Test-retest reliability of the GO-QOL: a disease-specific quality of life questionnaire for patients with Graves' ophthalmopathy.

To assess the test-retest reliability of a recently developed disease-specific quality of life questionnaire for evaluative studies in patients with Graves' ophthalmopathy (the GO-QOL), measuring visual functioning and psychosocial consequences of changed appearance. Ninety-three patients were included and completed the GO-QOL. Additional information on general quality of life and disease characteristics was obtained. Construct validity and internal consistency of the two subscales was determined, based on principal component analyses, Cronbach's alpha's and correlations with MOS-24, three subscales of the SIP, and clinical measures. Eighty-nine patients completed a second GO-QOL after two weeks including four additional questions about perceived changes in health status. Test-retest reliability was assessed by calculating intraclass correlation coefficients (ICCs) and limits of agreement, using several definitions of stable patients. Slight modifications from the original questionnaire were evaluated for their effect on the validity and reliability. The construct validity of the two subscales was confirmed and Cronbach's alpha's were 0.89 for visual functioning and 0.87 for appearance. The substantial ICCs found for both scales of the GO-QOL (ICCs above 0.80) reflect that the errors of measurement were relatively small, which supports the value of this questionnaire for clinical studies with relatively small sample sizes. The modification of the appearance scale improved the validity of the scale and resulted in less missing values. Following the recommendations of the joint committee of thyroid associations, we recommend the inclusion of HRQL-measures in clinical studies that evaluate treatments for patients with GO. The GO-QOL is a promising tool for this purpose.

Multidrug resistance-related proteins in primary choroidal melanomas and in vitro cell lines.

PURPOSE: Metastatic uveal melanoma is strongly resistant to chemotherapy, and multidrug resistance (MDR) may be involved. To investigate the role of MDR, the presence of the MDR-associated proteins P-glycoprotein (Pgp), MRP, and lung resistance protein (LRP) was determined on primary choroidal melanomas and cell lines. METHODS: A panel of primary choroidal melanomas was examined for the presence of MDR-associated proteins by immunohistochemical analysis. In cell lines established from four primary choroidal melanomas and one metastatic choroidal melanoma, the expression of MDR-associated proteins was determined with monoclonal antibodies in cytospin preparations and flow cytometry. In addition, the functional capacities of transporter proteins Pgp and MRP as adenosine triphosphate-driven efflux pumps were determined by measuring the cellular accumulation and efflux of the fluorescent dyes rhodamine 123 and calcein-AM, with and without the presence of specific pump inhibitors PSC833 and probenecid. RESULTS: Low levels of Pgp and MRP were detected in most primary tumors and in some cell lines. Measurable transporter function of Pgp could be determined in cell line OCM-1. Lung-resistance protein was present in all primary tumors and cell lines and showed high expression levels. CONCLUSIONS: This study revealed the involvement of LRP and at least a minor role of Pgp and MRP in chemoresistance of choroidal melanoma. Compared with cutaneous melanomas, uveal melanomas appear to express slightly higher levels of Pgp. These findings provide insights into the drug-resistant phenotype of this disease and can aid in the design of therapeutic protocols.

Coronal approach for rehabilitative orbital decompression in Graves' ophthalmopathy.

AIMS: To determine the effectiveness and safety of three wall orbital decompression by the coronal approach in Graves' ophthalmopathy. METHODS: The records of 125 patients with Graves' ophthalmopathy, who had undergone three wall orbital decompression by coronal approach between April 1984 and October 1993, were studied retrospectively. Special attention was paid to proptosis reduction, changes in ocular motility, and complications. RESULTS: The preoperative Hertel values ranged from 15 to 30 mm (mean 22.43 mm). The mean proptosis reduction was 4.34 mm (range 0-10 mm). Proptosis reduction in patients with preoperative Hertel values higher than 27 mm was significantly more than in patients with preoperative values between 25 and 27 mm (p < 0.05). This last group showed significantly more proptosis reduction than patients with preoperative Hertel values of 23 and 24 mm (p < 0.01). Postoperatively, 3.2% of the patients showed new diplopia in primary and/or reading position. In 4% of the patients with normal ocular motility preoperatively, diplopia in the extreme directions of gaze developed. In 4% of the patients, preoperative motility disturbances decreased or disappeared postoperatively. CONCLUSION: Three wall orbital decompression by coronal approach is a safe and effective technique, to achieve proptosis reduction in patients with Graves' ophthalmopathy, with fewer complications than other techniques thus far described.

[Surgical rehabilitation in patients with Graves' ophthalmopathy; favorable results of orbital decompression via coronal approach]. / Chirurgische rehabilitatie bij patiënten met Graves-oftalmopathie; gunstige resultaten van orbitadecompressie via coronale benadering.

Bilateral decompression of the orbit by a coronal approach was performed for cosmetic rehabilitation in 53 female patients with proptosis in the non-inflammatory stage after Graves' ophthalmopathy. Proptosis reduction averaged 5.9 mm Hertel value one year after surgery. All patients were satisfied with the cosmetic result obtained. Advantages of the technique used are: good access to all orbital walls facilitating adequate proptosis reduction; no visible scars after surgery; only very few complications. In our group there was no loss of visual acuity and the incidence of diplopia after surgery of only 4% is the lowest reported in the literature.

Radioimmunoscintigraphy and immunohistochemistry with melanoma-associated monoclonal antibodies in choroidal melanoma: a comparison of the clinical and immunohistochemical results.

Radioimmunoscintigraphy with monoclonal antibodies (MoAbs) to melanoma associated antigens is a new technique that can be used as an additional test to detect ocular melanomas in clinically difficult cases. Immunoscintigraphy with 99mtechnetium-labelled monoclonal antibody fragments of MoAb 225.28S in 14 patients with melanoma yielded a positive image in only six cases (43%). The expression of high molecular weight melanoma-associated antigen (HMW-MAA) was immunohistochemically assessed in melanoma tissue obtained from these 14 patients to find a possible correlation between the results of immunoscintigraphy and expression of the HMW-MAA. The melanoma tissues were immunohistochemically stained by a sensitive immunoperoxidase procedure with three different monoclonal antibodies to the HMW-MAA: 225.28S, Mel-14, and AMF-6. Expression of the antigen detected by MoAb 225.28S was found in 13 of 14 melanomas; the MoAbMel-14 reacted positively with all 14 melanomas; staining with MoAb AMF-6 was achieved in 10 melanomas. No correlation was found between the immunohistochemical staining results, the conventional histopathological findings, and the immunoscintigraphic results. The immunohistochemical staining results suggest that anti-HMW-MAA MoAbs bind to the melanoma tissue and are therefore potentially suitable for immunoscintigraphy.

Decreased expression of HLA class II antigens on human uveal melanoma cells after in vivo X-ray irradiation.

In order to determine the presence of HLA antigens on human uveal melanomas, we tested anti-HLA monoclonal antibodies on tissue sections of these tumors. A great variety in expression of HLA class I and II antigens was present. A significantly lower expression of HLA class II antigens was present on uveal melanomas that had been irradiated before enucleation. These tumors lacked a lymphocytic infiltrate in comparison with nonirradiated tumors. These data suggest that radiotherapy affects expression of histocompatibility antigens on tumors.

Heterogeneous expression of melanoma-associated antigens in uveal melanomas.

Twenty-five uveal melanomas were stained with seven monoclonal antibodies (MoAbs) recognizing different antigens on cutaneous melanomas. A two step immuno-peroxidase procedure was used. Phenotypic heterogeneity was observed for four MoAbs (M.2.2.4, AMF-7, 225.28S, PAL-M1) while two MoAbs (NKI-beteb, CL203.4) reacted strongly with most (85%) uveal melanomas, and one MoAb (R-24) showed very low reactivity. Despite heterogeneity, co-expression of some antigens was observed. Expression of the antigen recognized by MoAb M.2.2.4. was significantly lowered by pre-enucleation irradiation while the other antigens remained unchanged. Expression of antigens on uveal melanomas differed markedly from primary cutaneous melanomas. The clinical relevance of these findings awaits further study.