Sequential ocular surgeries and multimodal immunosuppression for bilateral, medically refractory seronegative scleritis with severe peripheral corneal stromal thinning: a case report

Abstract

Background

Severe peripheral corneal stromal thinning and perforation can occur in autoimmune or idiopathic scleritis despite intensive systemic immunosuppression.

Case presentation

A 36-year-old man with bilateral, seronegative, treatment-refractory scleritis developed circumferential peripheral corneal stromal thinning, progressing to multiple perforations in one eye and traumatic dehiscence of a previous patch graft in the fellow eye. Multiple steroid-sparing agents—including mycophenolate, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) inhibitors, alkylating agents, calcineurin inhibitors, and Janus kinase (JAK) inhibition—were ineffective or poorly tolerated. Annular penetrating keratoplasty (14 mm outer / 6.5 mm inner diameter) restored anterior-segment anatomy and provided 360° structural support. Visual acuity improved from counting fingers to 20/200 before a later decline due to posterior subcapsular cataract, while the graft and central cornea remained clear. Maintenance therapy with methylprednisolone 28–48 mg/day, intravenous immunoglobulin every three weeks, and weekly rituximab achieved sustained inflammatory quiescence without recurrence of scleritis or uveitis.

Conclusions

In extensive peripheral stromal thinning refractory to standard therapy, early annular keratoplasty can preserve ocular integrity when localized grafts are inadequate. Long-term disease control may require biologic escalation—particularly rituximab, with or without intravenous immunoglobulin, under multidisciplinary supervision.

Background

Scleritis is a potentially vision-threatening, immune-mediated inflammation that may extend to adjacent ocular structures and, in severe cases, lead to peripheral corneal stromal thinning or perforation [1, 2]. Modern management emphasizes distinguishing infectious from non-infectious causes, longitudinal assessment of disease activity, and timely escalation of systemic therapy [2, 3].

When corneal thinning is diffuse or circumferential, localized lamellar or patch grafts may fail to maintain long-term tectonic stability. Annular (ring-shaped) keratoplasty distributes tension circumferentially along the limbus, restores anterior-chamber depth, and provides continuous structural reinforcement [4–6]. In parallel, B-cell-directed biologic therapy with rituximab has shown efficacy in refractory non-infectious scleritis, achieving durable remission when guided by B-cell monitoring [7–10].

This case highlights a rare presentation of bilateral, seronegative scleritis with circumferential peripheral stromal thinning that was successfully stabilized through annular penetrating keratoplasty and multimodal biologic therapy. It underscores a novel combination of structural and systemic management, suggesting that early, full-circumference keratoplasty in conjunction with rituximab-based immunosuppression can effectively preserve globe integrity in diffuse, medically refractory disease.

Case presentation

A 36-year-old Black/African American man with hypertension, obstructive sleep apnea, and bilateral astigmatism had long-standing bilateral scleritis with intermittent nongranulomatous anterior uveitis. The inflammation was refractory to corticosteroids and multiple steroid-sparing agents, including mycophenolate mofetil, adalimumab, infliximab, tocilizumab, cyclophosphamide, chlorambucil, cyclosporine, and tofacitinib. Rituximab was administered earlier in the disease course (1 g intravenously, two doses) but achieved only partial and transient control, with ongoing corticosteroid dependence. As the disease progressed with bilateral structural complications despite additional immunosuppressive and biologic therapies, rituximab was later re-introduced using a weekly dosing regimen (375 mg/m²). Autoimmune and infectious evaluations—including antinuclear antibody, antineutrophil cytoplasmic antibody, rheumatoid factor, HLA-B27, syphilis, tuberculosis, Lyme disease, and hepatitis serologies—were negative, consistent with seronegative non-infectious scleritis.

Serum IgG subclasses, including IgG4, were within normal limits. Despite high-dose systemic corticosteroids, progressive peripheral corneal thinning developed in both eyes without epithelial defect or ulceration. In late 2022, the left eye developed a full-thickness peripheral perforation involving approximately three clock hours, which was managed with a crescentic corneal patch graft, amniotic membrane transplantation (AMT), and a bandage contact lens. At the time of perforation, the patient was receiving high-dose systemic corticosteroids in combination with intravenous immunoglobulin (IVIG) and chlorambucil for refractory inflammatory disease, without clinical signs of intraocular infection. Postoperative anterior-segment optical coherence tomography (AS-OCT) confirmed stable graft thickness without recurrent thinning, and best-corrected visual acuity (BCVA) improved to 20/200 (pinhole 20/80).

Several months later, the right eye acutely worsened with pain and blurred vision. Slit-lamp examination revealed mild conjunctival injection, diffuse scleral thinning with uveal show, and circumferential (360°) peripheral corneal stromal thinning with multiple pinpoint perforations and vascularized pannus (Fig. 1). Despite systemic immunosuppression, the anterior chamber flattened with focal iris prolapse. Because focal grafting would not provide adequate tectonic stability, and because the central cornea remained relatively preserved, annular (donut-shaped) penetrating keratoplasty was selected to provide circumferential limbal-proximal structural support while avoiding unnecessary replacement of uninvolved central tissue and potentially reducing immunologic rejection risk compared with large-diameter full penetrating keratoplasty. Annular penetrating keratoplasty (PKP) using a donut-shaped corneal graft (14 mm outer diameter / 6.5 mm inner diameter), combined with 360° conjunctival recession and conjunctivoplasty with tissue glue, was performed with perioperative administration of intravenous methylprednisolone (1 g).

Fig. 1.

Slitlamp photograph showing mild conjunctival injection, 360° peripheral corneal thinning with pannus formation, multiple small perforations (notably between 7–11 and 4–6 o’clock), focal iris prolapse, and early anterior staphyloma at 3–4 o’clock

Surgically, a 14-mm outer trephination was fashioned and a 6.5-mm central corneal button was preserved, creating a circumferential donor ring to replace the thinned peripheral cornea. The graft was secured with interrupted sutures circumferentially. Conjunctival recession and conjunctivoplasty consisted of 360° recession of inflamed conjunctiva from the limbus with ocular surface closure to reduce inflammatory burden, improve exposure of peripheral host tissue, and facilitate postoperative epithelialization and graft coverage.The procedure re-formed the anterior chamber and restored circumferential integrity. Postoperatively, the graft remained clear and watertight (Fig. 2). BCVA improved from counting fingers to 20/200, later declining again to counting fingers because of a posterior subcapsular cataract, while the graft and central cornea remained clear on serial AS-OCT.

Fig. 2.

Postoperative slit-lamp photograph of the right eye following annular penetrating keratoplasty (14 mm outer / 6.5 mm inner diameter) showing an intact circumferential graft with a re-formed anterior chamber and no evidence of leakage

The systemic regimen included methylprednisolone 28–48 mg orally once daily, IVIG 2 g/kg per cycle every three weeks, and rituximab 375 mg/m² intravenously once weekly for eight weeks, followed by B-cell-guided maintenance. This achieved sustained quiescence without recurrent scleritis or uveitis. Given the prolonged exposure to high-dose systemic corticosteroids and combination immunosuppression, including perioperative pulse corticosteroid therapy and B-cell–depleting treatment, infectious prophylaxis was instituted. Trimethoprim–sulfamethoxazole double-strength administered three times weekly was used for Pneumocystis jirovecii prophylaxis during periods of highest immunosuppressive burden. Valacyclovir was administered during periods of increased viral reactivation risk; when prescribed at 1 g three times daily, this represented a treatment-level suppressive strategy selected based on clinical risk assessment rather than active infection, with the intent to de-escalate dosing as systemic immunosuppression stabilized.Treatment-related adverse effects included steroid-induced hyperglycemia, posterior subcapsular cataract, and biopsy-proven calcineurin-inhibitor nephrotoxicity during prior cyclosporine therapy, prompting its discontinuation and subsequent avoidance of further calcineurin inhibition.

Approximately three months after annular PKP, blunt trauma to the left eye caused dehiscence of the previous peripheral patch graft with uveal and vitreous prolapse, resulting in no-light-perception vision. Emergency globe repair with repeat crescentic grafting, anterior vitrectomy, and AMT restored structural integrity. Postoperative B-scan ultrasonography demonstrated dome-shaped peripheral choroidal detachments and a funnel-shaped membranous elevation consistent with retinal detachment (Fig. 3). Subsequent 23-gauge pars plana vitrectomy with choroidal drainage and partial fluid–air exchange achieved retinal reattachment, though functional recovery remained limited because of aphakia and choroidal scarring.

Fig. 3.

B-scan ultrasonography of the left eye on postoperative day one showing (A) a longitudinal scan with a smooth, dome-shaped peripheral elevation consistent with choroidal detachment and shortened axial length, and (B) a vertical macular scan demonstrating a funnel-shaped membranous elevation suggestive of retinal detachment with mobile vitreous hemorrhage

At the most recent follow-up, approximately five months after annular keratoplasty, the right eye maintained an intact, clear graft with counting-fingers vision at 4 feet; vision was limited due to irregularity, intraocular pressure (IOP) 10–12 mm Hg, and stable peripheral thickness on AS-OCT. The left eye preserved globe integrity but remained without light perception. Under continued methylprednisolone, IVIG, and rituximab, no recurrence of scleritis or uveitis occurred in either eye.

Discussion and conclusions

This case illustrates the management of severe, medically refractory scleritis complicated by circumferential peripheral corneal stromal thinning and perforation. Peripheral keratopathy in scleritis is a known marker of disease severity and warrants early systemic escalation and multidisciplinary coordination [1, 2]. Recent reviews emphasize standardized assessment and exclusion of infection before initiating aggressive immunosuppression [2, 3].

When thinning becomes diffuse or circumferential, localized patch grafts may fail to provide lasting reinforcement. Annular or ring-shaped keratoplasty redistributes corneal tension circumferentially, re-establishes anterior-chamber depth, and preserves globe integrity in extensive peripheral disease [4–6]. In this patient, annular PKP achieved long-term anatomic stability; visual decline was most likely related to corticosteroid-induced posterior subcapsular cataract rather than graft failure.

From a mechanistic perspective, peripheral stromal thinning and corneal melt in immune-mediated disease are thought to result from inflammatory-cell infiltration and cytokine-driven upregulation of proteolytic enzymes, particularly matrix metalloproteinases (MMPs), leading to progressive collagen degradation [11]. While adjunctive MMP-modulating therapies such as oral doxycycline have been described in peripheral ulcerative keratitis due to their inhibitory effects on MMP-2 and MMP-9, their role in severe scleritis-associated corneal melt is considered supportive rather than definitive. In advanced, immune-driven disease such as in this case, durable control typically depends on systemic immunosuppression and timely surgical stabilization, rather than local or antimicrobial adjuncts alone [6, 12]. Systemic control of refractory scleritis frequently requires biologic escalation beyond antimetabolites and calcineurin inhibitors. Rituximab has demonstrated efficacy in both idiopathic and systemic-disease–associated scleritis, with durable remission in B-cell-monitored cohorts [7–10]. In this case, rituximab was not simply delayed but was re-introduced after an earlier partial response, using an alternative weekly dosing strategy in the setting of progressive corneal compromise and repeated therapeutic failures. This approach reflects real-world, response-guided escalation commonly required in severe ocular inflammatory disease. Adjunctive IVIG may further enhance immune modulation in recalcitrant ocular inflammation and has been used successfully in severe cicatricial ocular surface disease [13]. The combined regimen here produced stable remission after multiple prior therapeutic failures.

IgG4-related ophthalmic disease was also considered in the differential diagnosis, as it can present with scleritis and may respond favorably to rituximab. In this patient, serum IgG4 levels were within normal limits, and tissue confirmation was not feasible due to the absence of safely accessible biopsy sites and the urgent need for tectonic intervention. While IgG4-related disease could not be entirely excluded, available clinical and laboratory findings made this diagnosis less likely.

Chronic corticosteroid and immunosuppressant exposure can cause systemic toxicity, including hyperglycemia, nephrotoxicity, and cataract formation, highlighting the importance of close systemic monitoring and interdisciplinary collaboration between ophthalmology, rheumatology, and internal medicine. Visual prognosis ultimately depends on posterior-segment integrity and treatment-related lens changes. Even after inflammation subsides, previously thinned or grafted corneas remain susceptible to traumatic dehiscence [14–17].

Future advances in the management of refractory scleritis may involve more personalized immunologic and molecular profiling to guide therapeutic escalation. Areas of active investigation include pathways involved in stromal degradation (such as MMP- and ADAMTS-mediated extracellular matrix remodeling), broader genetic susceptibility and HLA associations beyond routine clinical testing, and targeted biomarker assessment in atypical or treatment-resistant cases. Such approaches may facilitate earlier identification of patients at high risk for progressive corneal melt and support more tailored biologic intervention.In treatment-refractory scleritis with circumferential peripheral corneal stromal thinning, early annular penetrating keratoplasty can provide continuous structural support and restore anterior-segment anatomy when localized grafting is inadequate. Durable remission may require biologic escalation—particularly rituximab, with or without intravenous immunoglobulin, under multidisciplinary supervision. Long-term outcomes are influenced by posterior-segment status, cataract progression, and multidisciplinary care.

Abbreviations

AMT

Amniotic membrane transplantation

AS–OCT

Anterior segment optical coherence tomography

BCVA

Best–corrected visual acuity

IL–6

Interleukin–6

IOP

Intraocular pressure

IVIG

Intravenous immunoglobulin

JAK

Janus kinase

PKP

Penetrating keratoplasty

TNF–α

Tumor necrosis factor–alpha

Author contributions

D.G.F. conceived the study, collected the clinical data, performed the literature review, and drafted the initial manuscript, prepared figures. N.B. contributed to the interpretation of clinical data and provided critical revisions to the manuscript. S.K. contributed to the diagnostic evaluation, interpretation of clinical findings, and substantive editing of the manuscript. C.L. assisted with data acquisition and contributed to the critical review of the manuscript. L.Y.S. supervised patient management, contributed to the interpretation of clinical data, and critically reviewed the manuscript for important intellectual content. T.D. supervised overall clinical care, provided senior guidance, contributed to manuscript revision, and approved the final version as the corresponding author. All authors read and approved the final manuscript.

Funding

No funding was received for this work.

Data availability

All data generated or analyzed during this report are included within the article.

Declarations

Ethics approval and consent to participate

Ethical approval was not required for this single-patient case report in accordance with institutional policy. The report adhered to the principles of the Declaration of Helsinki.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and the accompanying clinical images. All identifying information has been removed.

Competing interests

The authors declare no competing interests.