Radiotherapy for the treatment of thyroid eye disease-a prospective comparison: Is orbital radiotherapy a suitable alternative to steroids?

BACKGROUND AND AIMS: To evaluate the efficacy of orbital radiotherapy (OR) for the treatment of thyroid eye disease (TED). METHODS: Thirty-five consecutive patients with active TED with contraindications to steroid therapy received a course of OR. Bilateral retrobulbar irradiation was performed with a total dose of 20 Gy. 7-points clinical activity score (7-CAS), ocular motility, visual acuity (VA), exophthalmos and eyelid retraction were prospectively evaluated at 3, 6 and 12 months and compared with baseline data. RESULTS: There was a statistically significant improvement in 7-CAS at 3, 6 and 12 months post-treatment (p < 0.05). Ocular motility disturbances improved at 6 and 12 months (p < 0.05). Visual acuity remained stable; there was no significant change in exophthalmos (mean 24 mm, SD 3 mm) or eyelid retraction (marginal reflex distance mean 6 mm, SD 1.5 mm) during the follow-up period. No side effects were registered. CONCLUSIONS: This study suggests that OR might be effective in reducing 7-CAS and ocular motility disturbances. No significant improvement in proptosis or eyelid retraction should be expected from this treatment. OR might be considered a suitable alternative treatment in TED for patients who cannot tolerate steroids.

Tumor infiltrating lymphocytes in uveal melanoma: a link with clinical behavior?

Experimental and clinical evidence indicate that immunological mechanisms might be important in the clinical course of uveal malignant melanoma (UMM). We analyzed the amount and phenotype of tumor infiltrating lymphocytes (TIL) and the expression of the apoptosis-inducing molecule Fas and its ligand, FasL, on tumor cells and TIL in a selected series of UMM with the aim to establish if a correlation between their expression and the clinical behavior of UMM exists. TIL phenotype and Fas/FasL expression were evaluated by immunohistochemistry in 61 cases of formalin-fixed, paraffin-embedded UMM. Results were compared with the follow-up data of patients. Most of the UMM showed a prevalence of CD8+ CD3+ T lymphocytes, or CD4+ and CD8+ cells in equal amounts. UMM showed a variable expression of FasL, ranging from 0 to > 40% of neoplastic cells. Fas was always expressed in TIL, although with a variable extent. A subgroup of UMM showed in TIL a strongly reduced or even absent expression of TCR zeta-chain, involved in activation of T-lymphocytes. This subgroup was characterized by a worse outcome. We hypothesized that an impaired cytotoxic immune response due to the loss of the zeta-chain expression plays a primary role in the biological course of UMM. Our results indicate that the overcoming of the impairment of TCR function may represent a prerequisite for the development of new therapeutic strategies for managing UMM, suggesting that elimination of tumor cells may be possible by activation of cytotoxic cells present within ocular melanomas.

Unilateral exophthalmos associated with ipsilateral mucosal turbinate hypertrophy: benign exophthalmos syndrome (BES). A description of a new clinical condition.

PURPOSE: To report the clinical and radiologic characteristics of a group of patients who experienced unilateral exophthalmos associated with ipsilateral mucosal turbinate hypertrophy. The clinical features of these patients are presented and a hypothesis proposed to explain this condition for which the authors introduce the term benign exophthalmos syndrome (BES). METHODS: Retrospective, noncomparative case series. PARTICIPANTS: Four patients experienced slow progressive unilateral exophthalmos associated with ipsilateral mucosal turbinate hypertrophy, with no evidence of orbital mass or extraocular muscles involvement. INTERVENTION: Main Outcome Measures. Symptomatic outcome and measurement of the degree of relative exophthalmos. RESULTS: The onset of exophthalmos was associated with clinical and radiologic features that resemble BES. In all patients, radiologic examination demonstrated an ipsilateral mucosal turbinate hypertrophy and not the presence of orbital disease or expanding lesions of paranasal sinus. After daily intranasal spray of steroid, in three of the four cases the globe returned to within 1 mm of exophthalmometry of the contralateral eye. CONCLUSIONS: The relationship between the feature of paranasal sinus disease and the development of ipsilateral exophthalmos has been described in the literature. The four cases described herein appear peculiar for the slow progressive onset of the exophthalmos, without inflammatory and mass effect signs. This condition associated in all cases with ipsilateral hypertrophy of the nasal mucosa provides a guide to a hypothetical mechanism for BES. According to these hypothesis, the therapy should be devoted to the nasal disease more than the orbital.

Orbital scintigraphy with [111In-diethylenetriamine pentaacetic acid-D-phe1]-octreotide predicts the clinical response to corticosteroid therapy in patients with Graves' ophthalmopathy.

Corticosteroid treatment is successfully used in Graves' ophthalmopathy, and its effect varies according to the phase of the disease. The infiltration of the orbit by activated lymphocytes may explain the effectiveness of corticosteroid therapy. Scintigraphy with [111In-DTPA-D-Phe1]-octreotide was recently used to reveal the presence of activated lymphocytes in foci of autoimmune diseases, because elevated amounts of somatostatin receptors are expressed in the surface of these cells. The aim of the current study was to evaluate whether the degree of orbital [111In-DTPA-D-Phe1]-octreotide uptake is able to predict the response to corticosteroid therapy in patients with Graves' ophthalmopathy. Ten patients with Graves' ophthalmopathy entered the study. In all patients scintigraphy was performed, and subsequently, corticosteroid therapy (methylprednisolone, 1 g i.v. for 2 consecutive days a week for 6 weeks) was given. Clinical activity of Graves' ophthalmopathy was evaluated before and after treatment by calculating the ophthalmopathy index (OI). Planar and single photon emission computed tomography (SPECT) images of the head were obtained 24 h after the i.v. injection of 120-190 MBq of [111In-DTPA-D-Phe1]-octreotide. Radioligand uptake within each orbit (O) and brain (B) was measured using the region of interests (ROI) method and the O-to-B ratio was determined. According to the O-to-B ratio, the images were classified using the following three points score: 0 = O-to-B ratio < or =1; 1 = O-to-B ratio between 1 and 2.5; 2 = O-to-B ratio > or =2.5. The value of OI, measured before and after corticosteroid treatment, was correlated to the scintigraphic score. A significant change of OI was observed between posttreatment and pretreatment evaluation both in orbits with score 2 (OI: 15.4 +/- 1.5 vs. 9.6 +/- 0.5, P < 0.005) and in those with score 1 or 0 (OI: 12.9 +/- 1.5 vs. 11.5 +/- 1.4, P < 0.05) at the scintigraphy. However, when the OI was calculated excluding the changes in the soft tissue, which generally occur in all patients independently from the phase of the disease, a significant change of OI was observed only in the orbits with score 2 (OI: 12.9 +/- 1.3 vs. 8.3 +/- 0.5, P < 0.01) but not in those with score 0 or 1 (OI: 11.2 +/- 1.3 vs. 10.4 +/- 1.3). In particular, 6 weeks after corticosteroid treatment, the patients with orbital score 2 at the scintigraphy had a significant improvement of soft tissue changes, proptosis, lagophthalmos, extraocular muscle movements impairment, and diplopia, whereas patients with score 0 or 1 had only a significant improvement of the soft tissue inflammation. In conclusion, the current preliminary data suggested that [111In-DTPA-D-Phe1]-octreotide scintigraphy is able to predict the clinical response to corticosteroid treatment in patients with Graves' ophthalmopathy, and may be considered an useful approach to select the patients for the proper treatment.

Somatostatin receptor gene expression and inhibitory effects of octreotide on primary cultures of orbital fibroblasts from Graves' ophthalmopathy.

To explore the mechanism underlying the effects of the somatostatin (SST) analogue octreotide in Graves' ophthalmopathy (GO), we investigated the expression of SST and of SST receptor (sst(1-5)) genes in primary cultures of fibroblasts established from retroorbital tissue of GO patients and of control subjects. We determined also SST specific binding sites by competitive binding of [(125)ITyr(11)]SST-14 and the effect of octreotide on cell growth, cAMP accumulation, Bcl-2 intracellular levels and apoptosis in GO fibroblast primary cultures. All primary cultures expressed the SST gene transcript and one or more ssts that have a high affinity for the two analogues (class 1 sst. The sst(2) transcript was found in nine, sst(3) in five and sst(5) in eight out of ten GO cell cultures. Sst(2) was detected in all six, and sst(3) in four out of the six control cell cultures. Sst(4) was absent from all samples, and sst(1) was found only in six out of the ten GO samples. SST-14 and octreotide inhibited the binding of [(125)I-Tyr(11)]SST-14 with a half-maximal inhibition of binding (IC(50)) of 0.80+/-0.37 and 33. 7+/- 33.1 nmol/l respectively in GO cell cultures, and with an IC(50) of 0.9 and 1.5 nmol/l in control cultures. Octreotide (10(-6) and 10(-7) M) significantly decreased (P<0.001) forskolin-induced but not basal cAMP accumulation; at both doses for 72 h it inhibited cell growth (20 and 55% respectively), and induced apoptosis (20 and 40%), and abolished Bcl-2 protein in cell lysates. In conclusion, SST and sst transcripts are expressed and functional in cultured retroorbital fibroblasts. The presence of class 1 sst in GO tissue and the inhibition exerted by octreotide on retroorbital cell growth and activity in vitro may account for the effects of SST analogue administration in vivo in GO.

Primary Ewing's sarcoma of the maxilla, a rare and curable localization: report of two new cases, successfully treated by radiotherapy and systemic chemotherapy.

Primary maxillary localization of Ewing's sarcoma is unusual. Involvement of facial bones is characterized by clinical and radiological features distinct from those commonly observed in other sites. Because of the above peculiarities a delay in diagnosis and thus in starting treatment is very probable in such cases. We report here two new cases of Ewing's sarcoma localized to facial bones, successfully treated by local high dosage radiotherapy and systemic chemotherapy. Our experience suggests that, especially for particular sites not suitable to radical surgery, radiation therapy can represent an effective tool to achieve local control of the tumor.

Radiation late effects in children treated for orbital rhabdomyosarcoma.

BACKGROUND AND PURPOSE: The experience resulting from large cooperative studies shows that correct radiation therapy at doses adequate to the tumor bulk are crucial for local control of rhabdomyosarcoma. The aim of the present study was to document the correlation between modalities and doses of radiotherapy and radiation side effects. PATIENTS AND METHODS: Between 1980 and 1997, 19 patients affected by primary orbital rhabdomyosarcoma have been followed at the University Federico II of Naples. All but three patients, who received 45, 54 and 55 Gy respectively, have been treated by immediate radiation at the dose of 60 Gy, delivered in 2 Gy fractions, five times per week, by cobalt 60 megavoltage equipment. Combined chemotherapy using vincristine and vincristine plus dactinomycin on alternate weeks was also administered as part of induction therapy. RESULTS: An overall survival rate of 94.7% was registered. In our patients the majority of radiation late effects were paid by orbit and ocular adnexa. Side effects to lens and ocular structures were fewer and of low grade. CONCLUSIONS: Radiation therapy is still essential for local control of orbital rhabdomyosarcoma, however radiation side effects have to be carefully considered together with the therapeutic goal to be obtained.

Orbital venous-lymphatic malformations (lymphangiomas) mimicking cavernous hemangiomas.

PURPOSE: To illustrate that orbital venous-lymphatic malformations (lymphangiomas) may rarely simulate cavernous hemangiomas. METHODS: Retrospective case review. RESULTS: Five patients were identified from a series of 85 patients with venous-lymphatic malformations. The age range was 21 to 69 years, and all cases presented with a history of slowly progressive or long-standing proptosis. Computerized tomography revealed relatively homogeneous intraconal masses that were well defined anteriorly. Two of the cases had expansion of the orbit, and one had focal calcification. The three who had magnetic resonance imaging showed heterogeneous contrast enhancement. The preoperative diagnosis in every case was cavernous hemangioma, and intraoperatively the lesions resembled cavernous hemangiomas. However, posterior dissection was difficult in all patients because of dense adhesions and, in one case, led to a central retinal artery occlusion. The histology was characteristic of orbital venous-lymphatic malformations in all five cases. CONCLUSIONS: Deep orbital venous-lymphatic malformations presenting in adulthood may be rarely confused with cavernous hemangiomas. In doubtful cases, significant intralesional heterogeneity, best seen on magnetic resonance imaging, and focal calcification may help distinguish the two entities. This differentiation is important, because dissection of venous-lymphatic malformations is fraught with more complications than surgical excision of a cavernous hemangioma.

Traumatic displacement of the globe into the ethmoid sinus.

PURPOSE: To describe displacement of the globe into the ethmoid sinus after an orbital trauma. METHOD: Case report. A 58-year-old man sustained trauma of the left eye and orbit, which resulted in displacement of the globe into the ethmoid sinus. One day after injury, surgery was performed to restore the intact globe into position within the orbit. RESULTS: After operation, the globe held in its anatomical site, and 10 months after surgery the visual acuity was 20/100, slight pallor of the optic disk was present, and there was no limitation of the horizontal and vertical ductions. CONCLUSIONS: To our knowledge, this is the first case of traumatic displacement of the globe into the ethmoid sinus with satisfactory restoration of normal globe position and preservation of vision.

Warthin tumor of the lacrimal gland.

PURPOSE: To describe a case of Warthin tumor involving the lacrimal gland. METHODS: Case report. The patient underwent a lateral orbitotomy to remove a nodular lesion involving the lacrimal gland. The specimen was submitted for histopathologic examination. RESULTS: The lesion was characterized by epithelial columnar cells arranged in solid nests or lining cystic spaces containing an exudative fluid and by pronounced lymphoid infiltrate with focal follicular formation. CONCLUSIONS: To our knowledge, this is the first case of Warthin tumor involving the lacrimal gland. Management requires complete excision of the lesion.

[Somatostatin receptor genes expression and effects of octreotide on orbital fibroblasts from Graves' ophthalmopathy]. / I recettori della somatostatina ed effetto in vitro dell'octreotide nei fibroblasti retro-orbitari di pazienti con oftalmopatia di Graves'.

BACKGROUND: Recent data demonstrated that somatostatin (SRIH) analogues octreotide is effective in Graves' ophthalmopathy (GO), but their mechanism of action in GO is still unclear. In this study we investigated the expression of SRIH receptor (sst1-5) genes and the effect of octreotide treatment on primary cultures of fibroblasts established from retroorbital tissue of GO patients and of control subjects. METHODS: Retro-orbital connective tissue was obtained from 10 patients with GO and from 6 control subjects undergoing eye surgery. Fibroblasts were established in MEM with 5-10% FCS. The expression of sst1-5 genes was studied by RT-PCR using specific primers and GAPDH as internal control. Cells were treated with octreotide (10-8M, 10-9M) for 48-72-96 h to evaluate cell growth by MTT, cAMP accumulation by RIA and apoptosis by TUNEL techniques. RESULTS: All primary cultures expressed one or more ssts genes that have a high affinity for the two analogues (class 1 sst). The sst2 transcript was found in 9, sst3 in 5 and sst5 in 8 out of 10 GO cell cultures. sst2 was detected in all 6, and sst3 in 4 of the 6 control cell cultures. Octreotide (10-6 and 10-7M) significantly inhibited cell growth (p<0,01-0,05), significantly decreased forskolin-induced-cAMP accumulation, and determined apoptosis (10-18%). CONCLUSIONS: Our study demonstrated that sst transcripts are expressed and functional in cultured retroorbital fibroblasts. The presence of class 1 sst in GO tissue and the inhibition exerted by octreotide on retroorbital cell growth and activity in vitro may account for the effects of SRIH analogue administration in vivo in GO.

Treatment of carotid-cavernous fistula by trans-venous anterior (trans-orbital) approach. Case report and review of previous report.

A case is reported of successful occlusion of a dural carotid-cavernous fistula (type D) by means of a transvenous anterior approach. Through the left angular vein, the distal superior ophthalmic vein (SOV) and the cavernous sinus were cannulated and three Gianturco coils were delivered close to the fistulous communications. Obliteration of the carotid-cavernous communication was achieved sparing the internal carotid artery and its branches. The major advantage of entering the sinus from the venous route is to preclude any damage to the artery, distal migration of the detachable balloon or of thrombi, intracavernous pseudoaneurysm formation. The trans-orbital approach may be considered chiefly when the openings are in the antero inferior compartment and the SOV is enlarged. Its applications, quite sporadic until now, probably will become more popular, mainly in treating D type fistulas, thanks to the good results achieved and to its safety.

Orbital dermis-fat graft using periumbilical tissue.

Dermis-fat grafts are currently used in orbital reconstruction in a variety of procedures. The most frequent harvesting site is the gluteal area. However, we encountered some patients with anophthalmic socket who wished to avoid a visible scar on the buttock. In this article, we describe the effort to offer the patient an alternative donor site. Of the last 36 patients with anophthalmic socket who needed a dermal fat implant, 11 wished to avoid a visible scar on the buttock. To satisfy their requests we have endeavored to harvest the dermis graft from the periumbilical area. The rate of absorption, the motility, and the satisfaction of the patients were used as outcome measures and were analyzed carefully. Of 11 patients, 4 were women and 7 were men. The ages of these patients ranged from 24 to 56. The maximum follow-up was 137 months and the minimum 22 months, with a mean follow-up of 79 months. Some degree of absorption of the graft developed in one patient who had a severe absorption and required further operation. Of 11 cases, there were 7 with excellent motility, 3 with good motility, and 1 not evaluated. The motility was measured with the final prosthesis. The results for all patients were satisfactory. The periumbilical area has sufficient concentration of subdermal fat, and it is a relatively hair-free region as the lateral quadrant of the buttock. This area is a suitable alternative donor site of dermal fat implant for anophthalmic socket, especially in young women.

Ophthalmic complications after surgery for nasal and sinus polyposis.

PURPOSE: To describe ophthalmic complications after nasal and sinus surgery. METHODS: Four cases with orbital complications were retrospectively selected from among more than 2000 cases of orbital pathologies. RESULTS: Motility disturbances due to extraocular muscle injury occurred in two patients after intranasal ethmoidectomy and in one patient after a Caldwell-Luc procedure. In the fourth case an orbital apex syndrome was noted after intranasal ethmoidectomies. CONCLUSIONS: Ophthalmic complications may occur after nasal and sinus surgery, even using an endoscopic procedure. Successful handling of these complications could be reached by on their early recognition and treatment.

[Outcome of drug-induced pregnancies]. / Esiti di gravidanze farmacologicamente indotte.

The authors analysed 153 pregnancies achieved after different drug treatment to induce ovulation. The outcome of single and multiple pregnancies, the fetal malformation and male/female ratio were considered. The results obtained show that induction of ovulation seem to raise the risk of miscarriage when compared with outcome of spontaneous pregnancies; the malformation risk is not considerable.

[Curettage vs. hysteroscopic resection]. / Curettage v/s resezione isteroscopica.

The aim of the present study was to evaluate the therapeutic efficacy of curettage vs hysteroscopic resection in the treatment of endometrial polyps. A group of 25 patients were examined and during surgery underwent diagnostic hysteroscopy, curettage of the uterine cavity, control hysteroscopy and resectoscopy in the event of residual polyps. Thirteen cases revealed the total persistence of the polyp after curettage and in 6 cases the polyp was only partially removed; the polyp was detached but not removed from the uterine cavity in 4 cases and the polyp was fully removed using the curette in only 2 cases. The considerable limits of curettage which emerge from this study appear to be linked to three main factors: the localization, nature and size of endometrial polyps. Curettage may therefore now be considered a method which has been surpassed in not only diagnostic but also therapeutic terms by hysteroscopic techniques.

[Juvenilis macular degeneration in a family affected by cystinuria]. / Dégénérescence maculaire juvénile chez une famille atteinte de cystinurie.

This paper deals with a family affected by cystinuria associated with eye signs of juvenilis macular degeneration.