Giovanni Maraini

The ageing lens.

The human lens grows by a process of epithelial cell division at its equator and the formation of generations of differentiated fibre cells. Despite the process of continuous remodelling necessary to achieve growth within a closed system, the lens can retain a high level of light transmission throughout the lifetime of the individual, with the ability to form sharp images on the retina. Continuous growth of the lens solves the problem imposed by terminal differentiation within a closed, avascular system, from which cells cannot be shed. The lens fibre tips arch over the equator to meet anteriorly and posteriorly and form branching sutures of increasing complexity. The stages of branching may create the optical zones of discontinuity seen on biomicroscopy. The lens is exposed to the cumulative effects of radiation, oxidation and postranslational modification. These later proteins and other lens molecules in such a way as to impair membrane functions and perturb protein (particularly crystallin) organisation, so that light transmission and image formation may be compromised. Damage is minimised by the presence of powerful scavenger and chaperone molecules. Progressive insolublisation of the crystallins of the lens nucleus in the first five decades of life, and the formation of higher molecular weight aggregates, may account for the decreased deformability of the lens nucleus which characterises presbyopia. Additional factors include: the progressive increase in lens mass with age, changes in the point of insertion of the lens zonules, and a shortening of the radius of curvature of the anterior surface of the lens. Also with age, there is a fall in light transmission by the lens, associated with increased light scatter, increased spectral absorption, particularly at the blue end of the spectrum, and increased lens fluorescence. A major factor responsible for the increased yellowing of the lens is the accumulation of a novel fluorogen, glutathione-3-hydroxy kynurenine glycoside, which makes a major contribution to the increasing fluorescence of the lens nucleus which occurs with age. Since this compound may also cross-link with the lens crystallins, it may contribute to the formation of high-molecular-weight aggregates and the increases in light scattering which occur with age. Focal changes of microscopic size are observed in apparently transparent, aged lenses and may be regarded as precursors of cortical cataract formation.

Oxidative Stress and Age-Related Cataract

The authors review the available evidence supporting the possible role of oxidative stress in cataract formation from an epidemiological and a clinical point of view. They discuss in more detail what is presently known about the molecular mechanisms of response of the mammalian lens to an oxidative insult and report unpublished data on gene modulation upon oxidative stress in a bovine lens model. Main research endeavors that seem to be a most promising source of new insights into the problem of age-related cataract formation are briefly discussed.

Blood levels of vitamin C, carotenoids and retinol are inversely associated with cataract in a north Indian population

PURPOSE To examine the association of blood antioxidants with cataract. METHODS Cross-sectional study of people aged >or=50 years identified from a household enumeration of 11 randomly sampled villages in North India. Participants were interviewed for putative risk factors (tobacco, alcohol, biomass fuel use, sunlight exposure, and socioeconomic status) and underwent lens photography and blood sampling. Lens photographs (nuclear, cortical, and posterior subcapsular) were graded according to the Lens Opacities Classification System (LOCS II). Cataract was defined as LOCS II grade >or=2 for any opacity or ungradable, because of dense opacification or history of cataract surgery. People without cataract were defined as LOCS II <2 on all three types of opacity, with absence of previous surgery. RESULTS Of 1443 people aged >or=50 years, 94% were interviewed, 87% attended an eye examination, and 78% gave a blood sample; 1112 (77%) were included in the analyses. Compared with levels in Western populations, antioxidants were low, especially vitamin C. Vitamin C was inversely associated with cataract. Odds ratios (OR) for the highest (>or=15 micromol/L) compared with the lowest (<or=6.3 micromol/L) tertile were 0.64, (95% confidence interval [CI] 0.48-0.85; P < 0.01). Tertiles of zeaxanthin (P < 0.03), alpha-carotene (P < 0.05), and retinol (P < 0.02) were associated with decreased odds of cataract. In analysis of continuous data, significant inverse associations were found for vitamin C, zeaxanthin, lutein, lycopene, alpha- and beta-carotene, and beta-cryptoxanthin, but not for alpha- or gamma-tocopherol. CONCLUSIONS Inverse associations were found between cataract and blood antioxidants in an antioxidant-depleted study sample.

A randomized, double-masked, placebo-controlled clinical trial of multivitamin supplementation for age-related lens opacities. Clinical trial of nutritional supplements and age-related cataract report no. 3.

OBJECTIVE To evaluate the effect of a multivitamin/mineral supplement on development or progression of age-related lens opacities. DESIGN Randomized, double-masked, single center, placebo-controlled clinical trial. PARTICIPANTS One thousand twenty participants, 55 to 75 years old and with early or no cataract, were randomly assigned to a daily tablet of a multivitamin/mineral formulation or a placebo. METHODS Baseline and annual lens photographs were graded for severity of lens opacities according to a modification of the Age-Related Eye Disease Study system for classifying cataracts. MAIN OUTCOME MEASURES The primary outcome was a prespecified increase from baseline in nuclear, cortical, or posterior subcapsular cataract (PSC) opacity grades or cataract surgery. Secondary outcomes included an increase in type-specific opacity grades, cataract surgery, and visual acuity (VA) loss from baseline > or =15 letters. RESULTS Participants were observed for an average of 9.0+/-2.4 years. There was a decrease in total lens events in participants assigned to the multivitamin/mineral formulation compared with those assigned to the placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.68-0.98; P = 0.03). Nuclear events were significantly less common (HR, 0.66; 95% CI, 0.50-0.88; P = 0.004) and PSC events significantly more common (HR, 2.00; 95% CI, 1.35-2.98; P<0.001) in participants taking the multivitamin/mineral formulation than in those assigned to the placebo. No statistically significant treatment effects were seen for cortical opacities, moderate VA loss, or cataract surgery. CONCLUSIONS Lens events were less common in participants who took the multivitamin/mineral formulation, but treatment had opposite effects on the development or progression of nuclear and PSC opacities, the 2 most visually important opacity subtypes.

Prevalence of Early and Late Age-Related Macular Degeneration in India: The INDEYE Study

PURPOSE To estimate the prevalence of early and late age-related macular degeneration (AMD) in India. METHODS Of 7518 people aged 60 years and older identified from randomly sampled villages in North and South India, 5853 (78%) attended an eye examination including fundus photography. Fundus images were graded according to the Wisconsin Age-Related Maculopathy Grading System. RESULTS Fundus images were ungradable in 1587 people, mainly because of cataract. People 80 years of age and older were less likely to attend the eye examination and more likely to have ungradable images. For ages 60 to 79 years, the percent prevalence (95% confidence interval [CI]) were late AMD 1.2 (0.8-1.5); and early AMD: grade 1 (soft distinct drusen or pigmentary irregularities), 39.3 (37.2-41.5); grade 2 (soft distinct drusen with pigmentary irregularities or soft indistinct or reticular drusen), 6.7 (5.8-7.6); and grade 3 (soft indistinct or reticular drusen with pigmentary irregularities), 0.2 (0.1-0.4). For ages 80 and older, the respective percent prevalence was: late AMD, 2.5 (0.4-4.7); and early AMD: grade 1, 43.1(35.7-50.6); grade 2, 8.1 (4.3-12.0); and grade 3, 0.5 (0-1.5). CONCLUSIONS The prevalence of early AMD (grades 1 and 2) is similar to that observed in Western populations, but grade 3 appears to be lower. The prevalence of late AMD is comparable to that in Western populations in the age group 60 to 79 years. It is likely that the prevalence in the 80 and older age group is underestimated.

An Independent Evaluation of the Lens Opacities Classification system II (LOCS II)

The Lens Opacities Classification System II (LOCS II) has been offered for use in clinical studies of cataract. The system uses slit lamp and retroillumination photographic standards to grade lens opacities into classes of increasing severity. The authors evaluated the reproducibility and validity of LOCS II before its possible use in a natural history study of age-related cataract. The authors found excellent inter- and intraobserver reproducibility when the LOCS II standard photographs were used for clinical or photographic gradings of cataract. There was a tendency to underestimate posterior subcapsular cataracts on photographic gradings compared with slit-lamp gradings. The accuracy of the photographic gradings of posterior subcapsular opacities tended to decrease as the severity of coexisting opacities increased.

Prevalence of Cataract in an Older Population in India: The India Study of Age-related Eye Disease

Purpose To describe the prevalence of cataract in older people in 2 areas of north and south India. Design Population-based, cross-sectional study. Participants Randomly sampled villages were enumerated to identify people aged ≥60 years. Of 7518 enumerated people, 78% participated in a hospital-based ophthalmic examination. Methods The examination included visual acuity measurement, dilatation, and anterior and posterior segment examination. Digital images of the lens were taken and graded by type and severity of opacity using the Lens Opacity Classification System III (LOCS III). Main Outcome Measures Age- and gender-standardized prevalence of cataract and 95% confidence intervals (CIs). We defined type of cataract based on the LOCS III grade in the worse eye of: ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any unoperated cataract was based on these criteria or ungradable dense opacities. Any cataract was defined as any unoperated or operated cataract. Results The prevalence of unoperated cataract in people aged ≥60 was 58% in north India (95% CI, 56–60) and 53% (95% CI, 51–55) in south India (P = 0.01). Nuclear cataract was the most common type: 48% (95% CI, 46–50) in north India and 38% (95% CI, 37–40) in south India (P<0.0001); corresponding figures for PSC were 21% (95% CI, 20–23) and 17% (95% CI, 16–19; P = 0.003), respectively, and for cortical cataract 7.6% (95% CI, 7–9) and 10.2% (95% CI, 9–11; P<0.004). Bilateral aphakia/pseudophakia was slightly higher in the south (15.5%) than in the north (13.2%; P<0.03). The prevalence of any cataracts was similar in north (73.8%) and south India (71.8%). The prevalence of unoperated cataract increased with age and was higher in women than men (odds ratio [OR], 1.8). Aphakia/pseudophakia was also more common in women, either unilateral (OR, 1.2; P<0.02) or bilateral (OR, 1.3; P<0.002). Conclusions We found high rates of unoperated cataract in older people in north and south India. Posterior subcapsular cataract was more common than in western studies. Women had higher rates of cataract, which was not explained by differential access to surgery. Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Selective binding of aged α-crystallin to lens fibre ghosts ☆

Abstract Among the different types of soluble lens crystallins only the “aged” fraction of α-crystallin can interact with lens fibre membranes (the urea-insoluble fraction of lens homogenate) and thus become water-insoluble. These observations are in keeping with several well-established facts and offer a plausible explanation for the origin of the albuminoid.

Inverse Association of Vitamin C with Cataract in Older People in India

Objective To examine the association between vitamin C and cataract in the Indian setting. Design Population-based cross-sectional analytic study. Participants A total of 5638 people aged ≥60 years. Methods Enumeration of randomly sampled villages in 2 areas of north and south India to identify people aged ≥60 years. Participants were interviewed for socioeconomic and lifestyle factors (tobacco, alcohol, household cooking fuel, work, and diet); attended a clinical examination, including lens photography; and provided a blood sample for antioxidant analysis. Plasma vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid, and other antioxidants were measured by reverse-phase high-pressure liquid chromatography. Main Outcome Measures Cataract and type of cataract were graded from digital lens images using the Lens Opacity Classification System III (LOCS III), and cataract was classified from the grade in the worse eye of ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any cataract was defined as any unoperated or operated cataract. Results Of 7518 enumerated people, 5638 (75%) provided data on vitamin C, antioxidants, and potential confounders. Vitamin C was inversely associated with cataract (adjusted odds ratio [OR] for highest to lowest quartile = 0.61; 95% confidence interval (CI), 0.51–0.74; P=1.1×10−6). Inclusion of other antioxidants in the model (lutein, zeaxanthin, retinol, β-carotene, and α-tocopherol) made only a small attenuation to the result (OR 0.68; 95% CI, 0.57–0.82; P < 0.0001). Similar results were seen with vitamin C by type of cataract: nuclear cataract (adjusted OR 0.66; CI, 0.54–0.80; P < 0.0001), cortical cataract (adjusted OR 0.70; CI, 0.54–0.90; P < 0.002), and PSC (adjusted OR 0.58; CI, 0.45–0.74; P < 0.00003). Lutein, zeaxanthin, and retinol were significantly inversely associated with cataract, but the associations were weaker and not consistently observed by type of cataract. Inverse associations were also observed for dietary vitamin C and cataract. Conclusions We found a strong association with vitamin C and cataract in a vitamin C–depleted population. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Cation pump activity and membrane permeability in human senile cataractous lenses.

Abstract The majority of human senile cataractous lenses show a progressive alteration of electrolyte levels resulting in increased lens sodium and decreased potassium, and a concomitant increase in lens water. These changes are known to be associated with the cortical type of senile cataract. The aim of this study was to investigate the mechanisms responsible for the osmotic imbalance in cortical cataract. Determination of Na,K-ATPase activity gave a wide range of values that were not significantly different from normal controls, but rubidium influx showed a normal accumulation in cataractous lenses demonstrating a normal functioning of the cation pump. Both sodium influx and rubidium efflux are increased in the cataractous lenses and the increase is proportional to the absolute level of lens sodium. These results suggest that the biochemical change responsible for the osmotic imbalance in human senile cataract is not a defect in the cation pump mechanism but rather an increase in lens membrane permeability.