Prevalence of HIV-associated ophthalmic disease among patients enrolling for antiretroviral treatment in India: a cross-sectional study.

BACKGROUND: The ocular manifestations of HIV may lead to visual impairment or blindness. In India, patients typically initiate antiretroviral treatment (ART) with low CD4 cell counts when the risk of ocular complications may be high. The objective of this study was to determine the prevalence and types of HIV-associated ocular conditions in patients referred for ART in India. METHODS: This cross-sectional study was undertaken at a large public sector ART centre in Mumbai, India. Data collection including a standardised symptom screen, and an ophthalmic examination were performed on all consecutive patients satisfying the criteria for enrollment into the ART clinic irrespective of the presence or absence of ophthalmic/visual symptoms. RESULTS: Enrolled patients (n = 149) had a median CD4 cell count of 180 cell/microL (inter-quartile range [IQR], 106-253 cells/microL). The prevalence of HIV-associated ocular disease was 17.5% (95% CI, 11.2-23.6%) in all participants and 23.8% (95% CI: 14.5-33.1) in those with CD4 cell counts <200 cells/microL (n = 84). Only 7.7% of patients with HIV-associated ocular disease reported any eye symptoms in the standardised symptom screen. Objective visual impairment was detected in 20% of those with HIV-associated ocular disease compared to 6% in those without ocular manifestations (p = 0.02). Vitreoretinal disease was the most common manifestation, of which cytomegalovirus retinitis (CMVR) was the most frequent retinal infection (overall prevalence 8.7%, 95% CI: 4.1-13.3%). In a multivariable analysis, HIV-associated ocular disease was independently associated with a CD4 count <100 cells/microL (odds ratio [OR], 6.3, 95% CI: 1.5-25.9) and WHO clinical stages 3 and 4 (OR 9.4, 95% CI: 2.4-37.2). However, symptoms were not independently predictive of ocular disease. Sensitivity of ocular symptom screening was 7.7%, with a positive predictive value of 18% in this population. CONCLUSION: Over a fifth of unselected patients who are eligible for ART in this setting have HIV-related ocular disease of which CMVR is the most common form. Such patients may be at risk of developing ocular immune reconstitution phenomena during ART. Screening for ocular symptoms is not a reliable method to identify those with ocular morbidity and this highlights the need for routine ophthalmic screening prior to commencement of ART

Increased ocular lens density in HIV-infected individuals with low nadir CD4 counts in South Africa: evidence of accelerated aging.

BACKGROUND: HIV infection is thought to be associated with an increased risk of age-related morbidity and premature aging. Lens density increases with age and may function as a biomarker of aging. The relationship of lens density measurements with clinical and demographic characteristics in HIV-infected individuals in comparison with a matched population of HIV-seronegative individuals was investigated. METHODS: Case-control study of 490 adults aged greater than or equal to 30 years composed of 242 HIV-infected adults and 248 age- and sex-matched HIV-seronegative individuals. Lens density was assessed using lens densitometry (Pentacam) imaging. Measurements were divided into quartiles, and comparison of HIV status and HIV-related factors was assessed by multivariate and multinomial logistic regression. RESULTS: The mean age was 41.2 years in HIV-infected adults and 42.3 years in HIV-seronegative individuals (P = 0.14). Of the HIV-infected adults, 88% were receiving antiretroviral therapy (ART) (median duration, 58 months), and within this group, their median CD4 count was 468 cells per microliter and 84% had undetectable viral load. Although adjusted lens densities were similar by HIV serostatus, participants on ART and who had nadir CD4 counts less than 200 cells per microliter had a higher risk of high lens density compared with HIV-seronegative individuals (P trend = 0.04). Lens density was weakly associated with detectable HIV viremia despite ART, but not with current CD4 count. CONCLUSIONS: HIV-infected individuals on ART with nadir CD4 counts <200 cells per microliter had increased risk of higher lens density. Lens density may represent a novel biomarker of aging, providing insight into accelerated aging trajectories in HIV infection

Retinal nerve fibre layer thickness and contrast sensitivity in HIV-infected individuals in South Africa: a case-control study

BACKGROUND: Antiretroviral treatment (ART) has altered the spectrum of HIV-related eye disease, resulting in a lower prevalence of retinal opportunistic infections (OIs). However, abnormalities in visual function have been reported in HIV-infected individuals despite effective viral suppression and the absence of retinal OIs. These changes may be mediated by an HIV-associated 'neuroretinal disorder', characterized by changes in the retinal nerve fibre layer (RNFL). HIV infection may also be associated with accelerated biological aging. The aim of this study was to investigate the relationships between contrast sensitivity, RNFL thickness, HIV infection and frailty in South African adults. METHODS: Case-control study of 225 HIV-infected individuals without retinal OIs and 203 gender/age-matched HIV-seronegative individuals. Peri-papillary RNFL thickness was determined with spectral domain optical coherence tomography in four quadrants. CS was measured using a Pelli-Robson chart. Frailty was assessed using standard criteria. Multivariable linear and logistic regression were used to assess associations between HIV status and RNFL/CS and frailty. RESULTS: The median age of both groups was similar (41.2 vs. 41.9 years, p = 0.37). 88% of HIV-infected individuals were receiving ART and their median CD4 count was 468 cells/μl. Adjusted CS score was lower in HIV-infected participants compared to HIV-seronegative individuals (1.76 vs. 1.82, p = 0.002). Independent predictors of poor CS in the HIV-infected group were positive frailty status and current HIV viral load >2 log copies/ml. Lower CS score was also associated with thin temporal RNFL in HIV-infected individuals (p = 0.04). Superior quadrant RNFL thickness was greatest in ART-naïve participants relative to the HIV-uninfected group (p-trend = 0.04). Longer ART duration was associated with thinning of inferior and nasal RNFL quadrants (p-trend = 0.03 and 0.04, respectively). CONCLUSIONS: Contrast sensitivity is reduced in HIV-infected individuals and functionally associated with frailty and unsuppressed viraemia. This may reflect structural changes in the RNFL that are evident despite the absence of OIs

Prevalence of and early-life influences on childhood strabismus: findings from the Millennium Cohort Study.

BACKGROUND: Strabismus is a common disorder of largely unknown cause reported to occur more frequently in children with neurodevelopmental conditions and in children born prematurely or of low birth weight. Population-based investigation of other potential early-life influences has been limited. OBJECTIVE: To investigate the prevalence of and the early-life risk factors associated with childhood strabismus. DESIGN: Cross-sectional analytical study of a nationally representative sample of children participating in the Millennium Cohort Study. SETTING: United Kingdom. PARTICIPANTS: A population-based sample of 14 980 children aged 3 years. MAIN OUTCOME MEASURES: Parental report of "isolated" strabismus and "neurodevelopmental" strabismus (ie, in the context of neurologic disorders), considered separately. RESULTS: Three hundred forty-three children had strabismus (of whom 20 [5.8%] had neurodevelopmental/neurologic disorders), giving a total weighted prevalence of 2.1% (95% confidence interval, 1.8%-2.4%). In multivariable analysis, the risk of isolated strabismus was reduced in children of nonwhite maternal ethnicity and was increased in those born after an assisted or cesarean delivery and in those who were of low birth weight and preterm (in particular, late preterm). An increased risk of neurodevelopmental strabismus was independently associated with maternal smoking into later pregnancy, maternal illnesses in pregnancy, and decreasing birth weight for gestational age and sex. Socioeconomic status was associated with isolated (inverse relationship) and neurodevelopmental (U-shaped relationship) strabismus. CONCLUSIONS: Several early-life social and biological factors are associated with strabismus, with differences in patterns between isolated and neurodevelopmental forms. Further collaborative research could explore this hypothesis to identify modifiable risk factors

The eye as a model of ageing in translational research--molecular, epigenetic and clinical aspects.

The eye and visual system are valuable in many areas of translational research such as stem cell therapy, transplantation research and gene therapy. Changes in many ocular tissues can be measured directly, easily and objectively in vivo (e.g. lens transparency; retinal blood vessel calibre; corneal endothelial cell counts) and so the eye may also be a uniquely useful site as a model of ageing. This review details cellular, molecular and epigenetic mechanisms related to ageing within the eye, and describes ocular parameters that can be directly measured clinically and which might be of value in ageing research as the translational "window to the rest of the body". The eye is likely to provide a valuable model for validating biomarkers of ageing at molecular, epigenetic, cellular and clinical levels. A research agenda to definitively establish the relationship between biomarkers of ageing and ocular parameters is proposed

Prevalence of eye disease in early childhood and associated factors: findings from the millennium cohort study.

PURPOSE: To report the prevalence and distribution of eye conditions and visual impairment and associations with early social and biological factors using parental report of diagnosed eye conditions and additional chronic illnesses. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: We included 14 981 children, aged 3 years, participating in the United Kingdom Millennium Cohort Study. METHODS: Data on demographic, socioeconomic, and maternal and child health factors were obtained by maternal report through structured interview and verbatim reports of diagnosed eye problems and additional chronic illnesses were recorded. Multinomial regression analyses were used to calculate risk ratios of the association of eye disease (with or without associated visual impairment), with socioeconomic and early life factors. MAIN OUTCOME MEASURES: Parental report of diagnosed eye conditions and other chronic illnesses. RESULTS: Overall, at 3 years, 5.7% (95% confidence interval, 5.2-6.3%; n = 881) of children had ≥ 1 eye condition with 0.24% (0.15-0.3%; n = 45) reported to have associated visual impairment. In the majority, time of onset was reported to be the first year of life. Eye disorders without report of visual impairment were independently associated with lower socioeconomic status, decreasing birth weight, and prematurity. Visual impairment was more likely in those of low birthweight for gestational age and from an ethnic minority group. Maternal illnesses during pregnancy were associated with eye disease without reported visual impairment, as was white ethnicity. CONCLUSIONS: Good research opportunities exist within the context of population-based general health surveys to use parental report to estimate minimum prevalence, investigate associations of eye disease with a broad range of environmental factors, and as a mechanism for "flagging" individuals with eye disease in a population sample for further study. Our findings regarding the association of parentally reported childhood eye disease with early life factors such as modest degrees of prematurity, ethnicity and maternal ill-health warrant further investigation. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article