Lens opacities increase over the age of 50 years and only a few studies have reported the prevalence of LO among individuals aged less than 50 years (Table 3).(26-37) Our prevalence estimate (13.8%) is comparable to the south Indian Aravind Comprehensive Eye Study (AECS), which used similar methods (age range 40–49 years, 15.7%),(36) but higher than in a Chinese study of 45-49 year olds (5.9%,95%CI 4.9-7.0).(30) The prevalence of LOs using the LOCS II grading of 2 or more in the Barbados Eye studies (age range 40-49 years) were between 3.0 and 4.7%.(26, 29, 38) Comparing prevalence estimates between studies needs caution, due to methodological differences in the definitions and classification systems used for LOs (Table 3). However, the prevalence does seem to be lower in high-income countries than in middle-income countries, which may be explained by lower exposure to modifiable risk factors, such as lifestyle factors, and better control of blood glucose amongst people with diabetes.
In our study, nuclear LOs were the commonest type (8.1%), which is similar to other Indian studies such as AECS (8.2%),(36) but higher than in the Andhra Pradesh Eye Disease Survey (APEDS)(3.5%).(39) In high-income countries cortical LO are commoner in both younger and older populations.(29) Different LO types may be associated with specific risk factors, the most commonly reported being cortical LO and high UVB exposure.(40) However, in our study the number of participants with LOs were too few for analysis by type of LO.
Men had a slightly higher prevalence of LO than women, but this was not statistically significant. This differs from other studies where women generally have a higher prevalence, particularly those done earlier.(29, 41, 42) Reasons for the gender difference are not fully understood, but may be due to a fall in oestrogen-mediated anti-ageing effects on the lens in women.(43) Less pronounced gender differences in LO in younger populations were also reported from the Swedish national cataract register.(44)
The Beaver Dam Eye Study showed a U-shaped relationship between SES and cataracts, with higher frequencies at extremes of SES,(45) reflecting different exposure to risk factors amongst those very poor and very affluent. Our study did not show any significant relationship with SES, despite a detailed SES assessment using multiple indicators such as household assets and education. This is in contrast to APEDS, where the prevalence of LOs was higher among those with a lower SES based on monthly income.(39) The different indicators used to calculate SES may explain the differences.
The absence of an association between current smoking and LO in our study is similar to other studies undertaken in East Asia,(41, 46) but differs from other studies in India(39, 42). A recent meta- analysis showed that ‘ever smokers’ had a higher risk of cataract in both cohort and case control studies.(47) Current exposure to biomass cooking fuels also did not show any significant association, which differs from other Indian studies(48) possibly because participants in our study were exposed to fewer cumulative years of biomass smoke due to the use of gas for cooking. Though there is evidence to link cigarette smoking and exposure to biomass smoke with LOs, and the reversibility of early changes if the exposure was removed, (49) as oxidative damage generated by smoke constituents is thought to be an important mediator.(50), we were unable to examine this with our data.
The increased risk of LO among individuals with asthma has been reported previously,(51, 52) which may reflect steroid use. In a large general practice study in the United Kingdom, (n=201,816; age 3-90 years), corticosteroid use was associated with increased cataract risk (relative risk 1.3) but this was not evident in those under the age of 40 years.(53) Our study lacked information on duration of steroid exposure, nevertheless our results reinforce the risk associated with history of asthma and LO.
Previous studies show variable associations between obesity and LOs.(41, 54, 55) Pooled estimates from a meta-analysis of 17 studies, including one from Asia, demonstrated a 2% increase in age-related cataracts with every 1kg/m2 increase in BMI for PSC only, but the pooled effect showed a weak association.(56) In our study, there was no significant difference in cataract prevalence between individuals who were underweight, overweight and obese (Table 2). However, an insignificant, marginal increase was seen with higher quartiles of waist circumference and waist-hip ratio (data not shown).
Our finding that individuals with higher HbA1C are associated with greater risk of LO concurs with other studies(41, 42, 54, 57) reinforcing that hyperglycaemia is an important risk factor for LO. This is attributed to increased osmotic and oxidative stress and non-enzymatic glycation of lens proteins(58)
The high prevalence of overweight and obesity, and diabetes compared with other populous countries was also reported in the Phase 5 VBC study.(17) The prevalence of diabetes in our cohort was also higher than other NCD-RisC estimates for India, with little difference between rural and urban populations.(17) In India, the number of people with diabetes is predicted to increase to more than 130 million by 2045,(59) which is likely to further increase the burden of diabetic retinopathy and cataract. In India, the age of onset of diabetes is generally lower than in other populations, which may in part be explained by the “thin-fat” Indian phenotype.(60) India is also undergoing rapid urbanization, with easy access to unhealthy food and reduced levels of physical activity.(61) Considering the inadequate resources for diabetes care and eye care, India faces a huge public eye health problem.
A meta-analysis reported hypertension to be a risk factor for LO, particularly posterior subcapsular opacities.(16, 62) Some pathogenetic mechanisms have been postulated, the most likely being inflammatory, but findings are not consistent across studies. Our estimates (aOR 1.73, 95% CI 1.1, 2.7) are comparable to the findings of a meta-analysis of cohort studies (RR 1.08; 95% CI: 1.05–1.12) and case-control or cross-sectional studies (OR 1.28; 95% CI: 1.12–1.45).(62) Hypertension is also an important risk factor for diabetic retinopathy and could exacerbate the increase in avoidable blindness from cataract and diabetic retinopathy. (59)
Despite other studies of sunlight exposure and cataract showing a modest association, including in India, (63) sunlight exposure was not significantly associated with LO in our study. This may reflect underestimation of sunlight exposure which was questionnaire based and prone to recall bias.
In the subgroup analysis, vitamin-D deficiency gave a 5-fold higher odds of LO, which has been reported to a weaker extent in other studies,(64-67) for example in South Korean men(67) and in younger women in the USA.(66) Vitamin D deficiency is more frequent in individuals with pigmented skin, lower midday sunlight exposure and those who live at higher latitudes.(67, 68) Photoxidation of lens proteins(69) and altered calcium signaling are implicated in cataractogenesis.(70) LOs in vitamin-D deficiency may be mediated through reduced antioxidant activity,(67) and alteration in calcium homeostasis.(71) Lower levels of vitamin D have also been detected in aqueous and vitreous humor in patients with cataract than those with retinal diseases .(72) To our knowledge, this is the first study to show such a strong association between vitamin D deficiency and any cataract in young adults, and further studies are warranted.
This is the first observational study of a birth cohort, which provides insights into early ageing manifested by early onset of LOs. The relatively large sample size with rich phenotype and risk factor data adds strength to the study and allows for further follow-up studies of eye conditions. Our study may be limited by selection bias, which is inherent in longitudinal cohort studies where participants can be hard to trace. The absence of association with some of the recognized risk factors for LO, such as smoking and sunlight exposure in our cohort, suggests the need for more accurate exposure assessments, and exploration of dose responses.
Rapid socioeconomic development in India, with changing lifestyles, leading to more obesity, hypertension and diabetes, is likely to increase the burden of cataract blindness in younger adults with alarming public health implications. Modifiable risk factors need to be addressed through eye health promotion, which needs to be integrated into policies and programs for the control of NCDs.
In conclusion, the prevalence of LOs in this birth cohort was higher than in many other studies, but similar to another study in south India. Nuclear cataracts were the commonest form of cataract. A history of bronchial asthma, hypertension and hyperglycemia were significantly associated with LOs. The strong association between lower serum vitamin D levels needs further investigation in India, as it is a potentially modifiable risk factor.