Clinical Characteristics of Inflammatory Eye Disease in Patients with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Retrospective Cohort Study

Background/Purpose: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic small vessel vasculitis characterized by presence of cytoplasmic-ANCA or perinuclear-ANCA, that can virtually affect any organ system. Inflammatory eye disease (IED) is a well-recognized manifestation of AAV though the data on its clinical characteristics and outcome are limited.

Methods: Medical records of 501 patients with AAV seen at our institution were reviewed. Data on demographics, ophthalmologic manifestation, laboratory investigations, treatment (ocular and systemic), disease activity, systemic organ involvement, and outcomes were abstracted. Descriptive statistics were used to summarize the data.   

Results: 77 patients (mean age 50.1 years; 52% female; 96% Caucasian) with median follow-up of 6.1 years had IED.  Proteinase-3 (PR-3) serology was positive in 39 patients (51%); myeloperoxidase (MPO) serology was positive in 24 patients (31%) and ANCA serology was negative in 14 patients (28%). IED was one of the initial manifestations leading to diagnosis of AAV in the majority of patients (68%) with median time from IED to diagnosis of AAV of 1.6 months. IED occurred after the diagnosis of AAV in about one-third of patients with median time from diagnosis of AAV to IED of 41.2 months. Mean Birmingham Vasculitis Activity Score (BVAS) during active IED was 6.0. Mean erythrocyte sedimentation rate during active IED was 41.8 mm/hr.             Episcleritis was the most common type of IED (17%) followed by scleritis (14%), orbital inflammation (orbital pseudotumor/orbital myositis) (12%), cranial nerve III, IV or VI palsy (12%), conjunctivitis (9%), optic neuritis (8%), amaurosis fugax (8%), uveitis (5%), lacrimal duct stenosis (5%), peripheral ulcerative keratitis (4%), retinal vasculitis (4%) and dacryoadenitis (4%). The most common manifestation of IED was redness (49%) followed by eye pain (35%), visual acuity loss (27%; gradual visual acuity loss 17% and sudden visual acuity loss 10%), diplopia (19%), and photophobia (13%). IED occurred bilaterally in 52% of patients.                 Oral glucocorticoids were used to treat IED in the majority of patients (91%) while topical glucocorticoids were used in 31%.  Cyclophosphamide was the most frequently used immunosuppressive agent (53%) followed by methotrexate (34%), rituximab (26%), azathioprine (26%), mycophenolate (9%) and intra-orbital glucocorticoid injection (6%) in patients with orbital pseudotumor/orbital myositis.  Complete remission was achieved in 94% of patients. However, relapse was common (18%). The median number of relapses was 1 during the period of observation.

Conclusion: IED occurs in about 15% of patients with AAV. Episcleritis, scleritis, orbital inflammation and cranial nerve palsy were the most common subtypes of IED. Inflammation from IED responded well to treatment although relapse was common.