Lack of Association of Vascular Risk Factors with HIV-Associated Neurocognitive Disorders in cART-Treated Adults Aged ≥ 50 Years in Tanzania.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP (p 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.

Delayed follow-up of medical retina patients due to COVID-19: impact on disease activity and visual acuity.

PURPOSE: The coronavirus pandemic has prompted unprecedented delays to treatment with anti-VEGF intravitreal injections due to the need to reduce hospital attendances and prioritise the patients at highest risk of vision loss. This study aims to quantify the effect of these delays on visual acuity (VA) outcomes and optical coherence tomography (OCT) features for patients receiving treatment for neovascular age-related macular degeneration (nAMD), retinal vein occlusions (RVO) and diabetic macular oedema (DMO) and correlate to the Royal College of Ophthalmologists guidelines (RCOphth). METHODS: A retrospective data analysis of an electronic medical record was performed on a random sample of eyes receiving anti-VEGF injections for nAMD, RVO or DMO. Data collected included age, sex, reason for injection, number of weeks delay if > 8 weeks from that planned, VA at baseline and follow-up and the OCT features, if delayed. For those eyes not delayed, a visual acuity at 20 weeks was recorded to provide a control group. RESULTS: A sample of 981 eyes (858 patients) were analysed. There was a delay in review of 8 weeks or more in 39.6% of patients of which 30.4% had since returned for review (28.4% nAMD, 37.6% RVO and 30.0% DMO). There was no demographic difference identified between the delayed and non-delayed patients; however, the delayed group was significantly more likely to have better vision in their non-treated eye (p = 0.0003). A statistically significant difference was found in the change in VA between the delayed and the not-delayed group for eyes with nAMD (p = 0.001) but not for RVO or DMO. For the delayed group, mean CMT increased by 33 and 100 µm, respectively, for nAMD and RVO and decreased by 7.8 µm for DMO. The VA of 89.7% of DMO eyes returned to baseline, compared to 74.6% and 76.9% of nAMD and RVO eyes. CONCLUSION: The RCOphth guidance to prioritise intravitreal injections for nAMD over DMO appears appropriate in this cohort but not for RVO. Eyes with nAMD experienced the greatest loss of vision with treatment delay, and nAMD and RVO eyes were less likely to return to baseline on restarting treatment.

Long-term follow-up of a patient with JAG1-associated retinopathy.

PURPOSE: To report the long-term structural and functional changes in the posterior segments of an adult with an unusual retinal dystrophy caused by a novel mutation in JAG1. METHODS: A 33-year-old female underwent comprehensive ophthalmic examination, including best corrected visual acuity (BCVA) measurement, dilated fundus imaging (wide-angle fundus colour and short wavelength autofluorescence imaging), macular and peripheral spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG) at baseline and 10 years later at the age of 43. The patient also underwent systemic review with detailed cardiac, brain and renal investigations. During follow-up, genetic analysis using whole-exome sequencing was performed on the patient and her parents to identify disease-causing variants. RESULTS: The patient's main complaint was of a recent onset of bilateral photophobia and blurred vision in the left eye. On examination, the most striking retinal finding was of bilateral well-demarcated, anterior circumferential chorioretinal atrophy with scattered pigment clumping from the mid periphery to the ora. In addition, she had posterior pole RPE hypopigmentation, peripapillary chorioretinal atrophy, left macular choroidal folds and retinal vasculature tortuosity with atypical branching. Her retinal electrophysiology was consistent with a cone rod photoreceptor dystrophy and left macular dysfunction. Ten years later, her BCVA, the anterior circumferential chorioretinal atrophy and her visual field constriction all remained stable. Her retinal electrophysiology demonstrated deterioration of left rod function, while cone dysfunction remained stable. Macular function deteriorated in both eyes. During follow-up, she was also noted to have progressive aortic root dilatation, posterior embryotoxon and an x ray diagnosis of butterfly vertebrae. Whole-exome sequencing revealed a novel c.2412C > A p.(Tyr804Ter) truncating mutation in JAG1 that was predicted to be pathogenic and suggested a diagnosis of Alagille syndrome. CONCLUSION: This is the first report of the long-term detailed follow-up of a patient with Alagille syndrome whose most striking ophthalmic finding was bilateral well-demarcated, anterior circumferential chorioretinal atrophy. During follow-up, this finding remained stable, suggesting that this may be developmental in origin. This is in contrast with the progressive deterioration in the posterior pole retinal and macular function.

Macula service evaluation and assessing priorities for anti-VEGF treatment in the light of COVID-19.

PURPOSE: To assess the treatment position of all patients who have had an anti-VEGF injection in 2020, prior to the UK lockdown on 23 March. To assess methods of service quality evaluation in setting benchmarks for comparison after the situation stabilized. To consider what proportion could be delayed based on national guidelines and varying vision parameters. Finally, to measure how many patients actually attended. METHOD: A retrospective analysis of data collected from our electronic medical record was performed. Age, sex, reason for injection, visual acuity (VA) for both treated and untreated eyes and number of injections were recorded. The proportion of patients and eyes with ≥ 70 letters were calculated as an assessment of quality of service provision. The proportion of patients that could be delayed was estimated based on published guidelines and varying the parameters of difference between treated and untreated eyes. Finally, the number of patients who actually attended was recorded. RESULTS: About 3364 eyes (2229 neovascular age-related macular degeneration (nAMD), 427 diabetic macular oedema (DMO), 599 retinal vein occlusion (RVO) and 109 other) from 2924 patients were analysed. At the last appointment with injection, 64.4% of patients achieved ≥ 70 letters in their better-seeing eye. Mean VA of the treated eye was 61.5 letters, and 36.9% achieved ≥ 70. The mean number of injections was 16, 90% with aflibercept. Of the patients receiving treatment to one eye, 57.6% was receiving treatment to their worse seeing eye. In 18.2% this eye was > 20 letters worse and in 5.07% > 40 letters worse than the untreated eye. Using Royal College of Ophthalmologists (RCOphth) guidelines, (treat nAMD 8 weekly, delay majority of RVO and DMO) 24.8% would be delayed. From 2738 appointments during the first 4 weeks of lockdown (booked prior to lockdown), doctors rescheduled 1025 and patients did not attend 820, leaving 893 who were seen (33%). CONCLUSIONS: Assessing the treatment position of patients prior to COVID-19 lockdown enables objective stratification for prioritization for continued treatment. If RCOphth guidelines were followed 24.8% could be delayed and if treating the worse seeing eye up to 57.6%. Many scheduled patients elected not to attend, with 67% not seen in the first 4 weeks. The impact of non-attendance and delays may be evaluated later.

Screening for Instrumental Activities of Daily Living in Sub-Saharan Africa: A Balance Between Task Shifting, Simplicity, Brevity, and Training.

BACKGROUND: Task shifting has been suggested as one way to help manage the increasing burden of dementia in sub-Saharan Africa (SSA). However, brief, easy-to-use and valid screening tools are needed to support this approach. Our team has developed an 11-item questionnaire to assess instrumental activities of daily living (IADLs) in SSA, the Identification and Intervention for Dementia in Elderly Africans (IDEA)-IADL questionnaire. We aimed to externally validate the questionnaire and develop a shorter, more efficient version. METHODS: A community-based sample of 329 older adults in 4 rural villages was screened for dementia using the validated IDEA cognitive screen and the 11-item IDEA-IADL questionnaire. A stratified sample was assessed for Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) dementia by a United Kingdom-based doctor, who was blinded to the results of screening. Area under the receiver operating characteristic (AUROC) curve analysis was used to assess validity, and factor analysis and regression modeling were used to develop a shorter version of the questionnaire. RESULTS: A 3-item IDEA-IADL questionnaire was developed and externally validated in the study sample. The questionnaire was deemed to be valid and enhanced screening performance in 2 villages (AUROC: 0.857 and 0.895) but detracted from the accuracy of the IDEA cognitive screen in the other 2 villages (AUROC: 0.591 and 0.639). These differences appeared to be due to differences in interpretation of responses to questions by the assessors. CONCLUSIONS: A brief IDEA-IADLs scale was developed and worked well in some villages. However, our study highlights a training need if brief screening tools to assess IADLs are to be effectively used by nonspecialists in low-resource settings.

A longitudinal study of cognitive decline in rural Tanzania: rates and potentially modifiable risk factors.

ABSTRACTBackground:The number of people living with dementia in sub-Saharan Africa (SSA) is expected to increase rapidly in the coming decades. However, our understanding of how best to reduce dementia risk in the population is very limited. As a first step in developing intervention strategies to manage dementia risk in this setting, we investigated rates of cognitive decline in a rural population in Tanzania and attempted to identify associated factors. METHODS: The study was conducted in the rural Hai district of northern Tanzania. In 2014, community-dwelling people aged 65 years and over living in six villages were invited to take part in a cognitive screening program. All participants from four of the six villages were followed-up at two years and cognitive function re-tested. At baseline and follow-up, participants were assessed for functional disability, hypertension, and grip strength (as a measure of frailty). At follow-up, additional assessments of visual acuity, hearing impairment, tobacco and alcohol consumption, and clinical assessment for stroke were completed. RESULTS: Baseline and follow-up data were available for 327 people. Fifty people had significant cognitive decline at two-year follow-up. Having no formal education, low grip strength at baseline, being female and having depression at follow-up were independently associated with cognitive decline. CONCLUSIONS: This is one of the first studies of cognitive decline conducted in SSA. Rates of decline at two years were relatively high. Future work should focus on identification of specific modifiable risk factors for cognitive decline with a view to developing culturally appropriate interventions.