Technique for modified transantral orbital decompression for improved cosmesis in stable thyroid eye disease.

Functional and aesthetic rehabilitation of exophthalmos in stable thyroid eye disease (TED) can be achieved with a variety of surgical approaches. This article illustrates modifications of the classic transantral technique to provide a graded orbital decompression and achieve improved cosmesis. A retrospective chart review was performed of stable TED patients who elected to undergo the modified transantral decompression; illustrative cases are described. This modified transantral orbital decompression allows for graded orbital decompression surgery, adding to the range of treatment options for stable TED patients.

Angiosarcoma metastatic to the orbit.

Angiosarcoma is a rare malignant endothelial cell tumor. Few reports of primary orbital angiosarcoma exist in the literature. A 46-year-old woman had a 3-month history of progressive diplopia and right-sided exophthalmos. Magnetic resonance imaging showed a right intraconal mass, consistent with a cavernous hemangioma. Ultrasound examination showed a isolated mass with moderate vascularity, consistent with a metastatic lesion. Subtotal excision through a lateral orbitotomy was performed. Tissue was stained with hematoxylineosin, periodic acid-Schiff, and immunohistochemical stains for factor-VIII-related antigen and Ulex europaeus agglutinin I lectin. Lateral orbitotomy biopsy specimens showed an angiosarcoma, similar to a primary breast angiosarcoma that had been resected 2 years previously. The patient initially underwent orbital exenteration for her only known metastasis. Despite a multidisciplinary and aggressive approach to this tumor, the tumor recurred, and the patient died.

Periocular granuloma annulare, nodular type. Occurrence in late middle age.

We describe the two oldest individuals with nodular granuloma annulare (pseudorheumatoid nodules) in the ophthalmologic literature and propose a unified classification scheme that recognizes pseudorheumatoid nodules to be granuloma annulare, nodular type. All lesions in both cases revealed so-called necrobiotic granulomas, characterized by an acellular central area containing mucin (hyaluronic acid) surrounded by palisading histiocytes (macrophages), diagnostic of granuloma annulare. These features are identical to those reported in the ophthalmologic and older general pathology literature as pseudorheumatoid nodules and the contemporary general and dermatologic pathology literature as granuloma annulare. We believe the diagnosis of nodular granuloma annulare should be employed for necrobiotic lesions displaying distinctive clinicopathologic features to unite the ophthalmologic, general, and dermatologic pathology literature. Granuloma annulare, nodular type, must also be considered in the differential diagnosis of ocular and periocular lesions at any age.

Inverted papillomas that invade the orbit.

We describe 10 patients with inverted papillomas (IPs), uncommon endophytic epithelial tumors that arose in the nose, paranasal sinuses, and lacrimal sac, that invaded the orbit; review the world literature on IP; and discuss treatment options. Patients ranged in age from 49 to 72 years (mean age, 62 years; median age, 66 years). Six patients were men and four were women. Presenting symptoms and signs included a medial canthal mass (n = 5), epiphora/lacrimal drainage obstruction (n = 3), inability to wear eyeglasses (n = 2), diplopia (n = 1), and painful dentures (n = 1). Histopathologic examination was performed in each patient and revealed all patients to have areas with malignant transformation: six patients with IPs that contained areas of squamous cell carcinoma and four with areas of transitional cell carcinoma in the tumor within the orbit. Eight of the patients with IPs had a recurrence after initial resection. In two patients, the IPs were completely excised and did not recur; yet, follow-up was short. Eight patients required orbital exenteration for local control of disease. Nevertheless, local spread of tumor through bone to brain occurred in three patients with orbital involvement. Indeed, IPs that invade the orbit have a high incidence of malignancy and are locally aggressive tumors. Treatment is difficult, and the recurrence rate is high. Early, wide excision of this aggressive tumor provides the best chance of cure.

Golf-related ocular injuries.

PURPOSE: To examine patient outcomes from golf-related ocular injuries. METHODS: Retrospective case review of patients treated at the University of Michigan during the six-year period from November 1989 to October 1995. RESULTS: Of nine injuries treated in the six-year period, six of the patients with ocular injuries from golfing required enucleation. Seven of the injuries were from golf balls, and remaining two were injuries from golf clubs. CONCLUSION: Although unpredictable and difficult to avoid, proper golf etiquette and safety may diminish the incidence of golf-related ocular injures.

Migration of intraocular silicone oil into the subconjunctival space and orbit through an Ahmed glaucoma valve.

PURPOSE: To report a patient with intraocular silicone oil migration into the subconjunctival space and orbit through an Ahmed glaucoma valve implant. METHODS: Observational case report. A 29-year-old female with diabetes mellitus and proliferative diabetic retinopathy underwent three left eye pars plana vitrectomies and ultimately intraocular silicone oil placement for tractional retinal detachment. Subsequently, she developed neovascular glaucoma and underwent an inferotemporal Ahmed glaucoma tube implant, left eye. RESULTS: Intraocular silicone oil migrated through the Ahmed glaucoma valve into the subconjunctival space and orbit. Left eye evisceration with silicone oil removal was performed for a blind painful left eye and improvement of appearance. CONCLUSION: Silicone oil migration through an Ahmed valve may be observed after retinal detachment repair with intraocular silicone oil. An Ahmed valve may be contraindicated in eyes of patients with intraocular silicone oil.

Wilson's disease: presymptomatic patients and Kayser-Fleischer rings.

PURPOSE: We evaluated patients with Wilson's disease to determine (1) whether presymptomatic patients who have Kayser-Fleischer (K F) rings demonstrate a more significant alteration of copper metabolism than those who do not have K F rings, and (2) whether presymptomatic patients have smaller K F rings than symptomatic Wilson's disease patients. METHODS: Thirty-two patients with presymptomatic Wilson's disease were retrospectively analyzed. Sixteen of these had received no prior anti-copper therapy and underwent testing for baseline copper metabolism (24-hour urine copper, liver copper, and plasma ceruloplasmin). Quantitative measurements of K F rings were made for the group of untreated presymptomatic patients and a control group of symptomatic Wilson's disease patients. RESULTS: We hypothesized that the 24-hour urine copper, in particular, would correlate with the presence of a K F ring. However, no significant difference was found between any of the baseline copper variables for presymptomatic patients who had K F rings compared to those who did not. K F rings of presymptomatic patients were found to be significantly smaller than K F rings of patients with symptomatic Wilson's disease (p < 0.05). CONCLUSIONS: While this study does not show any relationship between urinary copper excretion and the presence of K F rings, it suggests that the larger K F ring size correlates with Wilson's disease severity.

Orbital fibroblast chemokine modulation: effects of dexamethasone and cyclosporin A.

AIM: Orbital inflammation is common, but the mechanisms underlying leucocytic infiltration of orbital tissue are poorly understood. Human orbital fibroblasts (OF) express chemokines, interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1), when exposed to proinflammatory cytokines. The effect of dexamethasone (DEX) and cyclosporin A (CSA) on OF IL-8 and MCP-1 were examined. METHODS: Cultured human OF were incubated with recombinant interleukin 1 beta (rIL-1 beta; 0.2, 2.0, 20 ng/ml) alone or incubated with rIL-1 beta and DEX (10(-8), 10(-7), 10(-6) M) or CSA (3, 30, 300 ng/ml) for 24 hours. ELISA and northern blot analyses were performed to determine OF IL-8 and MCP-1 protein secretion and mRNA expression, respectively. RESULTS: OF lacked constitutive IL-8 or MCP-1 expression, but secreted significant amounts of these chemokines and expressed substantial steady state mRNA for both chemokines upon rIL-1 beta stimulation. DEX caused dose dependent inhibition of IL-1 induced IL-8 (p < 0.001) and MCP-1 (p < 0.05) secretion and mRNA expression at all concentrations of rIL-1 beta. CSA enhanced IL-1 induced OF IL-8 (p < 0.001) and suppressed rIL-1 beta induced OF MCP-1 (p < 0.05) secretion when lower doses of rIL-1 beta were used. These effects on secreted chemokines at different concentrations of rIL-1 beta and immunomodulating agents were corroborated by steady state OF IL-8 and MCP-1 mRNA expression. CONCLUSIONS: DEX is a potent inhibitor of OF IL-8 and MCP-1. In contrast, CSA enhances IL-1 induced OF IL-8 and suppresses OF MCP-1. These observations may explain the relative lack of CSA effectiveness in human orbital diseases that respond to corticosteroids.

Regression of Kayser-Fleischer rings during oral zinc therapy: correlation with systemic manifestations of Wilson's disease.

Fourteen patients presenting with neuropsychiatric manifestations of Wilson's disease were treated with oral tetrathiomolybdate (TM) for 8 weeks followed by oral zinc (Zn) maintenance therapy. The patients were evaluated prospectively at baseline and at yearly intervals for up to 5 years by slit-lamp biomicroscopy and photography, quantitative neurologic and speech pathology examinations, 24-h urine copper collection, and a quantitative scoring of magnetic resonance imaging (MRI) of the brain. Kayser-Fleischer (KF) ring size decreased significantly during the 5-year study period (p < 0.0001). Although results of neurologic examination, speech pathology examination, and 24-h urine copper level analysis in symptomatic Wilson's disease patients improved during the study period, KF ring regression did not correlate with the improvement in these clinical parameters (p > 0.05). However, there was a correlation between MRI scores and KF ring regression (p = 0.02). Anticopper therapy with TM followed by zinc maintenance therapy is a safe and effective treatment for patients with neurologically symptomatic Wilson's disease. This treatment leads to reduction in KF ring size; however, KF ring reduction is not a good predictor of clinical improvement for patients with neuropsychiatric manifestations of Wilson's disease.

Lacrimal canalicular diverticulum: a cause of epiphora and discharge.

PURPOSE: To report a rare cause of epiphora and chronic discharge: lacrimal canalicular diverticulum. METHODS: Case report. RESULTS: A distended left lower eyelid canaliculus was associated with chronic epiphora and discharge. A suspected canalicular diverticulum was noted on dacryocystogram. CONCLUSIONS: Canalicular diverticula should be considered in the differential diagnosis in patients that present with epiphora and discharge with a patent nasolacrimal system. Dacryocystography is diagnostic.

Upper blepharoplasty: a novel approach to improving progressive myopathic blepharoptosis.

OBJECTIVE: To describe the results of upper blepharoplasty for the treatment of progressive myopathic upper eyelid blepharoptosis. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Six consecutive patients treated bilaterally. INTERVENTION: Upper blepharoplasty in 6 patients (12 eyelids) with progressive myopathic ptosis. MAIN OUTCOME MEASURES: Subjective visual improvement, ocular comfort, preoperative and postoperative margin reflex distances, lagophthalmos, and degree of corneal keratopathy at last follow-up date. RESULTS: All patients had subjective visual improvement and denied ocular discomfort. Upper eyelid ptosis, measured by margin reflex distances, was improved. No worsening of lagophthalmos or corneal keratopathy was noted. CONCLUSIONS: Upper blepharoplasty may be an excellent alternative for ptosis treatment in patients with progressive myopathies. Improvement in ptosis, margin reflex distance, without concomitant lagophthalmos, and corneal keratopathy can be achieved.

Glabellar rhytids in thyroid-associated orbitopathy.

PURPOSE: To correlate the presence and severity of glabellar rhytids with disease severity in patients with thyroid-associated orbitopathy (TAO). METHODS: Retrospective, noncomparative medical record review of 113 consecutive new patient visits with the clinical diagnosis of TAO. Ocular examination features studied included assessment of visual acuity, optic nerve appearance and function, proptosis, strabismus, eyelid position, and exposure keratopathy. These features were correlated with graded clinical photographs evaluating rhytid severity using the Fisher exact text. RESULTS: Eighty of 97 patients included in the study (82.5%) had glabellar rhytids. Eyelid retraction was present in 95 of the 97 patients (98%). Patients with diplopia had more severe rhytids (p < 0.05). Patients with at least three abnormal clinical findings tended to have more severe rhytids. CONCLUSIONS: Glabellar rhytids are a common finding in patients with TAO, and tend to be present in patients with diplopia and multiple stigmata of the disease.

Rhabdomyomatous mesenchymal hamartoma of the eyelid: report of a case and literature review.

PURPOSE: To report a rare case of rhabdomyomatous mesenchymal hamartoma and to compare its features with those cases previously reported. DESIGN: Interventional case report and literature review. INTERVENTION: Complete ophthalmologic and systemic examinations followed by excisional biopsy and histopathologic examination. MAIN OUTCOME MEASURES: Clinical examination features and histopathologic findings. RESULTS: A 6-month-old Latino male presented with a congenital, elevated, smooth, flesh-colored right lower eyelid lesion. An ipsilateral right limbal dermoid and an upper eyelid coloboma were also present. Excisional biopsy of the eyelid lesion revealed randomly oriented mature striated muscle tissue with associated adipose tissue, blood vessels, pilosebaceous units, and peripheral nerves, findings consistent with rhabdomyomatous mesenchymal hamartoma. Of the 24 reported cases (including the current case), eight had associated congenital anomalies. CONCLUSIONS: Although rhabdomyomatous mesenchymal hamartomas are rare and benign, they may be associated with other congenital anomalies and anomaly syndromes. As a result, we recommend systemic evaluation of patients diagnosed with this entity.

Anterior ischemic optic neuropathy following neck dissection.

BACKGROUND: Ischemic optic neuropathy (ION) is a rare but devastating complication of surgery. It has traditionally been associated with intraoperative hypotension in patients with underlying arteriosclerosis. METHODS: We present a case of ION following bilateral neck dissections in which there was minimal intraoperative hypotension and preservation of both internal jugular veins. The potential etiology of this disease is discussed along with a review of the literature. RESULTS: Five cases of ION following neck dissection have been documented. This complication is associated with the combination of intraoperative hypotension and anemia in the setting of prolonged bilateral neck dissection. Treatment is supportive, and final visual prognosis is variable. CONCLUSIONS: Ischemic optic neuropathy following neck dissection is best avoided by intraoperative blood pressure and anemia management. When it does occur, supportive therapy must be given. Final visual outcome is variable.

Orbital fibroblast interleukin-6 gene expression and immunomodulation.

PURPOSE: Orbital inflammation is common, but the mechanisms underlying leukocytic infiltration of orbital tissue are poorly understood. We studied human orbital fibroblast (OF) interleukin-6 (IL-6) gene expression in response to proinflammatory stimuli and the effects of dexamethasone (DEX) and cyclosporin A (CSA) on cytokine-stimulated OF IL-6 gene expression. METHODS: Cultured OFs were left unstimulated or incubated with varying concentrations of lipopolysaccharide (LPS), or recombinant (r) interleukin-1-beta (rIL-1beta), tumor necrosis factor-alpha (rTNF-alpha), or interferon-gamma (rIFN-gamma) for 2, 4, 8, or 24 hours. OFs were also incubated with rIL-1beta (0.2, 2.0, 20 ng/ml) alone or in the presence of DEX (10(-8), 10(-7), 10(-6) mol/l) or CSA (3, 30, 300 ng/ml) for 8 hours to determine the effects of these immunomodulating drugs on IL-6 expression. Northern blot analyses were performed to determine OF IL-6 mRNA expression in response to varying concentrations of these agents. Experiments were repeated four times on different cell lines. RESULTS: OFs lacked constitutive IL-6 gene expression. Substantial time- and dose-dependent increases in steady-state IL-6 mRNA expression occurred by 4 hours of LPS or cytokine stimulation (rIL-1beta>rTNF-alpha(>LPS>rIFN-gamma), peaked at 8 hours, and were maintained at 24 hours. DEX caused dose-dependent inhibition of IL-1-induced IL-6 mRNA expression, while CSA potentiated IL-1-induced OF IL-6 mRNA expression. CONCLUSIONS: OFs express IL-6 mRNA in response to proinflammatory stimuli. DEX is a potent inhibitor of OF IL-6 mRNA while CSA increases IL-1-induced OF IL-6 gene expression. These observations may in part explain the lack of CSA effectiveness in human orbital diseases that respond to corticosteroids.

Interleukin-8 and monocyte chemotactic protein-1 gene expression and protein production by human orbital fibroblasts.

Orbital inflammation is common, but the mechanisms underlying leukocytic infiltration of orbital tissue are poorly understood. We studied resident human orbital fibroblasts (OF) interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) mRNA expression and protein secretion in response to lipopolysaccharide (LPS) or recombinant human cytokines that are present during inflammation. Third-passaged cultured human OF were left unstimulated or incubated with varying concentrations of LPS, recombinant interleukin-1-beta (rIL-1 beta), recombinant tumor necrosis factor-alpha (rTNF-alpha), or recombinant interferon-gamma (rIFN-gamma) for 2, 4, 8, or 24 h. Northern blot analysis and ELISA were performed to determine OFIL-8 and MCP-1 mRNA expression and protein secretion, respectively. Experiments were performed in triplicate and repeated four times on different cell lines. OF lacked constitutive IL-8 or MCP-1 gene expression, but produced substantial dose-dependent increases in steady-state IL-8 and MCP-1 mRNA expression by 2 h of LPS or cytokine stimulation (rIL-1 beta > fTNF-alpha > LPS > rIFN-gamma), maintained at 24 h ELISA for IL-8 and MCP-1 proteins showed significant time- and dose-dependent OF secretion after exposure to recombinant cytokine or LPS (rIL-1 beta > rTNF-alpha > LPS), measured after 4 h of exposure (p < 0.01). This increased in the media over the next 20 h. rIFN-gamma was a potent stimulant of OF MCP-1, significant by 2 h (p < 0.05), but only a weak stimulant of IL-8 at 24 h. OF secreted IL-8 and MCP-1 in response to LPS and proinflammatory cytokines, indicating that these resident cells within the orbit have the capacity to actively participate in the initiation and propagation of orbital inflammation. Strategies aimed at modulating local mediators may be helpful in the management of orbital inflammatory disease.

Cell-associated human retinal pigment epithelium interleukin-8 and monocyte chemotactic protein-1: immunochemical and in-situ hybridization analyses.

Human retinal pigment epithelial (RPE) cells secrete chemokines, interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) in response to pro-inflammatory cytokines. In this study we (1) examined the efficiency of human RPE IL-8 and MCP-1 secretion, (2) determined the amount of neutrophil and monocyte chemotactic activity in human RPE cell conditioned media and cell extracts that is attributable to IL-8 and MCP-1, respectively, and (3) assessed the sensitivity of immunohistochemistry and in situ hybridization for detecting chemokine production by cytokine-stimulated human RPE cells. Conditioned media and extracts from human RPE cells stimulated with various physiologic concentrations of interleukin-1 beta (IL-1 beta) (0.2-20 ng ml-1), tumor necrosis factor (TNF-alpha) (0.2-20 ng ml-1) or interferon-gamma (IFN-gamma) (10-1000 U ml-1) were examined to compare secreted and cell associated levels of IL-8 and MCP-1 at various time points up to 24 hr. ELISA demonstrated that IL-8 and MCP-1 are both efficiently secreted by pro-inflammatory cytokine treated human RPE cells. Substantial dose- and time-dependent RPE secretion of IL-8 was observed following stimulation with IL-1 beta or TNF-alpha, but cell associated IL-8 was detectable only after high dose (20 ng ml-1) IL-1 beta stimulation and comprised less than 1% of the total IL-8 induced. Dose- and time-dependent RPE cell MCP-1 secretion was also observed following IL-1 beta > TNF-alpha > IFN-gamma stimulation, with an average of 4% of the total MCP-1 retained within RPE. Bioassays demonstrated neutrophil and monocyte chemotactic activity in conditioned media from stimulated RPE cells, but not in human RPE cell extracts. Inhibition of conditioned media-induced chemotaxis by specific anti-IL-8 or anti-MCP-1 antibodies demonstrated that IL-8 and MCP-1 were responsible for the majority of HRPE-derived neutrophil (> 60%) and monocyte (53-57%) chemotactic activity, respectively. Using in situ hybridization IL-8 mRNA was readily detected within IL-1 beta > TNF-alpha stimulated RPE cells and MCP-1 mRNA easily visualized within IL-1 beta > TNF-alpha > or IFN-gamma stimulated cells. Immunohistochemistry to detect IL-8 was positive only in RPE cells exposed to high dose IL-1 beta (20 ng ml-1) for 8 or 24 hr and was weak. Immunohistochemical staining for MCP-1 in RPE cells was more intense and was visualized within RPE cells stimulated with IL-beta, TNF-alpha, or IFN-gamma. This study demonstrates that: (1) RPE cells efficiently secrete IL-8 and MCP-1 upon stimulation with pro-inflammatory cytokines; (2) secreted IL-8 and MCP-1 account for the majority of human RPE neutrophil and monocyte chemotactic activity; (3) in situ hybridization readily detects IL-8 and MCP-1 mRNA in cytokine stimulated RPE cells; and (4) immunohistochemistry demonstrates cell-associated MCP-1 in cytokine stimulated RPE cells, but only minimal cell-associated IL-8.

Nucleolar organizer regions in optic gliomas.

The biological nature of optic gliomas is controversial, with some considering them benign hamartomatous lesions, and others believing them to be true neoplasms. We evaluated the use of colloid silver impregnation of nucleolar organizer region-associated proteins (AgNORs) in making this distinction. Thirty-one optic gliomas, 14 optic nerve meningiomas, and a single case of giant cell glioblastoma multiforme (monstrocellular glioma) of the optic chiasm were stained for AgNORs and counted in a masked fashion. The optic gliomas contained 2.01 +/- 0.09 AgNORs per nucleus, similar to that of optic nerve meningiomas (2.15 +/- 0.15) and our previously reported counts for diffuse fibrillary astrocytoma (2.22 +/- 0.10), and significantly more than that of reactive astrocytosis (1.18 +/- 0.02). Six of the seven optic gliomas examined had compound AgNORs, a feature associated with malignancy in other tumour types. AgNOR counts did not correlate with clinical features, including those seen during the post-operation course. These data suggest that optic gliomas may be true neoplasms, and not benign hamartomas.