Biopsy-proven recurrence of unilateral IgG4-related orbital inflammation after 20 years.

A 38-year-old female patient presented with a painful swelling in the lateral part of the upper eyelid, a diffuse scleritis and slight hypoglobus of the right eye. An orbital biopsy showed a fibrotic idiopathic orbital inflammation (IOI) with, on immunohistochemical staining, an increased number of IgG4-positive plasma cells scored as >200 per high-power field, with IgG4/IgG ratio >0.50, indicating orbital IgG4 related autoimmune disease. On treatment with oral prednisone and azathioprine the symptoms resolved within 6 months. Twenty years prior, the patient had been diagnosed with an IOI of at the same side, for which at that time a biopsy had been taken similarly. Reclassification of the previous biopsy specimen with immunohistological staining also showed evidence of orbital IgG4 related disease. To our knowledge this is the first report of a biopsy-proven unilateral IgG4-related orbitopathy that recurred after 20 years.

PDGF enhances orbital fibroblast responses to TSHR stimulating autoantibodies in Graves' ophthalmopathy patients.

PURPOSE: Thyroid-stimulating hormone receptor (TSHR) stimulating autoantibodies are associated with Graves' ophthalmopathy (GO), the orbital manifestation of Graves' disease (GD). TSHR autoantibody levels and orbital TSHR expression levels correlate positively with GO disease activity. Platelet-derived growth factors (PDGF) are increased in GO and potently activate orbital fibroblast effector functions. We investigated the possible relationship between PDGF and TSHR expression on orbital fibroblasts and how that influences the immunopathological effects of TSHR autoantibodies on orbital fibroblast activity. METHODS: Orbital fibroblasts were stimulated with PDGF-AA, PDGF-AB, and PDGF-BB, and TSHR expression was determined by flow cytometry. Stimulatory effects of bovine TSH and GD immunoglobulins on orbital fibroblasts (with or without PDGF-BB preincubation) were determined by IL-6, IL-8, chemokine (C-C motif) ligand (CCL)-2, CCL5, CCL7, and hyaluronan ELISA. The TSHR blocking antibody K1-70 and the cAMP inhibitor H89 were used to determine involvement of TSHR signaling. RESULTS: PDGF-AB and PDGF-BB stimulation increased TSHR expression on orbital fibroblasts, whereas PDGF-AA did not. Furthermore, stimulation with bovine TSH and immunoglobulins from GD patients induced IL-6, IL-8, CCL2, and hyaluronan production by orbital fibroblasts, and PDGF-BB preincubation enhanced this response of orbital fibroblasts. Blocking studies with a TSHR blocking antibody and a cAMP inhibitor inhibited these effects, indicating the involvement of TSHR signaling and thus of TSHR stimulating autoantibodies herein. CONCLUSIONS: These findings indicate that PDGF-B containing PDGF isoforms amplify the immunopathological effects of TSHR-stimulating autoantibodies in GO patients by stimulating TSHR expression on orbital fibroblasts.

Orbit-infiltrating mast cells, monocytes, and macrophages produce PDGF isoforms that orchestrate orbital fibroblast activation in Graves' ophthalmopathy.

PURPOSE: Platelet-derived growth factors (PDGF) are regulators of fibroblast activity that may be involved in the pathophysiology of Graves' ophthalmopathy (GO). We unraveled the expression and origin of PDGF family members in GO orbital tissue and investigated the effect of PDGF isoforms on IL-6 and hyaluronan production and proliferation by orbital fibroblasts. METHODS: PDGF-A, PDGF-B, PDGF-C, PDGF-D, PDGF-Rα, and PDGF-Rß expression was determined by real-time quantitative PCR and PDGF-A and PDGF-B protein expression was determined by Western blot in orbital tissues. Orbital tissues were immunohistochemically stained for PDGF-A and PDGF-B expression, together with stainings for T cells, monocytes, B cells, macrophages, and mast cells. Effects of PDGF-AA, PDGF-AB, and PDGF-BB on orbital fibroblast proliferation and IL-6 and hyaluronan production were examined. Finally, effects of PDGF-BB- and PDGF-AA-neutralizing antibodies on IL-6 and hyaluronan production in GO whole orbital tissue cultures were tested. RESULTS: GO orbital tissue showed increased PDGF-A and PDGF-B mRNA and protein levels. Increased numbers of PDGF-A- and PDGF-B-positive monocytes, macrophages, and mast cells were present in GO orbital tissue. PDGF-BB stimulated proliferation and hyaluronan and IL-6 production by orbital fibroblasts the most, followed by PDGF-AB and PDGF-AA. Finally, in particular imatinib mesylate and PDGF-BB-neutralizing antibodies reduced IL-6 and hyaluronan production by whole orbital tissue cultures from GO patients. CONCLUSIONS: In GO, mast cells, monocytes, and macrophages may activate orbital fibroblasts via secretion of especially PDGF-AB and PDGF-BB. Preclinical studies with whole orbital tissue cultures show that blocking PDGF-B chain containing isoforms can be a promising treatment for GO.

[Orbital metastases of breast cancer. Radiologic features]. / Mammakarzinommetastasen der Orbita. Radiologische Eigenschaften.

BACKGROUND: We reviewed the radiologic features of 15 patients with orbital metastases originating from breast cancer. METHODS: This was a retrospective consecutive case series. Fifteen consecutive patients with orbital metastases originating from breast carcinoma were identified between March 1997 and September 2008. A retrospective chart review was carried out, and the radiologic findings were reviewed. RESULTS: The metastases were preseptal in 53%, intraconal in 60%, and both intraconal and extraconal in 33%. Lacrimal gland enlargement was noted in 33%, episcleral space involvement in 33%, bone involvement in 13%, and globe dystopia in 53%. The extraocular muscles were involved in 87%; in 60%, two or more muscles were involved. The medial and lateral rectus muscles were affected in 53% and 47%, respectively, and the inferior and superior rectus muscles in 33%. In 47% one or more radiologic features had not been noted by the radiologist, and in 20% the findings were misinterpreted as an"orbital pseudotumor." CONCLUSION: Orbital metastases originating from breast cancer may present heterogeneously. Orbital imaging most commonly shows unilateral and multifocal involvement of multiple extraocular muscles and intraconal and preseptal areas by an irregular lesion.

Efficacy and side effects of 'swinging eyelid' orbital decompression in Graves' orbitopathy: a proposal for standardized evaluation of diplopia.

OBJECTIVES: To evaluate the efficacy and side effects of 'swinging eyelid' orbital decompression in patients with Graves' orbitopathy (GO). To calculate the incidence of postoperative new-onset diplopia (NOD) using a newly proposed scoring system for diplopia. METHODS: We reviewed the clinical data on proptosis, visual acuity, and diplopia in 104 consecutive patients (198 orbits) with GO, who underwent orbital decompression. A combined lateral canthal and inferior fornix incision ('swinging eyelid' approach) was used for removal of the medial wall, the orbital floor and, if indicated, the lateral wall. Indications for surgery were disfiguring/congestive GO (DGO) in 79 patients (149 orbits) and compressive optic neuropathy (CON) in 25 patients (49 orbits). Diplopia was scored according to four grades. In both groups, the incidence of new-onset (continuous) diplopia (NOD), deterioration of diplopia (DOD), and improvement of diplopia (IOD) were calculated, using strictly defined criteria. Our data on NOD were compared to those from other series, after recalculation according to our criteria. RESULTS: The mean proptosis reduction was 4.6 mm (range 0-9.5 mm) after three-wall decompression (95 patients, 180 orbits) vs 3.1 mm (range 0-7 mm) after two-wall decompression (nine patients, 18 orbits). The visual acuity improved in 98% of the patients with CON. In patients with DGO, NOD occurred in 14%. In patients with CON, NOD was not observed, but DOD occurred in 41%. Our data compare favourably to the reported incidence of NOD after either transantral or transnasal decompression. CONCLUSIONS: "Swinging eyelid' orbital decompression is efficacious for proptosis reduction as well as for optic nerve decompression. A scoring system for standardized evaluation of diplopia is proposed.

[Giant mucocele of all paranasal sinuses with massive bilateral globe displacement]. / Riesen-Mukozele der Nasennebenhöhlen mit bilateraler Bulbusverlagerung.

Although of benign nature and slowly progressive, paranasal sinus mucoceles may, depending on their localization, cause a multitude of ophthalmological symptoms due to compression and displacement of adjacent tissue. Here we report the unusual case of a patient suffering from a progressively growing giant mucocele that developed years after ENT surgery and that was neglected for almost 2 decades despite massive symptoms. This case report demonstrates the importance of including mucoceles of the paranasal sinuses into the differential diagnosis of unilateral or bilateral proptosis.

The effect of etanercept on Graves' ophthalmopathy: a pilot study.

PURPOSE: To assess the effect of etanercept, an antitumour necrosis factor (anti-TNF) drug, on clinical signs in Graves' ophthalmopathy (GO). METHODS: A total of 10 consecutive patients (seven female, three male) with recent-onset, active, mildly-to-moderately severe GO were treated with subcutaneous injections of 25 mg etanercept (Enbrel) twice weekly during 12 weeks. The average age was 50 years (range: 39-59 years). The average duration of GO was 4 months (range: 2-6 months). All patients were at least 2 months euthyroid with medication. The mean pretreatment clinical activity score (CAS) was 4 (range: 3-6). RESULTS: The mean CAS prior to treatment was 4, at 6 weeks 2.6, and at 12 weeks 1.6. The mean ophthalmopathy index (OI) prior to treatment was 5.8, at 6 weeks 4.8, and at 12 weeks 4.4. Thus, after 12 weeks of treatment the mean CAS had decreased by 2.4+/-1.3 (60%), and the mean OI had decreased by 1.4+/-1.2 (24%). The main decrease of the CAS and OI was noted at 6 weeks of treatment. The difference was particularly evident on soft-tissue changes, including periocular chemosis and redness. The mean exophthalmometry values did not change. In all, 60% percent of patients reported moderate to marked improvement. In three patients, the GO flared up again after cessation of treatment. There were no serious adverse events or side effects during a mean follow-up time of 18 months. CONCLUSIONS: This study strongly suggests that etanercept may suppress the clinical signs in GO, but randomized controlled trials are needed to further evaluate the effect of anti-TNF treatment and to compare its side-effects with those of corticosteroids.

The effect of retrobulbar irradiation on exophthalmos, ductions and soft tissue signs in Graves' ophthalmopathy: a retrospective analysis of 90 cases.

PURPOSE: Retrospective analysis of the effect of retrobulbar irradiation on exophthalmos, ductions and soft tissue signs in patients with Graves' ophthalmopathy. METHODS: We analysed the charts of 111 consecutive patients who were treated with retrobulbar irradiation according to standardised intake criteria between 1992 and 1997. After exclusion of patients who underwent other treatment (with steroids or orbital decompression) shortly before or within 6 months after irradiation, and on whom insufficient data were available, 90 patients were included. For these 90 patients, we analysed the exophthalmometry, ductions, soft tissue signs and visual acuity shortly before irradiation and after 3 and 6 months, respectively. RESULTS: In the whole group, the Hertel value was on average 22 mm (SD 2.9) both before irradiation and after 3 and 6 months of follow-up. Separate analysis of data on 25 patients with bilateral exophthalmos of more than 24 mm also revealed no change in exophthalmos at follow-up. In the whole group, both abduction and elevation had improved by about 1 degree (SD 6.6 degrees; p = 0.05) after 3 months. This improvement has little clinical significance. In a subgroup of 14 patients who showed more than 10 degrees of restricted eye motility in one or more directions, both abduction and elevation had increased by about 4 degrees (SD 10 degrees; p = 0.02) at 3 and 6 months follow-up. Soft tissue signs had improved at 6 months after irradiation. We found no change in visual acuity after irradiation. CONCLUSION: Retrobulbar irradiation in Graves' ophthalmopathy does not seem to reduce exophthalmos. It probably improves eye motility in patients with severe restrictions. The late improvement in soft tissue signs may either be a late effect of irradiation or be related to the natural history of the disease.

Comparison of artificial eye amplitudes with acrylic and hydroxyapatite spherical enucleation implants.

PURPOSE: To compare artificial eye amplitudes in patients who randomly received either a hydroxyapatite or an acrylic, scleral-covered spherical implant after enucleation. DESIGN: Randomized, controlled trial. PARTICIPANTS: Thirty-four consecutive patients who underwent enucleation because of an intraocular melanoma and 21 healthy control participants from the hospital staff. METHODS: Eligible patients randomly received a hydroxyapatite or an acrylic, scleral-covered spherical orbital implant. Fourteen patients were fitted with a hydroxyapatite implant, and 16 were fitted with an acrylic implant. We measured horizontal and vertical saccadic amplitudes of both the artificial eye and the healthy eye. Measurements were performed with the magnetic search coils technique. Saccadic amplitudes of the artificial eye were compared with the healthy eye of the patient. The amplitudes of the healthy eyes were compared with saccadic amplitudes of control participants. The interval from surgery to measurements was at least 3 months in all patients. Saccadic gain (artificial eye and eye amplitude divided by target amplitude) and saccadic symmetry (artificial eye amplitude divided by healthy eye amplitude) were calculated. MAIN OUTCOME MEASURES: Saccadic gain and saccadic symmetry. RESULTS: The gain in the healthy eyes of the patients was comparable with the gain of the control eyes. Saccadic symmetry was 1.0 in control participants. In patients, it was 0.334 in horizontal saccades and 0.577 in vertical saccades. However, saccadic symmetry did not differ significantly between the acrylic group and the hydroxyapatite group (P: > 0.1 for any saccadic direction). Equivalence was detectable with a power more than 90% for horizontal saccades and more than 80% for vertical saccades. Curvilinearity was rejected for both patient groups and for all saccadic directions (P: > 0.5). CONCLUSIONS: When no motility peg is placed, acrylic and hydroxyapatite spherical implants yield comparable saccadic amplitudes of the artificial eye. Artificial eye amplitudes were markedly more restricted horizontally than vertically. In all saccadic directions, the relation between target amplitude and artificial eye amplitude was linear.

Transconjunctival orbital decompression in Graves' ophthalmopathy: lateral wall approach ab interno.

AIMS: A modified surgical technique is described to perform a one, two, or three wall orbital decompression in patients with Graves' ophthalmopathy. METHODS: The lateral wall was approached ab interno through a "swinging eyelid" approach (lateral canthotomy and lower fornix incision) and an extended periosteum incision along the inferior and lateral orbital margin. In addition, the orbital floor and medial wall were removed when indicated. To minimise the incidence of iatrogenic diplopia, the lateral and medial walls were used as the first surfaces of decompression, leaving the "medial orbital strut" intact. During 1998, this technique was used in a consecutive series of 19 patients (35 orbits) with compressive optic neuropathy (six patients), severe exposure keratopathy (one patient), or disfiguring/congestive Graves' ophthalmopathy (12 patients). RESULTS: The preoperative Hertel value (35 eyes) was on average 25 mm (range 19-31 mm). The mean proptosis reduction at 2 months after surgery was 5.5 mm (range 3-7 mm). Of the total group of 19 patients, iatrogenic diplopia occurred in two (12.5%) of 16 patients who had no preoperative diplopia or only when tired. The three other patients with continuous preoperative diplopia showed no improvement of double vision after orbital decompression, even when the ocular motility (ductions) had improved. In the total group, there was no significant change of ductions in any direction at 2 months after surgery. All six patients with recent onset compressive optic neuropathy showed improvement of visual acuity after surgery. No visual deterioration related to surgery was observed in this study. A high satisfaction score (mean 8.2 on a scale of 1 to 10) was noted following the operation. CONCLUSION: This versatile procedure is safe and efficacious, patient and cost friendly. Advantages are the low incidence of induced diplopia and periorbital hypaesthesia, the hidden and small incision, the minimal surgical trauma to the temporalis muscle, and fast patient recovery. The main disadvantage is the limited exposure of the posterior medial and lateral wall.

Orbital chondrosarcoma developing in a patient with Paget disease.

PURPOSE: To describe the radiologic, histopathologic, and cytogenetic features of an orbital chondrosarcoma developing in a patient with Paget disease. METHODS: A 64-year-old woman presented with rapidly progressive proptosis of her right eye. Computed tomographic scans, histopathologic examination, and cytogenetic analysis were performed. RESULTS: Computed tomographic scans disclosed osseous changes of the temporal and frontal bones, with areas of high density consistent with Paget disease. A soft-tissue tumor in the right lateral orbital wall was consistent with Paget sarcoma. On histology, a chondrosarcoma was diagnosed, which was confirmed by fluorescent in situ hybridization. CONCLUSION: This is a unique case of orbital chondrosarcoma developing in a patient with Paget disease.

Eyeball position in Graves orbitopathy and its significance for eyelid surgery.

The goal of this article is to investigate the effect of Graves orbitopathy and orbital decompression on the position of the eyeball, and to relate this to a straight upper eyelid contour, observed in several patients after correction of upper eyelid retraction. The positions of the pupil center and the upper and lower eyelid margin were measured in relation to a reference line through the medial canthi, on slides obtained from 120 eyelids before and after correction of upper eyelid retraction, and on similar slides obtained from 90 control eyelids. In control subjects, the distance between the reference line and the pupil center was, on average, 4.5 mm (SD 1.2 mm). In decompressed patients, the pupil center was, on average, 2.2 mm lower (SD 1.3 mm), and in nondecompressed patients it was, on average 1.0 mm lower (SD 1.2 mm). A relatively straight upper eyelid contour after otherwise satisfactory correction of upper eyelid retraction was observed in 14 eyelids of 8 patients. All cases occurred in decompressed patients with a distance between the pupil center and the reference line of 2 mm or less. No significant difference was found in the position of the lateral canthal angle between the three groups. Many patients with Graves orbitopathy show a downward shift of the pupil center in relation to a reference line through the medial canthi. This is partially caused by orbital decompression, but also by other factors discussed by the authors. If the distance between this reference line and the pupil center is 2 mm or less, otherwise satisfactory correction of upper eyelid retraction may cause visible straightening of the upper eyelid contour.

Involutional lower eyelid entropion: results of a combined approach.

BACKGROUND AND OBJECTIVE: To evaluate the effect of adding horizontal eyelid tightening and the removal of orbital fat to reinsertion of the lower eyelid retractors to correct involutional entropion. PATIENTS AND METHODS: During 6 consecutive years, 266 cases (229 patients) were treated. Of these, 240 cases (207 patients) showed horizontal laxity, in which reinsertion of the lower eyelid retractors was combined with lower eyelid tightening in the lateral canthal angle. In 60 of these cases (47 patients), prolapsing orbital fat was removed during the operation. In 26 cases (22 patients), no horizontal laxity was found. Their treatment consisted of reinserting the lower eyelid retractors without eyelid tightening. Follow-up of 28 weeks postoperatively was available in all cases. In 213 cases (178 patients), follow-up of 5 months or longer (range 5 to 80 months, average 42 months) was available. RESULTS: The most common complication of surgery was persistent ectropion, which occurred in 12 cases (5.6%). It occurred significantly more often after reinsertion without horizontal eyelid tightening than after combined reinsertion and horizontal tightening (P = .04). Adding the excision of orbital fat to the latter procedure did not significantly influence the results. Transient ectropion also occurred significantly more often after retractor reinsertion alone than after combined retractor reinsertion and horizontal tightening (P = .01). The entropion recurred in 9 cases (3.3%), 5 of which within 24 months (2.4%). The authors found no difference in recurrence rate between the three groups. A disadvantage of eyelid tightening is tenderness, which was reported by 42 (29%) of the patients. In 9 patients this had persisted longer than 4 months. CONCLUSION: Horizontal eyelid laxity is common in involutional entropion. Tightening of the lower eyelid in the lateral canthus, added to reinsertion of the lower eyelid retractors, significantly lowers the incidence of surgical overcorrection, but has no effect on the recurrence rate. A disadvantage of eyelid tightening in the lateral canthus is that it may lead to mostly transient eyelid tenderness.

[111In-DTPA-D-Phe1] octreotide scintigraphy in thyroidal and orbital Graves' disease: a parameter for disease activity?

Visualization of malignant lymphomas and granulomatous disease is possible by [111In-DTPA-D-Phe1]octreotide scintigraphy through binding of the radioligand to somatostatin receptors on activated leukocytes. Because thyroidal and orbital tissues are infiltrated by activated leukocytes in Graves' disease, a cross-sectional study to visualize disease activity with [111In-DTPA-D-Phe1]octreotide scintigraphy was performed. A correlation between thyroidal [111In-DTPA-D-Phe1]octreotide accumulation and free T4 (disease expression) and thyroid binding-inhibiting immunoglobulins (disease activity) is present in untreated hyperthyroid Graves' disease. There is also a correlation between orbital [111In-DTPA-D-Phe1]octreotide uptake and the clinical activity score (disease activity) and total eye score (disease expression), respectively, in Graves' orbitopathy. Visualization of thyroidal and orbital Graves' disease is feasible, but further investigation is necessary to establish the role of [111In-DTPA-D-Phe1]octreotide scintigraphy in representing disease activity and expression and in predicting therapeutical outcome.