Discussion of case-control studies of Peleg, Stähelin, and Willett.

The combined results from the case-control studies of Peleg, Stähelin, and Willett were found to provide no evidence of a relationship between serum retinol levels and the risk of cancer in all sites combined or of lung cancer. However, a relationship between serum retinol levels and the risk of gastrointestinal cancer was suggested.

Factors associated with visual outcome after photocoagulation for diabetic retinopathy. Diabetic Retinopathy Study Report #13.

Six risk factors for severe visual loss despite panretinal (scatter) photocoagulation were identified by analyzing data collected during the first 5 years after randomization in the Diabetic Retinopathy Study. Proportional hazards regression revealed NVD (neovascularization on/around the optic disc) to be the most important risk factor. The risk of severe visual loss rose with increasing NVD, hemorrhages/microaneurysms, retinal elevation, proteinuria, and hyperglycemia and fell with increasing "treatment density." These results are similar to previous DRS findings on untreated eyes. The importance of "treatment density" as an independent predictor of visual outcome is a new finding and lends support to the common clinical practice of repeating photocoagulation if initial treatment does not reduce or stabilize retinal neovascularization.

Serum zinc and serum lipid profiles in 778 adults.

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.

Lens opacities and senile maculopathy.

Analysis of data from a population survey, the Framingham Eye Study, shows that when the various senile lens changes are pooled, no associations with senile maculopathy are evident. Subgroup analysis shows the relative risk of senile maculopathy to be lower than 1.00 in the presence of nuclear sclerosis for all age groups and greater than 1.00 for persons between 52 and 74 years in the presence of cortical changes. Nuclear-cortical interaction tests are highly significant, indicating that nuclear sclerosis and cortical opacities have opposite effects on the relative risk of senile maculopathy.

Prevalence of myopia in the United States.

Data from the 1971 to 1972 National Health and Nutrition Examination Survey were used to estimate myopia prevalence rates for persons in the United States between the ages of 12 and 54 years. When persons were classified by the refractive status of their right eye, 25% were myopic. Significantly lower prevalence rates were found for male subjects than for female subjects and for blacks than for whites. Myopia prevalence rose with family income and educational level. The importance of income and educational level may result from their association with near work, a factor that has been implicated in the pathogenesis of myopia.

Clinical course of macular holes: the Eye Disease Case-Control Study.

OBJECTIVE: To describe the clinical course of affected and unaffected eyes in patients with idiopathic macular holes. PATIENTS: Prospective study of patients with macular holes enrolled in the Eye Disease Case-Control Study. MAIN OUTCOME MEASURES: The best-corrected visual acuity at follow-up was compared with that at baseline. Changes in the macular holes, including increases in size or spontaneous regression, were assessed. The rates of development of new macular holes in fellow unaffected eyes were estimated. RESULTS: Of the 198 patients examined at baseline, 28 (14.1%) died before reevaluation. Of those who survived, 122 (71.8%) had a follow-up examination. Approximately 34% (34.4%) of all eyes with macular holes had an increase in the size of the macular hole. Forty-five percent of eyes had a decrease in visual acuity of 2 or more lines and 27.8%, of 3 or more lines; 40.9% remained stable, with a gain or loss of fewer than 2 lines. The rate of development of a new macular hole during follow-up in fellow eyes that were unaffected at baseline was 4.3% for 3 or fewer years of follow-up, 6.5% for 4 to 5 years of follow-up, and 7.1% for 6 or more years of follow-up. Spontaneous regression of the macular hole occurred in 3 (8.6%) of 35 patients with a follow-up interval of 6 or more years, whereas no regression occurred in patients with a shorter follow-up. CONCLUSIONS: The visual acuity of 45.0% of eyes with macular holes deteriorated by 2 or more lines during follow-up. The rate of development of macular holes in unaffected fellow eyes was low.

Thromboembolism and oral contraceptives.

PIP: A 1970 study by Fuertes-de la Haba et al. (Obstetrics and Gynecology 36: 597-602) on thromboembolism in Puerto Rican women taking oral contraceptives is criticized. Fuertes-de la Haba et al. interpreted their results as failing to corroborate previous publications indication an increased mortality rate from thromboembolic disorders in women using the oral contraceptive. Siegel indicates that the limitations in the study preclude the possibility of its affecting the understanding of the relationship of oral contraceptives to thromboembolic mortality. The data in the study were inadequate, the number of cases too small to give statistically valid results, and the follow-up of subjects was too faulty to allow accurate inferences.^ieng

Senile lens and senile macular changes in a population-based sample.

Eye examinations performed on the survivors of the Framingham Heart Study Cohort showed a prevalence of senile lens changes ranging from 42% at ages 52 to 64 years to 91% at ages 75 to 85 years. The prevalence of senile macular changes increased from 35% at 52 to 64 years to 50% at 75 to 85 years. Persons affected with either condition usually had bilateral involvement. No association between the two conditions was shown.

Survival rates after enucleation of eyes with malignant melanoma.

We investigated the rates of mortality for several types of malignant melanomas for evidence that surgery accelerates metastasis. Additionally, we reanalyzed uveal melanoma survival rates from the Armed Forces Institute of Pathology. Our computations showed higher death rates in years two to five after diagnosis than in years one or six to ten. The same pattern of a peak mortality in the early years after diagnosis and lower rates six to ten years thereafter was seen in all tumor types studied. Our analysis of survival rates produced no evidence to alter the existing pattern of treatment for malignant melanoma of the uvea.

Extended use of prefilled humidifier reservoirs and the likelihood of contamination.

UNLABELLED: We sought to determine the potential for disposable prefilled humidifiers to become contaminated during extended patient use. METHODS & MATERIALS: We sampled the water in 55 humidifier reservoirs, which were being used by patients or which had been used by patients and then been placed on 'standby,' and had the samples cultured by a commercial clinical laboratory. RESULTS: None of the humidifiers showed contamination after 72 hours of continuous patient use, and 33 of the 55 were used by patients for an additional 3-9 days with no contamination. Fifteen humidifiers that had been in use on patients were put in a standby mode for 30-32 days, with 5 continuing for 60-62 days, with no contamination seen. CONCLUSIONS: An automatic 72-hour change-out for prefilled humidifiers used with low-flow oxygen (less than or equal to 4 L/min) is wasteful. Our study demonstrates that the use-time of humidifiers can be safely extended to as long as 6-12 days.

Oral contraceptives: epidemiologic problems. (The chairman's summary of a conference).

PIP: Focus of the conference on Epidemiologic Problems in Studies of the Medical Effects of Oral Contraceptives was on diagnostic bias; risk for women with predisposing conditions, medical care for oral contraceptive users, and long term oral contraceptive users. Diagnostic bias indicates contraceptive users are more likely to be hospitalized because their physicians are cautious and alert to symptoms, therefore thromboembolic disorders may likely be seen as ill-effects from oral contraceptives since information on non-users would be lacking or limited. Data on predisposing conditions is completely lacking as is the lack of controls with exactly the same predisposing conditions. There is no available information on diagnosis and hospitalization of oral contraceptive users. Data on long term users is subject to many of the inadequate statistical evidences lacking in the other areas.^ieng

Surrogate endpoints in clinical trials: ophthalmologic disorders.

We examined three examples of surrogate observations in ophthalmology. The first represents a simple case: the status of one eye is used as a surrogate for the (unobservable) status of the opposite eye in the same individual. The second and third examples represent possible extrapolation of long term results on the basis of early changes. These examples are used to illustrate the assumptions intrinsic in the use of surrogate variables.

Grading of images in a clinical trial.

We developed a computer model to compare the power in clinical trials that use either of two grading schemes for objectively recorded dependent variables. The example we use is an eye lens photo. The first grading system consists of side by side comparison of the before and after treatment photos; the second involves separate grading of the two photos. This modelling experience suggests that separate grading may often yield more power than side by side comparison, and offers other advantages as well. For applications in which grading error is considerably smaller in the side by side method, power may be markedly better. Most importantly, strong prejudice in favour of one or the other approach in all situations seems unwarranted.