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Association of inhaled corticosteroid use with cataract extraction in elderly patients.

CONTEXT: The use of systemic corticosteroids is a known risk factor for the development of cataracts. OBJECTIVE: To determine whether treatment with inhaled corticosteroids is associated with cataract extraction in the elderly. DESIGN: Case-control study. SETTING: Quebec universal health insurance program for all elderly (provincial health insurance plan database [RAMQ database]). PATIENTS: RAMQ enrollees 70 years and older. The 3677 cases were patients with a cataract extraction between 1992 and 1994. The 21868 controls were randomly selected from patients who did not have a diagnosis of cataract and matched to cases on the index date of the case. MAIN OUTCOME MEASURES: Odds ratio of cataract extraction in patients with prolonged cumulative exposure to inhaled corticosteroids compared with nonusers. RESULTS: Excluding patients with systemic steroid treatment and after adjusting for age, sex, diabetes, systemic hypertension, glaucoma, ophthalmic steroids, and the number of physician claims for services, use of inhaled corticosteroids for more than 3 years was associated with undergoing cataract extraction (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.53-6.13). For high average daily doses of beclomethasone or budesonide (>1 mg), the OR was elevated after more than 2 years of treatment (OR, 3.40; 95% CI, 1.49-7.76), whereas for low to medium doses (< or =1 mg) of these drugs, the OR was 1.63 (95% CI, 0.85-3.13) after 2 years. CONCLUSION: Prolonged administration of high doses of inhaled corticosteroids increases the likelihood of undergoing cataract extraction in elderly patients. Further studies are needed to investigate the risk of developing cataracts for low to medium doses over longer periods.

Administration, Inhalation↗

Day care versus in-patient surgery for age-related cataract.

BACKGROUND: Age-related cataract accounts for more than 40% of cases of blindness in the world with the majority of people who are blind from cataract found in the developing world. With the increased number of people with cataract there is an urgent need for cataract surgery to be made available as a day-care procedure. OBJECTIVES: The objective of this review is to provide reliable evidence regarding the safety, feasibility, effectiveness and cost-effectiveness of cataract extraction performed as day-care versus in-patient procedure. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group trials register) on The Cochrane Library (Issue 4 2002), MEDLINE (1966 to November 2002), EMBASE (1980 to November 2002) and LILACS (November 2002). SELECTION CRITERIA: This review includes randomised controlled trials comparing day-care and in-patient surgery for age-related cataract. The primary outcome was the achievement of a satisfactory visual acuity six weeks after the operation. DATA COLLECTION AND ANALYSIS: Although two trials are included in the review, adequate data were available for only one trial and therefore pooling of data from studies was not attempted. A descriptive summary is presented. MAIN RESULTS: Two trials, involving a total of 1284 people, are included in this review. One trial reported statistically significant differences in early postoperative complication rates in the day-care group, with an increased risk of increased intraocular pressure, which had no clinical relevance to visual outcomes four months postoperatively. The mean change in visual acuity (Snellen lines) of the operated eye four months postoperatively was 4.1 (standard deviation (SD) 2.3) for the day-care group and 4.1 (SD 2.2) for the in-patient group and not statistically significant. The four-month postoperative mean change in quality of life score measured using the VF14 showed minimal differences between the two groups. Costs were 20% more for the in-patient group and this was attributed to higher costs for overnight stay. One study only reported hotel costs for the non-hospitalised participants making aggregation of data on costs impossible. REVIEWER'S CONCLUSIONS: This review provides some evidence that there is a cost saving but no significant difference in outcome or risk of postoperative complications between day-care and in-patient cataract surgery. This is based on one detailed and methodologically sound trial conducted in the developed world. The success, safety and cost-effectiveness of cataract surgery as a day-care procedure appears to be acceptable but additional well-designed trials are required to confirm these perceptions.

Ambulatory Surgical Procedures↗

Day care versus in-patient surgery for age-related cataract.

BACKGROUND: Age-related cataract accounts for more than 40% of cases of blindness in the world with the majority of people who are blind from cataract found in the developing world. With the increased number of people with cataract there is an urgent need for cataract surgery to be made available as a day care procedure. OBJECTIVES: To provide reliable evidence regarding the safety, feasibility, effectiveness and cost-effectiveness of cataract extraction performed as day care versus in-patient procedure. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 3 2004), MEDLINE (1966 to July 2004), EMBASE (1980 to August 2004) and LILACS (July 2004). SELECTION CRITERIA: This review includes randomised controlled trials comparing day care and in-patient surgery for age-related cataract. The primary outcome was the achievement of a satisfactory visual acuity six weeks after the operation. DATA COLLECTION AND ANALYSIS: Although two trials are included in the review, adequate data were available for only one trial and therefore pooling of data from studies was not attempted. A descriptive summary is presented. MAIN RESULTS: Two trials, involving a total of 1284 people, are included in this review. One trial reported statistically significant differences in early postoperative complication rates in the day care group, with an increased risk of increased intraocular pressure, which had no clinical relevance to visual outcomes four months postoperatively. The mean change in visual acuity (Snellen lines) of the operated eye four months postoperatively was 4.1 (standard deviation (SD) 2.3) for the day care group and 4.1 (SD 2.2) for the in-patient group and not statistically significant. The four-month postoperative mean change in quality of life score measured using the VF14 showed minimal differences between the two groups. Costs were 20% more for the in-patient group and this was attributed to higher costs for overnight stay. One study only reported hotel costs for the non-hospitalised participants making aggregation of data on costs impossible. AUTHORS' CONCLUSIONS: This review provides some evidence that there is a cost saving but no significant difference in outcome or risk of postoperative complications between day care and in-patient cataract surgery. This is based on one detailed and methodologically sound trial conducted in the developed world. The success, safety and cost-effectiveness of cataract surgery as a day care procedure appear to be acceptable but additional well-designed trials are required to confirm these perceptions.

Ambulatory Surgical Procedures↗

Effect of sorbitol dehydrogenase inhibition on sugar cataract formation in galactose-fed and diabetic rats.

Several recent studies with the sorbitol dehydrogenase inhibitors 4-[4-(N,N-dimethylsulfamoyl)-piperazino]-2-methylpyrimidine, SDH-1, and its active metabolite 4-[4-(N, N-dimethylsulfamoyl)piperazino]-2-hydroxymethylpyrimidine , SDH-2, suggest that inhibition of sorbitol dehydrogenase may be beneficial in delaying the onset of diabetic complications due to their ability to ameliorate redox changes associated with polyol metabolism. To compare the relative importance of sorbitol dehydrogenase versus aldose reductase inhibition on sugar cataract formation, cataract formation was monitored in 50% galactose-fed and diabetic rats treated with/without the sorbitol dehydrogenase inhibitors SDH-1 or SDH-2 or the aldose reductase inhibitors AL 1576 or Ponalrestat. For these studies, diabetes was induced in young 50 g rats with streptozotocin while galactosemia was produced by feeding a diet containing 50% galactose. Inhibitors were administered in the diet with the diet containing 0.06% (w/w) of the sorbitol dehydrogenase inhibitors or Ponalrestat, and 0.0125% (w/w) of AL 1576. Cataract formation was monitored by hand-held slit lamp and polyol levels were measured by gas chromatography. Sugar cataract formation was accelerated in diabetic rats treated with sorbitol dehydrogenase inhibitors while no difference in cataract formation was observed in galactose-fed rats treated with/without SDH inhibitors. Cataract formation was inhibited in both diabetic and galactosemic rats by either Ponalrestat or AL 1576. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalysed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase.

Aldehyde Reductase↗

Cataract development in gamma-glutamyl transpeptidase-deficient mice.

The present study was undertaken to analyse the relationship of lens glutathione (GSH) and light to cataract development in mice deficient in gamma-glutamyl transpeptidase (GGT). These mice have reduced levels of cysteine and GSH in the eye and develop cataracts. GGT-deficient mice raised under normal vivarium conditions, showed no cataractous changes at birth, but by 1 week they had developed nuclear opacities. By 3 weeks more severe cataracts develop, and lens GSH levels are approximately 6-7% of wild type levels. By 6-11 weeks cataracts show nuclear and cortical involvement, liquefaction and calcification. Single cell DNA electrophoresis (comet assay) demonstrated mild DNA damage in the lens epithelium. GGT-deficient mice raised in the dark beginning the day after conception all developed cataracts, but these were less severe than those in GGT-deficient mice raised with normal vivarium lighting. Administration of N -acetyl cysteine (NAC) raises lens GSH and almost completely prevents cataract development. Our data indicate that cataract development in GGT-deficient mice is multifactorial and results from exogenous damage (exposure to light), reduced lens GSH levels, and nutritional effects secondary to low cysteine levels.

Acetylcysteine↗

Topographical distribution of lactate dehydrogenase activity in human clear eye lenses and in lenses with different types of senile cataract: a histochemical investigation.

BACKGROUND: Homogenates of human clear lenses show an age-dependent reduction of enzyme activities. Topographical patterns of enzymes in clear and cataractous lenses can be visualized by histochemistry. MATERIAL AND METHODS: Human lenses were characterized by slit-lamp investigations as bearing different types of senile cataracts. Subsequently, lenses were removed by intracapsular extraction. Clear human lenses served as controls. Bovine lenses served to standardize freeze-cutting and incubation for lactate dehydrogenase histochemistry. RESULTS: Bovine lenses show a sharp demarcation between the enzyme reaction of cortical fibers bearing cell nuclei and the non-reacting deeper fibers not exhibiting cell nuclei. Clear human lenses, lenses with deep supranuclear cortical cataracts, and lenses with nuclear cataracts exhibit the same borderline. However, in lenses with a subcapsular cortical cataract only the epithelium and a very thin layer of the most superficially located fibers show positive enzyme reactions. CONCLUSION: In growing clear human and bovine lenses, independent of age, the more peripherally located cortical fibers bearing cell nuclei exhibit strong enzyme-histochemical reactions. More centrally located lens areas lacking cell nuclei increase in volume in an age-dependent manner. These lens regions do not exhibit enzyme activities detectable by our histochemical technique. Therefore the lens areas free of histochemical reaction product become larger with increasing age, whereas the peripherally located lens fibers apparently do not change their enzyme activities with age. Thus, homogenates of total lenses show age-dependent reductions of enzyme activities, although enzyme activities remain at a physiological level in cortical lens fibers with recognizable cell nuclei. In lenses with immature supranuclear cortical and (particularly) in lenses with black nuclear cataracts, cortical fibers still can exhibit high enzyme activities. Unexpectedly, also ruptured and broken fibers in immature deep supranuclear cortical cataracts show strong enzyme activities. In contrast, in lenses with (incipient) subcapsular cortical cataracts only the most superficially located lens fibers exhibit some enzyme activity.

Aged↗

Expression of TGF-beta2 mRNA and PCNA, FN protein in lens epithelial cells in age-related nuclear and cortex cataract.

By using RT-PCR and immunohistochemistry, the expressions of transforming growth factor beta2 (TGF-beta2) mRNA, proliferating cell nuclear antigen (PCNA) and fibronection (FN) protein in lens epithelial cells (LECs) of age-related nuclear and cortex cataract were detected and compared. The results of RT-PCR revealed that the expression of TGF-beta2 mRNA was higher in cortex cataract than in nuclear cataract. Immunohistochemistry demonstrated that the expression of PCNA protein was lower and the expression of FN protein was higher in cortex cataract than in nuclear cataract. It was suggested that TGF-beta2, PCNA and FN might take important parts in the process of age-related cataract. Cortex cataract was related to the transdifferentiation of LECs, and nuclear cataract to the proliferation of LECs.

Aged↗

[Complicated cataracts in various forms of retinitis pigmentosa. Type and incidence].

PURPOSE: To study the incidence and types of cataract in retinitis pigmentosa (RP) and their variations among different forms of RP. PATIENTS AND METHODS: This analysis was based on data from 473 patients with RP (autosomal dominant, n = 87; autosomal recessive, n = 79; x chromosomal recessive, n = 23; simplex RP, n = 215; Usher's syndrome n = 80; M. Refsum and others, n = 9) that were retrieved from the literature and patient charts in our clinic. RESULTS: Posterior subcapsular cataract (PSC) developed with the following frequencies for the different genetic types of RP: autosomal dominant, 45.3%; autosomal recessive, 44.0%; x chromosomal recessive, 40.7%; simplex RP, 46.1%; Usher's syndrome, 52.9%. PSC was the only type of lens opacity in patients with Usher's syndrome and autosomal recessive RP.PSC development correlated with early onset of RP symptoms. Nuclear cataracts showed a statistically significant higher frequency in patients with simplex RP (14.8%) than in other genetic types (0-5.9%) (P < 0.01). In addition, nuclear cataracts developed in simplex RP at a significantly later age (69.6 +/- 12.4 years) than PSC (44.4 +/- 12.3 years) (P < 0.001). Patients with cataracts showed significantly worse visual fields than patients with clear lenses (P = 0.00067). CONCLUSIONS: The typical RP cataract (PSC) was found in similar frequencies among all genetic types of RP.PSC was the only type of lens opacity in patients with Usher's syndrome and autosomal recessive RP. Nuclear cataracts developed on average 20 years later than PSC and had their highest incidence in patients with simplex RP. Patients with cataracts showed significantly worse visual field results, indicating a more pronounced retinal pathology.

Adolescent↗

Cataract in traffic.

BACKGROUND: To obtain a driver's licence to drive a private passenger car, the binocular visual acuity required is 0.5 or better, and the minimum horizontal width of the visual field is 120 degrees . Persons who fulfill these requirements can obtain a driver's licence even if they have an eye disease such as cataract. However, contrast sensitivity and visual acuity in glare can be considerably decreased in eyes with cataract, and this may create a risk factor in traffic. METHODS: Examinations of the eyes, visual fields, contrast sensitivity and glare sensitivity (visual acuity in glare and macular photostress test) were performed for 35 cataract patients aged 60 to 87 years (mean 70.1 years+/-6.1 SD). They had cataract in one or both eyes. In spite of the cataract, the visual acuity was > or =0.5 in 50 of the eyes. Twenty-two control eyes of persons within the same age range were similarly tested. RESULTS: The results in the contrast sensitivity test were significantly worse in the cataract eyes than in the control eyes. Contrast sensitivity decreased significantly as the visual acuity became worse. In the glare test, none of the control eyes lost any of the lines in the visual acuity chart. In the cataract eyes, the loss of lines with the highest glare varied from 0 to 6 lines (mean 1.4+/-1.5). The recovery time in the macular photostress test was longer, but not significantly, in cataract eyes than in normal eyes. There was no significant correlation between the loss of visual chart lines and visual acuity or between the recovery time in the macular photostress test and visual acuity. CONCLUSION: It would be advisable for traffic safety if simple tests for contrast and glare sensitivity were added to the requirements for a driver's licence, at least for older drivers. The age and test result limits should be defined.

Aged↗

In utero and milk-mediated effect of aldose reductase inhibitor on galactose cataracts.

Our previously reported investigations showed that cataracts could be induced in fetal lenses through the maternal feeding of galactose during pregnancy. We also reported that the lens opacity present at birth reverses completely by 30 days of age if there is no further post-natal exposure to galactose. This investigation was designed to investigate if an aldose reductase inhibitor (ARI) has any cross-placental effect in preventing galactose-induced cataracts in fetuses. We have also evaluated if there are any milk-mediated effects of galactose on cataract induction and of galactose and ARI on the maintenance or reversal of opacities induced in utero. Pregnant Sprague-Dawley rats were fed either 50% galactose or rat chow with or without the ARI, (2R,4S)-6-fluoro-2-methyl spirochroman-4,4'-imidazolidine-2',5'-dione (Eisai compound E-0722). Following parturition, pups of mothers from the different dietary groups were either fed by their own mothers or foster fed by lactating females fed either rat chow or 50% galactose with or without the ARI. Lenses of the pups were examined at desired intervals with light and scanning electron microscopes. We observed that: (a) both galactose and the ARI had a cross-placental effect on the fetal lenses in the development and inhibition of cataracts, respectively; (b) galactose had very little, if any, milk-mediated effect on either the induction of cataracts in newborn pups that were born with transparent lenses or the maintenance of cataracts induced in utero; (c) the ARI appeared to have a milk-mediated effect, which accelerates the reversal of cataract associated alterations in lenses of pups with cataracts induced in utero, leading to further reinstatement of lens transparency; and (d) the presence of ARI in the diet of rats during pregnancy and/or post-parturition provided continued protection to the lenses of pups that were exposed to a galactose diet following birth.

Aldehyde Reductase↗

The frequency of dominant cataract and recessive specific-locus mutations in mice derived from 80 or 160 mg ethylnitrosourea per kg body weight treated spermatogonia.

A systematic comparison of the frequency of dominant cataract and recessive specific-locus mutations in mice has been extended to include results for 80 and 160 mg ethylnitrosourea per kg body weight spermatogonial treatment. The frequency of confirmed dominant cataract mutations in the historical control, 80 and 160 mg/kg ethylnitrosourea treatment groups was 1/22594, 8/5090 and 14/6435, respectively. The frequency of recessive specific-locus mutations in the same dose groups was, respectively, 19/227805, 20/13274 and 35/8658. These present results confirm previous results, which indicate that ethylnitrosourea is effective in inducing both recessive specific-locus and dominant cataract mutations although the per locus mutation rate to recessive alleles was observed to be approximately 6 times greater than the per locus mutation rate to dominant alleles. The exclusion of certain classes of lens opacity variant phenotypes, previously demonstrated not to be due to a dominant mutation, from the group of suspected dominant cataract mutations subjected to a genetic confirmation test has greatly improved the efficiency of the test. A total of 23 dominant cataract mutations were confirmed from a group of 67 phenotypic variants. Of the 23 confirmed dominant cataract mutations, 8 were shown to have reduced transmission to the following generation of offspring expressing the mutant phenotype. These results are also consistent with previous results for ethylnitrosourea or radiation treatment in which it was shown that approximately one-third of the recovered mutations have reduced penetrance. One group of dominant cataract mutations, with phenotypic effects on the polar, sub-capsular or corneal regions, is overly represented in the group of recovered mutations with a reduced transmission of offspring expressing the mutant phenotype. Two hypotheses are suggested for this observation, both dependent on the fact that the regions affected indicate that the mutations are expressed later in the development of the eye. Either all carrier individuals have not expressed the phenotype at the time of examination and classification, or later acting mutations are more subject to environmental interactions resulting in more variable expression. Finally, it is argued that a dominant cataract mutation test represents a most practicable protocol to screen for induced dominant mutations in germ cells of the mouse. The imposition of the criterion that suspected variants be subjected to a genetic confirmation test has at least two advantages beside the fact that results represent unambiguous mutational events.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Pars plana lensectomy by ultrasonic fragmentation. I. Versatile and simple technique for cataract removal.

A comparison has been made between pars plana lansectomy and intracapsular cataract extraction Pars plana lensectomy has been shown to have many advantages. It is applicable to any age, while intracapsular cataract extraction is restricted to patients over 30 years old. It can be used in any type of cataract, whereas intracapsular cataract extraction is restricted to senile cataracts. It requires less patient preparation, less instrumentation, and less surgical dexterity than does intracapsular cataract extraction. It allows intraocular examination at the time of surgery. It can be combined with other surgical procedures (intraocular lens implantation, vitrectomy, cryoretinopexy, scleral buckle, etc.). It leaves the eyes in better condition postoperatively with fewer postoperative complications, and it gives good or better visual results than intracapsular cataract extraction. It is now unnecessary to learn (and teach) multiple techniques to handle different ages and types of cataracts since pars plana lensectomy manages them all with fewer complications.

Adolescent↗

Taurine prevents galactose-induced cataracts.

Intact lenses from New Zealand white rabbits were incubated in tissue culture media containing either 5 mM glucose or 5 mM glucose plus 30 mM galactose. The standard media did not contain taurine. Lenses were also cultured in a third medium containing 30 mM galactose plus 0.2 mM taurine. The frequency of cataract formation was evaluated as a function of the culture media. One lens (1/10), in media containing 5 mM glucose, developed a lenticular opacification during a 72-h incubation. Lenses (12/15) incubated in 30 mM galactose, without taurine, developed cataracts; fewer lenses (2/13) exposed to 30 mM galactose plus 0.2 mM taurine developed cataracts (p < 0.005). Galactose cataracts have been associated with lens edema attributed to the osmotic stress of tissue polyol (galactitol) accumulation. The water content of the noncataractous and cataractous lenses in this experiment did not differ. Lens edema, therefore, was not thought to be important in cataract pathogenesis. Taurine, an organic osmolyte was lower (5.1 +/- 1.5 mumol/g protein) in cataractous lenses than in control lenses (10.0 +/- 1.0 mumol/g protein). Malondialdehyde, an indicator of lipid peroxidation, was higher (36.6 +/- 5.0 mumol/g protein) in lens-containing opacifications than in noncataractous lenses (10.1 +/- 1.9 mumol/gm protein) (p < 0.01). The levels of malondialdehyde suggest that lipid peroxidation was increased in the process of sugar cataractogenesis. The malondialdehyde content of all the lenses correlated inversely (r = -0.53, p < 0.01) with the coincident lens taurine levels. Taurine appears to protect the lens against the development of sugar cataracts; its inverse relationship with lens malondialdehyde suggests this is an antioxidant effect.

Animals↗

Cataract progression after intravitreal triamcinolone injection.

PURPOSE: To assess cataract progression after intravitreal triamcinolone injection. DESIGN: Retrospective, interventional, case-control study. METHODS: Forty-two phakic eyes of 37 patients were injected one, two, or three times with intravitreal triamcinolone for various indications. Noninjected phakic fellow eyes served as the control. The mean follow-up time for single injection was 12 months, for multiple injections was 14 months, and for control group was 13 months. Lens status, best-corrected visual acuity, and refractive errors were recorded at baseline and at each follow-up examination. RESULTS: At the last follow-up, changes in posterior subcapsular cataract and refractive error from baseline were significantly different between single triamcinolone-injected eyes and the control group [0.7 +/- 0.2 (mean +/- SEM [arbitrary unit] vs 0.2 +/- 0.1, P = .02; and -0.5 +/- 0.1 diopter vs -0.2 +/- 0.1 diopter, P = .01, respectively). For multiple-injected eyes and control eyes, change from baseline in corticonuclear cataract (1.1 +/- 0.2 vs 0.2 +/- 0.1), posterior subcapsular cataract (1.1 +/- 0.2) and refractive error (-1.8 +/- 0.4 diopters) were significantly different (P < .001, P < .001, and P < .001, respectively). Visual acuity did not change after single injection (P = .83) and in control group (P = .19) but decreased after multiple injections (P = .006). Eleven study eyes and two control group eyes underwent cataract extraction during study period. Corticonuclear and posterior subcapsular cataract progression significantly correlated with follow-up time (P = .003 and P = .02, respectively) and number of injections (P = .01 and P = .04, respectively). CONCLUSIONS: Single intravitreal triamcinolone injection induces posterior subcapsular cataract development, whereas multiple injections result in all-layer cataract progression.

Aged↗

Methylenetetrahydrofolate reductase genetic polymorphisms in patients with cataract.

PURPOSE: Hyperhomocysteinemia is commonly associated with polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. The level of homocysteine can be lowered by dietary intake of folate. A protective effect of folate supplementation has been reported against cataract. Here we investigate MTHFR polymorphisms in human cataract. DESIGN: Retrospective case-control association study. METHODS: Patients with nuclear (n = 77), cortical (n = 155), posterior subcapsular (n = 119), and mixed (n = 151) cataract, and 187 controls were analyzed for the MTHFR 677C-->T and 1298A-->C polymorphisms using minisequencing technique. RESULTS: The wild-type MTHFR 677CC/1298AA genotype was strongly overrepresented among cataract cases (P = .003). This effect was most pronounced in the mixed cataract group (P < .001). Hyperhomocysteinemia-associated genotypes had similar frequencies in cataract and control groups. CONCLUSIONS: The previously reported protective effect of folate against cataract is not due to overrepresentation of hyperhomocysteinemia-associated MTHFR genotypes. Instead, the strong predominance of wild-type MTHFR in cataract may suggest impaired DNA synthesis as a cataractogenic factor.

Adult↗

Cataract formation in a strain of rats selected for high oxidative stress.

The primary purpose of this study was to define the clinical and morphological features of cataractogenesis in the OXYS strain of rats that generate excess reactive oxygen species. Rats were sequentially examined from birth to the development of mature cataracts with slit lamp biomicroscopy. Morphology of selected stages of cataract development was studied using light and transmission electron microscopy (TEM), immunohistochemical localization of the lipid peroxidation product 4-hydroxynonenal (HNE) and fluorescent antibody labeling for DNA oxidation products. Lenses from age-matched normal rats were used as controls. OXYS rats developed cataracts as young as two weeks of age with progression to maturity by 1 year. Clinically, cataracts appeared initially either as nuclear or sub-capsular cortical changes and progressed to pronounced nuclear cataracts within months. TEM confirmed the light microscopic impression of region-specific alterations in both fiber cell cytoplasmic protein matrix and membrane structure. The outer adult nuclear region showed extensive cellular damage similar to osmotic cataracts, which is consistent with the postulated high uptake of glucose in the OXYS strain. The adult and outer fetal nuclear cells displayed several types of focal damage. The inner fetal and embryonic nuclear cells demonstrated textured cytoplasm, suggesting protein degradation or redistribution. Staining for HNE was increased in epithelium, cortex and nucleus compared to control lenses. Fluorescent antibody probes demonstrated increased levels of DNA oxidation products in OXYS rat lenses compared to age-matched controls. Fourier analysis of nuclear cytoplasm revealed significant components with corresponding sizes greater than 100 nm and, using a new theoretical approach, the texturing of the cytoplasm was shown to be sufficient to cause opacification of the nucleus. The OXYS rat appears to be an ideal model for oxidative stress cataractogenesis. The potential oxidative damage observed is extensive and characteristic of the developmental region. The source of oxidative damage may in part be a response to elevated levels of glucose. Because oxidative stress is thought to be a major factor in cataract formation in both diabetic and non-diabetic aging humans, this animal model may be a useful tool in assessing efficacy of antioxidant treatments that may slow or prevent cataract formation.

Aging↗

Age-related nuclear cataract-oxidation is the key.

Age is by far the biggest risk factor for cataract, and it is sometimes assumed that cataract is simply an amplification of this aging process. This appears not to be the case, since the lens changes associated with aging and cataract are distinct. Oxidation is the hallmark of age-related nuclear (ARN) cataract. Loss of protein sulfhydryl groups, and the oxidation of methionine residues, are progressive and increase as the cataract worsens until >90% of cysteine and half the methionine residues are oxidised in the most advanced form. By contrast, there may be no significant oxidation of proteins in the centre of the lens with advancing age, even past age 80. The key factor in preventing oxidation seems to be the concentration of nuclear glutathione (GSH). Provided that nuclear GSH levels can be maintained above 2 mm, it appears that significant protein oxidation and posttranslational modification by reactive small molecules, such as ascorbate or UV filter degradation products, is not observed. Adequate coupling of the metabolically-active cortex, the source of antioxidants such as GSH, to the quiescent nucleus, is crucial especially since it would appear that the cortex remains viable in old lenses, and even possibly in ARN cataract lenses. Therefore it is vital to understand the reason for the onset of the lens barrier. This barrier, which becomes apparent in middle age, acts to impede the flow of small molecules between the cortex and the nucleus. The barrier, rather than nuclear compaction (which is not observed in human lenses), may contribute to the lowered concentration of GSH in the lens nucleus after middle age. By extending the residence time within the lens centre, the barrier also facilitates the decomposition of intrinsically unstable metabolites and may exacerbate the formation of H(2)O(2) in the nucleus. This hypothesis, which is based on the generation of reactive oxygen species and reactive molecules within the nucleus itself, shifts the focus away from theories for cataract that postulated a primary role for oxidants generated outside of the lens. Unfortunately, due to marked variability in the lenses of different species, there appears at present to be no ideal animal model system for studying human ARN cataract.

Aged↗

Increased aqueous flare intensity in eyes with liquefied after-cataract.

PURPOSE: To describe aqueous flare intensity in eyes with white liquefied after-cataract. SETTING: Department of Ophthalmology, Toyama Medical and Pharmaceutical University, Toyama, Japan. METHODS: Seven patients with unilateral liquefied after-cataract and another 10 unaffected patients with an intraocular lens (IOL) were examined. The eyes were divided into 3 groups. The first group was composed of 7 eyes with liquefied after-cataract. The second group included the fellow eyes of the patients with unilateral liquefied after-cataract; 4 had an IOL, and 3 had cataract. The third group included 10 additional eyes without liquefied after-cataract. All patients underwent cataract operations consisting of phacoemulsification/aspiration with continuous curvilinear capsulorhexis and acrylic IOL implantation in the capsular bag. Aqueous flare was measured using a laser flare-cell meter. RESULTS: The mean +/- SD of aqueous flare intensity was significantly higher in the first group (11.8 +/- 1.8 photon counts/msec) than in the second group (6.4 +/- 0.8 photon counts/msec) and in the third group (6.3 +/- 0.7 photon counts/msec). CONCLUSION: It is possible that liquefaction of after-cataract and disruption of the blood-aqueous barrier may be related.

Aged↗