Colin Cook

Epidemiology of glaucoma: what's new?

Globally, there are an estimated 60 million people with glaucomatous optic neuropathy and an estimated 8.4 million people who are blind as the result of glaucoma. These numbers are set to increase to 80 million and 11.2 million by 2020. Glaucoma is the second leading cause of blindness globally. The highest prevalence of open-angle glaucoma occurs in Africans, and the highest prevalence of angle-closure glaucoma occurs in the Inuit. Population-based screening for open-angle glaucoma is not recommended. Screening for angle-closure may be feasible.

Glaucoma in Africa: Size of the Problem and Possible Solutions

PurposeTo obtain an estimate of the magnitude of the problem of glaucoma in sub-Saharan Africa, and to evaluate the existing evidence for including glaucoma as a priority disease in our Vision 2020 programs in Africa. MethodsA Pubmed search was carried out using “glaucoma prevalence Africa,” “glaucoma presentation Africa,” “glaucoma blindness Africa,” “glaucoma screening Africa,” and “glaucoma treatment Africa” as key words. ResultsMost glaucoma in Africa is primary chronic open angle glaucoma, it may occur at an earlier age, it may be associated with a higher intraocular pressure, it may be more rapidly progressive, and it may present late. The prevalence of glaucoma in East, Central, and Southern Africa can be conservatively estimated to be 10,000 people for every 1 million population. This prevalence may be higher in West Africa. The annual incidence of glaucoma can be conservatively estimated to be 400 new cases for every 1 million population. Glaucoma is the second leading cause of blindness after cataract, responsible for up to 30% of blindness. Case detection of glaucoma could be carried out at both the primary and secondary level. Primary trabeculectomy with mitomycin C or β irradiation adjunct may be a suitable treatment. Cases could be followed up after surgery by mid-level eye care workers, using the intraocular pressure as the indicator for adequacy of control, and using a glaucoma register to identify and trace defaulters. ConclusionsGlaucoma should be included as a priority disease in Vision 2020 programs in Africa.

Frailty in HIV-infected adults in South Africa.

Objectives:Some evidence suggests that HIV infection is associated with premature frailty—a syndrome typically viewed as being related to ageing. We determined the prevalence and predictors of frailty in a population of HIV-infected individuals in South Africa. Design:Case-control study of 504 adults more than the age of 30 years, composed of 248 HIV-infected adults and 256 age- and gender-matched, frequency-matched HIV-seronegative individuals. Methods:Frailty was defined by standardized assessment comprised of ≥3 of weight loss, low physical activity, exhaustion, weak grip strength, and slow walking time. Independent predictors of frailty were evaluated using multivariable logistic regression. Results:The mean ages of the HIV-infected and HIV-seronegative groups were 41.1 ± 7.9 years and 42.6 ± 9.6 years, respectively. Of the HIV-infected adults, 87.1% were receiving antiretroviral treatment (median duration, 58 months), their median CD4 count was 468 cells/&mgr;L (interquartile range = 325–607 cells/&mgr;L) and 84.3% had undetectable plasma viral load. HIV-infected adults were more likely to be frail than HIV-seronegative individuals (19.4% vs. 13.3%; P = 0.07), and this association persisted after adjustment for confounding variables [adjusted OR = 2.14; 95% confidence interval (95% CI): 1.16–3.92, P = 0.01]. Among HIV-infected individuals, older age was a strong predictor of frailty, especially among women (women: OR = 2.55 per 10-year age increase; men: OR = 1.29 per 10-year age increase, P-interaction = 0.01). Lower current CD4 count (<500 cells/&mgr;L) was also independently associated with frailty (OR = 2.84; 95% CI: 1.02 –7.92, P = 0.04). Conclusions:HIV infection is associated with premature development of frailty, especially in women. Since higher CD4 counts were associated with lower risk of frailty, earlier initiation of antiretroviral treatment may be protective.

Endophthalmitis prophylaxis with intracameral cefuroxime in South Africa.

We found a significant reduction in the incidence of endophthalmitiscasesaftertheintroductionofcefuroxime (P Z .0013). The relative risk reduction was 86% (95% confidence interval [CI], 53.9%-95.8%), the absolute risk reduction was 0.47% (95% CI, 0.2%-0.7%), and the number needed to treat was 212 (95% CI, 133419). Table 2 shows the vitreous culture results in the eyes that developed endophthalmitis. There were no cases of culture-positive endophthalmitis following the introduction of intracameral cefuroxime and no cases of drug hypersensitivity or drug ocular toxicity. A questionnaire was sent to all South African ophthalmologists and publicized at a national meeting of the Ophthalmology Society of South Africa. The responserate was 74%, with 245of330ophthalmologists responding.Only73respondents(30%)reportedusing intracameral cefuroxime as prophylaxis. Some cited the lack of a commercially available preparation that would eliminate the risk for dilution errors and the resulting ocular toxicity as their reason for not using it. 3 We have found intracameral cefuroxime to be an effective prophylaxis in our setting. South African ophthalmologists should be encouraged to use this prophylaxis. There may be merit in having a commercial preparation available.

Retinopathy of prematurity in South Africa: an assessment of needs, resources and requirements for screening programmes

Aims: Retinopathy of prematurity (ROP) is a major cause of blindness in children in middle-income countries. In 1995, it accounted for 10.6% of blindness in children in schools for the blind in South Africa. This study was undertaken to estimate the number of premature babies at risk and to investigate policies, practices and screening programmes. Materials and methods: 17 level 1–3 neonatal units were visited in four provinces. Published literature reports were reviewed and staff interviewed. Results: 13 000–15 000 surviving premature babies are at risk of ROP each year. Shortage of equipment precluded continuous oxygen monitoring in public units. Nursing levels were often below recommendations, and most nurses were unaware of target oxygen saturations. Private units were well staffed and adequately equipped. Ophthalmologists were only visiting four units on a regular basis for screening, using the birth weight criterion of <1500 g for ROP screening. ROP needing treatment rates were low (1.6–2.9%), as were rates of follow-up. Conclusions: Primary prevention of ROP requires meticulous neonatal care and adequately equipped and staffed units. Secondary prevention requires efficient screening and treatment programmes. Competing demands and limited resources in the public sector in South Africa have precluded prioritising the prevention of ROP. This should be re-evaluated.

Retinal Arterioles Narrow with Increasing Duration of Anti-Retroviral Therapy in HIV Infection: A Novel Estimator of Vascular Risk in HIV?

Objectives HIV infection is associated with an increased risk of age-related morbidity mediated by immune dysfunction, atherosclerosis and inflammation. Changes in retinal vessel calibre may reflect cumulative structural damage arising from these mechanisms. The relationship of retinal vessel calibre with clinical and demographic characteristics was investigated in a population of HIV-infected individuals in South Africa. Methods Case-control study of 491 adults ≥30 years, composed of 242 HIV-infected adults and 249 age- and gender-matched HIV-negative controls. Retinal vessel calibre was measured using computer-assisted techniques to determine mean arteriolar and venular diameters of each eye. Results The median age was 40 years (IQR: 35–48 years). Among HIV-infected adults, 87.1% were receiving highly active antiretroviral therapy (HAART) (median duration, 58 months), their median CD4 count was 468 cells/µL, and 84.3% had undetectable plasma viral load. Unadjusted mean retinal arteriolar diameters were 163.67±17.69 µm in cases and 161.34±17.38 µm in controls (p = 0.15). Unadjusted mean venular diameters were 267.77±18.21 µm in cases and 270.81±18.98 µm in controls (p = 0.07). Age modified the effect of retinal arteriolar and venular diameters in relation to HIV status, with a tendency towards narrower retinal diameters in HIV cases but not in controls. Among cases, retinal arteriolar diameters narrowed with increasing duration of HAART, independently of age (167.83 µm <3 years of HAART vs. 158.89 µm >6 years, p-trend = 0.02), and with a HIV viral load >10,000 copies/mL while on HAART (p = 0.05). HIV-related venular changes were not detected. Conclusions Narrowing of retinal arteriolar diameters is associated with HAART duration and viral load, and may reflect heightened inflammatory and pro-atherogenic states of the systemic vasculature. Measurement of retinal vascular calibre could be an innovative non-invasive method of estimating vascular risk in HIV-infected individuals.

South Africa's cataract surgery rates: why are we not meeting our targets?

Cataract is the leading cause of blindness in South Africa, responsible for about 50% of the prevalence of blindness and identified as a national health priority. The cataract surgery rate (CSR) should be at least 2 000 per million population per year for elimination of cataract blindness. The national CSR target was planned to increase from 1 000 in 2005 to 2 000 in 2010, but since CSRs have failed to reach targets each year, the national target for 2010 was reduced from 2 000 to 1 500. We reviewed data from a situational analysis in 2007 of cataract surgery services to ascertain the obstacles to achieving CSR targets.

Retinopathy in diabetic patients evaluated at a primary care clinic in Cape Town.

In South Africa, it is the third leading cause of blindness after cataract and glaucoma, and is responsible for 5% of blindness (0.04% of the total population). Cataract and refractive error are prioritised for the first phase of Vision 2020 in South Africa, while strategies to deal with diabetic retinopathy are recommended as a priority for the second phase. 2 These strategies will include provision of adequate screening and argon laser treatment. The prevalence of diabetes differs in different population groups in South Africa. Among black and coloured South Africans, diabetes has risen from 3% to 12% over the past 10 years. Overall, the prevalence is conservatively estimated to be 3 - 5% (30 000 - 50 000 per million population). 2 The prevalence of retinopathy in people with diabetes is estimated to be 20% (6 000 - 10 000 per million population), and the prevalence of blindness among these is estimated to be 5% (300 - 500 blind per million population). 2

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.

Corneal endothelial cells provide evidence of accelerated cellular senescence associated with HIV infection: a case-control study.

Background Cellular senescence may be a key factor in HIV-related premature biological aging. We assessed features of the corneal endothelium that are known to be associated with biological aging, and cellular senescence markers in HIV-infected adults. Methods Case-control study of 242 HIV-infected adults and 249 matched controls. Using specular microscopy, the corneal endothelium was assessed for features of aging (low endothelial cell density [ECD], high variation in cell size, and low hexagonality index). Data were analysed by multivariable regression. CDKN2A expression (a cell senescence mediator) was measured in peripheral blood leukocytes and 8-hydroxy-2′-deoxyguanosine (8-OHDG; an oxidative DNA damage marker) levels were measured in plasma. Results The median age of both groups was 40 years. Among HIV-infected adults, 88% were receiving antiretroviral therapy (ART); their median CD4 count was 468 cells/µL. HIV infection was associated with increased odds of variation in cell size (OR = 1.67; 95% CI: 1.00–2.78, p = 0.04). Among HIV-infected participants, low ECD was independently associated with current CD4 count <200 cells/µL (OR = 2.77; 95%CI: 1.12–6.81, p = 0.03). In participants on ART with undetectable viral load, CDKN2A expression and 8-OHDG levels were higher in those with accelerated aging, as reflected by lower ECD. Conclusions The corneal endothelium shows features consistent with HIV-related accelerated senescence, especially among those with poor immune recovery.