Thyroid Diseases: Mourits MP

Bartalena L, Baldeschi L, Dickinson AJ, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits MP, Perros P, Boboridis K, Boschi A, Currò N, Daumerie C, Kahaly GJ, Krassas G, Lane CM, Lazarus JH, Marinò M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM. · Department of Clinical Medicine, University of Insubria, Varese, Italy. · Thyroid. · Pubmed #18341379 No free full text.

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Mourits MP. · No affiliation provided · Orbit. · Pubmed #19085291 No free full text.

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Anonymous00251, Wiersinga WM, Perros P, Kahaly GJ, Mourits MP, Baldeschi L, Boboridis K, Boschi A, Dickinson AJ, Kendall-Taylor P, Krassas GE, Lane CM, Lazarus JH, Marcocci C, Marino M, Nardi M, Neoh C, Orgiazzi J, Pinchera A, Pitz S, Prummel MF, Sartini MS, Stahl M, von Arx G. · Department of Endocrinology, Academic Medical Centre, Amsterdam, The Netherlands. · Eur J Endocrinol. · Pubmed #16914591 links to  free full text

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Bijlsma WR, Mourits MP. · Department of Ophthalmology, University Medical Center, Utrecht, The Netherlands. · Orbit. · Pubmed #16754214 No free full text.

Abstract: OBJECTIVE: To evaluate and compare techniques for extraocular muscle (EOM) volume measurement and to provide guidelines for future measurements. DESIGN: Systematic review. RESULTS: Existing techniques used to measure extraocular muscle volumes on radiologic scans can be divided into manual outlining, computer assisted and automated segmentation. Both computed tomography (CT) and magnetic resonance (MR) image datasets can be used. On CT scans, one best measures muscle volume using region grow segmentation, accepting an overestimation of true volume by inevitable inclusion of non-muscular tissue. On high resolution MRI scans, single muscles can be outlined manually, but measurements include only part of the muscle due to poor tissue contrast at the orbital apex. Measurement errors can be reduced 3.5% by exact horizontal repositioning. A measured volume change of at least 6-17% is required to demonstrate a significant difference. CONCLUSION: Currently the best choice for EOM volume measurements on CT images is computer assisted grey value segmentation and on MRI images is manual outlining of individual muscles. Because of the time required and the complexity of the measurements, present EOM volume measurement is as yet only suitable for research purposes.

Mourits MP. · No affiliation provided · Br J Ophthalmol. · Pubmed #11806399 No free full text.

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Wakelkamp IM, Baldeschi L, Saeed P, Mourits MP, Prummel MF, Wiersinga WM. · Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. · Clin Endocrinol (Oxf). · Pubmed #16117821 No free full text.

Abstract: OBJECTIVE: Only a small percentage of Graves' ophthalmopathy (GO) patients develop optic neuropathy with impending loss of visual acuity. Therapy with methylprednisolone pulses is the treatment of first choice in severe and active GO patients. When the effect is insufficient, patients are usually treated with surgical decompression. We investigated whether surgery could become the first-line treatment, thus preventing treatment with steroids. DESIGN AND SUBJECTS: We performed a randomized trial in 15 patients with very active GO and optic neuropathy. Six patients were treated with surgical decompression, and nine with methylprednisolone i.v. pulses for 2 weeks, followed by oral prednisone for 4 months. The primary outcome was determined by changes in visual acuity. If the eye disease deteriorated despite treatment or did not improve sufficiently, patients were switched to the other treatment arm. RESULTS: The severity and activity of GO in both groups were similar at baseline. The Clinical Activity Score (CAS) was 6.3+/- 0.8 in the surgical group vs. 6.0+/- 0.5 in the steroids group and the Total Eye Score was 24+/- 6 vs. 25+/- 6. In the surgery group, 5/6 patients (82%) did not respond because of insufficient improvement in vision (n=3) or persistent chemosis (n=2), and all needed further immunosuppression. In the steroids group, 4/9 patients (45%) did not improve in visual acuity (P=0.132 vs. surgery group), and these needed decompressive surgery. All patients in whom therapy failed were switched to the other treatment arm and visual acuity improved in almost all patients. Visual acuity improved from 0.36 (0.02--0.40) to 0.90 (0.63--1.0) in the surgery group and from 0.50 (0.32--0.63) to 0.75 (0.32--1.0) in the steroids group at 52 weeks. At long-term follow-up in the surgery group 3/6 patients required squint surgery and 5/9 patients in the steroids group. Eyelid surgery was performed in 5/6 patients in the surgery group and in 4/9 patients in the steroids group. CONCLUSION: Immediate surgery does not result in a better outcome and therefore methylprednisolone pulse therapy appears to be the first-choice therapy.

Prummel MF, Terwee CB, Gerding MN, Baldeschi L, Mourits MP, Blank L, Dekker FW, Wiersinga WM. · Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. · J Clin Endocrinol Metab. · Pubmed #14715820 links to  free full text

Abstract: Radiotherapy is often used in Graves' ophthalmopathy, but its efficacy has been doubted. We compared its efficacy with sham irradiation in mild ophthalmopathy. In a double-blind randomized trial, 44 patients received orbital irradiation, and 44 were sham-irradiated. The primary outcome was assessed using major and minor criteria. As secondary outcome, we used a disease-specific quality of life questionnaire (the GO-QoL) and compared cost-effectiveness and need for follow-up treatment. The primary outcome was successful in 23 of 44 (52%) irradiated patients vs. 12 of 44 (27%) sham-irradiated patients at 12 months after treatment (relative risk, 1.9; 95% confidence interval, 1.1-3.4; P = 0.02). Radiotherapy was effective in improving eye muscle motility and decreasing the severity of diplopia. However, quality of life improved similarly in both groups. In the radiotherapy group there was less need for follow-up treatment; 66% vs. 84% of the patients needed further treatment (P = 0.049). Retrobulbar irradiation did not prevent worsening of ophthalmopathy, which occurred in 14% of the irradiated and 16% of the sham-irradiated patients. Radiotherapy is an effective treatment in mild ophthalmopathy. However, the improvement upon irradiation may not be associated with an increase in quality of life or a reduction in treatment costs.

Mourits MP, van Kempen-Harteveld ML, García MB, Koppeschaar HP, Tick L, Terwee CB. · Donders Institute of Ophthalmology (Orbital Unit), University Medical Centre, Utrecht, The Netherlands. · Lancet. · Pubmed #10801172 No free full text.

Abstract: BACKGROUND: The best treatment (steroids, irradiation, or both) for moderately severe Graves' orbitopathy, a self-limiting disease is not known. We tested the efficacy of external beam irradiation compared with sham-irradiation. METHODS: In a double-blind randomised clinical trial, 30 patients with moderately severe Graves' orbitopathy had radiotherapy (20 Gy in ten fractions), and 30 were assigned sham-irradiation (ten fractions of 0 Gy). Treatment outcome was measured qualitatively by changes in major and minor criteria and quantitatively in several ophthalmic and other variables, such as eyelid aperture, proptosis, eye movements, subjective eye score, and clinical-activity score at 24 weeks. FINDINGS: The qualitative treatment outcome was successful in 18 of 30 (60%) irradiated patients versus nine of 29 (31%) sham-irradiated patients at week 24 (relative risk [RR]=1.9 [95% CI 1.0-3.6], p=0.04). This difference was caused by improvements in diplopia grade, but not by reduction of proptosis, nor of eyelid swelling. Quantitatively, elevation improved significantly in the radiotherapy group, whereas all other variables remained unchanged. The field of binocular single vision was enlarged in 11 of 17 patients after irradiation compared with two of 15 after sham-irradiation. Nevertheless, only 25% of the irradiated patients were spared from additional strabismus surgery. INTERPRETATION: In these patients with moderately severe Graves' orbitopathy, radiotherapy should be used only to treat motility impairment.

Sasim IV, Berendschot TT, van Isterdael C, Mourits MP. · Department of Surgical Specialties, Division of Ophthalmology, University Medical Centre Utrecht, Utrecht, Netherlands. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #18581132 links to  free full text

Abstract: BACKGROUND: To describe disease parameters of patients with Graves' orbitopathy in a tertiary referral center in order to plan health care resource allocations. To investigate whether the clinical activity and/or the severity of the disease can be used as a predictor of the duration of treatment. METHODS: Retrospective, observational, non-comparative case series. One hundred and seventeen charts of GO-patients, randomly chosen out of a pool of 1600, referred to the Orbital Unit of the University Medical Centre Utrecht between 1 January 1992 and 1 January 2002, were analysed. Relevant parameters, such as age, gender, race, disease duration, smoking habits, concomitant diseases, previous treatment, symptoms and signs, number and sort of investigations, severity and activity scores, number and sort of treatments, treatment duration and outcome of treatment were retrieved and analysed. Disease activity and severity at entry were tested as possible predictors of disease duration and extent of treatment. RESULTS: Clinical profile at presentation; duration of the disease; extent of treatment; predictors of disease duration and of number of treatment interventions were the main outcome measures. Three percent of patients had Only Signs, but No Symptoms (OSNS), 61% had mild, 27% had moderately severe and 9% had severe GO. Fifteen percent had inactive disease at presentation, 65% had borderline activity and only 20% had active orbitopathy. Sixty percent complained about eyelid swelling and/or proptosis. The average period of eye treatment was 2.5 years (range: 0-110 months), during which patients were seen at an average of 8 times. Twenty percent needed no treatment at all. Fifteen percent were treated with nothing but lubricants and/or prisms. Twenty-five percent were treated with immunosuppressive modalities. Fifty-six percent underwent one or more surgical corrections. The Clinical Activity Score (CAS) was found to be significantly related to the duration of the treatment (p < 0.001), to the number of visits (p < 0.001), and to the number of surgical interventions (p < 0.001). CONCLUSIONS: The majority of GO patients referred to a tertiary referral centre has no or borderline disease activity and 'mild' orbitopathy, disfiguring eyelids and proptosis being the most frequent complaints. The disease activity as assessed with the CAS can be used to predict the duration and extent of the treatment.

van Geest RJ, Sasim IV, Koppeschaar HP, Kalmann R, Stravers SN, Bijlsma WR, Mourits MP. · Donders Institute of Ophthalmology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. · Eur J Endocrinol. · Pubmed #18230831 links to  free full text

Abstract: OBJECTIVE: To assess whether methylprednisolone (MP) pulse therapy is efficacious in the treatment of moderately severe Graves' orbitopathy (GO). DESIGN: Prospective, placebo (PL)-controlled, double-blind, randomized study. METHODS: Fifteen previously untreated patients with active, moderately severe GO participated in the study; 6 patients received MP and 9 patients a PL. Moderately severe disease was defined using the NOSPECS classification of clinical signs of GO . Activity was measured with the clinical activity score (CAS). A dose of 500 mg MP or only solvent was administered intravenously, over three consecutive days, in four cycles at 4 weekly intervals (6 g of MP in total). Qualitatively, a successful treatment outcome was defined as an improvement in one major and/or two minor criteria in the worst eye at week 48. The major criteria were: improvement in diplopia grade; improvement in eye movement; a decrease in CAS of three points. The minor criteria were: decrease of eyelid retraction; decrease of proptosis; improvement in grade of soft tissue swelling; a decrease in CAS of two points. RESULTS: The qualitative treatment outcome was successful at the end of the trial in five out of six (83%) patients receiving MP and in one out of nine (11%) patients given the PL (relative risk=7.5; (95% confidence interval 1.1-49.3), P=0.005). The treatment was well tolerated. CONCLUSIONS: In spite of the small number of patients, a significant difference in outcome was observed between MP- and PL-treated patients. We conclude that MP pulse therapy appears to be an effective treatment for active, moderately severe GO.

Le Moli R, Baldeschi L, Saeed P, Regensburg N, Mourits MP, Wiersinga WM. · Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands. · Thyroid. · Pubmed #17465867 No free full text.

Abstract: BACKGROUND: Intravenous methylprednisolone pulses (IVMP) are more efficacious and better tolerated than oral prednisone in Graves' ophthalmopathy (GO) patients. However, acute and severe liver damage has been reported in sporadic cases during IVMP, resulting in fatal acute liver failure in four patients so far. The mechanism causing the liver damage is incompletely understood. DESIGN: We performed a prospective observational study in 13 patients with dysthyroid optic neuropathy (group A) and in 14 patients with moderately severe GO (group B) who were treated with high-dose (group A) or low-dose (group B) IVMP; cumulative steroid doses were 8.45 g in group A and 4.5 g in group B, and follow-up time was 24 weeks. MAIN OUTCOME: Slight increases in serum aminotransferases (in alanine aminotransferase [ALAT] more than in aspartate aminotransferase [ASAT]) were observed, in seven patients exceeding the upper normal limit of 40 U/L. These changes were more prominent in group A than in group B as was also evident from a decrease in ASAT/ALAT ratio in group A but not in group B. Changes in serum aminotransferases occurred especially in the first 6 weeks of IVMP, becoming smaller thereafter with the decrease in steroid dosage. Pretreatment liver steatosis or diabetes were not related to liver damage, but preexistent viral hepatitis was. CONCLUSION: IVMP in GO patients causes dose-dependent liver damage by a direct toxic effect of glucocorticoids on hepatocytes. Nevertheless, IVMP seems to be pretty safe if cumulative doses exceeding 8 g are avoided and liver function is checked before and at regular intervals during pulse therapy.

McKeag D, Lane C, Lazarus JH, Baldeschi L, Boboridis K, Dickinson AJ, Hullo AI, Kahaly G, Krassas G, Marcocci C, Marinò M, Mourits MP, Nardi M, Neoh C, Orgiazzi J, Perros P, Pinchera A, Pitz S, Prummel MF, Sartini MS, Wiersinga WM, Anonymous00103. · Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff CF 4 4XN, UK. · Br J Ophthalmol. · Pubmed #17035276 No free full text.

Abstract: BACKGROUND: This study was performed to determine clinical features of dysthyroid optic neuropathy (DON) across Europe. METHODS: Forty seven patients with DON presented to seven European centres during one year. Local protocols for thyroid status, ophthalmic examination and further investigation were used. Each eye was classified as having definite, equivocal, or no DON. RESULTS: Graves' hyperthyroidism occurred in the majority; 20% had received radioiodine. Of 94 eyes, 55 had definite and 17 equivocal DON. Median Clinical Activity Score was 4/7 but 25% scored 3 or less, indicating severe inflammation was not essential. Best corrected visual acuity was 6/9 (Snellen) or worse in 75% of DON eyes. Colour vision was reduced in 33 eyes, of which all but one had DON. Half of the DON eyes had normal optic disc appearance. In DON eyes proptosis was > 21 mm (significant) in 66% and visual fields abnormal in 71%. Orbital imaging showed apical muscle crowding in 88% of DON patients. Optic nerve stretch and fat prolapse were infrequently reported. CONCLUSION: Patients with DON may not have severe proptosis and orbital inflammation. Optic disc swelling, impaired colour vision and radiological evidence of apical optic nerve compression are the most useful clinical features in this series.

Anonymous00698, Perros P, Baldeschi L, Boboridis K, Dickinson AJ, Hullo A, Kahaly GJ, Kendall-Taylor P, Krassas GE, Lane CM, Lazarus JH, Marcocci C, Marino M, Mourits MP, Nardi M, Orgiazzi J, Pinchera A, Pitz S, Prummel MF, Wiersinga WM. · Department of Endocrinology, Freeman Hospital, Newcastle upon Tyne, UK, and Department of Ophthalmology, Orbital Center, Academic Medical Center, Amsterdam, The Netherlands. · Eur J Endocrinol. · Pubmed #16868132 links to  free full text

Abstract: OBJECTIVE: To determine management patterns among clinicians who treat patients with Graves' orbitopathy (GO) in Europe. DESIGN AND METHODS: Questionnaire survey including a case scenario of members of professional organisations representing endocrinologists, ophthalmologists and nuclear medicine physicians. RESULTS: A multidisciplinary approach to manage GO was valued by 96.3% of responders, although 31.5% did not participate or refer to a multidisciplinary team and 21.5% of patients with GO treated by responders were not managed in a multidisciplinary setting. Access to surgery for sight-threatening GO was available only within weeks or months according to 59.5% of responders. Reluctance to refer urgently to an ophthalmologist was noted by 32.7% of responders despite the presence of suspected optic neuropathy. The use of steroids was not influenced by the age of the patient, but fewer responders chose to use steroids in a diabetic patient (72.1 vs 90.5%, P<0.001). Development of cushingoid features resulted in a reduction in steroid use (90.5 vs 36.5%, P<0.001) and increase in the use of orbital irradiation (from 23.8% to 40.4%, P<0.05) and surgical decompression (from 20.9 to 52.9%, P<0.001). More ophthalmologists chose surgical decompression for patients with threatened vision due to optic neuropathy, who were intolerant to steroids than other specialists (70.3 vs 41.8%, P<0.01). CONCLUSION: Deficiencies in the management of patients with GO in Europe were identified by this survey. Further training of clinicians, easier access of patients to specialist multidisciplinary centres and the publication of practice guidelines may help improve the management of this condition in Europe.

Sasim IV, de Graaf ME, Berendschot TT, Kalmann R, van Isterdael C, Mourits MP. · Division of Ophthalmology, Department of Surgical Specialities, University Medical Center Utrecht, Utrecht, The Netherlands. · Ophthalmology. · Pubmed #15950284 No free full text.

Abstract: PURPOSE: To compare 2 different approaches for 3-wall orbital decompression in patients with disfiguring proptosis due to Graves' orbitopathy, and to determine which technique is preferable. DESIGN: Retrospective nonrandomized study with a concurrent comparison group. PARTICIPANTS: Charts of 74 consecutive patients with disfiguring proptosis due to Graves' orbitopathy who underwent coronal (46) or swinging eyelid (28) decompression between January 1, 2000 and January 1, 2004 were studied retrospectively. Patients with dysthyroid optic neuropathy were excluded. METHODS: We analyzed the following parameters: proptosis reduction, ocular motility, number of additional operations, number and kind of complications, patients' satisfaction, patients' estimation of numbness or abnormal sensations in the field of operation and surgical scars, and duration of hospitalization time. MAIN OUTCOME MEASURES: Reduction of proptosis, changes in eye motility, and duration of hospitalization. RESULTS: Mean proptosis reductions were 4.8 mm (range, 1-11) after coronal decompression and 5.6 mm (range, 0-8) after swinging eyelid decompression (P = 0.025). Patients who were operated by the swinging eyelid approach had no more deteriorated motility and a shorter hospitalization time. Complications were seen rarely. Both groups of patients showed high satisfaction scores. CONCLUSION: Relative to the coronal approach, swinging eyelid decompression results in at least the same proptosis reduction, no greater motility disturbance, and a shorter hospitalization time.

Mourits MP, Lombardo SH, van der Sluijs FA, Fenton S. · Department of Ophthalmology, University Medical Center, Utrecht, Mashhad, The Netherlands. · Orbit. · Pubmed #15545129 No free full text.

Abstract: AIM: The purpose of this study was to test the reliability of an exophthalmometer commonly used in the Netherlands; to determine the exophthalmometry value distribution with this instrument and to assess the upper exophthalmometry limits of normal in a healthy, adult, Caucasian, Dutch population. Furthermore, to assess the effects of gender and age on exophthalmometry readings in this group and in a group of Graves' patients by comparing healthy, adult, Caucasian, Dutch individuals with adult, Caucasian, Dutch Graves' patients. METHODS: To test the reliability of our Hertel exophthalmometer, we determined the interobserver variation between two observers by measuring 160 eyes in healthy, adult, Caucasian, Dutch females and males (10 females and 10 males in each decade between 20 and 60 years of age). These data were also used for the assessment of the Hertel value distribution and for defining the upper limits of normal in these individuals by logistic regression analysis. The effects of disease, age and gender were established using these data plus data of a retrospective study of 393 adult, Caucasian, Dutch females (n=294) and males (n=99) with Graves' orbitopathy in whom Hertel values were measured with the same exophthalmometer. RESULTS: Exophthalmometry using an Hertel exophthalmometer appeared reliable (Pearson correlation coefficient for interobserver variation 0.89; 96% of the Hertel values measured by two observers were within the limits (of 2 mm) of agreement). Hertel values usually show a normal distribution in healthy individuals and in Graves' patients and are sex- and age-dependent, but there was no dependence on age in this small series in adults. Logistic regression analysis revealed an upper limit of normal of 16 mm in females and 20 mm in males in our group, using the exophthalmometer described. CONCLUSIONS: Exophthalmometry is reliable and absolute measurement of proptosis is feasible. International standardization of Hertel exophthalmometry is required in order to compare exophthalmometry data in the literature reliably.

Prummel MF, Bakker A, Wiersinga WM, Baldeschi L, Mourits MP, Kendall-Taylor P, Perros P, Neoh C, Dickinson AJ, Lazarus JH, Lane CM, Heufelder AE, Kahaly GJ, Pitz S, Orgiazzi J, Hullo A, Pinchera A, Marcocci C, Sartini MS, Rocchi R, Nardi M, Krassas GE, Halkias A. · Department of Endocrinology and Metabolism, F5-171 Academic Medical Center, University of Amsterdam, Meibergdreef 5, 1105 AZ Amsterdam, The Netherlands. · Eur J Endocrinol. · Pubmed #12720530 links to  free full text

Abstract: To improve management of patients with Graves' orbitopathy, a multi-center collaborative approach is necessary in order to have large enough sample sizes for meaningful randomized clinical trials. This is hampered by a lack of consensus on how to investigate the eye condition. The European Group on Graves' Orbitopathy aims to overcome this and has designed a preliminary case record form (CRF) to assess Graves' orbitopathy patients. This form was used in this first multi-center study. AIM: To investigate patient characteristics and treatment strategies in 152 new consecutively referred patients with thyroid eye disease seen in nine large European referral centers. METHODS: Newly referred patients with Graves' orbitopathy were included who were seen between September and December 2000. Demographic data and a complete ophthalmological assessment were recorded. RESULTS: One-hundred and fifty-two patients (77% females) were included. Diabetes was present in 9%, and glaucoma or cataract in 14% of patients. Forty percent were current smokers, 9% also had dermopathy, and only 33% reported a positive family history of thyroid disease. Mild eye disease was seen in 40%, moderately severe eye disease was seen in 33% and severe eye disease was seen in 28% of patients. Soft tissue involvement was the most frequent abnormality (seen in 75%), proptosis > or =21 mm was found in 63%, eye motility dysfunction in 49%, keratopathy in 16% and optic nerve involvement was found in 21% of patients. According to the clinical impression, 60% had active eye disease. Immunosuppressive treatment was planned more frequently in active patients (57/86; 66%) than in inactive patients (5/57, 9%; Chi-square 46.16; P<0.02). There were no important differences among the eight centers regarding the severity and the activity of their patients. CONCLUSIONS: In view of the large number of patients recruited in only 4 months, multi-center studies in the eight EUGOGO centers appear to be feasible.

Kalmann R, Mourits MP. · Orbital Unit, Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands. · Am J Ophthalmol. · Pubmed #11992884 No free full text.

Abstract: PURPOSE: To report a case of late recurrence of unilateral Graves orbitopathy on the contralateral side after 7 years. DESIGN: Interventional case report. METHODS: A 44-year-old woman with left unilateral Graves orbitopathy underwent two-wall orbital decompression on the left side. After strabismus surgery and left upper eyelid surgery, she was discharged. RESULTS: Seven years after discharge, the patient developed Graves orbitopathy on the right side, and she underwent two-wall orbital decompression on the right side. CONCLUSION: At least in patients with unilateral Graves orbitopathy, late recurrence of the disease in the contralateral orbit may occur.

Abràmoff MD, Kalmann R, de Graaf ME, Stilma JS, Mourits MP. · Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands. · Invest Ophthalmol Vis Sci. · Pubmed #11818370 links to  free full text

Abstract: PURPOSE: To study possible causes of motility disturbances that may result from orbital decompression surgery in patients with Graves orbitopathy and especially the role of rectus extraocular muscle paths. METHODS: Sixteen patients with Graves orbitopathy were studied before and 3 to 6 months after translid (6 patients) and coronal (10 patients) orbital decompression surgery for disfiguring proptosis. Ocular motility changes were measured by comparing maximum ductions and severity of diplopia, and the positions and the displacements of the anterior rectus muscle paths were objectively measured using cine magnetic resonance imaging (MRI). RESULTS: Averaged preoperative rectus muscle path positions were not different from those in normal subjects. Averaged postoperative muscle path positions were generally the same as preoperative paths. The only significant exceptions were centrifugal (outward from the orbital axis) displacements of the inferior rectus (IR) muscle path after translid surgery, and of the medial rectus (MR) muscle path after coronal surgery. The amount of IR path displacement with translid surgery was directly correlated with range of depression and with severity of vertical diplopia. The amount of MR path displacement with coronal surgery was inversely correlated with range of abduction and directly correlated with severity of horizontal diplopia. CONCLUSIONS: The anterior orbital connective tissue seems to form a "functional skeleton" that is usually (except as noted for IR and MR) capable of keeping the rectus muscle paths aligned after decompression surgery and preserving the normal functions of rectus muscle pulleys. The centrifugal displacement of the IR and MR may increase the elastic component of the muscle force, leading to the specific patterns of motility disturbance that may occur in some patients after translid and coronal surgery. These findings suggest that standard surgical management of Graves orbitopathy should be supplemented.

Terwee CB, Dekker FW, Mourits MP, Gerding MN, Baldeschi L, Kalmann R, Prummel MF, Wiersinga WM. · Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, the Netherlands. · Clin Endocrinol (Oxf). · Pubmed #11298093 No free full text.

Abstract: OBJECTIVE: The Graves' ophthalmopathy quality of life questionnaire (GO-QOL) is the first instrument available to measure health-related quality of life (HRQL) of patients with Graves' ophthalmopathy. The main objective of this study was to define a minimal clinically important difference (MCID) in score on the GO-QOL that can be considered an important improvement in HRQL by examining changes in GO-QOL scores in patients who subjectively report improvement from their treatment. A secondary objective was to test the longitudinal validity of the GO-QOL, using prespecified hypotheses about expected treatment effects. DESIGN: A prospective cohort study. PATIENTS: We included 164 patients who were scheduled for radiotherapy (23), orbital decompression (10 for sight loss, 38 for exophthalmos), eye muscle surgery (31), eyelid lengthening (43) or blepharoplasty (19). MEASUREMENTS: Patients completed the GO-QOL and three general HRQL questionnaires, before and three or six months after treatment, depending on the performed procedure. Clinical characteristics were collected from the medical records. Mean changes in GO-QOL scores and effect sizes were calculated after different treatments, and in subgroups of responders and nonresponders according to clinical characteristics and according to the patients themselves. RESULTS: A clinical response to treatment was associated with a change in GO-QOL scores of approximately 10--20 points after major treatments (radiotherapy or decompression), and with a change of approximately 3--10 points after minor surgery (eye muscle surgery, eyelid lengthening, blepharoplasty). Changes in GO-QOL scores of about 6--10 points were considered important improvements by the patients themselves. The direction and amount of change in GO-QOL scores after different treatments were in accordance with our prespecified hypotheses about treatment effects. Effect sizes in the GO-QOL subscales were generally higher than effect sizes of the general HRQL subscales, supporting the longitudinal validity of the GO-QOL. CONCLUSIONS: As a general guideline, one could consider a mean change of at least 6 points on one or both subscales an important change in daily functioning for patients. For more invasive therapies, a change of at least 10 points is recommended as a minimal clinically important difference.

Kalmann R, Mourits MP. · Orbital Center Utrecht, Donders Institute of Ophthalmology, University Hospital, Utrecht, Netherlands. · Br J Ophthalmol. · Pubmed #10434871 links to  free full text

Abstract: AIMS: To assess the prevalence of dysthyroid optic neuropathy (DON) in patients with diabetes mellitus (DM) and Graves' orbitopathy (GO) and to investigate the complications of surgery for GO in these patients. METHODS: The records of 482 consecutive patients with GO referred in a 5 year period were studied. Those patients who also had DM were selected for further study. The prevalence of insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM) was registered, as well as the prevalence and course of DON. In the patients who underwent surgery for GO the postoperative complications were recorded. RESULTS: Out of 482 patients with GO, 15 (3.1%) also had DM. Eight (1.7%) had IDDM, 7 (1.4%) had NIDDM. Five patients (33.3%) three with IDDM and two with NIDDM developed DON with 50% improvement of visual acuity after treatment, whereas in the whole population of 482 GO patients 19 had DON (3.9%), showing 69.4% improvement of vision after treatment. 10 patients with GO and DM were operated for GO; in one of them an optic atrophy developed as a result of a postoperative haemorrhage directly after a three wall orbital decompression by coronal approach. No other postoperative complications occurred. CONCLUSIONS: The prevalence of IDDM in patients with GO is higher than in the normal population. DON occurs much more frequently in patients with GO and DM than in the total group of GO patients and seems to have a worse visual prognosis.

Mourits MP, Sasim IV. · Orbital Center Utrecht, Donders Institute for Ophthalmology, University Hospital Utrecht, Netherlands. · Br J Ophthalmol. · Pubmed #10209441 links to  free full text

Abstract: BACKGROUND: Several lengthening techniques have been proposed for upper eyelid retraction in patients with Graves' orbitopathy and variable rates of success have been reported. Most authors recommend different procedures for different degrees of retraction, but cannot prevent residual temporal retraction in a significant number of cases. The modified levator aponeurosis recession described by Harvey and colleagues, in which the lateral horn is cut completely, seems to be an exception to this rule, but was evaluated in a limited number of cases only. METHOD: The authors further modified Harvey's technique by dissecting the aponeurosis together with Müller's muscle of the tarsus and the conjunctiva medially only to the extent necessary to achieve an acceptable position and contour of the eyelid in upright position. They also used an Ethilon 6.0 suture, instead of Vicryl, on a loop. It is placed between the tarsal plate and the detached aponeurosis to prevent spontaneous disinsertion. This modification was used in 50 Graves' patients (78 eyelids) with a upper lid margin-limbus distance ranging from 1 to 7 mm and evaluated using strict criteria. RESULTS: A perfect or acceptable result was obtained in 23 of 28 patients (82%) with bilateral retraction and in 18 of 22 patients (82%) with unilateral retraction. Seven eyelids were overcorrected (too low) and three undercorrected, necessitating reoperation. All other eyelids had an almond-like contour and a lid crease of 10 mm or less. No complications except subcutaneous haematomas were seen. Two patients showed a recurrence of lid retraction 9 months after the operation. CONCLUSION: This technique is safe and efficacious and can be used for all degrees of eyelid retraction.

van der Pol R, Nieuwenhuis MG, Mourits MP. · Department of Ophthalmology, University Hospital Utrecht, The Netherlands. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #10090590 No free full text.

Abstract: BACKGROUND: Multifocal fibrosclerosis (MF) is a rare disease that may be misdiagnosed as Graves' orbitopathy. The combination of localisations of MF presented here has not been reported before. CASE REPORT: A 44-year-old man was referred with progressive bilateral exophthalmos. CT of his chest and abdomen revealed an intrathoracic and retroperitoneal peri-aortal soft-tissue process with hydronephrosis. Histological examination of orbital masses showed a fibrous process with low inflammatory activity. Later the sella was found to be involved as well. A diagnosis of MF was made. CONCLUSION: MF should be considered in the differential diagnosis of bilateral exophthalmos.