Histopathology of brow fat in thyroid-associated orbitopathy.

PURPOSE: We propose that brow enlargement seen in patients with thyroid-associated orbitopathy (TAO) occurs secondary to the autoimmune process in Graves disease and that the changes in brow fat are histologically identical to those seen in orbital fat. METHODS: With informed consent, brow and orbital fat was obtained from patients with TAO and from patients with no significant past medical history undergoing orbital decompression, blepharoplasty, and/or brow fat removal. Histologic examination was performed on the orbital and brow fat. RESULTS: Fat histologies obtained from patients with TAO and those without known systemic disease were compared. Specimens from patients with TAO showed an increase of fibrosis and fibrous septae. Furthermore, certain biologic markers, including insulin-like growth factor 1 receptor ß (IGF-1Rß) and thyroid-stimulating hormone receptor (TSHR), were increased in the fat obtained from patients with TAO. This was identical in both the brow and the orbital fat. Fat from patients with no significant past medical history showed normal fat histology, absence of fibrous septae, and decreased marker expression. CONCLUSION: Graves disease is a systemic autoimmune disease that affects patients in a variety of ways. In addition to the orbital changes seen in these patients, we have observed an increase in the brow fat compartment. We are intrigued to find that the histologic changes are identical in both the orbital and the brow fat of patients with TAO. The increased IGF-1Rß and TSHR expression in both the brow and the orbital fat further support their role as putative markers in patients with Graves disease.

Nonsurgical management of upper eyelid margin asymmetry using hyaluronic acid gel filler.

PURPOSE: To evaluate the efficacy of hyaluronic acid gel fillers as a nonsurgical alternative for the management of upper eyelid margin asymmetry in cases of relative retraction. METHODS: This is a retrospective study of 8 patients with upper eyelid margin asymmetry relating to relative upper eyelid retraction treated with hyaluronic acid gel injection to affect upper eyelid lowering. Digital photographs were used to quantitatively assess outcomes by comparing pretreatment and posttreatment differences between marginal reflex distance (MRD1) in the right and left eyelids. Image J was used for photographic analysis, and Student paired t test was performed. RESULTS: Eight patients (2 male; mean age, 50.9 years; range, 30-69 years) were injected with hylauronic acid gel in the upper eyelid. The etiology of upper eyelid margin asymmetry included Graves eyelid retraction (n = 3), asymmetry following reconstructive surgery (n = 1) and aesthetic surgery (n = 1), contralateral Horner syndrome (n = 1), Bell palsy (n = 1), and contralateral involutional ptosis (n = 1). The average volume injected in the upper eyelid was 0.2 ml (range, 0.1-0.4 ml). One of 8 patients was injected bilaterally. Average follow-up was 5.7 months (range, 2-12 months). Two of 8 patients requested repeat injection within a 6-month period for undercorrection. No overcorrections were noted, and no patient requested reversal with hyaluronidase. There was a statistically significant improvement in symmetry with mean pretreatment MRD1 difference of 1.53 mm (range, 0.78-3.36 mm) and mean posttreatment MRD1 difference of 0.70 mm (range, 0.02-2.03 mm), p = 0.007. At 4 to 8 months' follow-up, 8 of 8 demonstrated persistent improvement in asymmetry with statistically significant reduction in MRD1 difference when compared with pretreatment with average follow-up MRD1 difference of 0.74 mm (range, 0.11-1.65 mm), p = 0.018. CONCLUSION: This pilot study suggests that upper eyelid injection with hylauronic acid gel filler may be an effective nonsurgical alternative to improve upper eyelid margin asymmetry in cases of relative upper eyelid retraction.

A case of acute reversible Charles Bonnet syndrome following postsurgical unilateral eye patch placement.

A fully alert 70-year-old male with no significant medical or psychiatric history presented for surgical follow-up after uncomplicated right lower eyelid cicatricial ectropion surgery with postoperative unilateral, eye patch placement complaining of visual hallucinations. Preoperative unaided visual acuity was 20/20 in each eye. The patient described simple, nonformed and complex, formed images that were both static and animated. The images included crystal-like formations that appeared to bubble, green leaves against a vivid magenta backdrop, and an isolated hallucination of a lifelike plant with trembling leaves. These hallucinations began 2 days postoperatively and persisted 2 days following eye patch removal. The patient perceived the hallucinations multiple times a day over the 7-day period, without a stereotyped pattern. The images occurred when the eyes were open and ceased when they were closed. They were prompted by looking at a blank wall or white surface. The patient consistently recognized these images as unreal. They typically persisted for 1 to 2 minutes and could be extinguished by looking away. There were no associated auditory hallucinations, psychosis, or delirium and no history of visual, cognitive, or neurological deficit. The patient denied the use of hallucinogenic medications, including analgesics, or the initiation of any new medications. To the authors' knowledge, this is the first reported case of acute reversible CBS following unilateral eye patch placement. CBS may be a frightening postsurgical consequence of eye patch placement. It is important that the ophthalmic surgeon be aware of the potential for development of CBS and offer appropriate referral and reassurance should it occur.

Rare dural arteriovenous fistula of the lesser sphenoid wing sinus.

A fistula of the lesser sphenoid wing sinus is a rare dural arteriovenous fistula resulting from a connection between the middle meningeal artery and recipient vein in the sinus of the lesser sphenoid wing. In this report, MRI/magnetic resonance angiography of a 54-year-old man who presented with sudden-onset glaucoma and proptosis revealed a fistula in this anatomic location. Drainage patterns here may account for the absence of serious complications and optimistic prognosis following embolization. Care in diagnosis is required to avoid superfluous procedures, because classic signs of the more common carotid-cavernous fistula are absent.

Development of criteria for evaluating clinical response in thyroid eye disease using a modified Delphi technique.

OBJECTIVE: To identify components of a provisional clinical response index for thyroid eye disease using a modified Delphi technique. METHODS: The International Thyroid Eye Disease Society conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical trials in thyroid eye disease. The steering committee discussed the results in a face-to-face meeting (nominal group technique) and evaluated each criterion with respect to its feasibility, reliability, redundancy, and validity. Redundant measures were consolidated or excluded. RESULTS: Criteria were parsed into 11 domains for the Delphi surveys. Eighty-four respondents participated in the Delphi 1 survey, providing 220 unique items. Ninety-two members (100% of the respondents from Delphi 1 plus 8 new participants) responded in Delphi 2 and rated the same 220 items. Sixty-four members (76% of participants) rated 153 criteria in Delphi 3 (67 criteria were excluded because of redundancy). Criteria with a mean greater than 6 (1 = least appropriate to 9 = most appropriate) were further evaluated by the nominal group technique and provisional core measures were chosen. CONCLUSIONS: Using a Delphi exercise, we developed provisional core measures for assessing disease activity and severity in clinical trials of therapies for thyroid eye disease. These measures will be iteratively refined for use in multicenter clinical trials.

Biologic therapeutics in thyroid-associated ophthalmopathy: translating disease mechanism into therapy.

Graves' disease (GD) is a systemic autoimmune disease which targets the thyroid, orbit, and skin. Thyroid-associated ophthalmopathy (TAO) refers specifically to the orbital and periorbital manifestations of GD. Several important concepts have emerged from our enhanced understanding of the molecular mechanisms of the disease. Considerable debate remains concerning the specific identity and roles of inflammatory T-cell subsets, soluble and contact-mediated signalling, and autoantigens driving TAO. However B and T lymphocytes appear central in the process through production of disease mediators including activating autoantibodies to the thyrotropin receptor and insulin-like growth factor-1 receptor; cytokines including IL-1beta, IL-6, and IL-16; and chemokines including RANTES. Many of these molecules appear central to the inflammation, accumulation of extracellular matrix macromolecules, and fibrosis in the disease. Novel therapeutics targeting other autoimmune diseases may provide an opportunity for disrupting disease pathogenesis. It is imperative that agents targeting B-and T-cell functions be further evaluated in the treatment of aggressive forms of TAO utilizing multicenter clinical trials that allow adequate statistical power and sample size.

Cytokines, Graves' disease, and thyroid-associated ophthalmopathy.

Graves' disease, an autoimmune process associated with thyroid dysfunction, can also manifest as remodeling of orbital connective tissue. Affected tissues exhibit immune responses that appear to be orchestrated by resident cells and those recruited from the bone marrow through their expression and release of cytokines and surface display of cytokine receptors. Cytokines are small molecules produced by many types of cells, including those of the "professional" immune system. Aberrant cytokine expression appears to play an important role in the pathogenesis of many human diseases, including thyroid autoimmunity. The skewed pattern of cytokine expression in the thyroid, including the T helper cell bias, may condition the response to apoptotic signals and determine the characteristics of an autoimmune reaction. Furthermore, chemoattractant cytokines, including IL16, RANTES, and CXCL10, elaborated by resident cells in the thyroid and orbit may provoke mononuclear cell infiltration. Other cytokines may drive cell activation and tissue remodeling. Thus cytokines and the signaling pathways they activate represent attractive therapeutic targets. Interruption of these might alter the natural course of Graves' disease and its orbital manifestations.