Journal of Neuro-Ophthalmology, June 1995, Volume 15, Issue 2

Extreme Eyelid Swelling as an Unusual Presentation of Dysthyroid Orbitopathy

We describe seven cases of dysthyroid orbitopathy initially seen as severe periocular lid swelling. Imaging techniques typically demonstrate normal extraocular muscles, although moderate muscle enlargement may occur. Patients do not respond to steroids, radiation therapy, antihistamines, or diuretics. We believe this clinical picture represents a unique population of dysthyroid orbitopathy patients who are best managed by long-term observation followed by cosmetic surgery.

Journal of Neuro- Ophthalmology 15( 2): 84- 89, 1995. © 1995 Raven Press, Ltd., New York Extreme Eyelid Swelling as an Unusual Presentation of Dysthyroid Orbitopathy Carl E. Rosen, M. D., and John S. Kennerdell M. D. We describe seven cases of dysthyroid orbitopathy ini­tially seen as severe periocular lid swelling. Imaging techniques typically demonstrate normal extraocular muscles, although moderate muscle enlargement may occur. Patients do not respond to steroids, radiation therapy, antihistamines, or diuretics. We believe this clinical picture represents a unique population of dys­thyroid orbitopathy patients who are best managed by long- term observation followed by cosmetic surgery. Key Words: Dysthyroid orbitopathy- Eyelid Swelling- Blepharoplasty. Manuscript received October 18, 1994. From the Department of Ophthalmology, Allegheny Oph­thalmic and Orbital Associates, Allegheny General Hospital, Pittsburgh, Pennsylvania, U. S. A. Address correspondence and reprint requests to Dr. C. E. Rosen, Oculoplastics, Orbital Surgery and Neuro- Oph-thalmology, Ophthalmic Associates, 542 West Second Avenue, Anchorage, AK, 99501, U. S. A. It is estimated that clinically detectable ocular signs are present in at least 40% of patients with dysthyroid orbitopathy ( DO) ( 1). Dysthyroid orbi­topathy may appear at any time during the course of dysthyroidism ( 2,3) but seems to manifest within 18 months of clinically detectable thyroid dysfunction. Lid retraction is the most frequent ophthalmic abnormality associated with DO. Other clues to the diagnosis are previous treat­ment for hyperthyroidism or loss of weight with­out loss of appetite, palpitation, tremor, difficulty sleeping, and excessive perspiration. Even in pa­tients who have euthyroid DO without a previous or present history of thyroid dysfunction can have signs such as lid edema, conjunctival chemosis, injection over the horizontal rectus muscles, and exophthalmos. There are a number of practical clues with regard to the early diagnosis of DO secondary to the ef­fects of pressure and inflammation within the or­bit. The patient often has intermittent lid swelling that is usually worse in the morning after lying flat all night, causing many physicians first to consider allergic disease. Among the differential diagnosis of eyelid swell­ing are orbital fat herniation from aging, conjunc­tivitis, preseptal or orbital cellulitis, allergic reac­tions, chalazion, and anterior orbital disease pro­cesses such as nonspecific orbital inflammation ( 4), infiltrative or infectious processes, vascular malfor­mations, or orbital metastases. Less common causes are related to cardiac disease, renal disease, angioneurotic edema, dacryoadenitis, hypothy­roidism, and superior vena cava syndrome. We present seven DO patients with extreme pe­riocular lid swelling as their predominant manifes­tation. This unusual finding makes the diagnosis difficult and can lead to an unnecessary work- up and treatment. This subset of patients does not respond to the treatments beneficial to the broader group of DO patients. 84 EYELID SWELLING IN DYSTHYROID ORBITOPATHY 85 CASE REPORTS Case 1 A 62- year- old white man had a 5- month history of severe bilateral periorbital swelling, global ex­traocular motility restriction, and chemosis thought to be consistent with acute congestive DO. He was allergic to penicillin and was being treated with an oral antihistamine, naphazoline ( Vasocon) eyedrops, and 5 mg of prednisone daily. Best corrected visual acuity was 20/ 20 in both eyes ( OU). No afferent pupillary defect was noted. Ishihara color plates were 12/ 12 OU. Applanation tonometry was right eye ( RE) 24 mm Hg and left eye ( LE) 18 mm Hg that increased on upgaze to RE 30 mm Hg and LE 24 mm Hg. Goldmann visual fields were full OU, and the funduscopic examina­tion revealed bilateral healthy optic nerve heads, maculae, and retinal periphery. An eyelid skin bi­opsy performed before our examination yielded some neutrophils and an occasional eosinophil, re­sulting in the diagnosis of angioedema. At the time of our initial examination, there was asymmetric marked right inferior periorbital swelling ( Fig. 1A). A 100- mg prednisone taper was begun and pro­vided no relief over a 2- month period. Subse­quently, 2,000 cGy of radiation therapy to both or­bits was given. Computed tomography ( CT) scan­ning of the orbits revealed moderate asymmetrical medial rectus muscle enlargement with marked preseptal swelling ( Fig. IB). Further medical eval­uations resulted in diagnoses of hyperthyroidism treated with methimazole ( Tapazole) and essential hypertension treated with propranolol ( Inderal). He has been followed- up for 3 years with slow resolution of his periorbital swelling to a stage in which bilateral marked periorbital swelling of both the upper and lower lids is evident without ten­derness, pruritis, or erythema. No further changes have been noted for 1 year ( Fig. 1C); consequently, cosmetic surgery primarily for skin removal has been offered. Case 2 A 47- year- old white woman had marked bilat­eral upper eyelid swelling for ~ 5 months. Nonspe­cific orbital inflammation had been previously di­agnosed and treated with prednisone for 2 months ( A) ( C) ( B) FIG. 1. Case 1: demonstrating ( A) se­vere bilateral periorbital swelling as­sociated with DO showing asymmet­ric right inferior lid swelling; ( B) computed tomography scan reveal­ing unilateral moderate medial rec­tus muscle enlargement on an axial view; and ( C) 2 years later, chronic bilateral upper and lower lid swelling after steroid and radiation treat­ments. / Ncuro- Ophtlmlmol, Vol. 15, No. 2, 1995 86 C. E. ROSEN AND J. S. KENNERDELL without resolution of her eyelid swelling. She had a past medical history significant for insulin-dependent diabetes mellitus for - 10 years, and hypothyroidism treated with L- thyroxine ( Syn-throid). Best corrected visual acuity was RE 20/ 30 and LE 20/ 25. Color testing with Ishihara test plates was 12/ 12 OU. Pupils were briskly reactive, and no af­ferent pupillary defect was detected. Extraocular motility demonstrated a moderate upgaze deficit RE, with minimal abduction deficit LE. The patient was orthophoric in primary position. Hertel ex-ophthalmometry with a base of 99 was RE 20 and LE 18. Slit- lamp examination was unremarkable OU without evidence of exposure keratopathy. Applanation tonometry was RE 17 mm Hg and LE 15 mm HG. Funduscopic examination revealed clear lens and vitreous with healthy optic nerve heads OU. Background diabetic retinopathy was present OU. B- scan ultrasonography and magnetic resonance imaging ( MRI) scanning revealed a min­imally enlarged superior rectus of the RE. Gold-mann visual field testing was full OU. Case 3 A 41- year- old white woman had a 2- month his­tory of marked periorbital swelling. Past medical history included hyperthyroidism treated with io-dine- 131. Visual acuity was 20/ 20 OU. Color test­ing was 12/ 12 OU. No afferent pupillary defect was detected. Extraocular motility was full, and she was orthophoric in the primary position. Slit- lamp examination was unremarkable OU. Applanation tonometry was 22 mm Hg OU that increased to 26 mm Hg on upgaze OU. B- scan ultrasonography revealed mildly enlarged superior rectus muscles OU. Goldmann visual fields were full OU. Fundu­scopic examination revealed clear media and healthy discs, maculae, and retinal periphery OU. She was observed for 4 years with little change and underwent four lid blepharoplasties. Case 4 A 41- year- old white woman was first seen with 5 months of bilateral upper and lower eyelid swell­ing. Past medical history included hyperthy­roidism treated with iodine- 131 for a diffuse toxic goiter. Visual acuity was RE 20/ 30 and LE 20/ 25. No afferent pupillary defect was detected. Ishihara color plates were 15/ 15 OU. Extraocular motility was limited in upgaze OU. Applanation tonometry was 17 mm Hg OU that increased to 21 mm Hg OU. Goldmann visual fields were full on both sides. Funduscopic examination showed normal discs, maculae, and retinal periphery OU. CT scan revealed mild enlargement of extraocular muscles diffusely. Neither prednisone therapy nor radia­tion therapy with 2,000 cGy relieved her eyelid swelling. Case 5 A 61- year- old white man had 15 months of bi­lateral marked periorbital swelling. Treatment in­cluded antibiotics for possible orbital cellulitis without relief, followed by a 13- month prednisone taper, again without improvement. Thyroid func­tions were normal. A biopsy of the upper and lower eyelids showed chronic inflammation with fragments of normal skeletal muscle tissue. The patient denied any associated muscle weakness, difficulty swallowing, purpura on other areas, or frequent ingestion of raw meat. A chest radio­graph was normal. Visual acuity was RE 20/ 30 and LE 20/ 25. Color vision was 1/ 12 Ishihara plates OU, secondary to congenital red- green color blindness. Pupils were briskly reactive without an afferent pupillary de­fect. On most recent examination, the external ex­amination showed right greater than left perior­bital lid swelling. Applanation tonometry was 18 mm Hg OU, and slit- lamp examination was unre­markable. Funduscopic examination revealed nor­mal discs, maculae, and retinal periphery OU. A CT scan of the brain and orbits revealed normal-appearing extraocular muscles without enlarge­ment. The differential diagnosis included cellulitis, trichinosis, dermatomyositis, contact allergic reac­tion, hypothyroidism, amyloidosis, and CI es­terase inhibitor deficiency predisposing to angio-edema. After careful follow- up examinations, eu­thyroid DO was diagnosed. Case 6 An 82- year- old white woman had 6 months of bilateral chronic lid swelling. Previous extensive work- ups were performed by an otolaryngologist and an allergist. She had been treated with artifi­cial tears and topical steroids without benefit. She had been taking L- thyroxine ( Synthroid) since be­ing hyperthyroid in 1973 and was well controlled in a euthyroid state. Recent thyroid studies were within normal limits. On examination, visual acuity was RE 20/ 40 and LE 20/ 30 with full extraocular motility without re­striction or diplopia. Color plate testing using Ish­ihara color plates was normal, and there was no / Neuw- Ophthaltnol, Vol. 15, No. 2, 1995 EYELID SWELLING IN DYSTHYROID ORBITOPATHY 87 afferent pupillary defect. Hertel exophthalmome-try with a base of 95 was RE 18 and LE 19. Exter­nally, she had edematous and thickened eyelids, upper greater than lower on both sides ( Fig. 2a). There was no lid lag, and minimal scleral show interiorly was present. Slit lamp revealed mild blepharitis OU and applanation tonometry was 8 mm Hg OU in primary position that increased to 10 mm Hg OU in upgaze. Funduscopic examina­tion was unremarkable. CT scan of the brain and orbits using axial and coronal cuts ( Fig. 2b) re­vealed normal- appearing extraocular muscles. Case 7 A 51- year- old white woman had severe bilateral lower greater than upper lid swelling for ~ 3 months. Thyroid studies revealed a low supersen­sitive TSH. Previous medications included an oral antihistamine, naphazoline ( Vasocon) eyedrops, and an 8- day tapered course of prednisone starting with 60 mg without relief. She had no known drug FIG. 2. Case 6: demonstrating ( A) bilateral chronic lid swelling associated with DO and ( B) normal-appearing extraocular muscles on computed tomog­raphy scan of the orbits, showing a coronal view. FIG. 3. Case 7: demonstrating ( A) bilateral severe lower greater than upper eyelid swelling associated with DO and ( B) normal- appearing extraocular mus­cles on computed tomography scan of the brain and orbits, showing an axial view. allergies, no significant past medical history, and was on no medications. Best corrected visual acuity was 20/ 20 OU. Color vision testing using Ishihara color plates was 12/ 12 OU. Extraocular motility was full, and she was or-thophoric in primary position. Hertel exophthal-mometry with a base of 99 was 18 OU. External examination revealed severe lower lid swelling greater than upper lid swelling ( Fig. 3A) without erythema, pruritis, or tenderness. On slit- lamp ex­amination, mild temporal chemosis was present in both eyes. Applanation tonometry was RE 10 mm Hg and LE 11 mm Hg in primary position, increas­ing to RE 11 mm Hg and LE 13 mm Hg on upgaze. Goldmann visual field testing was full OU. B- scan ultrasonography demonstrated essentially normal muscles OU. Funduscopic examination revealed clear lens and vitreous OU with healthy discs, maculae, and retinal periphery OU. CT scan of the brain and orbits was performed using axial and coronal views and demonstrated normal- ap­pearing muscles ( Fig. 3B). / Ncuro- Ophihalmol, Vol. 15, No. 2, 1995 88 C. E. ROSEN AND }. S. KENNERDEEE DISCUSSION In a busy neuro- ophthalmic/ orbital diseases practice, one of the authors ( J. S. K.) has examined numerous DO patients over the years and has seen seven patients with severe eyelid swelling as the initial presentation. This clinical sign may be con­fused with other entities, leading the physician to work the patient up for unrelated disorders. Pa­tients have marked periorbital swelling of the up­per or lower eyelids that may be relatively asym­metric. Typically the skin is boggy and pendulous, without warmth or erythema, and the patient de­nies pain or visual acuity changes. The presenta­tion may be asymmetric, and the disease course can unevenly worsen or improve over periods of months. The neuro- ophthalmic examination is usually normal. The extraocular muscles character­istically are normal; however, moderate asymmet­ric muscle enlargement may be found, as in case 1. Extraocular muscle size does not appear to change with time when imaged with CT scanning or B- scan ultrasonography. Three of our patients ( cases 2, 5, and 7) were treated with prednisone, and two were treated with prednisone and radiation ( cases 1 and 4) without relief. Four of the patients were initially hyperthyroid ( cases 1, 3, 4, and 6), two were hy­pothyroid ( cases 2 and 7), and one patient was euthyroid ( case 5). Patients do not respond to the usual treatments for DO ( steroids or radiation). Di­uretics to mitigate eyelid tissue fluid accumulation do not work. We believe a modified blepharo-plasty can be used to remove excess skin and or­bital fat after the process has " burned out," which may require months to years. Rootman ( 5) described a similar group of pa­tients with a disproportionate degree of lid swell­ing when compared to their epibulbar and myo­pathic symptoms. Typically, their lower lids are pale and edematous with noninjected distention. Unlike that of our patients, the lid swelling is sen­sitive to steroids and radiotherapy. Although periorbital swelling is not an uncom­mon presentation for DO, severe swelling may cause the physician to consider other diagnoses such as angioneurotic edema. Mild edema not as­sociated with erythema is nonspecific except in the following circumstances ( 6). If localized to the temporal portion of the upper eyelids in adults, it may represent the early stage of a lacrimal gland tumor, particularly if the patient notes some dis­comfort or pain in this area. It is easy to misdiag­nose this edema as a localized contact allergy, a hordeolum, or the result of an insect bite. In chil­dren, edema localized to this area may be a man­ifestation of occult neurofibromatosis. Palpation reveals a ropy, ill- defined mass in the subcutane­ous tissue. Boggy edema localized to the nasal por­tion of the upper eyelid, particularly if episodic, suggests an underlying mucocele of the frontal si­nus that is slowly eroding the bony roof of the orbit. Unilateral edema, less localized in type, affect­ing one or both eyelids, may be an early sign of lymphoma of either the anterior orbit or the con­junctival fornix. Edema with a similar texture may be observed with an orbitocranial meningioma that either has been partially removed or has existed in the posterior orbit for several years. This depen­dent edema differs slightly from that seen in lym­phoma by affecting the lower eyelid more than the upper eyelid. A mass either is visible on eversion of the eyelid or is palpable in one of the quadrants of the anterior orbit in lymphoma, whereas a me­ningioma in the posterior orbit usually is not pal­pable. Other infiltrating secondary neoplasms of the posterior orbit such as sinus carcinoma, esthe-sioneuroblastoma, and bony tumors ( e. g., Ewing's sarcoma), may mimic the eyelid edema of orbi­tal meningioma. Some degree of eyelid edema may be associated with hard, infiltrating basal cell, squamous cell, and sebaceous carcinomas, and eyelashes are typically absent in the indurated area. Erythema of the eyelids ( with or without edema) suggests a more urgent orbital problem. Erythema and edema are most intense in infants with orbital cellulitis. Local heat and fever will differentiate this acute inflammatory process from other tumors. Er­ythema and edema without an increase in local heat may accompany fast- growing neoplasms or acute inflammatory tumors located in the more an­terior areas of the orbit. Neoplasms such as rhab­domyosarcoma and leukemia must be considered in children and adolescents with similar presenta­tions. Erythema should not be confused with the ecchymosis of the eyelids associated with he­matoma or orbital trauma, metastatic neuroblas­toma, amyloid deposit, and focal Langerhan's his­tiocytosis. We believe the clinician should be aware that severe periorbital swelling can be the predominant manifestation of DO. Understanding this presen­tation, although it is uncommon, may help the physician avoid discussions of tumors, vascular malformations, allergies, or infections. More im­portant, treatment with significant side effects or complications may be avoided by understanding this uncommon dramatic presentation of DO. / Ncuro- Ophthalmol, Vol. 15, No. 2, 1995 EYELID SWELLING IN DYSTHYROID ORBITOPATHY 89 REFERENCES 1. Sridama V, Degroot LJ. Treatment of Graves' disease and the course of ophthalmopathy. Am J Med 1989; 87: 70- 3. 2. Marcocci C, Bartalena L, Bogazzi F, et al. Studies on the occurrence of ophthalmopathy in Graves' disease. Acta En­docrinol 1989; 120: 473- 8. 3. Wiersinga WM, Smit T, van der Gaag R, et al. 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