A 79-year-old woman was referred to our institution with a 1-year history of tearing, blurry vision, pain, photophobia, and redness in her right eye. Past medical history was significant for breast cancer, which required right lumpectomy 14 years prior and left lumpectomy plus radiation that was completed about 1 year prior to referral. The patient’s symptoms in the right eye had begun about 1 month following the completion of the radiation treatment for breast cancer, at which point she was diagnosed with nodular scleritis inferotemporally in the right eye, and she was found to have elevated perinuclear accentuated anti-neutrophil cytoplasmic antibodies (p-ANCA), leading to suspicion for granulomatosis with polyangiitis. She was managed by multiple ophthalmologists and rheumatologists. Medical history also included insulin-dependent diabetes, hypertension, hyperlipidemia, anemia, and colon cancer about 16 years prior. There was a history of maxillary and sphenoid sinusitis, for which the patient had right mastoid surgery, as well as a history of bilateral ear tubes. The patient also had, at the time of presentation, bilateral renal oncocytomas treated with cryoablation, but renal function was normal. Past ocular history included open-angle glaucoma initially well-controlled with topical therapy alone but later exacerbated by an inflammatory/corticosteroid-induced component in the right eye. Prior to referral, the patient had been treated with oral prednisone, with good response, but experienced recurrences whenever the dose was tapered. She had also been treated with cyclophosphamide and indomethacin but had a history of poor response to azathioprine. Upon referral to our institution, best corrected visual acuity (BCVA) was 20/80 in the right eye. Slit-lamp examination demonstrated 360° of conjunctival and scleral injection, nodules in the temporal sclera, and 1+ nuclear sclerotic cataract. Dilated fundus examination and B-scan ultrasound showed panuveitis and serous retinal detachment associated with subretinal fluid (Fig. ). A “T” sign was also noted on ultrasound, consistent with posterior scleritis. Left eye exam was unremarkable. The differential diagnosis included inflammatory sclero-uveitis and intraocular lymphoma but favoring a diagnosis of inflammatory anterior/posterior scleritis and uveitis. An extensive work-up for sclero-uveitis was only positive for p-ANCA with a titer of >1:640 (normal <1:10). Pertinent negatives included rheumatoid factor, rapid plasma reagin, fluorescent treponemal antibody, and angiotensin converting enzyme. The leading diagnosis was granulomatosis with polyangiitis, and the patient was treated with oral prednisone, cyclophosphamide, and indomethacin and showed clinical improvement, with vision improving to 20/40.\nNine months later, our patient was referred again with an exacerbation of her inflammation after cataract surgery in the right eye (performed at an outside institution). Her BCVA was 20/200. Slit-lamp examination showed mild scleral injection with a fibrotic-appearing lesion adherent to the medial sclera. Dilated fundus examination demonstrated chorioretinal scars with subretinal fibrosis and pale optic nerve. The infiltrative fibrotic lesion on the sclera was biopsied, and histologic examination revealed mixed chronic inflammatory infiltrate with fibrosis consistent with orbital inflammatory pseudotumor (Fig. b–d). Although no actively necrotizing vasculitis was seen, a portion of the inflammation exhibited a vasculo-centric pattern, with hyalinization of vessels, raising the possibility that these findings represented the late stage of a vasculitic process, and accordingly, granulomatosis with polyangiitis remained in the differential diagnosis (Fig. b, c).\nTreatment subsequently included methotrexate and infliximab infusions, but the patient continued to have recurrent eye pain and eventually developed a blind, painful right eye with end-stage glaucoma and persistent vitritis, besides evidence of optic nerve sheath inflammation on imaging, leading to an enucleation. The histopathology of the globe showed necrotizing and fibrotic granulomatous scleritis and granulomatous panuveitis (Fig. ). Of note, microbial stains were negative. Chronic optic neuritis was also noted, with optic cupping and atrophy (Fig. a, e). There was serous detachment of the retina with subretinal protein, correlating with the clinical appearance (Fig. a). The retina exhibited severe atrophy, with chronic vasculitis seen in some of the retinal vessels (Fig. f), and a neovascular epiretinal membrane was appreciated overlying the pars plana. There were no atypical lymphocytes or any evidence of lymphoma on immunohistochemistry, with T cells (CD3-positive) far outnumbering the B cells (CD20-positive), and with in situ hybridization demonstrating a relatively even mixture of kappa- and lambda-positive plasma cells (not shown). Many of the plasma cells stained positive with IgG4 (Fig. g), i.e., about 70 per high-power field, comprising over 50 % of the total plasma cell population. (The total plasma cells were assessed with CD138 immunostain, not shown.) The previous episcleral/orbital biopsy was then retrospectively also stained with IgG4 immunostain, which likewise revealed positivity in >50 % of the plasma cell population (Fig. d). (Serum IgG4 was not obtained.)
A 23-year-old Indian female presented to a tertiary institute of Northeast India with the chief complaints of dimness of vision, pain and redness in the right eye (OD) for 3 months. The patient was previously treated elsewhere with two posterior sub-Tenon injections of triamcinolone acetonide given 6 weeks apart. She was also on topical steroids and cycloplegic. She did not report any benefit from the previous treatment. There was no history of trauma to the eye or elsewhere. Other medical, surgical, and family histories were unremarkable.\nOn examination, ocular alignment was normal with a visual acuity of counting finger at 3 m in the OD. There was minimal sclerouveitis noted in the inferior-temporal quadrant of OD. On slit-lamp examination, OD showed 360° posterior synechiae with anterior chamber flare and cells (+++) with 1 mm hypopyon []. There was a suspected mass in the inferior-temporal quadrant behind the iris, pushing it anteriorly. The left eye examination was unremarkable.\nB-scan ultrasound (B-scan USG) of OD was suggestive of ciliary body mass with adjoining exudative retinal detachment (ERD). USG bio-microscopy findings were consistent with the findings of B-scan USG. The patient was advised with complete blood count with peripheral blood smear which was within normal limit. Syphilis screening (venereal disease research laboratory) was nonreactive with normal thyroid function test and negative Mantoux test (5TU) reading. Based on the clinical examination and baseline investigations, we came to the differential diagnosis of ciliary body melanoma or similar tumors. Magnetic resonance imaging suggested the possibility of ciliary body melanoma in OD [Fig. and ]. After obtaining informed consent, enucleation was carried out in OD, and eyeball specimen was sent to ocular pathology laboratory for histopathological analysis. In grossing, there was a grayish-white-colored tumor seen in the inferior-temporal part of the ciliary body measuring (10.99 × 7.98) mm. Adjoining the grayish-white ciliary body mass, there was an ERD noted [].\nMicroscopic description of enucleated eyeball showed peripheral corneal vascularization. Few inflammatory cells were seen in the anterior chamber []. Part of the iris tissue showed inflammation. An eosinophilic mass was seen in the ciliary body with diffuse plasmacytoid cells, with reactive lymphoid follicle and other inflammatory cells []. Episcleral and scleral tissue were inflamed and infiltrated by various inflammatory cells [Fig. and ]. Occasional vascularization of the sclera was noted []. Cut end of the optic nerve did not show any tumor involvement. Immunohistochemistry (IHC) was advised to explore the possibility of various inflammatory lesions. The steps for IHC were carried by kit methods available commercially.\nIHC for both Kappa and Lambda was positive. Cluster differentiation (CD20, CD3, and CD45) was focal-positive. CD138 was positive in the specimen and HMB45 was negative. IHC for IgG4 was positive in occasional cells which also expressed CD138 (plasma cells). All positive controls showed appropriate positive immunostaining. Negative control slide did not show immunostaining. IgG4-positive plasma cells were seen in high-power field in the documented slides. Nearly, 30% of all the CD138 positive plasma cells were found to be IgG4-positive [].\nProtein chemistry revealed hypergammaglobulinemia with higher levels of total protein and gamma fraction. No myeloma band or Bence Jones protein was detected []. Serum IgG4 levels were also elevated. A hematologist was consulted, and bone marrow examination revealed mild anemia, for which she was given supportive treatment. In the postoperative period, the patient was given a course of oral steroids. On follow-up at 6 weeks, she was given prosthesis in OD, and the patient was doing well till her last review.