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Biomedical subjects

E S Gragoudas

Publications and source records attributed to E S Gragoudas.

At least 19 recordsLinked to original sources
PubMed1992

Occupation and risk of uveal melanoma. An exploratory study.

BACKGROUND: Little is known about the cause of uveal melanoma, the most common primary intraocular malignant lesion in adults. This population-based case-control study evaluated occupational exposures. METHODS: One hundred ninety-seven newly diagnosed cases of uveal melanoma participated. Approximately two control subjects matched for age, sex, and telephone exchange area were selected for each case by random-digit dialing. Data were collected by a structured telephone interview. Two systems of occupational coding were used: an occupation-exposure linkage system and the Bureau of Census data. Conditional logistic regression for matched studies was used to examine various occupational exposures while controlling for previously reported potential confounders and for family income. The occupation-exposure matrix was used to define clusters of cases exposed to a particular chemical group from various occupations. RESULTS: Odds ratios were elevated for agriculture and farming work for both industry and occupation; this was consistent across both classification systems. Elevated odds ratios also were found for occupations involving machine operations, fabrication, assembling, equipment cleaning, and exposure to metal industries. Exposure to alkylating agents and phenols was associated with a lower risk compared with all other exposures. Several self-reported exposures also were studied. Exposures associated with elevated odds ratios were inks, insecticides, gases, radioactive substances, polybromated biphenyls, and chemical solvents. CONCLUSIONS: This exploratory study suggests various occupational associations for uveal melanoma and areas for future research.

Adolescent↗
PubMed1992

Cataract extraction after proton beam irradiation for malignant melanoma of the eye.

We evaluated visual outcome and risk of metastases in patients who underwent cataract extraction after protonbeam irradiation of a uveal melanoma. A total of 84 patients underwent cataract extraction between 2 months and 11 years after irradiation. One year after cataract extraction, approximately half of the patients had visual acuity of 20/100 or better, and approximately one third had an acuity of 20/40 or better. Larger tumor size was highly correlated with poor visual outcome 1 year after extraction. Six patients underwent enucleation after cataract removal, five due to blind, painful eyes and one due to continued growth of a previously undiagnosed ring melanoma. The rate of metastases was not higher among patients who underwent cataract extraction (adjusted rate ratio, 0.83). Results suggest that cataract extraction offers improvement of vision in selected eyes previously irradiated for a uveal melanoma, without adding to the risk of metastases among patients undergoing the procedure.

Adult↗
PubMed1992

Histopathology of proton beam-irradiated vs enucleated uveal melanomas.

The histopathology of eyes with uveal melanoma was compared in a masked fashion in 47 eyes whose primary treatment was enucleation and a matched series of 47 eyes enucleated after proton beam irradiation. Irradiated tumors were more likely to show signs of necrosis (P less than .001) and fibrosis (P = .005) and to have balloon cells present (P = .002). In the irradiated group, mitotic figures were fewer in 40 high-power fields (P = .020), and the prevalence of tumor blood vessel damage (P less than .001) was higher. Changes in the retina were more common in the irradiated series, but damage was usually overlying or in close proximity to the tumor. Based on characteristic changes, the pathologist distinguished irradiated from nonirradiated eyes in 85% of the cases. These findings suggest that irradiation damages tumor cells and blood vessels, and alters the tumor's capacity for cellular reproduction.

Adult↗
PubMed1992

In vivo sodium chemical shift imaging.

The shift reagents thulium(III) 1,4,7,10-tetraazacyclododecane N,N',N",N"'tetramethylenephosphonate (TmDOTP5-), and dysprosium(III)triethylenetetramine-hexaacetate (DyTTHA3-) are compared in this work for their uses in sodium chemical shift imaging (NaCSI). In a series of experiments using phantoms we evaluated the relative contributions of bulk magnetic susceptibility (BMS) effects and hyperfine shifts to the induced 23Na chemical shift for these two shift reagents. The ratios of BMS effects to hyperfine shifts suggest that TmDOTP5- should be a more effective shift reagent than DyTTHA3- for 23Na NMR spectroscopy as well as NaCSI. The dependence on pH and free Ca2+ concentration of the 23Na NMR frequency shift induced by TmDOTP5- was evaluated. It was found that TmDOTP5- produces good spectral resolution under physiologic conditions. Examples presented from in vivo NaCSI experiments using TmDOTP5- to study diffusion in the posterior chamber of the rabbit eye and to monitor the rate of clearance of aqueous fluid from the anterior chamber demonstrate the effectiveness of this new shift reagent and of the NaCSI technique for in vivo studies.

Animals↗
PubMed1992

Radiation maculopathy after proton beam irradiation for choroidal melanoma.

PURPOSE: Radiation maculopathy is a microangiopathy of the retina, which is often observed after irradiation of the eye. To quantitatively determine the frequency of anatomic and functional features of this condition, the authors reviewed a large series of patients with choroidal melanomas who were treated by proton beam irradiation. METHODS: Color photographs and/or fluorescein angiograms of 218 patients with paramacular choroidal melanomas were graded by two independent masked readers to determine the frequency of the various lesions of radiation maculopathy. RESULTS: Overall, 194 (89%) of the 218 patients in this study developed some degree of radiation maculopathy. The earliest and most common finding was macular edema, which was observed in 87% of patients, overall, by the end of year 3. Microvascular changes (microaneurysms and/or telangiectasia), intraretinal hemorrhages, and capillary nonperfusion were noted in 76%, 70%, and 64% of eyes, respectively, by the end of postirradiation year 3. Visual acuity was retained at 20/200 or better in 90% of eyes 1 year after irradiation and in 67% of eyes 3 years after treatment. CONCLUSION: Radiation maculopathy is common after proton beam irradiation of paramacular choroidal melanomas. However, ambulatory vision is preserved in many eyes.

Adolescent↗
PubMed1992

Intraocular recurrence of uveal melanoma after proton beam irradiation.

The authors evaluated tumor recurrence as an end point in 1077 uveal melanoma patients treated by proton beam irradiation between 1975 and 1987, with a mean follow-up of 4.0 years. Twenty tumors (1.9%) exhibited definitive growth between 4 months and 66 months after irradiation (median, 19 months): 10 were marginal recurrences, 5 were ring melanomas, 3 were uncontrolled tumors, and 2 were extrascleral extensions. Ten of these eyes were enucleated without further intervention, 2 patients died of metastases soon after the growth was detected, and 8 patients had further conservative therapy. In 5 other patients, tumor growth was suspected but unconfirmed and the eye was enucleated elsewhere; the 5-year probability of local tumor control based on 25 recurrences was 97% +/- 1%. There was a nonsignificant increase in the rate of metastases among patients with documented tumor recurrence (adjusted relative risk, 1.5; 95% confidence interval, 0.66 to 3.4). Results suggest that recurrence of uveal melanomas treated by proton beam therapy is uncommon, but that treatment failure may increase risk of death from metastasis.

Adolescent↗
PubMed1992

Smoking and the risk of early metastases from uveal melanoma.

Smoking is suspected of altering host immunity and may therefore hasten the development of metastases among cancer patients. The authors followed 946 patients with melanomas of the choroid and/or ciliary body who had been treated with proton beam irradiation and who had provided a smoking history during their evaluation before treatment. After a mean follow-up of 33 months, 98 patients were diagnosed with metastatic disease. Metastasis-free survival rates 3 years after irradiation were similar in association with never, past, and current cigarette smoking (86%, 89%, and 90%, respectively; P = 0.90). Rates also were similar with increasing pack-years of exposure and when the product smoked was cigarettes versus pipes or cigars only. Estimates for smoking effects were unchanged after adjusting for established prognostic factors for metastases. Results suggest that smoking does not alter the risk of metastases during the first few years after irradiation of choroidal melanomas.

Adolescent↗
PubMed1992

Evaluation of skin microtopography as a measure of ultraviolet exposure.

A pilot study was conducted to investigate the use of skin microtopography as a semiquantitative noninvasive method for estimating cumulative sun exposure in epidemiologic studies of eye disease. The subjects received a kit through the mail containing materials needed to make a replica of the skin texture of a sun-exposed area of the hand. Each subject previously had undergone a skin biopsy around the same site to evaluate elastotic degeneration, and all were interviewed about past sun exposures. A gradable skin impression was obtained from 96 of 115 (83%) participants after two mailings. The impressions were graded according to the degree of skin texture alteration using standard photographs; interobserver reliability was 0.73 using a weighted kappa statistic. The impression score was correlated most strongly with age (r = 0.53). Independent predictors of higher impression scores (more skin texture changes) were older age, cigar or pipe smoking, less education, lighter iris color, lighter skin color, male gender, and tendency to sunburn. After adjustment for age and the other predictor variables, the biopsy score was not correlated with the impression grade (r = 0.18, P = 0.13). Behaviors indexing sun exposure were not correlated with microtopography. These results suggest that skin microtopography as done in this study reflects aging from intrinsic parameters more than from actinic damage.

Adolescent↗
PubMed1991

Retinal manifestations of neurofibromatosis. Diagnosis and management.

Five patients presented with vision-threatening retinal tumors and systemic signs of neurofibromatosis, including neurofibromatosis type 1 (four patients) and familial cafe-au-lait spots (one patient). These tumors included large retinal astrocytic hamartomas, multiple retinal capillary hemangiomas, and combined hamartomas of the retina and retinal pigment epithelium, which resulted in rubeotic glaucoma, vitreous hemorrhage, and retinal detachment. Surgical therapy included retinal cryopexy, xenon and argon photocoagulation, scleral buckling, and pars plana vitrectomy with excisional retinal biopsy. Retinal tumors may result in marked visual loss in patients with neurofibromatosis, and vitreoretinal surgery may restore useful vision in some of these patients.

Adolescent↗
PubMed1991

Survival of patients with metastases from uveal melanoma.

The authors evaluated a series of 145 consecutive patients with metastases from uveal melanoma, after proton beam irradiation, to assess the effect of early diagnosis and treatment for metastases on survival. Metastases were diagnosed between 7 weeks and 8.3 years (median, 2.4 years) after proton beam irradiation. Most patients (n = 94) were symptomatic before diagnosis; the remainder were first detected during screening examination. Liver involvement was documented in nearly all patients (n = 136). The majority of patients had died from metastases by the close of the study (n = 137). Significantly longer survival occurred among patients diagnosed during screening examination (P = 0.004) and among young patients (P = 0.03). The majority of patients received some form of treatment for metastases (69%). Median survival was 2.0 months for patients receiving no treatment compared with 5.2 months for those receiving treatment for metastases (P = .0001). However, the overall 1-year survival rate was poor (13%). Prophylactic adjuvant therapy could be explored as a means to increase disease-free survival in patients with uveal melanoma.

Adult↗
PubMed1991

Dynamic sodium chemical shift imaging for the study of aqueous humor flow.

Ocular images were obtained using sodium chemical shift imaging (CSI) and 1,4,7,10-tetraazacyclododecane-N,N'N",N"'-tetramethylenephospho nate thulium (III) [Tm(DOTP)5-], a paramagnetic chemical shift reagent. After injecting the shift reagent into the anterior chamber of rabbits, serial imaging was done, monitoring the change in chemical shift with time. Sodium CSI produced images of the eye in three dimensions, quantitatively depicting the spatial and temporal changes in the concentration of a paramagnetic tracer substance. The Tm(DOTP)5- is eliminated from the anterior chamber by first-order kinetics with a half-life of 49 min. These data suggest that this substance is eliminated from the anterior chamber at the same rate as aqueous humor is replaced. Sodium CSI shows promise as a valuable technique for monitoring fluid dynamics in the living eye.

Animals↗
PubMed1990

Host factors, UV radiation, and risk of uveal melanoma. A case-control study.

Uveal melanoma threatens life, as well as sight. To evaluate the effect of constitutional factors and UV radiation on the risk of uveal melanoma, 197 cases in New England were compared with 385 matched population controls, identified by random-digit dialing, and 337 cases residing within the United States were compared with 800 sibling controls. In the population-based comparison, estimated relative risks (RRs) of uveal melanoma, after adjustment for other factors, were elevated for the following: ancestry from more northern latitudes with a substantially elevated risk for Northern European ancestry (RR, 6.5; 95% confidence interval [CI], 1.9 to 22.4) and more than a twofold risk for British ancestry (RR, 2.4; 95% CI, 1.1 to 5.1), as compared with Southern European or other Mediterranean heritage; light skin color as compared with dark (RR, 3.8; 95% CI, 1.1 to 12.6); and 10 or more cutaneous nevi as compared with none (RR, 2.7; 95% CI, 1.5 to 4.9). There was a statistically significant trend for increasing risk with more northern heritage and more moles. Southern residence (below latitude 40 degrees N) for more than 5 years also increased risk (RR, 2.8; 95% CI, 1.1 to 6.9), as compared with none. In both comparisons, use of sunlamps was a risk determinant (RR, 3.4; 95% CI, 1.1 to 10.3 with random-digit dialed controls and RR, 2.3; 95% CI, 1.2 to 4.3 with sibling controls, comparing occasional or frequent use to never use), as was intense sun exposure (RR, 1.7; 95% CI, 0.9 to 3.0 and RR, 2.1; 95% CI, 1.4 to 3.2, respectively). However, birthplace below latitude 40 degrees N and outdoor work were associated with a lower risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Magnetic resonance imaging: an emerging technique for the diagnosis of ocular disorders.

With developments in proton and sodium imaging on eyes and ocular lesions, MRI has been rapidly advancing into the field of ophthalmology. Although many intraocular lesions have been T1 and T2 characterized, and MRI may aid in their diagnosis, there remain a few problems with the technique. One is the presence of motion artifacts which sometimes occur with lengthy scanning times. A patient must be imaged on the order of minutes with MRI. In addition ambiguities exist even with the T1 and T2 characterizations, although the specificity surpasses that of CT. Eventually these problems may be solved, but even now proton coupled with sodium imaging and other diagnostic techniques appear promising in the evaluation of ocular disorders.

Choroid Diseases↗
PubMed1990

Relative survival rates after alternative therapies for uveal melanoma.

Survival in a group of 556 patients with uveal melanoma treated by proton beam irradiation with a median follow-up of 5.3 years was compared with that of 238 patients enucleated during the same 10-year period as irradiated patients (July 1975 to December 1984) with a median follow-up of 8.8 years, and 257 patients enucleated during the preceding 10 years (January 1965 to June 1975) with a median follow-up of 17.0 years. Adjustments were made for known prognostic factors including age, tumor location, tumor height, and clinical estimate of tumor diameter (for enucleated patients this was estimated in a regression equation relating histologic to clinical measurement). The overall rate ratio for all cause mortality was 1.2 (95% confidence interval, 0.9-1.6) for the concurrent enucleation series versus proton beam, and 1.6 (95% confidence interval, 1.2-2.1) for the earlier enucleation series versus proton beam. Relative rates of metastatic death, cancer death, and all cause mortality comparing alternative treatments were found to vary with time after treatment. Interval-specific rate ratios were evaluated using proportional hazards models fitted to separate time intervals after treatment. For all three outcomes, rate ratios were over two and statistically significant for the first 2 years after treatment and closer to one and nonsignificant after year 6 comparing the two enucleation groups with proton beam. Results suggest that treatment choice has little overall influence on survival in patients with uveal melanoma.

Adult↗
PubMed1990

Case-control study of idiopathic retinal detachment.

A case-control study of idiopathic, rhegmatogenous retinal detachment (IRD) was conducted to investigate potential risk factors for developing IRD. These included some factors reported previously, such as cardiovascular disease, and some not under suspicion, such as cigarette smoking and iris colour. Cases (n = 198) were incident cases of IRD who were hospitalized for surgical repair of their detachments. Controls (n = 655) were patients hospitalized for conditions unrelated to suspected risk factors for IRD. The risk of IRD appeared to increase with increasing age, and the relative risk for self-reported myopes, compared with non-myopes, was elevated (RR = 3.4, 95% CI = 2.3 - 5.0). The relative risk of IRD was decreased in current smokers (RR = 0.5, 95% CI = 0.3 - 0.8); although there was not a significant trend of decreasing relative risk with increasing amount smoked, the estimate was lowest in those who smoked most heavily. Risk did not appear to be related to gender, eye colour, history of myocardial infarction, or history of hypertension.

Adolescent↗
PubMed1990

Evaluation of an iris color classification system. The Eye Disorders Case-Control Study Group.

A system for classification of iris color based on standard photographs, developed for use in a multicenter study, is described. Categories of iris color are distinguished based on predominant color (blue, gray, green, light brown, or brown) and the amount of brown or yellow pigment present in the iris. Two trained readers independently graded 339 iris photographs; discrepancies in grades were adjudicated. Measures of interobserver reliability were 0.76 by kappa for exact agreement and 0.97 for weighted kappa. The distribution of iris color grades demonstrates that the system achieved an appropriate level of detail within the authors' study population, which included patients with various racial backgrounds from five urban clinical centers. This simple, reliable classification system for iris color is offered for use in clinical research.

Analysis of Variance↗