ORIGINAL STUDY Systemic diseases associated with intermediate uveitis STEVEN A. BOSKOVICH, MD; CAREEN Y. LOWDER, MD, PHD; DAVID M. MEISLER, MD; FRONCIE A. GUTMAN, MD HE INTERNATIONAL BACKGROUND Intermediate uveitis is characterized by Uveitis Study Group has vitreal inflammation with associated inflammation of the vitre- proposed the term "in- ous base and peripheral anterior retina and choroid. It may be termediate uveitis" to Tdescribe ocular inflammation in- found as an isolated and idiopathic condition or in association with systemic disorders such as multiple sclerosis and sarcoidosis. volving the vitreous base and far anterior retina and choroid.1 The OBJECTIVE To identify the clinical features of intermediate spectrum of clinical findings in in- uveitis and assess its association with systemic diseases. termediate uveitis has included vitreal inflammation, pars plana METHODS Retrospective study of 83 patients presenting with exudates, peripheral retinal vascu- intermediate uveitis between 1970 and 1991. lar sheathing, and minimal associ- ated anterior segment inflamma- RESULTS Evidence of systemic disorders was found in 26 of 83 tion. When it has occurred in patients (31.3%). Of these 26 patients, 10 had presumed sarcoi- seemingly healthy individuals, it dosis, 6 had multiple sclerosis, 2 had isolated optic neuritis, 2 had has been called pars planitis, inflammatory bowel disease, 4 had isolated thyroid abnormalities, chronic cyclitis, peripheral uveitis, and 2 had histories suggestive of Epstein-Barr virus infection. As- or basal retinochoroiditis. sociated ocular findings included cystoid macular edema, periph- The numerous descriptive eral retinal perivascular sheathing, cataracts, posterior vitreous names used for this condition re- detachment, fine keratic precipitates, preretinal macular fibrosis, flect the lack of an understood retinal tears, retinal detachment, and optic disc edema. pathogenesis.2 Adding to the con- fusion about its etiology are reports CONCLUSIONS Patients with intermediate uveitis may have of intermediate uveitis associated associated systemic diseases and should have careful follow-up with systemic conditions such as with regular systemic evaluation. multiple sclerosis, sarcoidosis, in- • INDEX TERMS: UVEITIS, INTERMEDIATE; SARCOIDOSIS; MULTIPLE SCLEROSIS; flammatory bowel disease, Lyme OPTIC NEURITIS; INFLAMMATORY BOWEL DISEASES; THYROID DISEASES; EPSTEIN- disease, Behcet's disease, syphilis, BARR VIRUS • CLEVE CLIN ] MED 1993; 60:460-465 Vogt-Koyanagi-Harada syndrome, Whipple's disease, and amyloid- From the Department of Ophthalmology, The Cleveland Clinic 3-10 Foundation. osis Address reprint requests to C.Y.L., Department of Ophthalmology, We report the association of sys- A31, The Cleveland Clinic Foundation, 9500 Euclid Avenue, temic disorders with intermediate Cleveland, OH 44195. uveitis in our referral practice, 460 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 60 • NUMBER 6 Downloaded from www.ccjm.org on September 28, 2021. For personal use only. All other uses require permission. INTERMEDIATE UVEITIS • BOSKOVICH AND ASSOCIATES document intermediate TABLE 1 uveitis as a heralding in- SYSTEMIC CONDITIONS ASSOCIATED WITH INTERMEDIATE UVEITIS (N = 26) flammatory event for un- Noted prior Developed derlying diseases, and de- to diagnosis after diagnosis Total* scribe the clinical features Presumed sarcoidosis 1 9 10 of this condition. Multiple sclerosis 3 3 6 Isolated optic neuritis 1 1 2 PATIENTS AND METHODS Thyroid disease^ 5 0 5 We reviewed the records Inflammatory bowel disease 1 1 2 of 83 patients (42 women Epstein-Barr virus 2 0 2 and 41 men) at The Cleve- Total >26 because one patient had thyroid disease and inflammatory bowel disease land Clinic Foundation ^Graves' disease (2), Hashimoto's thyroiditis (1), unspecified hypothyroidism (2) who were found to have in- termediate uveitis between 1970 and 1991. All patients presented with ocular trolyte levels, liver function tests, the erythrocyte symptoms or were referred with ocular inflamma- sedimentation rate, and serum angiotensin-convert- tion. Intermediate uveitis was defined as the pres- ing enzyme and lysozyme levels. ence of vitreal inflammation in one or both eyes The chronologic order in which the diagnoses of with associated inflammatory deposits in the vitre- intermediate uveitis and the associated systemic dis- ous base or on the pars plana in at least one eye and orders were made was noted. Associated ocular find- minimal anterior chamber inflammation. Patients ings in patients with intermediate uveitis were docu- with unilateral and bilateral inflammation were in- mented. cluded. Patients were excluded if they had a pre- dominantly posterior uveitis, if they had more than RESULTS mild anterior chamber reaction, or if the anterior chamber inflammation was granulomatous in ap- Systemic disease associations were noted in 26 of pearance on presentation. The average age at which 83 patients (31.3%) with intermediate uveitis (Table intermediate uveitis was first observed was 23.3 1). In these 10 men and 16 women, the mean age at years (range 4 to 54 years). The mean follow-up presentation with intermediate uveitis was 24-7 period after the diagnosis of intermediate uveitis was years. 5.7 years (ranging up to 21 years). Evidence for presumed sarcoidosis was found in Associated systemic disorders were identified 10 patients (12%). One had sarcoidosis for 2 years from the patient history and the laboratory evalu- before developing intermediate uveitis. In 4 pa- ation. The diagnosis of sarcoidosis is usually estab- tients, presumed sarcoidosis was diagnosed during lished by systemic findings with histopathologic and the evaluation of the initial episode of intermediate radiologic abnormalities. In the absence of systemic uveitis. The remaining 5 patients were found to findings, the diagnosis of ocular sarcoidosis is pre- have laboratory evidence of presumed sarcoidosis sumptive.11 The diagnosis of presumed sarcoidosis beginning 2.5 to 20 years after intermediate uveitis was based on clinical suspicion and on the findings was first observed. Seven of the 10 patients with of anergy and abnormal serum lysozyme or angioten- presumed sarcoidosis presented with exudation pre- sin-converting enzyme levels; no patients had biop- dominantly from the pars plana, 2 presented with sies to confirm the diagnosis. The diagnosis of mul- vitreous "snowball" opacities without pars plana tiple sclerosis was based on Poser's classification.12 exudates, and one presented with both. Only 2 of Inflammatory bowel disease was documented by the 10 had peripheral retinal perivascular sheathing colonoscopy. Thyroid dysfunction was documented noted on initial evaluation, but half eventually dem- by history and need for thyroid replacement therapy. onstrated this on follow-up. Cystoid macular edema Lyme disease antibody titers were measured in two developed during the course of evaluation in 5 of the patients. The most commonly obtained studies in all 10 patients. patients included chest roentgenograms, serologic Multiple sclerosis was associated with intermedi- tests for syphilis, complete blood counts, serum elec- ate uveitis in six patients (7.2%). Three had clini- NOVEMBER • DECEMBER 1993 CLEVELAND CLINIC JOURNAL OF MEDICINE 461 Downloaded from www.ccjm.org on September 28, 2021. For personal use only. All other uses require permission. INTERMEDIATE UVEITIS • BOSKOVICH AND ASSOCIATES TABLE 2 mononucleosis that began ASSOCIATED OCULAR FINDINGS IN INTERMEDIATE UVEITIS 1 year before the onset of Idiopathic Intermediate uveitis intermediate uveitis. pars planitis with associations Fifty-seven of 83 pa- (N=57) (N=26) tients had idiopathic pars Cystoid macular edema 34 (60%)* 12 (46%)* planitis (31 men and 26 Peripheral retinal perivascular sheathing 16 (28%) 14 (54%) women). Their mean age Cataract 15 (26%) 6 (23%) at presentation was 22.6 years. They either had no Posterior vitreous detachment 12 (21%) 7 (27%) identifiable underlying dis- 10(18%) 5 (19%) Fine keratic precipitates ease or had other systemic Preretinal macular fibrosis 8(14%) 5 (19%) diagnoses of uncertain sig- Retinal tears 4 (7%) 4 (15%) nificance including essen- Retinal detachment or traction 4 (7%) 6 (23%) tial hypertension, peptic Optic disc edema 3 (5%) 5 (19%) ulcer disease, nephrolithi- asis, hemorrhoids, pilonidal Total >100% because multiple findings in individual patients are listed separately cyst, migraine headache, diabetes mellitus, degen- cally suspect multiple sclerosis 1 to 8 years before erative osteoarthritis, chronic otitis, polycystic kid- intermediate uveitis was first observed, and three neys, hiatal hernia, Gilbert's syndrome, mitral valve were found to have multiple sclerosis 6 to 15 years prolapse, coronary artery disease, sleep apnea, and after intermediate uveitis was first observed. Two atherosclerotic vascular disease. One patient with patients with intermediate uveitis were noted to idiopathic pars planitis had a long-standing history have isolated episodes of optic neuritis without other of bronchial asthma. clinical signs of multiple sclerosis; one episode oc- Nine of the patients with idiopathic pars planitis curred "several" years prior to the development of had abnormal laboratory test results other than intermediate uveitis, the other, 2 months after the those already described. Five of these patients had diagnosis. weakly positive antinuclear antibody titers, three at Intermediate uveitis was associated with thyroid a dilution of 1:40 (one of