive, although perhaps not always evidence-based, for sub-specialisation in the region. Available published scientific data on ophthalmic medical and surgical training in SSA is sparse, especially for Francophone and Lusophone countries. However, through a broad scoping review strategy it has been possible to obtain a valuable and detailed view of ophthalmology training in SSA. Training of ophthalmologists is a complex and multi-faceted task. There are challenges in appropriate selection, capacity, and funding of available training institutions. Numerous learning outcomes demand curriculum, time, faculty, support, and appropriate assessment. There are opportunities provided by modern training approaches. Partnership is key.

Intense Simulation-Based Surgical Education for Manual Small-Incision Cataract Surgery: The Ophthalmic Learning and Improvement Initiative in Cataract Surgery Randomized Clinical Trial in Kenya, Tanzania, Uganda, and Zimbabwe.

Importance: Cataracts account for 40% of cases of blindness globally, with surgery the only treatment. Objective: To determine whether adding simulation-based cataract surgical training to conventional training results in improved acquisition of surgical skills among trainees. Design, Setting, and Participants: A multicenter, investigator-masked, parallel-group, randomized clinical educational-intervention trial was conducted at 5 university hospital training institutions in Kenya, Tanzania, Uganda, and Zimbabwe from October 1, 2017, to September 30, 2019, with a follow-up of 15 months. Fifty-two trainee ophthalmologists were assessed for eligibility (required no prior cataract surgery as primary surgeon); 50 were recruited and randomized. Those assessing outcomes of surgical competency were masked to group assignment. Analysis was performed on an intention-to-treat basis. Interventions: The intervention group received a 5-day simulation-based cataract surgical training course, in addition to standard surgical training. The control group received standard training only, without a placebo intervention; however, those in the control group received the intervention training after the initial 12-month follow-up period. Main Outcomes and Measures: The primary outcome measure was overall surgical competency at 3 months, which was assessed with a validated competency assessment rubric. Secondary outcomes included surgical competence at 1 year and quantity and outcomes (including visual acuity and posterior capsule rupture) of cataract surgical procedures performed during a 1-year period. Results: Among the 50 participants (26 women [52.0%]; mean [SD] age, 32.3 [4.6] years), 25 were randomized to the intervention group, and 25 were randomized to the control group, with 1 dropout. Forty-nine participants were included in the final intention-to-treat analysis. Baseline characteristics were balanced. The participants in the intervention group had higher scores at 3 months compared with the participants in the control group, after adjusting for baseline assessment rubric score. The participants in the intervention group were estimated to have scores 16.6 points (out of 40) higher (95% CI, 14.4-18.7; P < .001) at 3 months than the participants in the control group. The participants in the intervention group performed a mean of 21.5 cataract surgical procedures in the year after the training, while the participants in the control group performed a mean of 8.5 cataract surgical procedures (mean difference, 13.0; 95% CI, 3.9-22.2; P < .001). Posterior capsule rupture rates (an important complication) were 7.8% (42 of 537) for the intervention group and 26.6% (54 of 203) for the control group (difference, 18.8%; 95% CI, 12.3%-25.3%; P < .001). Conclusions and Relevance: This randomized clinical trial provides evidence that intense simulation-based cataract surgical education facilitates the rapid acquisition of surgical competence and maximizes patient safety. Trial Registration: Pan-African Clinical Trial Registry, number PACTR201803002159198.

Interventions to improve the quality of cataract services: protocol for a global scoping review.

INTRODUCTION: Cataract is the leading cause of blindness globally and a major cause of vision impairment. Cataract surgery is an efficacious intervention that usually restores vision. Although it is one of the most commonly conducted surgical interventions worldwide, good quality services (from being detected with operable cataract to undergoing surgery and receiving postoperative care) are not universally accessible. Poor quality understandably reduces the willingness of people with operable cataract to undergo surgery. Therefore, it is critical to improve the quality of care to subsequently reduce vision loss from cataract. This scoping review aims to summarise the nature and extent of the published literature on interventions to improve the quality of services for primary age-related cataract globally. METHODS AND ANALYSIS: We will search MEDLINE, Embase and Global Health for peer-reviewed manuscripts published since 1990, with no language, geographic or study design restrictions. To define quality, we have used the elements adopted by the WHO-effectiveness, safety, people-centredness, timeliness, equity, integration and efficiency-to which we have added the element of planetary health. We will exclude studies focused on the technical aspects of the surgical procedure and studies that only involve children (<18 years). Two reviewers will screen all titles/abstracts independently, followed by a full-text review of potentially relevant articles. For included articles, data regarding publication characteristics, study details and quality-related outcomes will be extracted by two reviewers independently. Results will be synthesised narratively and presented visually using a spider chart. ETHICS AND DISSEMINATION: Ethical approval was not sought, as our review will only include published and publicly accessible information. We will publish our findings in an open-access peer-reviewed journal and develop an accessible summary of the results for website posting. A summary of the results will be included in the ongoing Lancet Global Health Commission on Global Eye Health. REGISTRATION DETAILS: Open Science Framework (https://osf.io/8gktz).

Ocular Surface Disorders in Patients with Human Immunodeficiency Virus (HIV) Infection.

Purpose: To describe ocular surface disorders associated with human immunodeficiency virus (HIV). Methods: Narrative review. Results: Ocular surface neoplastic conditions, such as Kaposi's sarcoma, conjunctival lymphoma and ocular squamous cell carcinoma along with blepharitis, dry eye disease, and vernal keratoconjunctivitis, constitute ocular surface complications in HIV-infected individuals. Conclusion: This review will provide a summary of clinical presentations and treatment options for the most common HIV-related ocular surface diseases, indicating the need for a comprehensive ocular examination including ocular surface in all HIV patients 22.

Survey of ophthalmologists-in-training in Eastern, Central and Southern Africa: A regional focus on ophthalmic surgical education.

Background: There are 2.7 ophthalmologists per million population in sub-Saharan Africa, and a need to train more. We sought to analyse current surgical training practice and experience of ophthalmologists to inform planning of training in Eastern, Central and Southern Africa. Methods: This was a cross-sectional survey. Potential participants included all current trainee and recent graduate ophthalmologists in the Eastern, Central and Southern African region. A link to a web-based questionnaire was sent to all heads of eye departments and training programme directors of ophthalmology training institutions in Eastern, Central and Southern Africa, who forwarded to all their trainees and recent graduates. Main outcome measures were quantitative and qualitative survey responses. Results: Responses were obtained from 124 (52%) trainees in the region. Overall level of satisfaction with ophthalmology training programmes was rated as 'somewhat satisfied' or 'very satisfied' by 72%. Most frequent intended career choice was general ophthalmology, with >75% planning to work in their home country post-graduation. A quarter stated a desire to mainly work in private practice. Only 28% of junior (first and second year) trainees felt surgically confident in manual small incision cataract surgery (SICS); this increased to 84% among senior trainees and recent graduates. The median number of cataract surgeries performed by junior trainees was zero. 57% of senior trainees were confident in performing an anterior vitrectomy. Only 29% of senior trainees and 64% of recent graduates were confident in trabeculectomy. The mean number of cataract procedures performed by senior trainees was 84 SICS (median 58) and 101 phacoemulsification (median 0). Conclusion: Satisfaction with post-graduate ophthalmology training in the region was fair. Most junior trainees experience limited cataract surgical training in the first two years. Focused efforts on certain aspects of surgical education should be made to ensure adequate opportunities are offered earlier on in ophthalmology training.

Peek Community Eye Health - mHealth system to increase access and efficiency of eye health services in Trans Nzoia County, Kenya: study protocol for a cluster randomised controlled trial.

BACKGROUND: Globally, eye care provision is currently insufficient to meet the requirement for eye care services. Lack of access and awareness are key barriers to specialist services; in addition, specialist services are over-utilised by people with conditions that could be managed in the community or primary care. In combination, these lead to a large unmet need for eye health provision. We have developed a validated smartphone-based screening algorithm (Peek Community Screening App). The application (App) is part of the Peek Community Eye Health system (Peek CEH) that enables Community Volunteers (CV) to make referral decisions about patients with eye problems. It generates referrals, automated short messages service (SMS) notifications to patients or guardians and has a program dashboard for visualising service delivery. We hypothesise that a greater proportion of people with eye problems will be identified using the Peek CEH system and that there will be increased uptake of referrals, compared to those identified and referred using the current community screening approaches. STUDY DESIGN: A single masked, cluster randomised controlled trial design will be used. The unit of randomisation will be the 'community unit', defined as a dispensary or health centre with its catchment population. The community units will be allocated to receive either the intervention (Peek CEH system) or the current care (periodic health centre-based outreach clinics with onward referral for further treatment). In both arms, a triage clinic will be held at the link health facility four weeks from sensitisation, where attendance will be ascertained. During triage, participants will be assessed and treated and, if necessary, referred onwards to Kitale Eye Unit. DISCUSSION: We aim to evaluate a M-health system (Peek CEH) geared towards reducing avoidable blindness through early identification and improved adherence to referral for those with eye problems and reducing demand at secondary care for conditions that can be managed effectively at primary care level. TRIAL REGISTRATION: The Pan African Clinical Trials Registry (PACTR), 201807329096632 . Registered on 8 June 2018.

Effectiveness of peer support to increase uptake of retinal examination for diabetic retinopathy: study protocol for the DURE pragmatic cluster randomized clinical trial in Kirinyaga, Kenya.

BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. TRIAL REGISTRATION: Pan African Clinical Trial Registry PACTR201707002430195 , registered 25 July 2017, www.pactr.org.

Surgery for postvitrectomy cataract.

BACKGROUND: Cataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique for removing the vitreous that is used in the treatment of many disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit the benefit from removal of the cataractous lens. OBJECTIVES: To evaluate the effectiveness and safety of surgery versus no surgery for postvitrectomy cataract with respect to visual acuity, quality of life, and other outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 5), MEDLINE Ovid (1946 to 17 May 2017), Embase.com (1947 to 17 May 2017), PubMed (1946 to 17 May 2017), Latin American and Caribbean Health Sciences Literature database (LILACS) (January 1982 to 17 May 2017), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com); last searched May 2013, ClinicalTrials.gov (www.clinicaltrials.gov); searched 17 May 2017, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 17 May 2017. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We planned to include randomized controlled trials (RCTs) and quasi-RCTs that had compared surgery versus no surgery to remove the lens from eyes of adults in which cataracts had developed following vitrectomy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results according to the standard methodological procedures expected by Cochrane. MAIN RESULTS: We found no RCTs or quasi-RCTs that had compared surgery versus no surgery to remove the lens from eyes of adults in which cataracts had developed following vitrectomy. AUTHORS' CONCLUSIONS: There is no evidence from RCTs or quasi-RCTs on which to base clinical recommendations for surgery for postvitrectomy cataract. There is a clear need for RCTs to address this evidence gap. Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the underlying disease process in the contralateral eye. Outcomes assessed in such trials may include changes (both gains and losses) of visual acuity, quality of life, and adverse events such as posterior capsular rupture and retinal detachment. Both short-term (six-month) and long-term (one- or two-year) outcomes should be examined.

Delay along the care-seeking journey of patients with ocular surface squamous neoplasia in Kenya.

BACKGROUND: In Africa, accessing eye health services is a major challenge. Ocular surface squamous neoplasia (OSSN) is a substantial ocular health problem in Africa related to solar UV light exposure and HIV infection among other risk factors. The disease causes visual loss and even death in advanced cases. This study was conducted to assess referral pathway and treatment delay for patients with OSSN in Kenya. METHODS: Adults with conjunctival lesions presenting to four eye centres were asked about their occupations, when they noticed the growth, health facilities visited in seeking care, cost of consultation, surgery, medicines and histopathology and dates at each step. The time-to-presentation was divided into quartiles and correlates analysed using ordinal logistic regression. RESULTS: We evaluated 158 first-time presenters with OSSN. Most were women (102 [65%]), living with HIV (78/110 tested [71%]), with low to medium income (127 [80%]). Most of the HIV patients (49/78 [63%]) were in antiretroviral care programs. About half (88/158, [56%]) presented directly to the study centres while the rest were referred. Indirect presenters sought care earlier than direct presenters (median 2.0 months vs 5.5 months) and travelled a shorter distance to the first health facility (median 20 km vs 30 km) but had surgery later (median 12.5 months vs 5.5 months). Visits beyond the first health facility for indirect presenters markedly increased delay (median 7.3, 29.0, 37.9, and 32.0 months for 1-4 facilities, respectively). Delay was associated with number of health facilities visited (adjusted ordered OR = 9.12; 95%CI 2.83-29.4, p < 0.001) and being female (adjusted ordered OR = 2.42; 95%CI 1.32-4.44, p = 0.004). At the time of presentation at the study centres for surgery the median tumour diameter in both directly and indirectly presenting patients was 6 mm (p = 0.52) and the histological spectrum of OSSN was similar between the groups (p = 0.87). CONCLUSIONS: Referral delays definitive treatment for OSSN. Women were more likely to experience delay. Despite regular contact with the health system for those with known HIV infection, delays occurred. Early detection and referral of OSSN in the HIV service might reduce delays, but reassuringly delay did not give rise to a larger proportion with more advanced grade of OSSN.

Risk factors for ocular surface squamous neoplasia in Kenya: a case-control study.

OBJECTIVE: To determine modifiable risk factors of ocular surface squamous neoplasia (OSSN) in Kenya using disease-free controls. METHODS: Adults with conjunctival lesions were recruited at four eye care centres in Kenya and underwent excision biopsy. An equal number of controls having surgery for conditions not affecting the conjunctiva and unrelated to ultraviolet light were group-matched to cases by age group, sex and eye care centre. Associations of risk factors with OSSN were evaluated using multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Continuous variables were compared using the t-test or the Wilcoxon-Mann-Whitney U-test depending on their distribution. RESULTS: A total of 131 cases and 131 controls were recruited. About two-thirds of participants were female, and the mean age of cases and controls was 42.1 years and 43.3 years, respectively. Risk factors for OSSN were HIV infection without antiretroviral therapy (ART) use (OR = 48.42; 95% CI: 7.73-303.31) and with ART use (OR = 19.16; 95% CI: 6.60-55.57), longer duration of exposure to the sun in the main occupation (6.9 h/day vs. 4.6 h/day, OR = 1.24; 95% CI: 1.10-1.40) and a history of allergic conjunctivitis (OR = 74.61; 95% CI: 8.08-688.91). Wearing hats was protective (OR = 0.22; 95% CI: 0.07-0.63). CONCLUSION: Measures to prevent and control HIV, reduce sun exposure such as wearing hats and control allergic conjunctivitis are recommended.

Topical fluorouracil after surgery for ocular surface squamous neoplasia in Kenya: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Ocular surface squamous neoplasia (OSSN) is an aggressive eye tumour particularly affecting people with HIV in Africa. Primary treatment is surgical excision; however, tumour recurrence is common. We assessed the effect of fluorouracil 1% eye drops after surgery on recurrence. METHODS: We did this multicentre, randomised, placebo-controlled trial in four centres in Kenya. We enrolled patients with histologically proven OSSN aged at least 18 years. After standard surgical excision, participants were randomly allocated to receive either topical fluorouracil 1% or placebo four times a day for 4 weeks. Randomisation was stratified by surgeon, and participants and trial personnel were masked to assignment. Patients were followed up at 1 month, 3 months, 6 months, and 12 months. The primary outcome was clinical recurrence (supported by histological assessment where available) by 1 year, and analysed by intention to treat. The sample size was recalculated because events were more common than anticipated, and trial enrolment was stopped early. The trial was registered with Pan-African Clinical Trials Registry (PACTR201207000396219). FINDINGS: Between August, 2012, and July, 2014, we assigned 49 participants to fluorouracil and 49 to placebo. Four participants were lost to follow-up. Recurrences occurred in five (11%) of 47 patients in the fluorouracil group and 17 (36%) of 47 in the placebo group (odds ratio 0·21, 95% CI 0·07-0·63; p=0·01). Adjusting for passive smoking and antiretroviral therapy had little effect (odds ratio 0·23; 95% CI 0·07-0·75; p=0·02). Adverse effects occurred more commonly in the fluorouracil group, although they were transient and mild. Ocular discomfort occurred in 43 of 49 patients in the fluorouracil group versus 36 of 49 in the placebo group, epiphora occurred in 24 versus five, and eyelid skin inflammation occurred in seven versus none. INTERPRETATION: Topical fluorouracil after surgery substantially reduced recurrence of OSSN, was well-tolerated, and its use recommended. FUNDING: British Council for Prevention of Blindness and the Wellcome Trust.

Clinical Presentation of Ocular Surface Squamous Neoplasia in Kenya.

IMPORTANCE: There is a trend toward treating conjunctival lesions suspected to be ocular surface squamous neoplasia (OSSN) based on the clinical impression. OBJECTIVE: To describe the presentation of OSSN and identify clinical features that distinguish it from benign lesions and subsequently evaluate their recognizability. DESIGN, SETTING, AND PARTICIPANTS: Prospective multicenter study in Kenya from July 2012 through July 2014 of 496 adults presenting with conjunctival lesions. One histopathologist examined all specimens. Six additional masked ophthalmologists independently examined photographs from 100 participants and assessed clinical features. EXPOSURES: Comprehensive history, slitlamp examination, and photography before excision biopsy. MAIN OUTCOMES AND MEASURES: Frequency of clinical features in OSSN and benign lesions were recorded. Proportions and means were compared using χ2, Fisher exact test, or t test as appropriate. Interobserver agreement was estimated using the κ statistic. Examiners' assessments were compared with a reference. RESULTS: Among 496 participants, OSSN was the most common (38%) histological diagnosis, followed by pterygium (36%) and actinic keratosis (19%). Patients with OSSN were slightly older (mean [SD] age, 41 [11.6] vs 38 [10.9] years; P = .002) and tended to have lower levels of education than patients with benign lesions (P = .001). Females predominated (67% of OSSN vs 64% of benign lesions; P = .65). Human immunodeficiency virus infection was common among patients with OSSN (74%). The most common location was the nasal limbus (61% OSSN vs 78% benign lesions; P < .001). Signs more frequent in OSSN included feeder vessels (odds ratio [OR], 5.8 [95% CI, 3.2-10.5]), moderate inflammation (OR, 3.5 [95% CI, 1.8-6.8]), corneal involvement (OR, 2.7 [95% CI, 1.8-4.0]), leukoplakia (OR, 2.6 [95% CI, 1.7-3.9]), papilliform surface (OR, 2.1 [95% CI, 1.3-3.5]), pigmentation (OR, 1.5 [95% CI, 1.0-2.2]), temporal location (OR, 2.0 [95% CI, 1.2-3.2]), circumlimbal location (6.7% vs 0.3%; P < .001), severe inflammation (6.7% vs 0.3%; P < .001), and larger mean (SD) diameter (6.8 [3.2] vs 4.8 [2.8] mm; P < .001). All OSSN signs were also observed in benign lesions. There was slight to fair interobserver agreement in assessment of most signs and diagnosis (κ, 0.1-0.4). The positive predictive value of clinical appearance in identifying OSSN was 54% (interquartile range, 51%-56%) from photographs in which prevalence was 32%. CONCLUSIONS AND RELEVANCE: With overlapping phenotypes and modest interobserver agreement, OSSN and benign conjunctival lesions are not reliably distinguished clinically. Point-of-care diagnostic tools may help.

Toluidine Blue 0.05% Vital Staining for the Diagnosis of Ocular Surface Squamous Neoplasia in Kenya.

IMPORTANCE: Clinical features are unreliable for distinguishing ocular surface squamous neoplasia (OSSN) from benign conjunctival lesions. OBJECTIVE: To evaluate the adverse effects, accuracy, and interobserver variation of toluidine blue 0.05% vital staining in distinguishing OSSN, confirmed by histopathology, from other conjunctival lesions. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study in Kenya from July 2012 through July 2014 of 419 adults with suspicious conjunctival lesions. Pregnant and breastfeeding women were excluded. EXPOSURES: Comprehensive ophthalmic slitlamp examination was conducted. Vital staining with toluidine blue 0.05% aqueous solution was performed before surgery. Initial safety testing was conducted on large tumors scheduled for exenteration looking for corneal toxicity on histology before testing smaller tumors. We asked about pain or discomfort after staining and evaluated the cornea at the slitlamp for epithelial defects. Lesions were photographed before and after staining. MAIN OUTCOMES AND MEASURES: Diagnosis was confirmed by histopathology. Six examiners assessed photographs from a subset of 100 consecutive participants for staining and made a diagnosis of OSSN vs non-OSSN. Staining was compared with histopathology to estimate sensitivity, specificity, and predictive values. Adverse effects were enumerated. Interobserver agreement was estimated using the κ statistic. RESULTS: A total of 143 of 419 participants (34%) had OSSN by histopathology. The median age of all participants was 37 years (interquartile range, 32-45 years) and 278 (66%) were female. A total of 322 of the 419 participants had positive staining while 2 of 419 were equivocal. There was no histological evidence of corneal toxicity. Mild discomfort was reported by 88 (21%) and mild superficial punctate keratopathy seen in 7 (1.7%). For detecting OSSN, toluidine blue had a sensitivity of 92% (95% CI, 87%-96%), specificity of 31% (95% CI, 25%-36%), positive predictive value of 41% (95% CI, 35%-46%), and negative predictive value of 88% (95% CI, 80%-94%). Interobserver agreement was substantial for staining (κ = 0.76) and moderate for diagnosis (κ = 0.40). CONCLUSIONS AND RELEVANCE: With the high sensitivity and low specificity for OSSN compared with histopathology among patients with conjunctival lesions, toluidine blue 0.05% vital staining is a good screening tool. However, it is not a good diagnostic tool owing to a high frequency of false-positives. The high negative predictive value suggests that a negative staining result indicates that OSSN is relatively unlikely.

Pathophysiology of ocular surface squamous neoplasia.

The incidence of ocular surface squamous neoplasia (OSSN) is strongly associated with solar ultraviolet (UV) radiation, HIV and human papilloma virus (HPV). Africa has the highest incidence rates in the world. Most lesions occur at the limbus within the interpalpebral fissure particularly the nasal sector. The nasal limbus receives the highest intensity of sunlight. Limbal epithelial crypts are concentrated nasally and contain niches of limbal epithelial stem cells in the basal layer. It is possible that these are the progenitor cells in OSSN. OSSN arises in the basal epithelial cells spreading towards the surface which resembles the movement of corneo-limbal stem cell progeny before it later invades through the basement membrane below. UV radiation damages DNA producing pyrimidine dimers in the DNA chain. Specific CC → TT base pair dimer transformations of the p53 tumour-suppressor gene occur in OSSN allowing cells with damaged DNA past the G1-S cell cycle checkpoint. UV radiation also causes local and systemic photoimmunosuppression and reactivates latent viruses such as HPV. The E7 proteins of HPV promote proliferation of infected epithelial cells via the retinoblastoma gene while E6 proteins prevent the p53 tumour suppressor gene from effecting cell-cycle arrest of DNA-damaged and infected cells. Immunosuppression from UV radiation, HIV and vitamin A deficiency impairs tumour immune surveillance allowing survival of aberrant cells. Tumour growth and metastases are enhanced by; telomerase reactivation which increases the number of cell divisions a cell can undergo; vascular endothelial growth factor for angiogenesis and matrix metalloproteinases (MMPs) that destroy the intercellular matrix between cells. Despite these potential triggers, the disease is usually unilateral. It is unclear how HPV reaches the conjunctiva.