Cell proliferation in carcinogenesis.

Chemicals that induce cancer at high doses in animal bioassays often fail to fit the traditional characterization of genotoxins. Many of these nongenotoxic compounds (such as sodium saccharin) have in common the property that they increase cell proliferation in the target organ. A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds. The carcinogenic dose-response relationship for genotoxic chemicals (such as 2-acetylaminofluorene) was also due in part to increased cell proliferation. Mechanistic information is required for determination of the existence of a threshold for the proliferative (and carcinogenic) response of nongenotoxic chemicals and the estimation of risk for human exposure.

Ethnicity-specific prevalences of refractive errors vary in Asian children in neighbouring Malaysia and Singapore.

AIM: To compare the prevalences of refractive errors in Malay, Chinese and Indian children in Malaysia and Singapore. METHODS: Children aged 7-9 years from three schools in the Singapore Cohort study of the Risk factors for Myopia (n = 1962) and similarly aged children from a random cluster sample in the metropolitan Kuala Lumpur area in the Malaysia Refractive Error Study in Children (n = 1752) were compared. Cycloplegic autorefraction was conducted in both countries. RESULTS: The prevalence of myopia (spherical equivalent of at least -0.5 diopters (D) in either eye) was higher in Singapore Malays (22.1%) than in Malays in Malaysia (9.2%; 95% confidence interval (CI) 11.2 to 14.7; p<0.001). Similarly, Singapore Chinese (40.1%) had higher prevalences than Malaysian Chinese (30.9%; 95% CI 1.5 to 16.9). Singapore Indians had a higher prevalence (34.1%) than Malaysian Indians (12.5%; 95% CI 17.4 to 25.9). The multivariate odds ratio of astigmatism (cylinder at least 0.75 D in either eye) in Singapore Malays compared with Malaysian Malays was 3.47 (95% CI 2.79 to 4.32). Ethnicity-specific hyperopia rates did not differ in Singapore and Malaysia. CONCLUSION: The ethnicity-specific prevalences of myopia in Singapore Malays, Chinese and Indians are higher than those in Malaysian Malays, Chinese and Indians. As Malays, Chinese and Indians in Malaysia have genetic make-up similar to that of Malays, Chinese and Indians in Singapore, environmental factors may contribute to the higher myopia rates.

Comparative bladder tumor promoting activity of sodium saccharin, sodium ascorbate, related acids, and calcium salts in rats.

Sodium saccharin and sodium ascorbate are known to promote urinary bladder carcinogenesis in rats following initiation with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) or N-butyl-N-(4-hydroxybutyl) nitrosamine. Sodium salts of other organic acids have also been shown to be bladder tumor promoters. In addition, these substances increase urothelial proliferation in short term assays in rats when fed at high doses. When they have been tested, the acid forms of these salts are without either promoting or cell proliferative inducing activity. The following experiment was designed to compare the tumor promoting activity of various forms of saccharin and to evaluate the role in promotion of urinary sodium, calcium, and pH as well as other factors. Twenty groups of 40 male F344 rats, 5 weeks of age, were fed either FANFT or control diet during a 6-week initiation phase followed by feeding of a test compound for 72 weeks in the second phase. The chemicals were administered to the first 18 groups in Agway Prolab 3200 diet and the last 2 groups were fed NIH-07 diet. The treatments were as follows: (a) FANFT----5% sodium saccharin (NaS); (b) FANFT----3% NaS; (c) FANFT----5.2% calcium saccharin (CaS); (d) FANFT----3.12% CaS; (e) FANFT----4.21% acid saccharin (S); (f) FANFT----2.53% S; (g) FANFT----5% sodium ascorbate; (h) FANFT----4.44% ascorbic acid; (i) FANFT----5% NaS plus 1.15% CaCO3; (j) FANFT----5.2% CaS plus 1.34% NaCl; (k) FANFT----5% NaS plus 1.23% NH4Cl; (l) FANFT----1.15% CaCO3; (m) FANFT----1.34% NaCl; (n) FANFT----control; (o) control----5% NaS; (p) control----5.2% CaS; (q) control----4.21% S; (r) Control----control; (s) FANFT----5% NaS (NIH-07 diet); (t) FANFT----control (NIH-07 diet). NaS, CaS and S without prior FANFT administration were without tumorigenic activity. NaS was found to have tumor promoting activity, showing a positive response at the 5 and 3% dose levels, with significantly greater activity at the higher dose. CaS had slight tumor promoting activity but without a dose response, and S showed no tumor promoting activity. In addition, NaCl showed weak tumor promoting activity, but CaCO3 was without activity. NH4Cl completely inhibited the tumor promoting activity of NaS when concurrently administered with it. NaCl administered with CaS or CaCO3 administered with NaS showed activity similar to that of NaS. Sodium ascorbate was also shown to have tumor promoting activity, with slightly less activity than NaS. Ascorbic acid showed no tumor promoting activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Linkage between research sponsorship and patented eye-care technology.

PURPOSE: To examine the linkage between the funding of ophthalmologic and related biomedical research and the development of patented eye-care technology using data on patents granted and the scientific literature cited by those patents. METHODS: The United States patents granted during the 20-year period from 1975 through 1994 were screened using patent office classifications and key words to identify all eye-care-related patents. Each patent's nonpatent references (references to literature other than previously granted patents) were examined, and those references to scientific papers then were reviewed to determine the authors' institutions and acknowledged funding sources. RESULTS: Major findings include the following: (1) Eye technology innovation has grown steadily, with a threefold increase in number of patents granted from 224 in 1975 to 662 in 1994. (2) The cited scientific base that supports this technology has grown even more rapidly, with a sixfold increase in the average number of nonpatent references, from fewer than 0.5 per patent in 1975 to more than 3.0 in 1994; as a result, the total number of nonpatent references has increased by a factor of 20, from 100 in 1975 to 2000 in 1994. (3) The National Eye Institute is the leading single institution in providing support for this research: 31% of all eye-care patents with science references cite papers that contain at least one acknowledgment to National Eye Institute (NEI) support; and when NEI is combined with the rest of the National Institutes of Health (NIH), 41% of the patents with science references are linked to NIH-funded research. (4) Patent science dependence, as measured by science references, is greatest for technologies related to medical treatment, surgical instruments, and intraocular lenses; moderate for diagnostic instruments and contact lens; and least for eyeglasses. CONCLUSIONS: The NIH and other sponsored vision research is of direct and increasing relevance to the growing number of US patented eye-care technologies.

Use of cell proliferation data in modeling urinary bladder carcinogenesis.

A multistage, probabilistic, biologically based model of carcinogenesis has been developed involving qualitative and quantitative aspects of the process. A chemical can affect the risk of cancer by directly damaging DNA and/or increasing the number of cell divisions during which errors in DNA replication can occur. Based on this model, carcinogens are classified as genotoxic versus nongenotoxic; nongenotoxic chemicals are further divided on the basis of whether or not they act through a specific cell receptor. Nongenotoxic compounds, particularly those acting through a nonreceptor mechanism, are likely to have dose and/or species-specific thresholds. This classification also implies the existence of chemicals that will be carcinogenic at high doses in animal models, but because of dose and/or mechanistic considerations, will not be carcinogenic to humans at levels of exposure. N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) and 2-acetylaminofluorene (AAF) are classical genotoxic bladder carcinogens that also cause proliferative effects at higher doses. Although there is an apparent no-effect level for the urinary bladder carcinogenicity of these two compounds at low doses, in reality, DNA adducts form at these low levels, and it is likely that there is a cancer effect (no threshold), but it is below the level of detection of the bioassay. These conclusions are based on studies involving multiple doses and time points in rodents, including results from the ED01. Pellets implanted directly into the rodent bladder lumen or calculi formed in the urine as a result of an administered chemical cause abrasion of the urothelium, and a marked increase in cell proliferation and cell number, and ultimately tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Multistage carcinogenesis in the urinary bladder.

The induction of cancer of the urinary bladder is a multi-stage process involving multiple exogenous and endogenous factors. Based on the classical initiation-promotion model, we have used N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) as initiator and sodium saccharin (SAC) or tryptophan as promoters. These latter chemicals have the properties expected of promoters: induction of hyperplasia, reversibility and nonmutagenicity. Also, tumors were induced whether the promoter was administered immediately after FANFT or beginning 6 weeks after FANFT was discontinued, but no tumors resulted if either promoter was given without initiation with FANFT. Factor(s) present in normal urine also are involved in the promotion process, in addition to the role of urine as a carrier of carcinogens. However, administration of SAC to animals with a rapidly proliferating bladder mucosa, induced by ulceration, pellet insertion, or in utero, resulted in bladder tumor induction, even without prior initiation with FANFT. To better understand the complex interaction of the multiple variables in bladder carcinogenesis, a stochastic computer model has been formulated based on long-term carcinogenicity and tissue kinetic studies in vivo. This model indicates the importance of cell proliferation and the development of hyperplasia in carcinogenesis.

Measurements of vision function and quality of life in patients with cataracts in southern India. Report of instrument development.

OBJECTIVE: To develop and validate vision function (VF) and quality of life (QOL) instruments in patients with cataracts in the context of large volume surgery in a developing country. MATERIALS AND METHODS: The instruments were developed using a consensus approach. One hundred patients who were undergoing cataract surgery at Aravind Eye Hospital, Madurai, India, were interviewed preoperatively and 3 and 12 months postoperatively. Standard clinical procedures were followed, including measurement of visual acuity. Between-interviewer reproducibility was measured by repeated administration of the preoperative questionnaire. Within-interviewer reproducibility was measured preoperatively in a separate study of 50 patients. RESULTS: Preoperative scores from the VF and QOL instruments were significantly associated with visual acuity (r = 0.4). Internal reliability (Cronbach alpha) was greater than .9. Both instruments showed large changes after surgery, with effect sizes of 3 or greater for most VF scales (range, 1.8-3.7) and 1 or greater for QOL scales (range, 1.0-2.2). Changes in visual acuity after surgery were correlated with changes in the VF (r = 0.44) and QOL (r = 0.41) scale scores. Between-interviewer reproducibility was acceptable (total VF scale, Spearman r = 0.7; total QOL scale; r = 0.74). The kappa values were lower for within-interviewer reproducibility. CONCLUSIONS: The study provided strong evidence for the validity, reproducibility, and responsiveness of the instruments, and for the feasibility of using them in the setting of a large volume of cataract surgery in a developing country.

Cellular proliferation and genetic events involved in the genesis of Burkitt lymphoma (BL) in immune compromised patients.

A mathematical model simulating lymphomagenesis based on the two-hit theory of carcinogenesis is presented by contrasting the biologic variables responsible for a high risk of developing Burkitt lymphoma (BL) in three immunosuppressed groups with that of nonendemic BL. In this model, the pro-B lymphocyte is considered to be the target for BL-specific translocations such as t(8;14). With repeated mitosis, the target cell pool expands in the high-risk individual, and, thereby, the opportunities for a spontaneous translocation to arise are increased. The chromosomal translocation endows the target cell with survival advantages, and, hence, lymphoma develops. Modeling results demonstrate that this increased cell proliferation is sufficient in accounting entirely for the increase in tumor prevalence. Preventing enhanced cellular proliferation by obviating immune deficiency and treating patients with agents that restore immunity or have antiviral and antiproliferative properties prior to conversion from polyclonal B-cell proliferation to monoclonal malignancy could obviate the development of BL.

Prevalence of blindness and cataract surgery in Shunyi County, China.

PURPOSE: To estimate the prevalence of blindness and cataract surgery among older adults in rural China. METHODS: Cluster sampling was used in randomly selecting men and women aged 50 years or older for visual acuity testing and an eye examination in 28 villages in Shunyi County. The survey, which was carried out in the fall of 1996, was preceded by a pilot study in which operational methods were refined and quality assurance evaluations carried out. RESULTS: Of 5,555 enumerated subjects > or =50 years of age, 91.5% (5,084/5,555) were examined and 90.9% (5,052/5,555) were tested for visual acuity. In this population, 2.8% (139/5,052) were blind, defined as presenting visual acuity less than 6/60 in both eyes. Blindness was associated with older age and female sex. Cataract was the principal cause of blindness in at least one eye in 48.2% (67/139) of blind people. The ratio of those blind from cataract who were operated on to the those who could have been operated on, cataract surgical coverage, was estimated to be 47.8% (54/113). Cataract surgery was associated with younger age but not sex or education. CONCLUSIONS: Blindness, particularly blindness related to cataract, continues to be a significant problem among the elderly, especially women, in this population-based sample of rural Chinese. Despite an active eye-care program in Shunyi County, only half of those who might benefit from cataract surgery are receiving it.

Refractive Error Study in Children: sampling and measurement methods for a multi-country survey.

PURPOSE: The Refractive Error Study in Children was designed to assess the prevalence of refractive error and vision impairment in children of different ethnic origins and cultural settings. METHODS: Population-based cross-sectional samples of children 5 to 15 years of age were obtained through cluster sampling. Presenting, uncorrected, and best-corrected visual acuity, along with refractive error under cycloplegia, were the main outcome measures. Amblyopia and other causes of uncorrectable vision impairment were determined. RESULTS: Study design and sample size calculations, survey enumeration and ophthalmic examination methods, quality assurance monitoring, and da ta analyses and statistical methods are described. CONCLUSIONS: The study design, sample size, and measurement methods ensure that the prevalence of age-specific and sex-specific refractive error can be estimated with reasonable accuracy in the target populations. With commonality of methods, a comparison of findings between studies in different ethnic origins and cultural settings is possible.

Refractive Error Study in Children: results from Shunyi District, China.

PURPOSE: To assess the prevalence of refractive errors and vision impairment in school-age children in Shunyi District, northeast of Beijing, the Peoples Republic of China. METHODS: Random selection of village-based clusters was used to identify a sample of children 5 to 15 years of age. Resident registration books were used to enumerate eligible children in the selected villages and identify their current school. Ophthalmic examinations were conducted in 132 schools on children from 29 clusters during May 1988 to July 1998, including visual acuity measurements, cycloplegic retinoscopy, cycloplegic autorefraction, ocular motility evaluation, and examination of the external eye, anterior segment, media, and fundus. Independent replicate measurements of all children with reduced vision and a sample of those with normal vision were done for quality assurance monitoring in three schools. RESULTS: A total of 6,134 children from 4,338 households were enumerated, and 5,884 children (95.9%) were examined. The prevalence of uncorrected, presenting, and best visual acuity 0.5 (20/40) or worse in at least one eye was 12.8%, 10.9%, and 1.8%, respectively; 0.4% had best visual acuity 0.5 or worse in both eyes. Refractive error was the cause in 89.5% of the 1,236 eyes with reduced vision, amblyopia in 5%, other causes in 1.5%, with unexplained causes in the remaining 4%. Myopia -0.5 diopter or less in either eye was essentially absent in 5-year-old children, but increased to 36.7% in males and 55.0% in females by age 15. Over this same age range, hyperopia 2 diopters or greater decreased from 8.8% in males and 19.6% in females to less than 2% in both. Females had a significantly higher risk of both myopia and hyperopia. CONCLUSIONS: Reduced vision because of myopia is an important public health problem in school-age children in Shunyi District. More than 9% of children could benefit from prescription glasses. Further studies are needed to determine whether the upward trend in the prevalence of myopia continues far beyond age 15 and whether the development of myopia is changing for more recent birth cohorts.

Refractive Error Study in Children: results from Mechi Zone, Nepal.

PURPOSE: To assess the prevalence of refractive error and vision impairment in school age children in the terai area of the Mechi zone in Eastern Nepal. METHODS: Random selection of village-based clusters was used to identify a sample of children 5 to 15 years of age. Children in the 25 selected clusters were enumerated through a door-to-door household survey and invited to village sites for examination. Visual acuity measurements, cycloplegic retinoscopy, cycloplegic autorefraction, ocular motility evaluation, and anterior segment, media, and fundus examinations were done from May 1998 through July 1998. Independent replicate examinations for quality assurance monitoring took place in all children with reduced vision and in a sample of those with normal vision in seven villages. RESULTS: A total of 5,526 children from 3,724 households were enumerated, and 5,067 children (91.7%) were examined. The prevalence of uncorrected, presenting, and best visual acuity 0.5 (20/40) or worse in at least one eye was 2.9%, 2.8%, and 1.4%, respectively; 0.4% had best visual acuity 0.5 or worse in both eyes. Refractive error was the cause in 56% of the 200 eyes with reduced uncorrected vision, amblyopia in 9%, other causes in 19%, with unexplained causes in the remaining 16%. Myopia -0.5 diopter or less in either eye or hyperopia 2 diopters or greater was observed in less than 3% of children. Hyperopia risk was associated with female gender and myopia risk with older age. CONCLUSIONS: The prevalence of reduced vision is very low in school-age children in Nepal, most of it because of correctable refractive error. Further studies are needed to determine whether the prevalence of myopia will be higher for more recent birth cohorts.

Refractive Error Study in Children: results from La Florida, Chile.

PURPOSE: To assess the prevalence of refractive errors and vision impairment in school-age children in a suburban area (La Florida) of Santiago, Chile. METHODS: Random selection of geographically defined clusters was used to identify a representative sample of children 5 to 15 years of age. Children in the 26 selected clusters were enumerated through a door-to-door survey and invited to report to a community health clinic for examination. Visual acuity measurements, cycloplegic retinoscopy, cycloplegic autorefraction, ocular motility evaluation, and examination of the external eye, anterior segment, media, and fundus were done from April through August 1998. Independent replicate examinations of all children with reduced vision and a sample of those with normal vision were done for quality assurance monitoring in six clusters. RESULTS: A total of 6,998 children from 3,830 households were enumerated, and 5,303 children (75.8%) were examined. The prevalence of uncorrected, presenting, and best visual acuity 0.50 (20/40) or worse in at least one eye was 15.8%, 14.7%, and 7.4%, respectively; 3.3% had best visual acuity 0.50 or worse in both eyes. Refractive error was the cause in 56.3% of the 1,285 eyes with reduced vision, amblyopia in 6.5%, other causes in 4.3%, with unexplained causes in the remaining 32.9%. Myopia -0.50 diopter or less in either eye was present in 3.4% of 5-year-old children, increasing to 19.4% in males and 14.7% in females by age 15. Over this same age range, hyperopia 2.00 diopters or greater decreased from 22.7% to 7.1% in males and from 26.3% to 8.9% in females. Females had a significantly higher risk of hyperopia than males. CONCLUSIONS: Refractive error, associated primarily with myopia, is a major cause of reduced vision in school-age children in La Florida. More than 7% of children could benefit from the provision of proper spectacles. Efforts are needed to make existing programs that provide free spectacles for school children more effective. Further studies are needed to determine whether the upward trend in myopia continues far beyond 15 years of age.

Visual acuity and quality of life outcomes in patients with cataract in Shunyi County, China.

PURPOSE: To measure visual acuity and vision-related quality of life in individuals in rural China operated on for cataract. METHODS: Five thousand fifty-two persons age 50 years and older, 90.9% (5,052/5,555) of a randomly selected population in Shunyi County, were examined in the fall of 1996. Visual functioning and quality of life questionnaires were administered to those with presenting visual acuity less than 6/60 in either eye and to those who were aphakic or pseudophakic. RESULTS: Of the 87 individuals operated on for cataract, 12% (10/87) had presenting visual acuity of 6/18 or more in both eyes, and 24.1% (21/87) had less than 6/60. Twenty-five percent (29/116) of the 116 eyes operated on for cataract had presenting visual acuity of 6/18 or more, and 44.8% (52/116) had less than 6/60. Aphakic cases without glasses and uncorrectable aphakia attributable to surgical complications were common. In a multivariate regression model, including time period of surgery, hospital type, and surgical procedure, only pseudophakia was associated with better outcomes (P = .05). On a scale from 0 (maximum problems) to 100 (no problems), the mean visual functioning score (+/-SD) for the operated-on population was 61.9 +/- 30.0, and 71.0 +/- 31.8 for the quality of life questionnaire. These scores were comparable to those of the unoperated-on population with moderate bilateral blindness (<6/60 to > or =3/60 in the better eye). Visual functioning and quality of life scores were closely correlated with visual acuity in operated-on (r = 0.64 and r = 0.61, respectively) and unoperated-on populations (r = 0.68 and r = 0.59, respectively). CONCLUSIONS: Both clinical and patient-reported cataract surgery outcomes are below what should be achievable. Improvement in outcomes must be given greater emphasis if the potential of cataract surgery in restoring sight is to be realized.

The madurai intraocular lens study IV: posterior capsule opacification.

PURPOSE: To estimate the cumulative incidence of posterior capsule opacification 4 years after surgery in patients who participated in the Madurai Intraocular Lens Study and had extracapsular cataract extraction with posterior chamber intraocular lens implantation. METHODS: In the Madurai Intraocular Lens Study, 1,700 patients with best-corrected visual acuity 20/120 or worse in the better eye had extracapsular cataract extraction with posterior chamber intraocular lens implantation, and 1,474 (86.7%) of these completed the 1-year follow-up examination. From this group of 1,474 pseudophakic patients, 400 were randomly selected for reexamination 4 years after the original surgery. The eye that was operated on was examined by an ophthalmologist who was involved in the 1-year follow-up examinations and posterior capsule opacification grading. A grading of I to III was used to reflect the degree of opacification. With grades II and III, posterior capsule opacification detectable with an undilated pupil was present in the central axis. RESULTS: Three hundred twenty-seven (81.8%) of the selected population were examined between October 1997 and December 1998. Thirty-four (8.5%) were confirmed as being deceased, and 39 (9.8%) were unavailable for follow-up. The median age was 60 years, and 57.2% were women. The 4-year incidence of grade II or III posterior capsule opacification, including eyes already treated with laser capsulotomy, was 13.1% (95% confidence interval [CI], 9.7% to 17.3%). Each year of increased age was associated with a decreased risk of posterior capsule opacification (odds ratio, 0.96; 95% CI, 0.92 to 1.00). Based on best-corrected visual acuity of 20/40 or worse without co-existing pathology, the 4-year incidence of posterior capsule opacification was 13.5%. CONCLUSION: Because patients with relatively mature cataracts routinely receive extracapsular cataract extraction with posterior chamber intraocular lens implantation instead of the traditional intracapsular extraction, the subsequent need for laser capsulotomy may be less than that anticipated, based on previous reports.

The Madurai Intraocular Lens Study. III: Visual functioning and quality of life outcomes.

PURPOSE: To compare the effects of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL) vs intracapsular cataract extraction with aphakic glasses (ICCE-AG) on everyday visual functioning and quality of life. METHODS: In a nonmasked randomized controlled clinical trial, 3,400 bilateral vision-impaired patients, aged 40 to 75 years, with operable cataract were randomly assigned to receive one of the two treatment options. One half in each group were randomly selected for interviewer administration of visual functioning and quality of life questionnaires before surgery and at 6 and 12 months after surgery. RESULTS: Both ICCE-AG and ECCE/PC-IOL produced dramatic improvements in visual functioning and quality of life scores. Patients receiving ECCE/PC-IOL reported larger beneficial changes than did those receiving ICCE-AG, compatible with additional beneficial effects of a moderate magnitude for visual functioning and of a smaller beneficial magnitude for quality of life. All between-group differences were highly statistically significant (P < .00001). The additional benefits of ECCE/PC-IOL are not explained by visual acuity differences. A higher proportion of patients in the ICCE-AG group reported problems on a vision problem checklist at 6 months (more than 50%) than did patients in the ECCE/PC-IOL group (approximately 30%). CONCLUSIONS: In this developing-country setting, ICCE-AG and ECCE/PC-IOL were associated with substantial benefits in improved everyday vision function and vision-related quality of life. Patients who received ECCE/PC-IOL reported greater benefits and fewer problems with vision than did patients who received ICCE-AG.

The Madurai Intraocular Lens Study. I: A randomized clinical trial comparing complications and vision outcomes of intracapsular cataract extraction and extracapsular cataract extraction with posterior chamber intraocular lens.

PURPOSE: The Madurai Intraocular Lens Study (MIOLS) was designed to compare safety, efficacy, and quality of life outcomes after either intracapsular cataract extraction with aphakic glasses (ICCE-AG) or extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/ PC-IOL). METHODS: The Madurai Intraocular Lens Study was a nonmasked randomized controlled clinical trial conducted at a single hospital. Thirty-four hundred patients with age-related cataracts and having a best-corrected visual acuity less than or equal to 20/120 in the better eye were randomly assigned to either of the two cataract operative procedures. The main clinical outcomes were safety (complication rates) and efficacy (best-corrected visual acuity at 1 year equal to or better than 20/40). In addition, a subset of 1,700 trial participants received questionnaires before surgery, at 6 months after surgery, and at 1 year after surgery to measure visual functioning and vision-related quality of life. RESULTS: Details of study design, study organization, clinical and quality of life outcome variables, sample size calculations, patient eligibility criteria and recruitment, randomization and masking, participant flow, adherence to follow-up, quality assurance, and statistical methods are presented. CONCLUSIONS: The Madurai Intraocular Lens Study has sufficient power to detect clinically significant differences between the treatment options. There were no statistically significant differences between the two treatment groups for any of the major study variables at baseline. A high level of quality assurance was maintained throughout the October 1993 to June 1996 study period. The results should be applicable to all settings where the requisite expertise and resources are present.

The Madurai Intraocular Lens Study. II: Clinical outcomes.

PURPOSE: To evaluate the safety and efficacy of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL) compared with intracapsular cataract extraction with aphakic glasses (ICCE-AG). METHODS: In a nonmasked randomized controlled clinical trial, 3,400 bilaterally vision-impaired patients aged 40 to 75 years with operable cataract were randomly assigned to receive either ICCE-AG or ECCE/PC-IOL at the Aravind Eye Hospital in India. The surgery was performed by one of four study surgeons. Patients were hospitalized for 5 postoperative days, with follow-up visits at 2, 6, and 12 months after discharge. Postsurgery evaluations were conducted by two independent study ophthalmologists. RESULTS: At any single postoperative follow-up time point, there were no statistically significant differences of clinical relevance between treatment groups for any complication of a serious nature except cystoid macular edema, which was more common with ICCE (4.2% vs 1.6%). In general, whether of a trivial, intermediate, or serious nature, complication rates were low at each evaluation time point. Cumulatively, the incidence of serious complications of all types throughout the 1-year study period was 14.5% for patients in the ICCE-AG group and 7.7% in the ECCE group (P < .001). Best-corrected visual acuity of 20/40 or better at 12 months was attained by 90.7% of ICCE-AG patients and 96.3% of ECCE/PC-IOL patients (P < .001). CONCLUSION: Although both operative procedures are safe and effective for cataract patients with bilateral impairment, ECCE/PC-IOL is superior to ICCE-AG in terms of both visual acuity restoration and safety.

An assessment of the impact of urine cytology screening using a computer-based model of bladder cancer.

Utilizing a computer-based model of bladder cancer, the applications of various urine cytology screening strategies are assessed. Outcomes for patients diagnosed by screening with respect to numbers of cases diagnosed, mean length of life, and numbers of cancer deaths are compared with a similar population of patients diagnosed after the development of symptoms. Diagnostic and treatment modality costs can be used to predict the cost per man-year of life extension afforded by a screening program.