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Purpose: To evaluate whether dietary intake of luteiin/zeaxanthin and B vitamins is associated with cataract prevalence and incidence., Design: Clinic-based, baseline cross-sectional and prospective cohort study designs., Participants: Three thousand one hundred fifteen patients (6129 eyes) enrolled in the Age-Related Eye Disease Study 55 to 80 years of age followed up for mean of 9.6 years., Methods: Participants completed baseline food frequency questionnaires. Baseline and annual lens photographs were graded centrally. Multivariate models controlling for previously identified risk factors for cataracts tested for the association of cataracts with reported dietary intake, using the lowest quintile as reference., Main Outcome Measures: Cataract surgery, cataract status (type and severity) at baseline, and development of cataracts., Results: At baseline, increased dietary riboflavin and B12 were associated inversely with nuclear and cortical lens opacities. In comparisons of persons with and without cataract, persons with the highest riboflavin intake versus those with the lowest intake had the following associations: mild nuclear cataract: odds ratio (OR), 0.78; 95% confidence interval (CI), 0.63-0.97; moderate nuclear cataract: OR, 0.62; 95% CI, 0.43-0.90; and mild cortical cataract: OR, 0.80; 95% CI, 0.65-0.99. For B12, the results were: mild nuclear cataract: OR, 0.78; 95% CI, 0.63-0.96; moderate nuclear cataract: OR, 0.62; 95% CI, 0.43-0.88; and mild cortical cataract: OR, 0.77; 95% CI, 0.63-0.95. Highest dietary B6 intake was associated with a decreased risk of moderate nuclear lens opacity developing compared with the lowest quintile (OR, 0.67; 95% CI, 0.45-0.99). Highest dietary intake levels of niacin and B12 were associated with a decreased risk of development of mild nuclear or mild cortical cataracts in participants not taking Centrum (Pfizer, New York, NY) multivitamins. For participants taking multivitamins during the study, the highest intake of dietary folate was associated with an increased risk of mild posterior subcapsular lens opacity development. No statistically significant associations were found between lutein plus zeaxanthin intake and presence at baseline or development of nuclear or cortical lens opacity outcomes., Conclusions: These findings are consistent with earlier studies suggesting that dietary intake of B vitamins may affect the occurrence of age-related lens opacities. Further investigations are warranted., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate whether the 2-year change in lens opacity severity on the Age-Related Eye Disease Study (AREDS) lens grading scale predicts progression to cataract surgery or loss of visual acuity by 5 years., Design: Prospective cohort study within a randomized clinical trial of oral supplements., Participants: The AREDS participants whose eyes were phakic at baseline and free of late age-related macular degeneration throughout the study., Methods: Baseline and annual lens photographs of AREDS participants (n = 3466/4757; 73%) were graded for severity of cataracts using the AREDS system for classifying cataracts from photographs. Clinical examinations conducted semiannually collected data on cataract surgery and visual acuity. Association of the change in lens opacities at 2 years with these outcomes at 5 years was analyzed with adjusted Cox proportional hazard models., Main Outcome Measurements: Progression of lens opacities on stereoscopic lens photographs at 2 years, cataract surgery, and visual acuity loss of 2 lines or more at 5 years., Results: The adjusted hazard ratios (HRs) for association of progression to cataract surgery at 5 years were: nuclear cataract increase of 1.0 unit or more compared with less than 1.0-unit change at 2 years, 2.77 (95% confidence interval [CI], 2.07-3.70; P < 0.001); cortical cataract increase of 5% or more in lens opacity in the central 5 mm of the lens compared with less than 5% increase at 2 years, 1.91 (95% CI, 1.27-2.87; P = 0.002); and posterior subcapsular cataract increase of 5% or more versus less than 5% in the central 5 mm of the lens, 8.25 (95% CI, 5.55-12.29; P < 0.001). Similarly, HRs of vision loss of 2 lines or more at 5 years for this degree of lens changes at 2 years were the following: nuclear, 1.83 (95% CI, 1.49-2.25; P < 0.001); cortical, 1.13 (95% CI, 0.78-1.65; P = 0.519); and posterior subcapsular cataract, 3.05 (95% CI, 1.79-5.19; P < 0.001)., Conclusions: Two-year changes in severity of lens opacities on the AREDS lens grading scale are predictive of long-term clinically relevant outcomes, making them potential surrogate end points in follow-up studies., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the long-term effects (10 years) of the Age-Related Eye Disease Study (AREDS) formulation of high-dose antioxidants and zinc supplement on progression of age-related macular degeneration (AMD)., Design: Multicenter, randomized, controlled, clinical trial followed by an epidemiologic follow-up study., Participants: We enrolled 4757 participants with varying severity of AMD in the clinical trial; 3549 surviving participants consented to the follow-up study., Methods: Participants were randomly assigned to antioxidants C, E, and β-carotene and/or zinc versus placebo during the clinical trial. For participants with intermediate or advanced AMD in 1 eye, the AREDS formulation delayed the progression to advanced AMD. Participants were then enrolled in a follow-up study. Eye examinations were conducted with annual fundus photographs and best-corrected visual acuity assessments. Medical histories and mortality were obtained for safety monitoring. Repeated measures logistic regression was used in the primary analyses., Main Outcome Measures: Photographic assessment of progression to, or history of treatment for, advanced AMD (neovascular [NV] or central geographic atrophy [CGA]), and moderate visual acuity loss from baseline (≥15 letters)., Results: Comparison of the participants originally assigned to placebo in AREDS categories 3 and 4 at baseline with those originally assigned to AREDS formulation at 10 years demonstrated a significant (P<0.001) odds reduction in the risk of developing advanced AMD or the development of NV AMD (odds ratio [OR], 0.66, 95% confidence interval [CI], 0.53-0.83 and OR, 0.60; 95% CI, 0.47-0. 78, respectively). No significant reduction (P = 0.93) was seen for the CGA (OR, 1.02; 95% CI, 0.71-1.45). A significant reduction (P = 0.002) for the development of moderate vision loss was seen (OR 0.71; 95% CI, 0.57-0.88). No adverse effects were associated with the AREDS formulation. Mortality was reduced in participants assigned to zinc, especially death from circulatory diseases., Conclusions: Five years after the clinical trial ended, the beneficial effects of the AREDS formulation persisted for development of NV AMD but not for CGA. These results are consistent with the original recommendations that persons with intermediate or advanced AMD in 1 eye should consider taking the AREDS formulation., Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate potential risk factors associated with incident nuclear, cortical, and posterior subcapsular (PSC) cataracts and cataract surgery in participants in the Age-Related Eye Disease Study (AREDS)., Design: Clinic-based prospective cohort study., Participants: Persons (n = 4425) 55 to 80 years of age enrolled in a controlled clinical trial of antioxidant vitamins and minerals, AREDS, for age-related macular degeneration and cataract., Methods: Lens photographs were graded centrally for nuclear, cortical, and PSC opacities using the AREDS system for classifying cataracts. Type-specific incident cataracts were defined as an increase in cataract grade from none or mild at baseline to a grade of moderate at follow-up, also with a grade of at least moderate at the final visit, or cataract surgery. Cox regression analyses were used to assess baseline risk factors associated with type-specific opacities and cataract surgery., Main Outcome Measures: Moderate cataract was defined as a grade of 4.0 or more for nuclear opacity, 10% or more involvement within the full visible lens for cortical opacity, and 5% or more involvement of the central 5-mm circle of the lens for PSC opacity. These were graded on baseline and annual lens photographs., Results: A clinic-based cohort of 4425 persons 55 to 80 years of age at baseline was followed up for an average of 9.8±2.4 years. The following associations were found: increasing age with increased risk of all types of cataract and cataract surgery; males with increased risk of PSC and decreased risk of cortical cataracts; nonwhite persons with increased risk of cortical cataract; hyperopia with decreased risk of PSC, nuclear cataract, and cataract surgery; Centrum (Wyeth Consumer Healthcare, Madison, NJ) use with decreased risk of nuclear cataract; diabetes with increased risk of cortical, PSC cataract, and cataract surgery; higher educational level with decreased risk of cortical cataract; and smoking with increased risk of cortical cataract and cataract surgery. Estrogen replacement therapy in female participants increased the risk of cataract surgery., Conclusions: These findings largely are consistent with the results of previous studies, providing further evidence for possible modifiable risk factors for age-related cataract., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the grading (interrater) reliability of the Age-Related Eye Disease Study (AREDS) Clinical Lens Grading System (ARLNS)., Design: Evaluation of diagnostic test or technology., Participants: One hundred fifty volunteers (284 eyes)., Methods: Participants with lens opacities of varying severity were independently graded at the slit lamp for cataract severity by 2 examiners (retinal or anterior segment specialists) using the ARLNS, which employs 3 standard photographs of increasing severity for classifying each of the 3 major types of opacity. Lens photographs were taken and graded at a reading center using the more detailed AREDS System for Classifying Cataracts from photographs., Main Outcome Measures: The Pearson correlation, weighted-kappa, and limits-of-agreement statistics were used to assess the interrater agreement of the gradings., Results: Examinations were performed on 284 lenses (150 participants). Tests of interrater reliability between pairs of clinicians showed substantial agreement between clinicians for cortical and posterior subcapsular opacities and moderate agreement for nuclear opacities. A similar pattern and strength of agreement was present when comparing scores of retinal versus anterior segment specialists. Interrater agreement between clinical and reading center gradings was not as great as inter-clinician agreement., Conclusions: Interrater agreements were in the moderate to substantial range for the clinical assessment of lens opacities. Inherent differences in cataract classification systems that rely on slit lamp vs photographic assessments of lens opacities may explain some of the disagreement noted between slit lamp and photographic gradings. Given the interrater reliability statistics for clinicians and the simplicity of the grading procedure, ARLNS is presented for use in studies requiring a simple, inexpensive method for detecting the presence and severity of the major types of lens opacities., Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article., (Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: omega-3 (n-3) Long-chain polyunsaturated fatty acids (LCPUFAs) affect processes implicated in vascular and neural retinal pathogenesis and thus may influence the risk of developing age-related macular degeneration (AMD)., Objective: We investigated whether omega-3 LCPUFA intake was associated with a reduced likelihood of developing central geographic atrophy (CGA) and neovascular (NV) AMD., Design: We undertook a nested cohort study within a multicenter phase 3 clinical trial, the Age-Related Eye Disease Study (AREDS), to study progression to advanced AMD in 1837 persons at moderate-to-high risk of this condition. The AREDS was designed to assess the clinical course, prognosis, risk factors, and nutrient-based treatments of AMD and ran from November 1992 to December 2005. We obtained baseline data on omega-3 LCPUFA intake with a validated food-frequency questionnaire. Trained fundus graders ascertained AMD status from annual stereoscopic color photographs by using standardized methods at a single reading center across a 12-y period. We applied multivariable repeated-measures logistic regression with the incorporation of generalized estimating equation methods, because this permitted determination of progression to outcome at each visit., Results: Participants who reported the highest omega-3 LCPUFA intake (median: 0.11% of total energy intake) were 30% less likely than their peers to develop CGA and NV AMD. The respective odds ratios were 0.65 (95% CI: 0.45, 0.92; P

Purpose: To assess the risk of advanced age-related macular degeneration (AMD) developing after cataract surgery., Design: Cohort study., Participants: Four thousand five hundred seventy-seven participants (8050 eyes) from a multicenter, controlled, randomized clinical trial, the Age-Related Eye Disease Study (AREDS)., Methods: Development of advanced AMD, either neovascular (NV) AMD or geographic atrophy (GA), was evaluated with annual fundus photographs, and history of cataract surgery was assessed every 6 months. Cox proportional hazard models with time-dependent covariates were conducted for NV AMD and GA separately., Main Outcome Measures: Neovascular AMD, GA, and central GA (CGA; involving the center of the macula)., Results: The Cox proportional hazards model of right eyes showed nonsignificant hazard ratios of 1.20 (95% confidence interval [CI], 0.82-1.75) for NV AMD, 0.80 (95% CI, 0.61-1.06) for GA, and 0.87 (95% CI, 0.64-1.18) for CGA. Similar results were obtained for left eyes: 1.07 (95% CI, 0.72-1.58) for NV AMD, 0.94 (95% CI, 0.71-1.25) for GA, and 0.86 (95% CI, 0.63-1.19) for CGA. For participants with advanced AMD in 1 eye (AREDS category 4), the hazard ratios for fellow eyes were 1.08 (95% CI, 0.65-1.72) for NV AMD and 0.98 (95% CI, 0.64-1.49) for CGA., Conclusions: The AREDS results showed no clear effect of cataract surgery on the risk of progression to advanced AMD., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

Purpose: To evaluate the effect of the multivitamin Centrum on the development and progression of age-related lens opacities., Design: Clinic-based prospective cohort study., Participants: Four thousand five hundred ninety individuals with at least one natural lens and photographic follow-up (median, 6.3 years) were assessed for development or progression of lens opacities., Main Outcome Measures: Progression of "any" lens opacity or type-specific opacity was ascertained from lens photographs taken at baseline and at annual visits beginning at year 2., Methods: The Age-Related Eye Disease Study (AREDS) showed no statistically significant effect of a high-dose antioxidant formulation on progression of lens opacities. Centrum also was provided to approximately two thirds of the study participants. Because Centrum use was elective, a logistic regression model of baseline characteristics was used to generate a propensity score for Centrum use. Repeated-measures logistic regression, adjusted for propensity score and other covariates, was used to evaluate associations of Centrum use and lens opacity., Results: Centrum use, adjusted for propensity score and other covariates, was associated with a reduction in "any" lens opacity progression (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.72-0.98, P = 0.025). Results for individual lens opacity types suggested that Centrum use was protective for nuclear opacity events (OR = 0.75, 95% CI = 0.61-0.91, P = 0.004)., Conclusion: Observational data from the AREDS and other studies suggest that use of a multivitamin may delay the progression of lens opacities. A National Eye Institute-sponsored clinical trial scheduled for completion in 2007 will provide additional data on Centrum use and cataract development.

Objective: To investigate whether serum lipid/lipoprotein levels are independent risk factors for nuclear, cortical, or posterior subcapsular (PSC) cataracts., Design: Case-control study nested in a cohort study., Participants and Methods: Eye examinations were conducted on surviving members of the Framingham Offspring Heart Study cohort from 1989 to 1991 (Framingham Offspring Eye Study) to determine cataract case-control status. Data from the Framingham Offspring Heart Study, including fasting serum total cholesterol, high-density lipoprotein cholesterol, and triglyceride measurements collected first in 1971, again approximately 8 years later, and approximately every 4 years thereafter were used to examine associations between lipid levels (mean levels across examinations and slope of measurements over time) and the presence of specific cataract types. The multistage analyses included 1869 persons aged 45 years and older., Main Outcome Measures: A standardized grading system was used to grade cortical, nuclear, and PSC cataracts., Results: The median age of participants was 55 years; 49% were males. In multivariable logistic regression models adjusted for potential confounders, fasting hypertriglyceridemia (>/=250 mg/dl) was associated with an increased risk of PSC cataract in men (P = 0.02). High-density lipoprotein cholesterol levels

Objective: The purpose of the study was to determine whether body mass index (BMI) is an independent risk factor for the development of nuclear, cortical, or posterior subcapsular lens opacities., Design: A cohort study., Participants and Methods: Eye examinations were conducted on surviving members of the Framingham Heart Study Cohort from 1973 to 1975 (Framingham Eye Study I) and again from 1986 to 1989 (Framingham Eye Study II). Data from the Framingham Heart Study, including weight measurements collected biennially from 1948, were used to examine associations between BMI (mean BMI across examinations, slope of BMI over time, and fluctuations in BMI) and the development of lens opacities. This analysis included 714 individuals, aged 52-80 years, who were free of lens opacities at the first eye examination., Main Outcome Measures: Development of nuclear, cortical, and posterior subcapsular lens opacities., Results: A total of 444 persons developed lens opacities during the approximately 13 years between eye examinations. In logistic regression analyses that controlled for age, sex, education, diabetes, and smoking, the risk of developing cortical opacity increased with higher BMI at the time of the first eye examination (P = 0.002). Risk of cortical opacities also increased, at a borderline level of significance, with higher average BMI (P = 0.09) across examinations and increasing BMI levels over time (P = 0.10). There was a strong association between increasing BMI over time and the development of posterior subcapsular lens opacities (P = 0.002). No associations were found for nuclear lens opacities., Conclusions: Although the mechanism explaining the association is unclear, these findings suggest that BMI, a potentially modifiable characteristic, is associated with the development of cortical and posterior subcapsular lens opacities.

Objective: Possible risk factors for hemiretinal vein occlusion were identified and compared with risk factor profiles for central and branch retinal vein occlusion., Design: The design was a multicenter case-control study., Methods: The authors identified 79 patients with hemiretinal vein occlusion (HRVO), 258 patients with central retinal vein occlusion (CRVO), 270 patients with branch retinal vein occlusion (BRVO), and 1142 control subjects at 5 clinical centers. Risk factor data were obtained through interviews, clinical examinations, and laboratory analyses of blood specimens., Results: Systemic hypertension and history of diabetes mellitus were associated with increased risk of HRVO. Risk of CRVO increased with history of diabetes, systemic hypertension, and higher erythrocyte sedimentation rate (females only); risk of CRVO decreased with increasing amounts of physical activity and increasing amounts of alcohol consumption. Systemic hypertension, higher body mass index, and higher alpha2-globulin levels were associated with increased risk of BRVO, whereas higher high-density lipoprotein levels and increasing levels of alcohol consumption were associated with decreased risk of BRVO. Glaucoma history was associated with all three types of retinal vein occlusion., Conclusion: Patients presenting with retinal vein occlusion should be evaluated for cardiovascular disease, diabetes, and glaucoma.

There has been increasing use of high-dosage zinc supplementation in the population, in particular as a potential treatment for age-related macular degeneration. We examined the relationship between fasting serum zinc and serum lipid levels in 778 adults, aged 22 to 80 years, who were control subjects in a multicenter, clinic-based case-control study. The samples were taken during 1987 to 1990, a time when vitamin/mineral supplementation was becoming increasingly common. We found that higher serum zinc levels, most notably those above the highest quintile, were associated with higher levels of total serum cholesterol, low-density-lipoprotein cholesterol, and triglycerides. No significant trend was noted for high-density-lipoprotein cholesterol. Previous studies demonstrated that high-dosage zinc supplements raise serum zinc levels. The possibility that use of such supplements can adversely affect serum lipid profiles suggests that chronic ingestion of such supplements should not be done without adequate medical supervision.

To explore the existence of a dose-response relationship between sunlight exposure and risk of age-related cataracts, we analyzed data collected from 1008 patients with cataracts and 469 control subjects enrolled in the Italian-American Case-Control Study of Age-Related Cataracts. Fourteen variables related to sunlight exposure history were included in the questionnaire administered to the study participants. A sunlight index was constructed and its relationship to the presence of cataracts was modeled by logistic regression. After adjustments for potential confounding variables and for age and sex, a significant dose-response effect (P = 0.01) was detected between the sunlight exposure index and the presence of pure cortical cataracts. With the exception of corticonuclear cataracts, all the other mixed types of opacity also showed a dose-response association with the sunlight index. These data support the hypothesis that sunlight exposure is a risk factor in the development of cortical cataracts, and demonstrate the existence of a dose-response relationship in this association.

Purpose: The study was designed to evaluate the relative anatomic position of the crossing vessels at the site of occlusion in eyes with branch retinal vein occlusion (BRVO)., Methods: Fundus photographs of 106 eyes (104 patients) with recent BRVO from the Eye Disease Case-Control Study were used to examine the relative position of artery and vein at occluded crossings. Three separate comparison groups were formed by identifying corresponding arteriovenous crossings for each occluded crossing in: (1) the ipsilateral but opposite vessel arcade within eyes affected by BRVO; (2) the same quadrant in unaffected eyes of BRVO patients; and (3) the same quadrant in eyes of patients without BRVO, matched by age, sex, and race with the BRVO patients., Results: The site of obstruction of the branch vein was an arteriovenous crossing in all affected eyes. In 99% of eyes with BRVO, the artery was located anterior to the vein at the obstructed site. In the three comparison groups, the artery was anterior to the vein in 62%, 61%, and 54% of the crossings, respectively, yielding statistically significant differences for each group of control crossings compared with BRVO crossings (P < 0.001)., Conclusion: Finding the vein to be consistently between the more rigid artery and the retina at almost all arteriovenous crossings affected by BRVO suggests a possible role for mechanical obstruction in the pathogenesis of BRVO.

The Lens Opacities Classification System I (LOCS I) was used to classify lens opacities in the clinic-based Italian-American Case-Control Study of Age-Related Cataract. Data on the distribution of cataract types among the 1008 patients (age range, 45-79 years) are presented. A single type of cataract was found in 65% of all cases in whom both lenses could be graded. Among all patients and among patients with only one type of cataract, cortical opacities occurred most frequently and posterior subcapsular opacities least frequently. In patients with bilateral cataracts there was a high degree of concordance of cataract type and severity. The high degree of concordance of cataract type between eyes and the decreasing prevalence of unilateral cataract with increasing age suggest that patients with unilateral cataract are at high risk of developing the same opacity in the fellow eye. Cortical cataracts were found more frequently in women, and in patients with unilateral cataract, the left eye was more frequently affected. Clinic-based data on the distribution of cataract may be of assistance in planning future clinical studies of cataract.

Data from the 1973 to 1975 Framingham Eye Study were used to estimate the prevalence rates of nuclear, cortical, and posterior subcapsular lens opacities in persons between ages 52 and 85 years. The rates for each of the opacities increased rapidly with age, so that for the oldest age group, 75 years and over, nuclear, cortical, and posterior subcapsular opacities were found in 65.5%, 27.7% and 19.7% of persons, respectively. Nuclear opacities were the most commonly diagnosed lens change. Each of the opacities was found more often in women than in men. Among persons with senile lens changes, the proportion with more than one type of change increased from 26.5% for ages 52 to 64 years, to 47.1% for ages 75 to 85 years. The high prevalence rates for senile lens opacities (over 75% for persons aged 75 to 85 years) and the frequent occurrence of opacities in combination create methodological problems for epidemiologic studies of lens opacities.

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.