Barbara Mazzi

Orbital Decompression in Graves' Ophthalmopathy by Medial and Lateral Wall Removal

Objective The objective of this study is to describe a technique for balanced orbital decompression and to analyze the results. Methods and Materials We conducted a retrospective study of 140 patients (276 orbits). Orbital decompression was carried out by removal of the medial orbital wall by ethmoidectomy and complete removal of the lateral wall by bringing out the entire sphenoid wing together with part of the zygomatic bone down to the inferior orbital fissure. Results One hundred thirty-six patients underwent bilateral decompression, 4 patients underwent monolateral decompression. Proptosis was reduced on average by 5.3 mm; 28 (20%) patients showed onset or worsening of diplopia. Conclusions Medial and lateral approach allows a balanced orbital decompression. As some patients may present different degrees of proptosis and visual impairment, we stress the importance of carefully weighing the preoperative conditions of the individual patient when choosing the surgical approach.

Thyroglobulin in orbital tissues from patients with thyroid-associated ophthalmopathy: predominant localization in fibroadipose tissue.

UNLABELLED One of the hypotheses that explains the pathogenesis of thyroid-associated ophthalmopathy (TAO) is that thyroglobulin (Tg) is transported through a retrograde lymphatic route to orbital tissues (OT), where it elicits autoimmune damage. In a previous study we demonstrated the presence of intact Tg of thyroid origin in OT from three patients with TAO. The present study was undertaken to investigate this issue further, by increasing the number of patients, by analyzing the distribution of Tg in OT, and by investigating possible relations between the presence of Tg in OT and the clinical features of patients. OT was obtained from seven patients with TAO who underwent decompressive orbitotomy via a transpalpebral approach. Patients were designated P10 to P16. Inflamed palpebral skin, retrobulbar fibroadipose tissue and extraocular muscle surgical samples were collected separately. Tissue extracts were prepared by homogenization and analyzed for the presence of Tg using two different techniques. We first performed immunoprecipitation experiments, in which a rabbit polyclonal anti-Tg antibody was used to capture Tg on protein A and a mouse monoclonal anti-Tg antibody was used to re-veal captured Tg by Western blotting. Intact 330-kd Tg was detected in retrobulbar fibroadipose tissue extracts from three patients (P10, P11, and P16), whereas no Tg was detected in retrobulbar fibroadipose tissue extracts from the remaining four patients. Tg was not detected in the extraocular muscle extracts from all patients studied. In addition, intact 330-kd Tg was found in the inflamed palpebral skin extract from one patient (P10). No Tg was detected in OT extracts from two patients without thyroid or eye disease and in abdominal adipose tissue extracts from two obese patients without thyroid or eye disease. We then searched for Tg by enzyme-linked immunosorbent assay (ELISA), using the same antibodies used for immunoprecipitation. Tg was detected in retrobulbar fibroadipose tissue extracts from four patients (P10, P11, P12, and P16) and in the inflamed palpebral skin extract from patient P10, in amounts ranging from approximately 125 to approximately 400 pg/microg of tissue protein. Again, Tg was not detected in extraocular muscle extracts. A positive gradient between Tg in OT and Tg in the serum was observed in patient P12. Using an ELISA approach, we found that Tg in OT from three TAO patients (P10, P11, and P12) contained thyroxine (T4) residues (mean T(4) CONTENT 2.42 molecules per molecule of Tg), indicating that Tg had originated in the thyroid. Combining the results obtained in our previous and present study, we found a possible relation between the presence of Tg in OT and the previous treatment with radioiodine. Thus, of the seven patients (3 in the previous and 4 in the present study) in whose OT Tg was found, six had been treated with radioiodine, whereas of the three patients with no Tg in their OT none had been treated with radioiodine. In conclusion, Tg was found in OT extracts from patients with TAO by immunoprecipitation in three of seven cases and by ELISA in four of seven cases. Tg was found in retrobulbar fibroadipose tissue, but not in extraocular muscles. There was a relation between the presence of Tg in OT and the previous treatment with radioiodine. Our results support the hypothesis that Tg may play a role as a coantigen in the pathogenesis of TAO. Further studies are needed to investigate this possibility.

Reasons for revision surgery after orbital decompression for Graves'Orbitopathy

Objectives An analysis of complications and causes of failure in orbital decompression necessitating a second operation. Methods Between December 1992 and April 2007, 375 patients (719 orbits) were operated on using various techniques. Fourteen patients were initially operated on in our unit: 8 (group A1) were re-operated on after a short time due to complications connected with the decompression operation, 7 (group A2) were operated on after some time due to recurrence of the illness or unsatisfactory decompression (one patient is in both group A1 and A2). Five patients (group B) underwent a first operation elsewhere. Results For group A1 the most serious complications were connected to the nasal approach. For group A2 the operations were performed either because of a neuropathy recurrence or for further proptosis reduction due to recurrence or patient dissatisfaction. Lack of preoperative data hinders conclusions about group B, apart from one patient where the operation had not resolved a serious optic neuropathy after decompression based on Olivari technique combined with three-wall operation according to Mourits and colleagues (1990). Conclusions We can deduce from group A1 that extreme attention is necessary during endonasal access, from group A2 that balancing the eyes is advisable, sacrificing maximum proptosis reduction to gain greater patient satisfaction, and from group B that decompression of the orbital apex is fundamental in the case of neuropathy.

VARIABLES AFFECTING THE LONG-TERM OUTCOME OF GRAVES ORBITOPATHY FOLLOWING HIGH-DOSE INTRAVENOUS GLUCOCORTICOID PULSE THERAPY IN PATIENTS NOT TREATED WITH ORBITAL RADIOTHERAPY.

OBJECTIVE Intravenous (iv) glucocorticoids (GC) (ivGC) are used for active Graves orbitopathy (GO), but factors affecting GO outcome are poorly understood. We performed a retrospective study to investigate the variables affecting GO after ivGC. METHODS We evaluated 83 consecutive GO patients treated with ivGC but not orbital radiotherapy (ORT) and re-examined them after a median of 47 months. The endpoints were the relationships between GO outcome or additional treatments with age, sex, smoking habits, thyroid volume, thyroid treatment, time since thyroid treatment, antithyroid-stimulating hormone receptor antibodies (TRAb), GO duration, GO features, and follow-up time. RESULTS GO features improved after treatment, resulting in moderate and marked amelioration in ~75% and ~41% of patients respectively. By multivariate analysis, a moderate GO improvement correlated with diplopia at first observation, which was more severe in responders. A marked GO improvement correlated with time between first and last observation and time after thyroid treatment, which were longer in responders. This likely reflected the combination of an early effect of GC and a late, spontaneous improvement of GO, as shown by analyses of GO outcome at various time points. Additional treatments after ivGC correlated by multivariate analysis with eyelid aperture, diplopia and NOSPECS score (NOSPECS stands for no GO signs [N], only eyelid sign [O], soft tissue involvement [S], proptosis [P], extraocular motility restriction [E], corneal involvement [C], and sight loss [S]) at first observation, which were more severe in responders. CONCLUSION Our study shows that response to ivGC increases with time, likely reflecting the known tendency of GO to improve spontaneously, and is more pronounced when GO is more severe to begin with, which is associated with more additional treatments. ABBREVIATIONS ANOVA = analysis of variance CAS = clinical activity score GC = glucocorticoids GO = Graves orbitopathy 131I = radioactive iodine iv = intravenous ivGC = high-dose intravenous glucocorticoid pulse therapy MMI = methimazole OD = orbital decompression ORT = orbital radiotherapy TRAb = antithyroid-stimulating hormone receptor antibodies.

Does Graves’ Orbitopathy Ever Disappear Answers to an Old Question

Objectives: There is a general belief that Graves’ orbitopathy (GO) is a “chronic” disease, namely that patients’ eyes do not return to how they were before GO appeared. Here, we investigate this issue from both the patient’s and the physician’s point of view. Study Design: We studied the disappearance of GO, regardless of treatment, in all consecutive patients with a GO history of at least 10 years who came for a follow-up visit over a period of 5 years. Patients underwent an ophthalmological examination and were asked to answer a questionnaire on self-perception related to GO. Results: We studied 99 consecutive patients with a GO duration ≥10 years. Between the first and the last observation, patients received several types of treatment for their thyroid disease and/or for GO. At the end of follow-up, GO was considered disappeared based on objective criteria in 8 patients (∼8%) and based on subjective criteria in 24 patients (∼24%). When we considered both subjective and objective criteria, only 2 patients (∼2%) had all criteria fulfilled and could be considered as GO-free. Conclusions: GO is a chronic disease in the vast majority of patients. Even after a very long time since its onset, complete disappearance is rare, although a minority of patients believe they do not have GO anymore and an even lower proportion do not have relevant GO signs. Our findings have obvious implications in patient management and counseling.