Bilateral corneoscleritis with retrocorneal plaque as the initial presentation of granulomatosis with polyangiitis

Abstract

Background

To report a case of bilateral corneoscleritis with retrocorneal plaque lesion as the presenting sign of granulomatous polyangiitis (GPA).

Case presentation

A 61-year-old female presented with bilateral extensive periphery corneoscleritis with retrocorneal plaque and prominent conjunctival injection. She suffered from progressively blurry vision and pain in both eyes for about 5 years, accompanied by sinusitis. No retinal or orbital abnormalities were noted on examination. A conjunctival and scleral biopsy was performed in the left eye, and the histopathological analysis was consistent with granulomatous inflammation. A full diagnostic workup revealed no obvious abnormal findings except positive cytoplasmic antineutrophil cytoplasmic antibody (cANCA) and proteinase 3-specific antineutrophil cytoplasmic antibody (PR3-ANCA). The patient achieved disease remission with cyclophosphamide and corticosteroid and remained on oral and topical medications with no further loss of vision or discomfort.

Conclusions

This is a unique documented case of corneoscleritis with retrocorneal plaque lesion as the initial presenting feature of GPA. Our case illustrates that the initial ocular manifestations of GPA involving the cornea and sclera may have atypical lesions. Clinicians should cautiously evaluate the patients to enhance the early diagnosis and promptly initiate treatment measures to prevent vision loss.

Background

Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, appears to be one of the most severe vasculitis of unknown etiology [1]. It affects small vessels through inflammation and necrotizing vasculitis, including the ear/nose/eyes, lungs, kidneys, and skin [2]. However, it has been reported that it usually takes 3–12 months from the appearance to the diagnosis of GPA, and only 7% of patients with GPA are diagnosed at the first visit [3]. Approximately 30–60% of patients with GPA have ocular invasion, with 46.7% having ocular symptoms as their first presentation [1,2,3,4]. For ophthalmologists, the early detection of GPA is vital for targeted treatment and prevention of impaired vision, especially in cases with localized ophthalmic presentations. However, the early ocular manifestations are not typical, and there is a dearth of publications on the detection of ophthalmic GPA cases, especially in Asian populations.

Case presentation

The patient was a 61-year-old woman who presented to our ophthalmology clinic with gradual vision loss and pain in both eyes for about 5 years, accompanied by sinusitis. She had previously been treated for conjunctivitis but experienced no improvement. Corrected distance visual acuity (CDVA) was light perception in the right eye and 20/30 in the left. Slit-lamp examination revealed deep corneal stromal neovascularization and opacity of nearly 1/2 of the cornea on the temporal side in the right eye (Fig. 1). The left eye demonstrated superior cornea neovascularization and opacity and anterior scleritis, the furrow-like peripheral ulcerative keratitis (PUK) with stromal thinning approaching 50% of corneal thickness. There was indistinct yellow-white colored retrocorneal plaque attached to both eyes. The anterior chamber was clear, and the posterior segment of both eyes was unremarkable. Anterior segment-optical coherence tomography (AS-OCT) showed the unclear and irregular boundary between the corneal endothelial surface and plaque, hyperreflectivity within the stroma, and structural disorganization of collagen fibers (Fig. 2). Confocal microscopy demonstrated that the affected cornea exhibited hyper-reflective, pinprick-like lines, with no identifiable endothelial cells or nerve fibers (Fig. 3). UBM clearly demonstrated the peripheral retrocorneal plaque, and localized peripheral anterior synechiae (Fig. 4).

Fig. 1

Anterior-segment photograph showed the deep corneal stromal neovascularization and opacity of both eyes and PUK in the left eye, and also the yellow-white colored retrocorneal plaque approaching the center of the cornea. (A: right eye; B: left eye)

Fig. 2

The representative AS-OCT illustration showed structural disturbances in the corneal stroma. The superficial stroma was closed to transparent, and the periphery deeper stroma was markedly cloudy and thickened with blurry demarcated retrocorneal plaque

Fig. 3

Confocal microscopy showed: (A) the border between the relatively normal cornea(right site) and the lesion(right site), which lacked recognizable endothelial cells (dotted line); (B) pinprick-like hyperreflectivity of scar tissue and hyporeflective shadows of neovascularization in the deep stroma; (C) the dense hyporeflective shadows of neovascularization in the stroma

Fig. 4

The UBM visualized the presence of peripheral anterior synechiae and retrocorneal plaque. (A: left eye, superior quadrant; B: right eye, temporal quadrant)

The laboratory investigations revealed a normal white blood cell count with a slightly elevated monocytes count of 0.72 × 10^9/L (reference value < 0.6 × 10^9/L). Erythrocyte sedimentation rate (ESR) and C-reactive protein(CRP) were normal. There was a positive expression of cytoplasmic antineutrophil cytoplasmic antibody (cANCA) and proteinase 3-specific antineutrophil cytoplasmic antibody (PR3-ANCA) (> 400 AU/mL). MRI findings suggested that the patient had maxillary and ethmoid sinusitis. Erythrocyte sedimentation rate (ESR), urinalysis, and chest X-ray showed no significant abnormality. The histopathology results revealed that conjunctival and scleral were infiltrated by lymphocytes, plasma cells, epithelioid cells, and multinucleated giant cells. The immunohistochemistry study demonstrated the staining of the macrophage surface markers CD68 and CD163 (Fig. 5).

Fig. 5

The histopathological examination. (A) Scleral and (B) conjunctival biopsy showed granulomatous inflammation with lymphocytes, plasma cells, epithelioid cells, and multinucleated giant cells. There were dilated blood vessels in the conjunctiva (magnification ×200, hematoxylin-eosin staining). The positive expression of macrophage surface markers (C) CD68 and (D) CD163 in conjunctival specimens. (magnification ×400, immunohistochemical staining)

Although ocular disease and sinusitis were the only manifestations, the laboratory assessment revealed positive c-ANCA and PR3-ANCA, with granulomatous inflammation on histopathology. Diagnosis of GPA was made through consultation with a rheumatologist. Treatment was initiated, which consisted of intravenous methylprednisolone 1 g for 3 days followed by oral methylprednisolone (60 mg/day for 7 days, 45 mg/day for 14 days, and 40 mg/day for continuous use), intravenous cyclophosphamide (600 mg, once), and topical 0.1% fluorometholone and levofloxacin ointment. The relief from ocular congestion was achieved, but the best-corrected visual acuity remained HM/BE and 20/30. A month later, under the supervision of the rheumatologists, the patient received another circle of intravenous cyclophosphamide (800 mg). The ocular symptoms showed improvement. As the patient could not continually attend in-person follow-ups at our institution due to transportation constraints, she was subsequently transferred to a local hospital but remained on remote consultation. Therapeutic regimens included a tapering dose of oral methylprednisolone in combination with mycophenolate mofetil 500 mg (once daily), topical ofloxacin eye ointment (once daily at bedtime), and loteprednol etabonate ophthalmic suspension (four times daily). She remained on regular follow-ups and continued her medications till now with no further loss of vision or discomfort. At the same time, the objective assessment via remote consultation with the local doctors reported no relapse, resulting in a significant improvement in her condition.

Discussion

GPA is a rare ANCA-associated small-vessel disease [5]. Ocular and systemic involvement are simultaneously present at onset in 41% of the patients; ocular lesions followed systemic involvement in 36% of the patients [6]. The three most common ophthalmologic manifestations are scleritis (36%), retro-orbital pseudotumor or orbital mass (23%), and episcleritis (13%) [6]. The presence of necrotizing changes or corneal involvement in the setting of scleral inflammation is highly suggestive of an underlying GPA [7]. It is reported that approximately 90% of GPA patients experience upper respiratory tract issues, including nasal pain and purulent discharge, sinus stuffiness, and epistaxis in the early stage [8].

Few studies describe the characteristics of ophthalmic GPA without evidence of pulmonary or renal disease. Recently, there was a documented case of presumed GPA initially presenting with sectoral scleritis, ciliary body granuloma, and nasal sinus granuloma without systemic involvement [9]. To our knowledge, this is the first reported limited ophthalmic GPA in a patient with binocular corneoscleritis who had a posterior corneal plaque as the first manifestation. The sinusitis may be our patient’s initial sign of upper respiratory tract involvement.

Retrocorneal plaques could be observed in patients with infectious keratitis, such as fungal and bacterial keratitis, which are speculated to be composed of a cluster of inflammatory cells, and AS-OCT could show a clear boundary, even a space between the cornea and the plaques [10]. Peripheral thickening and opacification of the stroma adjacent to the site of sclerosing keratitis have been reported to be one of the ocular manifestations of rheumatoid arthritis. Still, no specific details are described [11].

Since there is no cell structure under the confocal microscopy in our patient, such plaques are presumed to be mainly composed of proliferative membranes. It may arise from exudation with deep corneal neovascularisation. As a result, retrocorneal plaques are observed to be confined to the posterior peripherally vascularised corneosclera. Further histopathological analysis of the composition of these plaques is necessary if we can obtain tissue samples from the plaques in the future.

Pathological biopsy is an important method for diagnosing GPA. However, the classic pathologic triad of parenchymal necrosis, vasculitis, and granulomatous inflammation is not commonly seen in extrapulmonary sites [12]. In this case, the biopsy demonstrates infiltration of chronic inflammatory cells and dilated blood vessels with aggregates of CD68 (+) and CD163 (+) cells, consistent with granulomatous inflammation. However, the typical presence of vasculitis associated with zonal granulomatous inflammation surrounding a central necrotic sclera is not evident. This may also be attributed to the limited availability of scleral and conjunctival specimens. CD68 is a glycosylated glycoprotein commonly used as a pan-macrophage marker, and CD163 is a transmembrane hemoglobin-haptoglobin scavenger receptor expressed selectively on most macrophages. The enhanced CD163(+) staining in sarcoidosis patients indicates a shift towards anti-inflammatory M2 macrophage [13]. In this case, CD163 (+) cell expression may also suggest a change in the patient’s inflammatory status.

There is a case report of abnormal patterns of corneal endothelial cell loss after cataract surgery in GPA patients, suggesting a potential endothelial dysfunction in such patients [14]. Meanwhile, the interaction between endothelial cells and neutrophils is identified as the primary event in necrotizing vasculitis [15]. Activated neutrophils express ANCA-antigens, PR3, and myeloperoxidase, causing neutrophils to degranulation and release protease and reactive oxygen species, eventually leading to apoptosis and necrosis of endothelial cells and triggering vasculitis [5, 15].

This case highlights the importance of implementing systematic diagnostic workups in patients with long-lasting ocular inflammation, especially those with corneoscleritis. Ocular manifestations may vary in GPA, and early detection and treatment of this disease is vital for better prognosis and prevention of impaired vision.