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PURPOSE: To describe corneal astigmatism in patients under the age of 55 years with Graves' ophthalmopathy and to compare it to a control group. METHODS: Retrospective, nonrandomized comparative observational case series. A total of 109 patients with inactive Graves' ophthalmopathy and 109 age- and gender-matched control individuals without Graves' ophthalmopathy were examined with manual corneal keratometry. In the Graves' patients, 52% had a CT scan available for review, and 41% underwent orbital, strabismus, and/or eyelid surgery with a follow-up of keratometry over a mean period of 1.7 years after surgery. RESULTS: For the dioptres, there was a statistically significant difference between the Graves' and the control eyes at 3-3.25 dioptres in both eyes (t-test, right eyes, P=0.042; left eyes, P=0.041). For the meridians, the astigmatism was found to be greater at the meridians 95-100 degrees (t-test, P=0.044) and 105 degrees -110 degrees (t-test, P=0.017) in the right eyes only. In 10 (9%) Graves' patients, the astigmatism had caused newly acquired reduced visual acuity. Greater astigmatism in dioptres did not correlate with specific CT scan findings (chi(2)-test, df=2, P=0.187). Following orbital, strabismus, and eyelid surgery, the dioptres and meridians of the astigmatism did not change in 56 (68%) and 66 (81%) eyes, respectively. CONCLUSIONS: Graves' ophthalmopathy may be associated with greater with-the-rule corneal astigmatism, which, overall, is not influenced by orbital, strabismus, or eyelid surgery. The astigmatism may possibly be caused by soft-tissue fibrosis in the superolateral orbital region.

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AIM: To analyse the extent of bony orbital volume reduction after enucleation in humans. METHODS: Volumetric studies on bony orbital volumes based on three dimensional reconstructions acquired from high resolution computed tomograph (CT) scans were performed in 29 patients with acquired anophthalmia and four patients before enucleation (controls). Eight patients (follow up 25-52 years) were enucleated in childhood aged between 0.4 and 8 years (group I), 21 in adulthood aged between 15 and 53 years. Fifteen of these patients (group IIa) had long standing anophthalmia (follow up 7-53 years), six patients (group IIb) were enucleated 9 months to 4 years before CT. RESULTS: Bony orbital volumes were reduced in all patients with long standing anophthalmia. The median percentage reduction in enucleated orbits was 7.0% in group I, 3.8% in group IIa, and 1.9% in group IIb. In patients with long standing anophthalmia (I and IIa) the reductions were statistically significantly different (p <0.01) from zero. There was some evidence of a correlation between orbital volume reduction and age at enucleation (rho = 0.36, p = 0.09, Spearman rank correlation coefficient) and a statistically significant correlation between volume reduction and time interval since enucleation (rho = -0.5, p = 0.003). Clinically none of the patients showed significant facial asymmetry. CONCLUSIONS: These data provide strong evidence that enucleation both in children and adults is associated with a reduction of bony orbital volume and that this decrease in volume is associated with increasing time. However, the reduction is smaller than generally assumed and does not cause obvious facial asymmetry. It is more related to the time interval since enucleation than the age at enucleation, which makes a mechanism of volume adaptation more likely than just retardation of growth.

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The purpose of this paper was to evaluate the appearance and location of the healed intranasal ostium and the internal aperture of the common canaliculus after uncomplicated external dacryocystorhinostomy (DCR). In 21 patients who underwent uncomplicated external DCR, the distances between the lacrimal puncta and the internal aperture of the common canaliculus were measured during surgery. The measurements were taken with a 1 mm diameter Bowman probe graded in millimeters. These measurements were recorded and considered the landmarks for the spatial localization of the internal aperture of the canaliculus. After surgery, under endoscopic control, the same method was used to measure the distance between the lacrimal puncta and the internal ostium, which was defined as the aperture through which it was possible to visualize the very first protrusion of the probe into the nose. The intra- and post-operative measurements were compared. Endoscopic photos of the healed endonasal ostium were also taken. The photos showed that when DCR procedures were not complicated by scarring or mucosal adhesions, the lacrimal sac became a depression perfectly integrated within the nasal mucosa. The scar at the site of junction between the nasal and the lacrimal sac mucosa appeared as a large-diameter pearl-like colored frame that surrounded the depression. In the context of the depression a small aperture, which presented a diameter of around 2 mm, could be easily visualized. The spatial location of this aperture corresponded to the internal aperture of the common canaliculus (p < 0.05).

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OBJECTIVE: It is thought that immunosuppressive treatment of Graves' ophthalmopathy should be restricted to patients with active eye disease, but assessing disease activity is difficult. Octreotide scintigraphy has been claimed to differentiate active from inactive disease. Here we study the intraobserver variability and diagnostic accuracy of the quantitative measurement of orbital octreotide uptake. PATIENTS AND DESIGN: Twenty-two consecutive patients with moderately severe ophthalmopathy were treated with retrobulbar radiotherapy. Pretreatment octreotide scintigraphic data were related to the response at six months after radiotherapy, using Receiving-Operator-Characteristic curves. MEASUREMENTS: Octreotide uptake was measured at 4 and 24 h after i.v. injection of approximately 3 mCi (= 111 MBq; range 75-150 MBq) 111Indium-DTPA-Octreotide with a neuro-SPECT camera. Counts were measured in fixed regions-of-interest in 4 transversal slices of the orbit, the temporal and the occipital area. Measurements were done twice and intraobserver variability was analysed by coefficients of variations (CV). Uptake is expressed as orbital/background ratio. The nature of the temporal uptake was studied by matching an octreoscan with a technetium scan and MRI. RESULTS: Intra-observer variability of measuring octreotide uptake was acceptable, and the coefficient of variation slightly better using the orbital/occipital ratio (11%), than the orbital/temporal ratio (16%). From matching studies it appears that the temporal uptake takes place, in part, in the parotid gland. The orbital/occipital ratio was used to predict the outcome of radiotherapy. Mean (+/- SD) uptake on the 4 h scan was higher in responders (2.2 +/- 0.66) than in nonresponders (1.7 +/- 0.39; P = 0.04). From the Receiving-Operator-Characteristic curve we determined a cut-off value of 1.85, which yielded a positive predictive value of 92% and a negative predictive value of 70%. The 24 h scan could not predict a response. CONCLUSION: Quantitative measurement of orbital octreotide uptake is possible. Using the orbital/occipital ratio on the 4 h scan, the octreoscan seems useful in predicting response to subsequent radiotherapy. The 24 h scan seems not to be useful in predicting therapeutic outcome.

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BACKGROUND: Secondary orbital implants are used for the correction of the post-enucleation socket syndrome (PESS). This study evaluates retrospectively the post-operative course, complications, additional surgery, long-term cosmetic and functional results, and patient's satisfaction after secondary orbital implants. PATIENTS: Nineteen out of 24 patients who underwent secondary baseball implant insertion between 1986 and 1989 for the correction of PESS were re-examined. RESULTS: Five patients had complications, 11 patients (58%) further surgery. After a mean follow-up of 8.6 years, 17 patients (89%) showed findings better than preoperatively. Two patients were unchanged. The static overall impression, assessing particularly volume deficit and symmetry, using a scale of 1 to 5, was improved from 4.5 preoperatively to 2.5. CONCLUSIONS: Secondary orbital implants improve symptoms of PESS and patient's satisfaction in a high proportion of cases also in the long term. Complications are not rare, and frequently more than one operation is necessary. There is no significant risk of long-term side effects and no reduction of the positive effect with time.

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There is a need for more reliable and validated methods to assess the eye changes in Graves' disease. Such measurements are now available for the assessment of proptosis, eye muscle dysfunction, and optic nerve involvement. However, no validated objective measurement exists for NO SPECS class II signs. The present study compares the use of colour slides with clinical grading for assessing soft-tissue involvement. Forty-three patients were treated with retrobulbar irradiation. Pre-treatment, and 6 months post-treatment the severity of class II signs was graded from 0 to grade c in two ways; 1) Clinically, by two independent, experienced observers, who recorded their scores on the same day; 2) From colour slides, taken at the same visits, which were graded afterwards in one session independently by the same observers. Inter-observer agreement about clinical grading was low (Kappa 0.32), and was not improved by using the slides (Kappa 0.35). However, by using the clinical scores, the observers disagreed on treatment outcome in 21/43 patients (49%), whereas using the slides disagreement occurred in only 6/43 (14%, p < 0.01). It is concluded that the grading of soft-tissue involvement is highly subjective. However, the use of colour slides does provide a more reliable way to assess a treatment effect and should be used in clinical trials.

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A complex system of connective-tissue septa within the orbit has previously been described in serial histologic sections. The present study describes the anatomy of the orbital connective tissue system on high-resolution magnetic resonance (MR) images in vivo. Five volunteers aged 26 to 35 year underwent magnetic resonance imaging of the orbit on a 1 Tesla unit (Impact, Siemens, Germany). T1-weighted coronal images were obtained using a surface coil. Anatomical structures on the MR images were identified by comparison with corresponding histologic sections. On MR images of the anterior orbit, the levator aponeurosis, Lockwood ligament, transverse intermuscular ligament, common sheath, check ligaments, Tenon capsule, intermuscular septa, and palpebral ligaments can be seen. In the mid- and posterior orbit, the intermuscular orbital septa, especially the superolateral septum, the superior ophthalmic vein hammock, and septa of the radial connective tissue system are visualized. High-resolution magnetic resonance imaging is capable of delineating the major septa of the orbital connective tissue system.

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BACKGROUND AND PURPOSE: The levator palpebrae superioris (LPS) muscle courses anteriosuperiorly to culminate cranial to the posteriosuperior surface of the globe from where it courses anterioinferiorly to the trasal plate. Whitnall's superior transverse ligament (STL) has been suggested to suspend the LPS at its culmination. If this was the case, one would expect the STL to be located near the culmination of the LPS. In order to elucidate this functional aspect of the STL, the spatial relation of the STL of the LPS muscle is investigated in this study. METHODS: Surface coil MRI in an oblique sagittal plane along the optic nerve was performed in 6 orbits from 3 human cadavers in which the STL was marked with synthetic material. RESULTS: The MR images showed that in human cadaver specimens the STL is situated in the anterior descending portion of the LPS. CONCLUSION: This result suggests that the STL does not suspend the LPS at its culmination and is therefore not responsible for the curved course of the muscle.

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The relationship between upper lid elevation (h) and shortening (s) of the levator palpebrae superioris muscle (LPS) has an influence on the dose-response relationship in ptosis surgery. In order to investigate the relationship between upper lid elevation and shortening of the LPS, parasagittal T1-weighted MR images of the orbit were obtained in healthy subjects with the eye in down- and upgaze. The position of the upper lid margin and the length of the LPS were measured in the images in down- and upgaze and the amount of h and s was determined. For a mean (+/- SD) vertical upper lid elevation of 15 +/- 1 mm, the mean (+/- SD) shortening of the LPS muscle was 21 +/- 3 mm (n = 4). The mean ratio of his was calculated to be 1:1.4, which means that the levator muscle must contract by 1.4 cm in order to achieve a lid elevation of 1 cm. Therefore, the force of the LPS which is necessary to lift the upper eyelid can be smaller than the lid-closing force. This strongly suggests a physiological mechanism which reduces the muscle force necessary for lifting the upper eyelid.

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BACKGROUND/AIMS: External dacryocystorhinostomy (DCR) is a reliable but difficult surgical technique for the treatment of any obstruction of the lacrimal drainage system lying distal to the internal opening of the common canaliculus. In this prospective study, a simplified external DCR procedure and the results obtained on a series of 45 consecutive patients, in which traditional external DCR was indicated, are described. METHODS: In this modified procedure only very large and mobile anterior flaps of the lacrimal sac and nasal mucosa are created. Thanks to the large size and the great motility the two flaps can be easily sutured. Two double armed 6/0 polyglycolic acid sutures are used to join the two flaps, to elevate them anteriorly in order to avoid adhesions with underlying tissues, and to approximate the deep planes of the wound. The mean operative time was measured. RESULTS: At the end of follow up period (mean 17 months, range 14-24 months) all patients had no sign or symptoms of tearing and normal Jones I dye test. The mean operative time was 28.6 minutes (range 23-44 minutes). CONCLUSION: We believe that our modified technique can be used to simplify and speed up traditional external DCR without decreasing its well known reliability.

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High resolution MR imaging of the orbit enables visualization of anatomic details in the orbit, including important blood vessels, muscles, nerves and connective tissue structures. The best resolution of anatomic details currently is obtained by using surface coils and T1-weighted spin echo sequences. Some examples of clinical applications demonstrate that a detailed knowledge of orbital imaging anatomy is a prerequisite for successful interpretation of clinical MR images. Additionally, this noninvasive diagnostic technique may be used for anatomical in vivo studies.

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Three-dimensional imaging of the orbit and its adnexa provides an excellent topographic visualization of the deformity or tumor extent. This helps comprehension, communication, education, and documentation in the process of treating the patient. This article briefly describes the technique of three-dimensional imaging and classifies congenital orbital deformities which are extensively illustrated with relevant case material.

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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.

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PURPOSE: To evaluate whether the use of iridium-192 brachytherapy would reduce the incidence of complications noted with external beam radiation therapy in patients with orbital tumors. METHODS AND MATERIALS: This study is a retrospective review of a clinical series of 25 patients with various orbital tumors treated with brachytherapy between 1988 and 1995. RESULTS: Patients were observed for an average of 40 months (range, 16-88 months) during which one patient died of metastatic disease and 24 patients are alive with no evidence of disease. Recurrent disease was observed in four patients. In 3 patients, exenteration was necessary and in 22 patients, the eye was preserved. The visual acuities after therapy ranged from no light perception to 20/20 (average, 20/40). CONCLUSIONS: Since brachytherapy has been used as an alternative to exenteration, the results of this treatment have been excellent in most patients. However, in advanced disease, external radiation therapy or even mutilating surgery still remains inevitable.

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OBJECTIVE: Approximately 35% of patients with Graves' ophthalmopathy do not respond to immunosuppressive treatment. A possible explanation for this finding is that only patients with active ophthalmopathy respond to immunosuppressive treatment, whereas patients with fibrotic end stage disease do not. To distinguish between these two groups and to predict the outcome of immunosuppressive treatment, we developed a clinical activity score (CAS) based on four of the five classical signs of inflammation and tested its efficacy in a double-blind, prospective study. DESIGN, PATIENTS AND MEASUREMENTS: The CAS was determined by an opthalmologist before, on the day of, and after the start of either oral prednisone or retrobulbar irradiation in 43 patients with moderate to severe Graves' ophthalmopathy. The therapeutic outcome was determined by a second ophthalmologist unaware of the CAS stores given. Success of treatment was defined as an improvement in NOSPECS class or grade. RESULTS: Responders (22) and non-responders (21) did not differ in age, sex, duration or severity of their Graves' ophthalmopathy. The pretreatment CAS, however, was significantly higher in responders than in non-responders. Twelve of 22 responders and three of 21 non-responders had a CAS > or = 4 (55% vs 14%; P < 0.01) [corrected]. Using this CAS cut-off point, the accuracy of CAS in predicting the therapeutic outcome was: specificity 86%, sensitivity 55%, positive predictive value 80%, negative predictive value 64%. Patients with a CAS > or = 4 had a similar duration of Graves' ophthalmopathy as patients with a CAS < 4. CONCLUSIONS: The clinical activity score has a high predictive value for the outcome of immunosuppressive treatment in Graves' ophthalmopathy. Disease activity, and not disease duration, is the prime determinant of therapeutic outcome.

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PURPOSE: This study describes the magnetic resonance imaging (MRI) anatomy of the blood vessels and nerves of the orbit to provide a morphological basis for the interpretation of clinical findings. METHODS: Seven volunteers aged 29 to 54 years underwent high-resolution MRI of the orbit on a 1 Tesla unit (Impact, Siemens, Germany). T1-weighted oblique-sagittal, coronal, and axial images were obtained using a surface coil. Anatomic structures on the magnetic resonance images were identified by comparison with corresponding histologic sections of the orbit. RESULTS: The ophthalmic artery and most of its branches (central retinal artery, posterior ciliary arteries, lacrimal artery, anterior and posterior ethmoidal arteries, supratrochlear artery, supraorbital artery, dorsal nasal artery) are visualized. The superior ophthalmic vein, the lacrimal vein, the medial ophthalmic vein, the inferior ophthalmic vein, the medial and lateral collateral veins, and the vorticose veins are also delineated. Furthermore, branches of the oculomotor nerve, the abducens nerve, the frontal nerve, the nasociliary nerve, the lacrimal nerve and the infraorbital nerve are identified in the magnetic resonance images. CONCLUSION: High-resolution MRI is capable of delineating the orbital arteries, veins, and nerves. This is mainly based on two principles. First, blood vessels appear mostly dark on magnetic resonance images because of the signal void of flowing blood. Second, the bright background of the orbital fat on T1-weighted magnetic resonance images accounts for the good soft-tissue contrast in the orbit. With improved MRI technology and reduced imaging time, high-resolution-MRI may be applied routinely for diagnostic purposes.

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PURPOSE: Orbital myositis is described as exquisitely sensitive to therapy with systemic corticosteroids. However, it may turn into a recurrent or chronic disease, requiring repeated courses or maintenance of corticotherapy that often is complicated with serious side effects. The authors conducted this study to evaluate their experience and the current status in the literature as to treatment of orbital myositis with corticosteroids and corticosteroid-sparing alternatives. METHODS: The clinical records and computed tomography scans of patients with orbital myositis who presented at the Orbital Center Amsterdam between 1977 and 1991 were studied for the clinical course and therapeutic outcome. Recurrences were defined as a new attack of the same or another extraocular muscle as the primary affected, in the same or the other orbit. RESULTS: The study group comprised 16 patients. All patients responded to initial treatment with oral corticosteroids (14/16) or nonsteroidal anti-inflammatory drugs (NSAID) (2/16). Of these 16 patients, 9 (56%) had 1 or more recurrences. Recurrences responded to repeated courses of corticosteroids, NSAID, or 20 Gy irradiation. Despite radiotherapy in six patients, recurrences continued to occur within a mean period of 2.7 years (range, 0.5 month-8.8 years). The mean follow-up after initial therapy in general was 9.7 years (range, 2.6-16.9 years), and after radiotherapy, in particular, was 7.4 years (range, 4.1-10.5 years). CONCLUSIONS: Orbital myositis responds well to oral corticosteroids, but recurs in 50% of the cases. Based on a long-term follow-up of six patients who received irradiation of 20 Gy, radiotherapy appears ineffective in stopping recurrent orbital myositis.

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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.

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PURPOSE: Magnetic resonance imaging (MRI) of the extraocular muscles has attracted growing interest for the evaluation of complex motility disorders. However, little information is available on the high-resolution MRI anatomy of the normal extraocular muscles and their connective tissue system. The study describes the imaging anatomy of the recti and oblique muscles and the levator palpebrae superioris muscle. METHODS: MRI of the orbit at 1 tesla was performed in four normal volunteers using a surface coil. RESULTS: Many anatomical details such as Zinn's tendinous annulus, the trochlea, the superior oblique tendon, the intermuscular septa, the check ligaments, Lockwood's ligament and the common sheath between the superior rectus muscle and the levator muscle were visualised. A striking imaging feature was the curved path of both the recti muscles and the levator palpebrae muscle. The inferior oblique muscle also showed a marked curvature in the region of Lockwood's ligament. CONCLUSIONS: High-resolution MRI is capable of demonstrating the anatomy of the extraocular musculature and parts of its connective tissue system. The curved path of the extraocular muscles can be explained by the configuration of the orbital connective tissue system which couples each extraocular muscle with the adjacent orbital wall. We discuss the clinical implications of our findings and review previous radiological studies regarding the functional anatomy of the extraocular muscles.

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