A Prospective, Randomized, Double-blind, Placebo-controlled Study of Orbital Radiotherapy for Graves' Ophthalmopathy.

CONTEXT: Although widely used for more than 85 years, the efficacy of radiotherapy for Graves' ophthalmopathy (GO) has not been established convincingly. OBJECTIVE: To evaluate the efficacy of radiotherapy for GO. DESIGN: Prospective, randomized, internally controlled, double-blind clinical trial in a tertiary care academic medical center. PARTICIPANTS: The patients were ethnically diverse males and females over age 30 seen in a referral practice. The patients had moderate, symptomatic Graves' ophthalmopathy (mean clinical activity score, 6.2) but no optic neuropathy, diabetes, recent steroid treatment, previous decompression, or muscle surgery. Forty-two of 53 consecutive patients were enrolled after giving informed consent and fulfilling study entry criteria. Eleven eligible patients declined to participate because of inconvenience, desire for alternative therapy, or concern about radiation. INTERVENTION: One randomly selected orbit was treated with 20 Gy of external beam therapy; sham therapy was given to the other side. Six months later, the therapies were reversed. MAIN OUTCOME MEASURES: Every 3 months for 1 year, we measured the volume of extraocular muscle and fat, proptosis, range of extraocular muscle motion, area of diplopia fields, and lid fissure width. Effective treatment for GO will modify one or more of these parameters. RESULTS: No clinically or statistically significant difference between the treated and untreated orbit was observed in any of the main outcome measures at 6 months. At 12 months, muscle volume and proptosis improved slightly more in the orbit that was treated first. CONCLUSIONS: In this group of patients, representative of those for whom radiotherapy is frequently recommended, we were unable to demonstrate any beneficial therapeutic effect. The slight improvement noted in both orbits at 12 months may be the result of natural remission or of radiotherapy, but the changes are of marginal clinical significance.

Optimizing weekend availability for sophisticated tests and procedures in a large hospital.

The reduced availability of sophisticated tests and procedures in hospitals on weekends (the so-called "weekend effect") delays care. Addressing this problem requires hospital managers to balance the desire for timeliness with the need for efficient operations. We illustrate how a hospital can profile timeliness, demand, and capacity utilization across the week for multiple testing areas. This simple, practical method; using data extracted from the hospital's accounting system, makes visible the pattern and magnitude of delays caused by reduced availability on weekends, while also showing how capacity is deployed. We combined the analytical tool with a process of transparent feedback and local problem solving that engages multiple stakeholders in the hospital. The goal is to optimally configure capacity so as to balance the imperatives of timely availability and efficient resource utilization.

Eyelid position measurement in Graves' ophthalmopathy: reliability of a photographic technique and comparison with a clinical technique.

PURPOSE: To evaluate intraobserver reliability and interobserver reliability of a computer-based digital image measurement of eyelid position in Graves' ophthalmopathy and to compare digital image measurement with clinical measurement. DESIGN: Cross-sectional study. PARTICIPANTS: Eighty-four eyes of 42 patients with mild to moderate bilateral Graves' ophthalmopathy. METHODS: Digital images were created from 35-mm color slides of both eyes of participants and projected onto a 15-inch flat-screen computer monitor. Three observers (2 oculoplastic surgeons and 1 ophthalmology resident) independently recorded eyelid fissure height, margin-reflex distance, and inferior scleral show for each eye. MAIN OUTCOME MEASURES: Intraobserver reliability and interobserver reliability of eyelid parameter measurements, as described by the intraclass correlation coefficient (ICC) and Bland-Altman plots. Agreement between digital image measurements of the investigators and clinical measurements taken on the same day as the photographs also was assessed. RESULTS: Excellent intraobserver agreement was found for the measurement of all eyelid parameters for all 3 investigators (ICC range, 0.93-0.99). Interobserver agreement for all eyelid parameters was also excellent for all investigators (ICC, 0.86-0.97). Agreement between the photographic and clinical measurements for eyelid parameters was fair to moderate (ICC range, 0.38-0.62). CONCLUSION: Measurement of several eyelid parameters in Graves' ophthalmopathy patients from computer-based digital images is reliable. Associations between photographic and clinical measurements for all parameters are weaker. Relative to clinical measurements, the photographic technique offers the advantages of potential for masking and ease of transmission that might be useful in clinical trials.

Optic neuropathy of Graves disease: results of transantral orbital decompression and long-term follow-up in 215 patients.

PURPOSE: To review demographic characteristics, clinical features, and long-term outcomes of patients with optic neuropathy of Graves disease after transantral orbital decompression. DESIGN: Retrospective analysis of noncomparative interventional case series; long-term follow-up by questionnaire. METHODS: Medical record data (preoperative and postoperative assessments) were collected from patients who had transantral orbital decompression to treat Graves optic neuropathy. Responses to two follow-up questionnaires concerning patient satisfaction were evaluated. Statistical analysis (reflected as P values) compared preoperative and early postoperative (< or =182 days) data. RESULTS: Between November 1969 and May 1989, 215 patients underwent transantral orbital decompression for Graves optic neuropathy. In 205 eyes with visual acuity of 20/40 or worse before decompression, visual acuity improved by 3 Snellen lines or more in 110 (54%) (P <.001). Of 291 eyes with visual field defects preoperatively, 120 (41%) had resolution, and 126 (43%) had improvement postoperatively (P <.001). Proptosis was reduced in 350 eyes by 4.4 +/- 2.3 mm (mean +/- SD) (P <.001). In 104 eyes, disk edema resolved in 72 (69%) and improved in 28 (27%). Responses to questionnaires mailed in 1990 and 2000 showed that 76% and 88% of respondents, respectively, were subjectively satisfied with the results of orbital decompression. CONCLUSIONS: Transantral orbital decompression appeared to be effective in treating optic neuropathy of Graves disease. Patient satisfaction was high at 10-year and 20-year follow-up.

Retinal microvascular abnormalities in patients treated with external radiation for graves ophthalmopathy.

BACKGROUND: A prospective study was conducted to determine if external ionizing radiation could favorably influence the orbital manifestations of Graves ophthalmopathy. Diabetes and untreated systemic hypertension were exclusion criteria. Radiation was directed to the orbits of 42 affected patients using 0.2 rad (20 Gy) delivered in 10 doses of 0.02 rad (2 Gy). Patients were periodically examined during a 3-year interval. OBJECTIVE: To report retinal microvascular abnormalities observed in our study cohort. METHODS: Fundus findings documented with ophthalmoscopy, stereoscopic color photography, and stereoscopic fluorescein angiography prior to radiation were compared with similarly documented findings approximately 3 years following radiation. RESULTS: Prior to orbital radiation, retinal microvascular abnormalities were identified in 2 patients. The abnormalities were present bilaterally in one patient and unilaterally in the other. During the course of the study, microvascular abnormalities developed de novo in the unaffected retina of the latter patient while the retinopathy in the fellow eye progressed. Retinal microvascular abnormalities and their sequelae developed de novo in both eyes in 2 more patients. In addition to the radiation, other confounding factors known to be associated with microvascular retinopathy (uveitis, inadequately controlled systemic hypertension, and borderline blood glucose levels) were identified among the 3 patients whose eyes developed new retinal microvascular abnormalities. CONCLUSIONS: Whether the retinal microvascular abnormalities observed in these patients were caused or aggravated by external beam irradiation cannot be precisely ascertained. However, the observed progression and de novo development of retinal microvascular abnormalities within 3 years of orbital radiation raise concern that 0.2 rad (20 Gy) delivered to the orbit in 10 doses of 0.02 rad (2 Gy) may aggravate existing retinal microvascular abnormalities or cause radiation retinopathy in some patients with Graves disease. These findings and the failure of external beam radiation with 0.2 rad (2000 cGy) to favorably affect Graves ophthalmopathy, as demonstrated in a previous study, have led us to discourage further treatment of Graves ophthalmopathy with radiation.

The aftermath of orbital radiotherapy for graves' ophthalmopathy.

OBJECTIVE: To determine whether long-term improvement could be observed after orbital radiotherapy for Graves' disease; in addition, to evaluate ancillary treatments needed for those who have received radiotherapy, to search for late-emerging adverse consequences of radiotherapy, and to relate orbital changes to serum levels of thyroid-stimulating immunoglobulin (TSI). DESIGN: Three-year follow-up of noncomparative interventional case series. PARTICIPANTS: Forty-two patients. INTERVENTION: All patients had received orbital radiotherapy within 6 months of study entry. Twelve months after study entry, patients were free to select any additional treatment for their ophthalmopathy. MAIN OUTCOME MEASURES: Need for surgery, steroid therapy, volume of extraocular muscles and fat, proptosis, area of diplopia fields and range of extraocular muscle motion, volume changes after decompression and correlations of eye findings with serum TSI levels, retinal status. RESULTS: Half of the patients elected to have a surgical procedure on their eyes or orbits. Among patients who were not decompressed, we found only slight improvement in some of the main outcome measures. TSI did not positively correlate with baseline status or with any observed change in major outcome measures. After orbital decompression, the volumes of both muscle and fat increase, but bony orbital volume increases more and proptosis diminishes. Retinal microvascular abnormalities consistent with radiation retinopathy developed de novo in five eyes of three patients within 3 years of radiation therapy. CONCLUSIONS: In this 3-year uncontrolled follow-up phase, limited evidence for a clinically significant improvement was observed, which may be the result of treatment or of natural remission. In either case, the changes are of little clinical significance. Because it is neither effective nor innocuous, radiotherapy does not seem to be indicated for treatment of mild to moderate ophthalmopathy.

The impact of planned care and a diabetes electronic management system on community-based diabetes care: the Mayo Health System Diabetes Translation Project.

OBJECTIVE: The Mayo Health System Diabetes Translation Project sought to assess models of community-based diabetes care and use of a diabetes electronic management system (DEMS). Planned care is a redesigned model of chronic disease care that involves guideline implementation, support of self-management, and use of clinical information systems. RESEARCH DESIGN AND METHODS: We studied adult diabetic patients attending three primary care practice sites in Wisconsin and Minnesota. We implemented planned care at all sites and DEMS in the practice of 16 primary care providers. We assessed quality of diabetes care using standard indicators for 200 patients randomly selected from each site at baseline and at 24 months of implementation. We used multivariable analyses to estimate the association between planned care and DEMS and each quality indicator. RESULTS: Planned care was associated with improvements in measurement of HbA(1c) (odds ratio 7.0 [95% CI 4.2-11.6]), HDL cholesterol (5.6 [4.1-7.5]), and microalbuminuria (5.3 [3.5-8.0]), as well as the provision of tobacco advice (6.9 [4.7-10.1]), among other performance measures. DEMS use was associated with improvements in all indicators, including microalbuminuria (3.2 [1.9-5.2]), retinal examination (2.4 [1.5-3.9]), foot examinations (2.3 [1.2-4.4]), and self-management support (2.6 [1.7-3.8]). Although planned care was associated with improvements in metabolic control, we observed no additional metabolic benefit when providers used DEMS. CONCLUSIONS: Planned care was associated with improved performance and metabolic outcomes in primary care. DEMS use augmented the impact of planned care on performance outcomes but not on metabolic outcomes. Optimal identification of the best translation of evidence to diabetes practice will require longer follow-up or new care-delivery models.

Comparability of proptosis measurements by different techniques.

PURPOSE: To compare measurements of proptosis obtained by clinicians and computed tomography. DESIGN: Cohort study. METHODS: In a prospective randomized study of orbital radiotherapy for Graves' ophthalmopathy, measurements of proptosis were made on the same visit by an endocrinologist and an ophthalmologist using the Krahn exophthalmometer and by a technician using orbital computed tomography (CT) scans taken with head fixation to minimize position artifact. RESULTS: Both clinical observers recorded proptosis measurements that were greater by 0.6 to 1.6 mm than those observed on the CT scan. This discrepancy resulted in part from the clinical measurements being made to the anterior corneal surface, whereas the CT measurements were made to the posterior corneal surface (a difference of approximately 0.5 mm). The aggregated observations of the clinicians did not vary significantly from each other but wide discrepancies (as much as 5 mm) were noted between single measurements made on the same patient and on the same day by different clinicians. CONCLUSIONS: The degree of variance observed in clinical measurements emphasizes the importance of defining reproducibility of the measurement techniques in prospective studies of therapeutic efficacy in patients with Graves' ophthalmopathy. The systematic difference between CT and clinical measurements of proptosis should be noted when results of clinical trials are compared.

Papillary thyroid carcinoma managed at the Mayo Clinic during six decades (1940-1999): temporal trends in initial therapy and long-term outcome in 2444 consecutively treated patients.

It is uncertain whether more extensive primary surgery and increasing use of radioiodine remnant ablation (RRA) for papillary thyroid carcinoma (PTC) have resulted in improved rates of cause-specific mortality (CSM) and tumor recurrence (TR). Details of the initial presentation, therapy, and outcome of 2444 PTC patients consecutively treated during 1940-1999 were recorded in a computerized database. Patients were followed for more than 43,000 patient-years. The 25-year rates for CSM and TR were 5% and 14%, respectively. Temporal trends were analyzed for six decades. During the six decades, the proportion with initial MACIS (distant Metastasis, patient Age, Completeness of resection, local Invasion, and tumor Size) scores <6 were 77%, 82%, 84%, 86%, 85%, and 82%, respectively (p = 0.06). Lobectomy accounted for 70% of initial procedures during 1940-1949 and 22% during 1950-1959; during 1960-1999 bilateral lobar resection (BLR) accounted for 91% of surgeries (p <0.001). RRA after BLR was performed during 1950-1969 in 3% but increased to 18%, 57%, and 46% in successive decades (p <0.001). The 40-year rates for CSM and TR during 1940-1949 were significantly higher (p = 0.002) than during 1950-1999. During the last 50 years the 10-year CSM and TR rates for the 2286 cases did not significantly change with successive decades. Moreover, the 10-year rates for CSM and TR were not significantly improved during the last five decades of the study, either for the 1917 MACIS <6 patients or the 369 MACIS < 6 patients. Increasing use of RRA has not apparently improved the already excellent outcome, achieved before 1970, in low risk (MACIS <6) PTC patients managed by near-total thyroidectomy and conservative nodal excision.

Lack of impact of radioiodine therapy in tg-positive, diagnostic whole-body scan-negative patients with follicular cell-derived thyroid cancer.

Several reports have suggested a benefit from radioactive iodine (RAI) therapy in Tg-positive, whole-body scan-negative patients with follicular cell-derived thyroid cancer, who were said to have high rates of visualization of uptake in metastases after therapeutic doses of RAI. We sought to evaluate the rate of visualization of RAI uptake in these patients and determine the effect of such therapy on tumor progression and Tg levels. We studied 24 consecutive patients who had been treated with high-dose RAI, four of whom had no evidence of metastasis or persistent cancer. Our results showed that four patients had some uptake in posttherapy scans: in the neck, lung, and mediastinal metastases in one patient, in the thyroid remnant in two, and in a possible neck microrecurrence in one. In 13 patients with macrometastases-tumors 1 cm or greater-tumors progressed and serum Tg increased; five have died of thyroid cancer. The disease remained stable in the seven patients with micrometastases. We concluded that in high-risk patients with follicular cell-derived thyroid cancer with high Tg levels and negative diagnostic whole-body scans, only a small number showed meaningful uptake after high doses of RAI. Therefore, widespread use of empiric RAI therapy for such patients who have a large tumor burden should not be encouraged.

Radiotherapy for Graves' ophthalmopathy: results at one year.

We report on a prospective, randomized, double-masked, internally controlled, clinical trial of external beam radiotherapy for patients with mild to moderate Graves' ophthalmopathy. Forty two patients entered the study and after giving informed consent had radiotherapy to one randomly selected orbit and sham radiotherapy to the other side. Six months later the alternate orbit was treated. Neither the patient nor those assessing treatment response were aware of which orbit had been treated. Measurements made included: lid fissure width, range of extraocular muscle motion, area of diplopia fields, volume of extraocular muscle and fat, proptosis. Patients were seen at three month intervals on a rigid follow up schedule. Six months after study entry no evidence of clinically or statistically significant benefit from radiotherapy was apparent in any measured parameter in the treated versus the untreated orbit. Patients treated six months earlier in the course of their illness fared no better than patients treated later. Previous steroid therapy and the value of the clinical activity score did not affect outcome. Since orbital radiotherapy is not free of risk and does not appear to be effective, it's place in therapy of Graves disease should be reassessed.