Ocular Manifestations in Granulomatosis with Polyangiitis Patients from Saudi Arabia

Eye and/or orbit involvement occurs in Granulomatosis with polyangiitis (GPA) patients frequently. The aim of our study was to describe the clinical manifestations, therapy and outcome of ocular involvement in our GPA patients. A retrospective study was conducted including patients with GPA who followed up in Rheumatology clinics during 1990-2016 at King Khalid University Hospital, Riyadh. Information relating to demographics, ocular manifestations, laboratory findings, therapy and outcome of GPA patients were noted. Ocular involvement was detected in 9 (39.1%) of the 23 GPA cases identified. The mean age of ocular GPA patients was 51.8 (range 27 - 62) years, the mean age at onset of disease was 39.6 (range 11 - 57) years and the mean duration of disease was 9.0 (range 2 - 19) years. Concomitant ear, nose, throat and sino-nasal manifestations occurred with ocular symptoms in 77.8% GPA patients. The most frequent manifestations were, eye pain (66.7%), scleritis/episcleritis (55.6%), eye redness and itching (55.6% each). Antineutrophil cytoplasmic antibodies (ANCA) were positive in 88.9% patients, 55.6% had c-ANCA


Introduction
Granulomatosis with polyangiitis (GPA) is an autoimmune granulomatous inflammatory disease that affects multiple organs and is characterized by small vessel necrotizing vasculitis. It predominantly affects upper and lower respiratory tracts and kidneys [1] [2]. Ophthalmic involvement of eye and/or orbit occurs in up to 60% of GPA patients and is the initial manifestation in 8% -16% [3] [4] [5] [6]. The eye is considered an immune-privileged site, with a high predisposition to develop anti-inflammatory and immunosuppressive mechanisms to prevent the consequences of inflammation [7]. The most common clinical findings are proptosis, scleritis, episcleritis, retinal, and optic nerve vasculitis, nasolacrimal duct obstruction, uveitis, and dacryocystitis [3] [8]. Permanent blindness may occur in 8% of the patients [1] [4]. GPA is the most common rheumatic disease to affect the orbit [9]. Orbital lesions are reported in 5% -31% GPA patients, which can be bilateral in 14% -58% while the lacrimal gland may be involved initially [1] [4] [10]- [15].
Our aim was to study the ocular manifestations in GPA patients from our region, its disease course, therapy and the outcome.

Materials and Methods
The medical charts of all GPA patients diagnosed and followed up in Rheumatology clinics at King Khalid University Hospital, King Saud University, Riyadh, during the period 1990-2016 were reviewed retrospectively. GPA was diagnosed as per Chapel Hill Consensus Conference (CHCC) definition [16]. Study approval was obtained from Institutional Review Board of College of Medicine, King Saud University, Riyadh. GPA patients who underwent ophthalmic evaluation for ocular symptoms and were diagnosed to have ocular manifestations of GPA were included in the present study. We recorded the demographic data including, patient's age, age at disease onset, gender, duration of disease, interval between onset of symptoms and diagnosis and duration of follow up. Clinical, hematological and immunological data were also retrieved. Eye and orbital/lacrimal gland computed tomography (CT) and biopsy findings were noted.
Antineutrophil cytoplasmic antibodies (ANCA) were detected by indirect immunofluorescence (for detecting c-ANCA and p-ANCA) and enzyme-linked immunosorbent assay (ELISA) for detecting proteinase 3 (PR3) and/or myeloperoxidase (MPO) ANCA). Treatment given to the patients, disease course and its outcome were also recorded.
Statistical Analysis: Statistical analysis of the data was performed using IBM

Results
Twenty-three cases of GPA were included in this study. Eye was involved in nine Laboratory findings in nine ocular-GPA patients are summarized in Table 2.
ANCA was positive in eight (88.9%) patients and negative in one patient.  (Table 3). There were no deaths and all patients were in remission on treatment at the time of follow up.
The results of comparison of ocular GPA with non-ocular GPA group of patients are presented in Table 4. There were more males compared to females (7:2) in ocular GPA group while equal number of males and females were affected in non-ocular GPA (7:7). The proportions of ear nose throat (ENT) and Table 2. Laboratory parameters in 9 Ocular GPA patients.
It is known to occur in both limited and severe forms of GPA and can be the ini-Open Journal of Rheumatology and Autoimmune Diseases tial symptom or occur in as high as 87% GPA patients at some time during the disease [1] [20] [21]. However, GPA with limited involvement of the orbit and/or the eye is seen rarely [22]. The Spanish registry of systemic vasculitis study reported that 24% of GPA patients had ocular involvement at diagnosis [23]. Ocular GPA often presents as stromal keratitis, blurred vision, and scleritis/episcleritis [7] [24] [25]. In our study scleritis/episcleritis was the most frequent ocular manife- The predominant findings of orbital biopsy are reported to be chronic fibrotic changes rather than the classic triad of vasculitis, tissue necrosis and granulomatous inflammation [33]. In our patients, eye CT showed granuloma and orbital/lacrimal gland biopsy showed non-necrotizing granulomatous vasculitis.
Orbital biopsy showed small vessel vasculitis in majority of the patients in some studies [34]. studies, however in contrast to their finding; we did not find an association with of age at onset [25]. There was no significant association of ocular disease with other manifestations of GPA in our patients.
To the best of our knowledge this is the first study reporting the disease manifestations, therapy and outcome in ocular GPA patients from our region. Some of the limitations of our study are the small sample size and the cohort being drawn from a single institution which cannot be generalized to the entire Saudi population. The other limitation is the retrospective nature of our study.

Conclusion
The frequency of ocular manifestations in our GPA patients was similar to reports elsewhere, with the most frequent symptoms being eye pain and scleritis/episcleritis. The ocular involvement was associated with sino-nasal manifestations and significantly with low risk of renal involvement. Patients responded well to corticosteroid and IV CYC therapy and rituximab was more effective in relapsing patients. Ocular symptoms may be the first sign of GPA and early diagnosis and appropriate therapy is crucial to lowering the morbidity and vision loss in GPA patients.