Development Of Nuclear Cataract Research Articles

Nuclear cataract shows significant familial aggregation in an older population after adjustment for possible shared environmental factors.

To quantify the association between siblings in age-related nuclear cataract, after adjusting for known environmental and personal risk factors. All participants (probands) in the Salisbury Eye Evaluation (SEE) project and their locally resident siblings underwent digital slit lamp photography and were administered a questionnaire to assess risk factors for cataract including: age, gender, lifetime sun exposure, smoking and diabetes history, and use of alcohol and medications such as estrogens and steroids. In addition, blood pressure, body mass index, and serum antioxidants were measured in all participants. Lens photographs were graded by trained observers masked to the subjects' identity, using the Wilmer Cataract Grading System. The odds ratio for siblings for affectedness with nuclear cataract and the sibling correlation of nuclear cataract grade, after adjusting for covariates, were estimated with generalized estimating equations. Among 307 probands (mean age, 77.6 +/- 4.5 years) and 434 full siblings (mean age, 72.4 +/- 7.4 years), the average sibship size was 2.7 per family. After adjustment for covariates, the probability of development of nuclear cataract was significantly increased (odds ratio [OR] = 2.07, 95% confidence interval [CI], 1.30-3.30) among individuals with a sibling with nuclear cataract (nuclear grade > or = 3.0). The final fitted model indicated a magnitude of heritability for nuclear cataract of 35.6% (95% CI: 21.0%-50.3%) after adjustment for the covariates. Findings in this study are consistent with a genetic effect for age-related nuclear cataract, a common and clinically significant form of lens opacity.

Oxygen tension in the rabbit lens and vitreous before and after vitrectomy

Oxygen is believed to be one of the potential causative agents for the development of nuclear cataract following vitrectomy. The aim of this study was to determine the partial pressure of oxygen (pO 2) in different compartments of the rabbit eye, and to describe the changes following vitrectomy. Twenty-six rabbits (3·5–5·3 kg) were anesthetized and oxygen tension was probed using a fiber-optic oxygen sensor system (optode). A micromanipulator was employed to ascertain the exact position of the probe within the eye. Measurements were taken pre- and post-vitrectomy at several defined positions within the vitreous, the lens and the anterior chamber. Follow-up measurements were performed 2 and 8 weeks after vitrectomy. The contralateral eye served as a control. Measurements in the normal rabbit eye showed that oxygen tension in the globe is asymmetrical with the lowest pO 2 in the nucleus of the lens (10·4mmHg±3·0). The region of the lens near the posterior capsule has an oxygen tension close to the values of the vitreous directly behind the posterior capsule (12·4mmHg±3·1). The highest pO 2 within the posterior compartment of the eye was measured close to the retinal surface (40–l60mmHg) depending on neighboring large vessels. The tension drops off rapidly to 20mmHg some 0·5 mm from the retina. From that position to the posterior surface of the lens there is a shallow gradient of decreasing pO 2. Immediately following vitrectomy the pO 2 in the BSS replacement varied from ca. 90–140mmHg, and decreased over approximately 30 min. to levels that were 2–3 times that of normal vitreous. Two weeks after vitrectomy the pO2 values in the lens were 2–3 times as high as in the control eye ( p<0·05). In addition there is no longer a gradient in the vitreous cavity, except close to the retina. Eight weeks after vitrectomy, pO2 levels in the lens were decreased but still remained higher than in the normal eye (13·83mmHg±0·02). The pO2 gradient in the vitreous was not detectable anymore. Overall the results provide evidence that oxygen levels in the lens increase significantly after vitrectomy in rabbits. If this occurs in humans it may contribute to cataract formation following surgery.

Five-year refractive changes in an older population: the Blue Mountains Eye Study

Purpose To examine 5-year changes in refractive error and astigmatism in an older population. Design Population-based cohort study. Participants The Blue Mountains Eye Study examined 3654 residents aged 49 years or older from 1992 to 1994. After excluding 543 persons who died since baseline, 2335 (75.1%) attended 5-year examinations from 1997 to 1999. Methods Both examinations included a detailed eye assessment, with subjective refraction performed according to a modified Early Treatment of Diabetic Retinopathy Study protocol. Main outcome measures Spherical equivalent (sum of sphere + 1 2 cylinder) was used as the measure of refractive error. Only phakic eyes with best-corrected visual acuity >20/40 were included (n = 3701). Results Similar changes in refractive error were observed for the two eyes. Symmetric changes were found in 72% of participants when the difference between eyes was within 0.5 diopters (D) and in 91% when the difference was within 1.0 D. The 5-year change in spherical power was in a hyperopic direction for younger age groups and in a myopic direction for older subjects, P < 0.0001. The gender-adjusted mean change in refractive error in right eyes of persons aged 49 to 54, 55 to 64, 65 to 74, and 75 years or older at baseline was +0.41 D, +0.30 D, +0.05 D, and −0.22D, respectively. Refractive change was strongly related to baseline nuclear cataract severity; grades 4 to 5 were associated with a myopic shift (−0.33 D, P < 0.0001). Education level and age of onset of myopia, but not gender or diabetes, also predicted refractive change. The mean age-adjusted change in refraction was +0.14 D for hyperopic eyes, +0.32 D for emmetropic eyes, and +0.15 D for myopic eyes. The mean change in cylinder power over the 5-year period was small, irrespective of baseline refraction. The axis of astigmatism remained stable in most cases (64%), whereas 12% changed to “against the rule” and 11% to “with the rule.” Conclusions This report has documented refractive error changes in an older population and confirmed reported trends of a hyperopic shift before age 65 years and a myopic shift thereafter associated with the development of nuclear cataract.

Cataract surgery in highly myopic eyes corrected by phakic anterior chamber angle-supported lenses

Purpose To assess the incidence of cataract, potential causes of its development, and the outcome of cataract surgery after previous implantation of phakic angle-supported anterior chamber intraocular lenses (AC IOLs) in highly myopic patients. Setting Instituto Oftalmológico de Alicante, Department of Refractive Surgery, Spain. Methods Two hundred sixty-three highly myopic phakic eyes of 160 patients had implantation of a phakic AC IOL. Follow-up was up to 8 years (range 38.4 to 103.2 months). Eyes that subsequently developed cataract had cataract extraction and were studied during follow-up for clinical association to other preoperative or postoperative data. Cataract surgery was performed after phakic IOL explantation by phacoemulsification and posterior chamber IOL (PC IOL) implantation (Domilens-Chiron AL3). Results Nuclear cataract developed in 9 cases (3.42%) a mean of 42.91 months ± 17.7 (SD) after phakic AC IOL implantation. Final best spectacle-corrected visual acuity (BSCVA) was not significantly different from that after phakic AC IOL implantation ( P = .25, paired Student t test). Mean endothelial cell loss after cataract surgery was 6.87% ± 0.42% cells/mm 2. Age at implantation of older than 40 years and axial length greater than 30.0 mm were the 2 factors significantly related to nuclear cataract development ( r = 1.69 and 1.98, respectively; P < .05). Conclusions There is a potential risk of nuclear cataract development after phakic AC IOL implantation to correct high myopia in patients older than 40 years and with very high (greater than 30.0 mm) axial myopia. Phakic IOL explantation, phacoemulsification, and PC IOL implantation successfully resolved this complication. The benefits in terms of BSCVA and spherical equivalent obtained after phakic AC IOL implantation were preserved after cataract surgery.

Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study.

The relation of antioxidant nutrients to the incidence of nuclear cataracts was investigated in a cohort of adults aged 43-84 years in the Beaver Dam Eye Study (Beaver Dam, Wisconsin). Nuclear opacity was assessed on a five-point ordinal scale using lens photographs taken at baseline (1988-1990) and at follow-up (1993-1995). Of the 1,354 persons eligible, 246 developed a nuclear cataract (level 4 or 5 opacity) in at least one eye. Antioxidant intakes were assessed using a food frequency questionnaire administered at baseline for time points corresponding to intake during the year preceding baseline and 10 years before baseline (the distant past). Lutein-zeaxanthin was the only carotenoid, out of five examined, that was associated with nuclear cataracts. Persons in the highest quintile of lutein intake in the distant past were half as likely to have an incident cataract as persons in the lowest quintile of intake (95% confidence interval 0.3-0.8). In the overall group, nuclear cataracts were not significantly related to intake of vitamin C or vitamin E. However, vitamins C and E were inversely associated with opacities in persons who had some other risk factors for cataracts. While results of this short term follow-up study are consistent with a possible protective influence of lutein and vitamins E and C on the development of nuclear cataracts, the evidence in the present study provides weak support for these associations.

Oxidation enhances calpain-induced turbidity in young rat lenses

Purpose. To determine if oxidation enhances turbidity after proteolysis of rat lens crystallins by the calcium-activated protease calpain (EC 3.4.22.17). Methods. Total soluble proteins from young rat lens were hydrolyzed for 24 hr by endogenous lens calpain, and the proteins were further incubated with the oxidant diamide for up to 7 days. Turbidity was measured daily at 405 nm. To measure proteolysis and turbidity in cultured lenses, rat lenses were cultured for 6 days in low calcium medium and diamide. The lenses were then photographed to assess transmission of light. SDS-PAGE and immunoblotting assessed proteolysis of crystallins, a-spectrin, and activation of calpain. Results. Appreciable in vitro turbidity occurred in soluble proteins from young rat lenses after proteolysis of crystallins by endogenous calpain. Calpain inhibitor E64, or anti-oxidants DTE and GSH, inhibited this turbidity. On the other hand, the oxidant diamide markedly enhanced calpain-induced turbidity. Cultured rat lenses showed elevated intra-lenticular calcium and proteolysis of crystallins by calpain, but no nuclear cataract. Addition of diamide to the culture medium caused development of nuclear cataract. Conclusions. Diamide enhanced turbidity only when crystallins were proteolyzed. Oxidation may be one of the factors promoting light scatter and insolubilization after proteolysis. These data are consistent with the hypothesis that proteolysis of crystallins from young rat lens may expose cysteine residues, which are then oxidized, become insoluble and scatter light.

Refractive index changes in the ocular lens result from increased light scatter

As the crystalline lens ages and as cataracts develop, highly concentrated proteins in lens fiber cells undergo rearrangements leading to substantial increases in scattered light. By exploiting a relationship between scattered light and refractive index, it is shown that a rearrangement of proteins necessarily leads to increased index as well. This change in refractive index is a second-order effect and must be quite small in most cases. However, it offers a possible explanation for the increase in index and refractive power associated with the development of nuclear cataract.

Biochemical changes and cataract formation in lenses from rats receiving multiple, low doses of sodium selenite

Nuclear cataract formed in rat lens in response to a protocol of multiple, low doses of sodium selenite. Nuclear cataract occurred, in both Wistar and Sprague-Dawley rats, following five subcutaneous injections of selenite over an 8-day period with an accumulated dose of 40–50 nmol selenite g −1 body weight. Glutathione content decreased within the first 24 hr of treatment and remained at 60% of controls. Lipid peroxidation occurred in Wistar rats prior to nuclear cataract formation. A two to three-fold increase in calcium concentration and decreased protein content accompanied nuclear cataract development. Enzyme activities were measured for glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and only the peroxidase activity remained constant through the period of cataract formation. This protocol resulted in nuclear cataracts similar in appearance to those observed with a single, acute dose of selenite. The opportunity to control the rate of selenite-dependent cataract formation allows further definition of precataractous events.

Quantitative Analysis of Lens Changes After Vitrectomy by Fluorophotometry

We measured the amount of autofluorescence in the lens to evaluate quantitatively lens changes after vitrectomy. Thirteen phakic patients, ranging in age from 12 to 75 years, were studied after unilateral vitrectomy, with a follow-up period of more than two years (range, 26 to 55 months). Autofluorescence in the lens was measured at the center along the ocular axis by fluorophotometry. Lens autofluorescence in the eyes that underwent vitrectomy was significantly higher than in the contralateral eyes that were not operated on (P = .0003). The increase of autofluorescence was correlated significantly with the age at time of vitrectomy (P = .0008). There was no correlation between the increase in autofluorescence and the length of postoperative follow-up or the use of air during vitrectomy. Based on these results, we believe that oxidation of lens proteins intraoperatively may be one of the causes of development of nuclear cataract after vitrectomy.

Selenium-induced cataract — A correlation of dry mass content and light scattering

Selenium-induced cataracts in young rats were used to compare light scattering and dry mass concentration along the lens axis. Selenium-treated rats and control rats were examined 1, 2, 4 and 6 days after subcutaneous injection of selenium or 0·9% NaCl. The development of nuclear cataract was followed with a Scheimpflug slit-lamp camera. Light-scattering was determined by densitometry of the negatives taken by the Scheimpflug camera. Dry mass concentration was determined by quantitative microradiography of the extracted lenses. Increasing light scatter was seen from day 2 to day 6. The dry mass concentration, however, was not changed until day 6. Two distinct zones were found surrounding the center of the nucleus, one with increased and one with decreased dry mass. The rapid changes in dry mass concentration were probably caused by shifts in water distribution within the lens. Similar zones of hydration have also been found in human senile nuclear cataract. Selenium-induced cataract in the rat is discussed in relation to human nuclear cataract.

Human Lens Nuclear Cataract: Hydrogen Peroxide Action and Anthranilic Acid Association with Lens Proteins

Yellow protein derived from European and Pakistani human nuclear cataractous lenses was digested. Anthranilic acid was found in 50 times greater amount in Pakistani than in European material. Treating tryptophan with free radicals, near-UV light and hydrogen peroxide, it was shown that only with hydrogen peroxide anthranilic acid was produced. Hydrogen peroxide might be the common factor involved in the development of nuclear cataract in old human lenses.

Changes in human lenses during nuclear cataract development

Changes in human lenses during nuclear cataract development

Changes in Blue Fluorescence Intensity and Coloration of Human Lens Protein with Normal Lens Aging and Nuclear Cataract

In the investigation reported here, intensity of blue fluorescence or coloration associated with human lens protein of nuclear cataract has been compared with that in the one of normal human. Blue fluorescence as well as coloration associated with proteins of aged normal lens and of nuclear cataractous lens appears to be localized in the nucleus which contains more water-insoluble protein than the cortex. In cortex and nucleus of normal lens, and in cortex of the cataractous lens, the blue fluorescence intensity of the lens protein seems to elevate linearly with an increase of percent urea-soluble protein, accompanied by a decrease of percent water-soluble protein. In nucleus of the cataractous lens, however, the fluorescence intensity tends to decrease significantly with an increase of percent urea-insoluble protein, mostly accompanied by a decrease of percent urea-soluble protein. Coloration of the lens protein tends to become deeper as human lens protein becomes insoluble. Particularly, in nucleus of the cataractous lens which contains urea-insoluble protein at a high concentration, the coloration seems to increase sharply as the content of urea-insoluble protein goes up. These results suggest the possibility that changes in the blue fluorescence intensity and coloration of human lens protein during aging of normal lens and development of nuclear cataract may be related to aggregation of the lens protein.