Management of peripheral corneal melts: a narrative review

Introduction

Background

Peripheral corneal melt is an inflammatory process that progressively thins the corneal stroma and can lead to perforation if left untreated (1). The true incidence is difficult to determine, as there is only one epidemiologic study that examined the incidence of both peripheral and central corneal melts associated with autoimmune disease; they estimated it at 3.01 cases per million adults per year (2). The disease is challenging to diagnose; thus, this figure may not be representative of the true incidence. While “peripheral corneal melt” has various etiologies, the existing literature disproportionately focuses on peripheral ulcerative keratitis (PUK), which is a subset of peripheral melts typically associated with autoimmune diseases (3). As a result, many sections of this review center on PUK, although it does not represent the majority of all peripheral melt etiologies.

The clinical presentation of peripheral corneal melt is typically uncomfortable and painful. Patients often report severe ocular discomfort, redness, tearing, photophobia, and blurry vision, with the latter being attributed to irregular astigmatism resulting from damaged stromal structure (1).

Peripheral corneal melting can also have systemic implications, and often indicates systemic autoimmune diseases or, less commonly, infection (3). Because many published studies focus specifically on PUK, data from PUK literature provide useful insight into peripheral corneal stromal disease that causes peripheral corneal melts. Most PUK cases in the United States and United Kingdom are a manifestation of systemic autoimmune disorders (4). Rheumatoid arthritis (RA) alone accounts for approximately 34% to 42% of autoimmune-associated PUK cases, with granulomatosis with polyangiitis (GPA), polyarteritis nodosa (PAN), and systemic lupus erythematosus (SLE) representing other common etiologies (1). Some have estimated that infections may account for up to 20% of PUK cases (5); however, this particular case series was in India, which has a higher incidence of infectious keratitis than other places, and 20% may be an overestimate of the incidence of infectious corneal melts in the West.

Rationale and knowledge gap

Peripheral corneal melt can cause permanent vision loss if not recognized and managed properly (3). It also has systemic relevance as it often presents along with autoimmune disease (6). Existing literature addresses specific aspects such as systemic immunosuppression, disease-specific etiology, and surgical interventions, but lacks integration of evolving medical and surgical management strategies. Surgical outcomes are not well reported, and optimal timing for intervention in relation to systemic disease control is often unclear.

Due to the devastating consequences associated with peripheral corneal melts, a synthesis of current knowledge, clinical considerations, and options for surgical intervention is necessary for timely, accurate diagnosis and effective management of this condition. Recent reviews have synthesized systemic immunomodulation approaches in PUK but have not integrated these updates with surgical decision-making. This review bridges evolving systemic therapies with modern surgical grafting techniques and interdisciplinary coordination, providing a framework with more clinical utility for ophthalmologists.

Objective

This review summarizes current evidence on pathogenesis, diagnostic challenges, medical therapy, and surgical management of peripheral corneal melt, serving as a guide for ophthalmologists managing this complex condition. We present this article in accordance with the Narrative Review reporting checklist (available at https://aes.amegroups.com/article/view/10.21037/aes-25-50/rc).

Methods

This narrative review synthesized literature on peripheral corneal melts, emphasizing pathogenesis, diagnosis, and management. A literature search was performed from July to October 2025, using PubMed and Google Scholar with combinations of the following keywords: peripheral corneal melt, peripheral ulcerative keratitis, autoimmune keratitis, corneal thinning, corneal transplantation, immunosuppressive therapy, and surgical management.

English-language articles published through October 2025 were included if they addressed the epidemiology, etiology, diagnosis, medical treatment, and/or surgical treatment of peripheral corneal melts. Non-English publications without an English abstract and unrelated studies were excluded (Table 1).

Pathophysiology

The pathogenesis of peripheral corneal melt is primarily immune-mediated, resulting from an interplay between corneal anatomy and systemic inflammation. It represents a localized manifestation of immune dysfunction, triggered by the deposition of immune complexes and driven by destructive enzymatic activity and cellular infiltration.

Immune complex deposition and inflammatory cascade

Most of peripheral corneal melts arise from autoimmune disorders in which circulating antigen-antibody complexes deposit within the peripheral corneal stroma. This immune complex deposition activates the classical complement pathway, which initiates a powerful inflammatory response (7).

Complement activation recruits polymorphonuclear neutrophils (PMNs), monocytes, and macrophages to the peripheral corneal tissue (8). These cells secrete pro-inflammatory cytokines that perpetuate local inflammation, including interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) (8). They also release matrix metalloproteinases (MMPs), especially MMP-1, MMP-2, MMP-8, and MMP-9, that degrade the primary structural components of the corneal stroma, type I and IV collagen (8). Resulting stromal degradation causes progressive thinning and risk for perforation.

Histologic analysis of melted corneal tissue often shows infiltration of inflammatory cells, including neutrophils, plasma cells, lymphocytes, and macrophages (1). This is consistent with a type III hypersensitivity reaction, an immune-complex mediated injury with complement activation (5).

Anatomical and immunologic vulnerability of the peripheral cornea

The peripheral cornea’s predisposition to immune-mediated processes can be attributed to its unique anatomical and immunological features. Unlike the central cornea, the peripheral 1–2 mm region adjacent to the limbus contains an extensive network of blood vessels and lymphatics (9). These structures allow for channeling of immune cells and deposition of immune complexes, leading to the peripheral cornea being more exposed to systemic inflammatory mediators (10).

The dense vascularity not only provides access for immune complexes but also supports antigen-presenting cells such as Langerhans cells and dendritic cells, which are in much lower numbers in the central cornea (9). Proximity to limbal vessels leads to deposition of large immune complexes, such as immunoglobulin M (IgM) and complement components including C3 and C1q, further driving local inflammation (10).

Structurally, the stromal collagen of the peripheral cornea is looser and more irregular near the limbus than in the central cornea, which can cause retention and entrapment of immune complexes (9). This results in the amplification of complement activation and immune cell recruitment.

In contrast, the central cornea remains avascular and immune-privileged. Central melts more commonly arise from local ocular surface disorders such as neurotrophic keratopathy or topical medication toxicity, while peripheral melts usually reflect systemic autoimmune or inflammatory conditions (11).

Differential diagnosis of peripheral corneal melt

Peripheral corneal thinning can arise from autoimmune, infectious, and non-inflammatory degenerative etiologies. Some cause true melting of the corneal stroma, while others mimic melt by causing peripheral non-inflammatory thinning. Recognizing these distinctions is crucial, as misusing immunosuppressive therapy in the setting of an infection or mistaking a non-ulcerative degeneration for an inflammatory melt can lead to serious complications. PUK may also present as the initial manifestation of severe underlying autoimmune disorders, making ophthalmologists essential in early diagnosis and prevention of systemic morbidity (12).

Autoimmune causes

Autoimmune disorders are the predominant cause of non-infectious peripheral corneal melts. RA is the most common association, followed by vascular diseases such as GPA, SLE, PAN, and relapsing polychondritis (1). These typically present with painful, rapidly progressive thinning often adjacent to scleritis, distinguishing them from other purely corneal processes (12) (Figure 1). Ulceration at the peripheral cornea that lacks a clear, uninvolved zone between the ulcer and the limbus is indicative of a systemic autoimmune disease etiology (13). These melts are found bilaterally more frequently than those with other etiologies due to their systemic nature. Prompt recognition is necessary, as aggressive systemic immunosuppression is critical to prevent corneal perforation and vasculitic complications (14).

Figure 1 Slit-lamp photograph showing peripheral corneal thinning with stromal infiltration, conjunctival hyperemia, and episcleral injection. The peripheral cornea demonstrates grayish opacification and active inflammation characteristic of rheumatoid arthritis-associated peripheral ulcerative keratitis. Reproduced from Peripheral Ulcerative Keratitis. Treasure Island (FL): StatPearls Publishing; 2025. Licensed under CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Mooren’s ulcer is an idiopathic autoimmune corneal ulceration that is a diagnosis of exclusion (15). It is not associated with a systemic disorder, and a thorough work-up for systemic autoimmune disease would be negative (16). Mooren’s ulcer can present in two clinical forms: a unilateral benign type, typically affecting older individuals with slower progression, and a bilateral aggressive type, which occurs in younger patients and tends to recur despite therapy. It presents as a painful, crescent-shaped peripheral corneal ulcer beginning 2–3 mm inside the limbus with a vascularized base (17). Inflammation of the sclera is absent adjacent to the peripheral ulcers, distinguishing it from ulcers caused by systemic autoimmune conditions (18). The corneal damage in Mooren’s ulcer also involves the stromal tissue only, leaving an intact endothelium and epithelium (19) (Figure 2).

Figure 2 Slit-lamp photograph demonstrating classic features of Mooren’s ulcer, with peripheral crescent-shaped stromal thinning extending circumferentially and progressing centrally. Areas of focal, critically thinned cornea are most prominent superonasally, accompanied by conjunctival injection and perilimbal vascular congestion. Reproduced from EyeRounds.org, The University of Iowa. Licensed under CC BY-NC-ND 3.0.

Marginal keratitis is an immune-mediated reaction to staphylococcal antigens, often seen in chronic blepharitis (20). It causes small, peripheral stromal infiltrates where the eyelid margin meets the limbus (21) (Figure 3). Lesions in marginal keratitis present with minimal pain, no progressive stromal damage, and a clear zone of about 1–2 mm of unaffected cornea between the inflammation and limbus, distinguishing it from Mooren’s ulcer. Marginal keratitis responds rapidly to topical medications such as antibiotics for blepharitis and topical steroids, differentiating it from PUK (5).

Figure 3 Slit-lamp photograph showing peripheral stromal infiltrates separated from the limbus by a clear zone, with adjacent conjunctival and limbal hyperemia. The localized inflammation is characteristic of active marginal keratitis associated with staphylococcal blepharitis. Reproduced from EyeRounds.org, The University of Iowa. Licensed under CC BY-NC-ND 3.0.

Several other immune-driven processes can cause peripheral corneal melts. Examples include thyroid eye disease (TED), which is an autoimmune condition associated with Graves’ disease that can lead to peripheral keratitis and thinning that mimics PUK (22). Ocular involvement of rosacea can cause chronic peripheral keratitis with superficial vascularization (5). Although rare, PUK has even been found to develop as a manifestation of sarcoidosis and inflammatory bowel disease (5).

In cases of suspected autoimmune or immune-mediated causes of peripheral corneal melts, diagnosis requires a systemic work-up that includes serologic evaluation. Baseline inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) should be obtained to assess systemic inflammatory activity (4). Autoimmune evaluation should include rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) for RA, antinuclear antibodies (ANA) for connective tissue diseases, and antineutrophil cytoplasmic antibodies (ANCA) for vasculitis. Complement levels (C3, C4, CH50) help assess immune complex activity, while elevated angiotensin-converting enzyme (ACE) levels may indicate sarcoidosis (4). Slit-lamp examination and collaboration with rheumatology are essential for diagnosis and management.

Infectious causes

Peripheral infectious keratitis must be excluded early, as immunosuppressive treatment can worsen the disease course. Bacterial ulcers, often associated with contact lens use, commonly involve Pseudomonas, Streptococcus, and Staphylococcus species (23). These ulcers present with intense pain, conjunctival injection, purulent discharge, and often hypopyon, unlike the dry appearance of an immune-related melt (23).

Mycobacterial and spirochetal infections are also on the differential. Mycobacterium tuberculosis infection can directly cause PUK, with ulcers improving after anti-tubercular therapy (24). Syphilitic interstitial keratitis, caused by Treponema pallidum, classically involves the deep corneal stroma, but may occasionally present with peripheral ulceration (25).

Fungal keratitis may also present with peripheral corneal ulcers, with features varying by causal species. Candida can cause stromal infiltration, epithelial defect, and increased conjunctival blood flow in the infected region, while filamentous fungal keratitis may present with a stromal infiltrate that has feathery margins (23). Viral causes of keratitis should also be considered, as herpes simplex virus (HSV) or varicella zoster virus (VZV) can cause a necrotizing stromal keratitis that leads to peripheral thinning and ulceration (5). Herpetic ulcers typically begin with an epithelial defect that then progresses to involve the stroma, and may be less acutely painful than bacterial ulcers (26). Acanthamoeba keratitis causes a ring-shaped infiltrate which can be paracentral or peripheral, often causing severe pain, perineural infiltrates, and nerve enlargement in immunocompromised patients (23).

Diagnosis of infectious PUK relies on corneal scraping for cultures and smears, along with polymerase chain reaction (PCR) testing in atypical cases (23). Treatment involves a pathogen-specific therapy regimen and avoidance of steroid use until the infection is controlled.

Degenerative and non-inflammatory conditions mimicking peripheral corneal melt

Not all peripheral corneal thinning represents true melt or ulceration. Several non-inflammatory degenerative disorders can mimic the appearance of peripheral corneal melt while not causing stromal necrosis or ulceration. These entities feature painless, slow, non-inflammatory thinning of the peripheral cornea that can be mistaken for immune-mediated or infectious processes.

Terrien’s marginal degeneration is an idiopathic corneal degeneration that often affects middle-aged males. It causes peripheral thinning that begins superonasally with a clear zone between the thinning area and the limbus and superficial vascularization at the leading edge of the degeneration (27). It causes slowly progressive thinning with an overhanging edge of intact epithelium, and possible lipid deposition at the margin (27). Patients often present with against-the-rule astigmatism due to the altered corneal shape (5). Absence of stromal infiltrate, ulceration, or pain distinguishes it from PUK (27). Treatment is conservative with glasses or contact lenses prescribed for astigmatism, and surgery is only considered when there is a high risk for perforation (Figure 4).

Figure 4 Slit-lamp photograph showing superior peripheral stromal thinning with an intact epithelium, mild overlying pannus, and lipid deposition at the advancing edge; features characteristic of Terrien’s marginal degeneration. Reproduced from EyeRounds.org, The University of Iowa. Licensed under CC BY-NC-ND 3.0.

Furrow degeneration, is a benign, shallow thinning that occurs in a narrow band in the peripheral cornea, usually between the limbus and an intact arcus senilis in elderly patients (28). It is asymptomatic, non-inflammatory, and non-progressive, requiring no treatment other than observation (5).

Autoimmune-associated peripheral corneal thinning can also occur in patients with systemic autoimmune diseases such as RA, SLE, or GPA. These cases differ from true inflammatory melts in PUK, presenting as painless, non-inflammatory, and slowly progressive thinning with smooth margins and an intact epithelium. Unlike PUK, there is no epithelial defect, vascularization, or adjacent scleritis, and inflammation is minimal or absent.

Careful slit-lamp evaluation is crucial, as misinterpreting these degenerations for ulcerative melts may lead to unnecessary immunosuppression. Ophthalmologists should correlate findings with systemic disease activity to ensure appropriate and timely management.

Ocular surface and local causes

Severe localized ocular surface disorders can cause peripheral corneal melts through mechanical exposure, neurotrophic dysfunction, or chronic inflammation. Recognizing these local causes is critical, as their management differs significantly from immune-mediated or infectious PUK.

Exposure keratopathy results from inadequate eyelid coverage or blinking, leading to epithelial breakdown of the peripheral cornea and eventual stromal melting in exposed areas (29). It is seen in floppy eyelid syndrome (FES) which is characterized by relaxed, easily everted eyelids. FES is often underdiagnosed, and persistent nocturnal exposure leads to recurrent corneal erosions and ulcers that can progress to perforation (30). Unlike autoimmune PUK, exposure-related ulcers are generally sterile and lack stromal infiltrates unless secondarily infected. Identifying lid laxity or incomplete eye closure on exam is key to diagnosis. Contact lens-related peripheral ulcers also cause small peripheral infiltrates with epithelial defects. They are often staphylococcal hypersensitivity or hypoxia-related, resolving with topical antibiotics and discontinued lens use (5).

Neurotrophic keratitis arises from loss of corneal sensation due to due to herpes zoster ophthalmicus, long-standing diabetes mellitus, trigeminal nerve injury, or neurosurgical trauma, impairing epithelial healing (31). These ulcers start as persistent epithelial defects that enlarge and lead to stromal melting, especially in regions with poor tear coverage (32). Neurotrophic ulcers are often painless and show mild inflammation despite sometimes causing severe thinning (31). Corneal sensitivity testing helps confirm diagnosis.

Ocular cicatricial pemphigoid (OCP) is a systemic autoimmune blistering disease that targets the conjunctiva, causing chronic conjunctival inflammation and scarring (33). Peripheral corneal ulcers may develop from limbal immune attack, and resulting melts if left untreated (34). A new onset of peripheral corneal ulcer in a patient with conjunctival scarring should raise suspicion for OCP (35). Conjunctival biopsy with immunofluorescence showing linear Ig/C3 deposition at the basement membrane confirms the diagnosis (33). Recent analysis highlights that OCP-related peripheral corneal ulceration requires early initiation of systemic immunosuppression to prevent scarring and melt progression, emphasizing the need for aggressive systemic therapy in these patients (36).

Steven-Johnson syndrome (SJS) is a condition triggered by factors such as medications and infections that can cause sloughing of the ocular surface, and limbal stem cell deficiency (37). The extreme dry eye and inflammation in chronic SJS can cause peripheral corneal thinning or melting in severe cases (38).

Ocular graft-versus-host disease (oGVHD) after bone marrow transplantation is another condition characterized by relentless inflammation of the conjunctiva, lacrimal glands, and cornea. Beyond the aqueous tear deficiency and filamentary keratitis observed in chronic disease, oGVHD creates a hostile ocular surface environment characterized by epithelial stem cell stress, matrix-degrading enzyme upregulation, and chronic subepithelial fibrosis (39). Together, these factors greatly increase susceptibility to corneal ulcers that can rapidly progress to perforation (40). Because oGVHD involves not only tear film instability but also dysregulated T-cell activity and elevated inflammatory cytokines, associated ulcers often require earlier and more aggressive intervention than other immune-mediated melts. Initial therapy includes lubrication, topical steroids, and serum tears, along with careful adjustment of the patient’s immunosuppressive regimen, as inadequate systemic control allows stromal destruction to continue unchecked (41). Early recognition of these conditions is vital, and the presence of conjunctival disease can be used to distinguish them from other causes.

Finally, chronic use of eye medications such as topical anesthetics and nonsteroidal anti-inflammatory drugs (NSAIDs) causes non-inflammatory stromal melts with minimal pain (42). Detailed medication history is essential for diagnosis, and if caught early, cessation of the offending agent and supportive care leads to gradual healing.

Diagnostic approach

Accurate differentiation among the causes of peripheral corneal melt is essential, as treatment strategies vary by etiology. A structured approach incorporating patient history, clinical presentation, slit-lamp findings, and targeted laboratory evaluation can significantly improve diagnostic accuracy and outcomes.

A detailed history often provides important diagnostic clues. Known autoimmune diseases such as RA, GPA, or PAN strongly favor an immune-mediated PUK, while contact lens use or ocular trauma suggests local or infectious causes. Bilateral ulcers usually indicate systemic disease, while unilateral ulcers in healthy patients would point towards infectious keratitis or Mooren’s ulcer. Inquiring about mucocutaneous disorders (for OCP and SJS) and topical medication use is also critical.

Symptom patterns help guide diagnosis. Severe pain with rapid progression over days to weeks is characteristic of autoimmune and infectious ulcers, while painless chronic thinning occurs in degenerative causes such as Terrien’s marginal degeneration or pellucid marginal degeneration (PMD). Mild irritation or chronic redness without severe pain may indicate marginal keratitis or exposure keratopathy. Painless necrosis may reflect neurotrophic keratopathy or corticosteroid-induced melt.

Slit-lamp microscopy remains essential in diagnosis. A clear zone of around 1 to 2 mm between the lesion and limbus suggests marginal keratitis, while absence of separation supports autoimmune PUK (43). Painful, crescent-shaped ulcers with a narrow clear zone are suggestive of Mooren’s ulcer. The morphology of the ulceration also provides diagnostic clues. An overhanging or undermined edge with adjacent stromal infiltrates indicates active immune destruction, while dense, necrotic infiltrates are more characteristic of infectious etiology. In contrast, thinning with intact epithelium and no infiltrate points to degenerative disease such as Terrien’s or furrow degeneration (27). Vascular and scleral involvement also aid differentiation: autoimmune PUK presents with adjacent necrotizing scleritis, Mooren’s ulcer spares the sclera, marginal keratitis shows superficial vascularization without scleritis, and degenerative thinning causes minimal vascular response.

Laboratory evaluation is essential when infectious or systemic causes are suspected. Corneal scraping for Gram stain, culture, and PCR, should precede corticosteroid or immunosuppressive therapy. Systemic work-up should include tests for RF, anti-CCP, ANA, ANCA, and inflammatory markers such as ESR and CRP (4). Additional tests, such as syphilis serology, thyroid function and antibody panels, serum ACE levels, and chest imaging (for sarcoidosis or tuberculosis) are obtained according to clinical suspicion. Rheumatology consultation is essential to ensure appropriate systemic work-up and management. The diagnostic approach can be summarized in a structured algorithm (Figure 5).

Figure 5 Flowchart outlining a systematic approach to evaluating peripheral corneal thinning or ulceration. The algorithm differentiates autoimmune, infectious, degenerative, and mechanical etiologies and emphasizes key diagnostic clues such as epithelial integrity, stromal infiltration, and serologic findings. The surgical management pathway (indicated by asterisks) includes cyanoacrylate glue application, amniotic membrane transplantation, conjunctival resection, corneal grafting, and limbal stem cell transplantation. *, surgical management options include cyanoacrylate glue application, amniotic membrane transplantation, conjunctival resection, corneal grafting, and limbal stem cell transplantation. ANA, antinuclear antibodies; ANCA, antineutrophil cytoplasmic antibodies; anti-CCP, anti-cyclic citrullinated peptide; CBC, complete blood count; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; GPA, granulomatosis with polyangiitis; PCR, polymerase chain reaction; PUK, peripheral ulcerative keratitis; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus.

Medical management

The management of peripheral corneal melt requires a stepwise, directed approach aimed at controlling the primary disease, halting corneal damage, and addressing structural instability when present. Early, coordinated intervention involving ophthalmologists, rheumatologists, and infectious disease specialists is essential for preserving vision and preventing exacerbation.

Control of the primary disease

The first priority is controlling the underlying cause of corneal melt, as ongoing inflammation will continue to drive stromal degradation. In immune-mediated melts such as those associated with RA, GPA, and SLE, systemic immunosuppression is the basis of treatment (11). Coexisting necrotizing scleritis should prompt urgent escalation of immunosuppression, as it signifies high risk for both ocular perforation and systemic vasculitis flares. However, immunosuppression is also indicated for autoimmune-mediated corneal melt without scleritis, as stromal melt can progress aggressively even when scleral inflammation is not visible. Systemic corticosteroids are used primarily for initial immunosuppressive therapy. Prednisone (1 mg/kg/day, up to 60 mg) is escalated to intravenous methylprednisolone (1 g/day for 3 consecutive days) if vision or tissue integrity is threatened (1). On their own, however, corticosteroids are not sufficient for sustained control of disease. Steroid-sparing immunosuppressants such as cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil are administered early to maintain long-term control (14).

Emerging data have expanded the available therapeutic options beyond traditional cytotoxic and antimetabolite agents. Biologic therapies, particularly anti-CD20 monoclonal antibodies like rituximab and TNF-α inhibitors such as infliximab, have proven effective in controlling systemic inflammation and stopping corneal destruction (14). Janus kinase (JAK) inhibitors such as Baricitinib have also been explored with promising results as an effective therapy in severe autoimmune-mediated melts that are resistant to biologics, thanks to their targeted modulation of interleukin 6 (IL-6) and interferon signaling pathways (44). Given the systemic nature of immune-mediated corneal melts, coordinated care with rheumatology improves diagnosis, therapy selection, and treatment timing (12). Proper coordination of shared protocols, such as tapering schedules for immunosuppressants and monitoring for hepatotoxicity or cytopenia improves both ocular and systemic outcomes (14). Incorporating a rheumatology evaluation at presentation of PUK should be standard practice.

When an infectious cause is suspected, pathogen-specific antimicrobial therapy must be initiated immediately after diagnostic corneal scraping. Broad-spectrum topical antibiotics such as levofloxacin or moxifloxacin are first-line for presumed bacterial ulcers (23). Viral ulcers caused by herpes simplex or varicella zoster respond well to topical or systemic antivirals such as ganciclovir or acyclovir (23).

Topical corticosteroids should be avoided in the acute infectious phase and only introduced after clear improvement or a culture-positive diagnosis to minimize the risk of worsening infection, as can happen with amebic or fungal disease. Infection control must be achieved before an immunosuppressive therapy is considered.

In cases related to contact lens use, discontinuation of lens wear is the priority to eliminate both mechanical irritation and exposure to microbes (5). Lubrication with preservative-free artificial tears promotes epithelial healing and topical antibiotics can be administered as necessary.

Halting corneal destruction

Once the underlying disease is controlled, the focus of treatment should shift to the prevention of further corneal stromal breakdown. This focuses on suppressing enzymatic degradation and preserving stromal integrity.

Stromal melting is driven by MMPs and neutrophil-derived collagenases. Oral doxycycline (100 mg twice daily) acts as a systemic MMP inhibitor, reducing the degradation of collagen and stabilizing corneal tissue (45). Topical anti-collagenase agents such as N-acetylcysteine (10–20%) or 1% medroxyprogesterone can also be utilized as adjunctive therapy to inactivate collagenases and protect from further damage (5). Vitamin C supplementation may support collagen synthesis, although evidence is limited (46).

Systemic corticosteroids are essential in the management of autoimmune PUK but should be used cautiously on the ocular surface. Topical corticosteroids are generally contraindicated in active corneal melt. These agents can suppress epithelial healing and accelerate stromal degradation, thereby worsening the melt (47). Topical calcineurin inhibitors such as cyclosporine A 1–2% or tacrolimus 0.03% may be used to suppress T-cell activity without derailing epithelial repair, providing an alternative treatment to steroids that achieves immune inhibition (5).

Preservative-free artificial tears are administered frequently to maintain ocular hydration, dilute inflammatory cytokines, and reduce frictional trauma (48). Lubricating ointments and bandage contact lenses can be utilized to aid in the process of restoring the epithelium (5). Topical antibiotics such as fluoroquinolones can also be used prophylactically to prevent infection while epithelial defects are still in the process of healing.

Management of perforation risk

If corneal thinning progresses to the point of severe perforation risk and threatens corneal integrity, or if a perforation develops despite medical therapy, surgical intervention is indicated as a last resort. The appropriate surgical approach varies depending on the size, location, and cause of the melt, as discussed in detail in the next section (surgical management).

Surgical management and techniques

Indications and timing of surgery

Although systemic immunosuppression is the foundation of management for peripheral corneal melting, surgical intervention becomes necessary when medical therapy fails to stop disease progression or when the structural integrity of the eye becomes compromised (49). Surgery can serve as a short-term solution during the acute phase of disease, particularly in the case of perforation, or as a definitive solution after inflammation is under control. The decision to proceed with surgery depends on many factors, including the severity of stromal thinning, the presence of active or impending perforation, and the underlying cause of the disease (50).

Tissue adhesives

Tissue adhesives are an effective tool to temporize acute corneal perforations. When small perforations, typically those with diameters under 3 mm, or focal areas of severe thinning are present in the acute phase of the disease, tissue adhesives such as cyanoacrylate glue can be applied directly to the target sites on the cornea (51). Cyanoacrylate is effective in both providing a mechanical seal to prevent aqueous leakage and in acting as a temporary barrier against matrix MMPs, thereby preventing further stromal degradation (51). A bandage contact lens is typically placed over the glue to improve patient comfort and promote epithelial healing (52).

The ultimate goal of tissue adhesives is to maintain ocular integrity while the systemic inflammation is controlled. Once this transpires, epithelialization of the defect can occur, and the glue can be removed or fall off on its own.

Amniotic membrane transplantation (AMT)

AMT is an increasingly utilized adjunct in the surgical management of peripheral corneal melt. Amniotic membrane is the innermost layer of the placenta and has immunomodulatory, anti-inflammatory, and epithelial healing factors (53). It downregulates pro-inflammatory cytokines such as IL-1 and TNF-α, inhibits neutrophil and macrophage activation, and suppresses T-cell infiltration (54). It also promotes epithelial cell migration by releasing growth factors such as epidermal growth factor (EGF) and transforming growth factor-β (TGF-β), while providing a scaffolding that supports epithelial and stromal regeneration (54).

Three AMT surgical techniques; the inlay, onlay, and sandwich methods, are particularly relevant to the treatment of peripheral stromal thinning. The inlay techniques places the amniotic membrane within a corneal stromal defect as a permanent basement membrane substitute, sutured with the epithelial side facing upward to allow migration of host epithelial cells across its surface to promote re-epithelialization (55). This method is particularly suitable for persistent epithelial defects and moderate stromal thinning, as it supports epithelial healing while also contributing to structural stabilization. In cases of deeper stromal involvement, multilayered grafting may be employed to reinforce the affected area.

The onlay technique serves as temporary surface patch. Rather than integrating into the corneal stroma, the membrane is placed loosely over the eye, providing a moist and protective environment that mitigates inflammation and promotes epithelial healing (55). It is generally used in the acute setting or as a short-term measure to halt exacerbation of the melt before transitioning to more definitive surgical intervention. The membrane typically detaches from the cornea in one to two weeks and may be replaced as needed.

The sandwich technique combines elements of both the inlay and onlay methods. In this technique, the amniotic membrane is first implanted within the stromal defect and then covered with an additional membrane applied as a patch (55). This dual-layer strategy provides both structural support and enhanced surface healing, making it especially appropriate in cases of deep corneal ulceration, descemetocele formation, or impending perforation. The inner graft integrates with the host tissue, while the external layer shields the repair site and helps preserve a favorable healing environment (55).

AMT is considered most effective in perforations that are smaller than 1 mm in diameter (56). Techniques such as the “Swiss-roll” method, where a rolled segment of amniotic membrane is inserted into the site of the ulcer, have also successfully been employed to stabilize small perforations (57). This technique’s viability in treating deep perforations makes it an important procedure in the surgical management of peripheral corneal melts. AMT is typically secured using tissue adhesive and a bandage contact lens and is often used in conjunction with other surgical procedures (58).

Conjunctival resection

Conjunctival resection plays an important role in the surgical management of immune-mediated corneal melts. This procedure involves the surgical excision of inflamed conjunctiva adjacent to the site of corneal melting, with the goal of removing the key source of immune cells along with inflammatory cytokines and enzymes (59). To carry out this procedure, the surgeon anesthetizes the patient’s target eye and makes peritomy incisions to separate and remove a strip of conjunctiva adjacent to the corneal ulcer, sometimes extending a few clock hours on each side. The site of the procedure is then either left bare or lightly cauterized (50).

By disrupting the pathway for local inflammation, conjunctival resection can effectively reduce disease activity and stabilize the cornea. The extent of resection varies depending on the size of the lesion and can range from a focal excision to a 360-degree peritomy, in which the conjunctiva is excised from the circumference of the cornea (60). In cases with concurrent scleritis, where the lesion is localized (1), and Mooren’s ulcer, where the adjacent conjunctiva is often densely infiltrated with plasma cells, conjunctival resection has been shown to be effective in controlling disease (50). This procedure is often combined with other therapies such as cyanoacrylate glue or systemic immunosuppression along with tissue adhesives for optimal success. The procedure is considered relatively low risk, and can be repeated if the ulcer enlarges (50).

Corneal grafting

In cases of severe melting or large perforations, particularly those with a diameter larger than 3 mm, corneal transplantation may become necessary. Lamellar keratoplasty (LK), involving crescentic or sectoral grafts tailored to the site of thinning, is preferred when the central cornea and endothelium remain intact (50). LK can provide structural support while preserving the patient’s corneal endothelium, leading to a diminished risk of graft rejection (61). This technique offers superior long-term stability compared to penetrating approaches.

Penetrating keratoplasty (PKP) carries a poor prognosis, especially when performed during active inflammation or systemic disease, and should be avoided whenever possible. Peripheral PKP is particularly challenging due to proximity to limbal vasculature, increasing vascularization, inflammation, and wound-healing complications (50).

For patients receiving a tectonic graft, the procedure must be coupled with post-operative and intra-operative systemic immunosuppression to prevent continued tissue destruction and graft failure (14). In a melt with imminent risk of perforation, urgent surgical intervention must be performed to preserve the eye, often through utilization of a tectonic graft. Because the keratoplasty on its own does not halt the underlying inflammatory process, corneal ulceration can recur if the disease remains active. Due to this, grafts placed during active PUK have high failure rates, with many patients requiring multiple grafts due to melt recurrence (62).

Controlling the underlying autoimmune disorder before and after repeat keratoplasty dramatically improves graft survival, and improves the likelihood of having clear, intact grafts in long-term follow-ups (50). Conversely, attempting a corneal transplant while the peripheral keratitis is still active increases risk of re-melting of the graft and transplant failure (63). For this reason, repeat procedures should be considered when inflammation of the eye is quiet, and the patient’s systemic conditions are well-controlled.

Recent surgical innovations have further expanded options for tectonic reconstruction. Lamellar keratoplasty techniques utilizing femtosecond laser-guided corneal grafts from small incision refractive lenticule extraction (SMILE) has been shown to be effective in treating corneal ulcer and perforation (63). Decellularized corneal scaffolds are under active investigation for use as alternatives in high-risk melts where rejection risk limits traditional keratoplasty. Recent studies have shown that this material demonstrates biocompatibility and effective structural restoration, meaning it could serve as a potential alternative that reduces recurrence of immune-mediated graft melt (64). Additionally, bioengineered collagen matrices are also in development as an alternative material, with promising signs of corneal stromal regeneration and human biocompatibility (65). Emergence of new surgical techniques and new corneal graft alternatives demonstrates the evolving landscape of surgical management.

Limbal stem cell transplantation (LSCT)

In cases of severe peripheral corneal melts, especially when associated with significant limbal stem cell deficiency or ocular surface failure, peripheral LSCT is an important adjunctive or standalone surgical option. The objective of modern corneal surface reconstruction has evolved beyond mere structural preservation toward the restoration of a physiologically functional ocular surface. LSCT seeks to re-establish the limbal microenvironment, which is vital in corneal epithelial regeneration and long-term graft survival (66).

Limbal stem cells maintain corneal homeostasis through slow cycling, asymmetric division, and centripetal migration of progenitor cells (67). Damage to these cells, as occurs in inflammatory or autoimmune conditions, predisposes the cornea to epithelial breakdown and vascularization. Replenishing this reservoir with autologous or allogenic limbal tissue can reduce postoperative complications such as graft melt, vascular ingrowth, and immune rejection, which are especially common in high-risk peripheral keratoplasty cases.

Experimental and clinical data support this approach. Clinical studies have demonstrated the effectiveness of LSCT in restoring the epithelium of compromised corneas, even in complex settings such as amniotic membrane dissolution or chronic inflammation (68). More recent advances in ex vivo techniques have allowed for transplantation of cultivated limbal epithelial sheets, achieving success rates of around 70 to 80% in restoring ocular surface stability and transparency (69).

LCST can be performed in conjunction with Lamellar keratoplasty to enhance epithelialization and protect the donor graft. By restoring the limbal barrier, LSCT promotes epithelial regeneration while suppressing conjunctival ingrowth and neovascularization, which are significant contributors to recurrent melt and graft failure (69).

In summary, surgical management of peripheral corneal melt must be individualized, with careful consideration of the stage of disease, extent of structural damage, and the underlying systemic condition in each specific case. While surgical techniques have expanded and advanced over time, their success remains dependent on how well systemic control is carried out (4).

Strengths and limitations

The review offers a comprehensive synthesis of the current understanding of peripheral corneal melt, encompassing pathogenesis, diagnosis, and management strategies. However, its conclusions are limited by the availability of high-quality evidence. A significant portion of the evidence utilized originates from case series, retrospective studies, and expert opinion, which may limit the generalizability of the review. Future research should focus on prospective, multicenter studies and be standardized to strengthen the evidence guiding both medical and surgical.

Conclusions

Peripheral corneal melt represents a severe, multifactorial condition requiring timely recognition and appropriate therapy. Accurate differentiation between autoimmune and infectious cases is vital, as treatment strategies for each differ significantly. In immune-mediated cases, systemic immunosuppression is the foundation of therapy and must be administered to stop stromal degradation. Surgical interventions, including tissue adhesives, conjunctival resection, AMT, and corneal grafting, provide structural support. However, they should be reserved for when there is imminent risk of perforation or as a last resort treatment when medical management is not sufficient. Elective surgery should be performed once systemic inflammation is controlled to optimize graft survival and reduce the risk of postoperative complications. This review consolidates current diagnostic and management strategies to guide clinicians in optimizing outcomes in this sight-threatening disease. Looking ahead, future research will be essential to develop stronger evidence, refine treatment algorithms, and improve patient outcomes in this vision-threatening condition.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Roy S. Chuck, Joann J. Kang and Viral V. Juthani) for the series “Inflammatory Disorders of the Cornea and Ocular Surface” published in Annals of Eye Science. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://aes.amegroups.com/article/view/10.21037/aes-25-50/rc

Peer Review File: Available at https://aes.amegroups.com/article/view/10.21037/aes-25-50/prf

Funding: This study was supported by the New York Eye and Ear Foundation grant (grant No. 1034-0887-0000 to S.A.) and a grant by the Research to Support Blindness (grant No. IN131551012 to S.A.).

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://aes.amegroups.com/article/view/10.21037/aes-25-50/coif). The series “Inflammatory Disorders of the Cornea and Ocular Surface” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Galor A, Thorne JE. Scleritis and peripheral ulcerative keratitis. Rheum Dis Clin North Am 2007;33:835-54. vii. [Crossref] [PubMed]
2. McKibbin M, Isaacs JD, Morrell AJ. Incidence of corneal melting in association with systemic disease in the Yorkshire Region, 1995-7. Br J Ophthalmol 1999;83:941-3. [Crossref] [PubMed]
3. Knox Cartwright NE, Tole DM, Georgoudis P, et al. Peripheral ulcerative keratitis and corneal melt: a 10-year single center review with historical comparison. Cornea 2014;33:27-31. [Crossref] [PubMed]
4. Maleki A, Valerio T, Massoudi Y, et al. Updates on Systemic Immunomodulation in Peripheral Ulcerative Keratitis. J Clin Transl Ophthalmol 2024;2:131-139.
5. Hassanpour K, H, ElSheikh R, Arabi A, et al. Peripheral Ulcerative Keratitis: A Review. J Ophthalmic Vis Res 2022;17:252-75. [Crossref] [PubMed]
6. Cao Y, Zhang W, Wu J, et al. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment. J Ophthalmol 2017;2017:7298026. [Crossref] [PubMed]
7. Ladas JG, Mondino BJ. Systemic disorders associated with peripheral corneal ulceration. Curr Opin Ophthalmol 2000;11:468-71. [Crossref] [PubMed]
8. Dana MR, Qian Y, Hamrah P. Twenty-five-year panorama of corneal immunology: emerging concepts in the immunopathogenesis of microbial keratitis, peripheral ulcerative keratitis, and corneal transplant rejection. Cornea 2000;19:625-43. [Crossref] [PubMed]
9. Messmer EM, Foster CS. Vasculitic peripheral ulcerative keratitis. Surv Ophthalmol 1999;43:379-96. [Crossref] [PubMed]
10. Mondino BJ, Brady KJ. Distribution of hemolytic complement in the normal cornea. Arch Ophthalmol 1981;99:1430-3. [Crossref] [PubMed]
11. Medsinge A, Gajdosova E, Moore W, et al. Management of inflammatory corneal melt leading to central perforation in children: a retrospective study and review of literature. Eye (Lond) 2016;30:593-601. [Crossref] [PubMed]
12. Artifoni M, Rothschild PR, Brézin A, et al. Ocular inflammatory diseases associated with rheumatoid arthritis. Nat Rev Rheumatol 2014;10:108-16. [Crossref] [PubMed]
13. Ngoei E. Mooren’s ulcer vs. PUK: The difference can mean life or death. EyeWorld [Internet]. 2012. Available online: https://www.eyeworld.org/2012/moorens-ulcer-vs-puk-the-difference-can-mean-life-or-death/
14. Kate A, Basu S. Systemic Immunosuppression in Cornea and Ocular Surface Disorders: A Ready Reckoner for Ophthalmologists. Semin Ophthalmol 2022;37:330-44. [Crossref] [PubMed]
15. Alhassan MB, Rabiu M, Agbabiaka IO. Interventions for Mooren's ulcer. Cochrane Database Syst Rev 2014;2014:CD006131. [Crossref] [PubMed]
16. Chow CY, Foster CS. Mooren's ulcer. Int Ophthalmol Clin 1996;36:1-13. [Crossref] [PubMed]
17. Watson PG. Management of Mooren's ulceration. Eye (Lond) 1997;11:349-56. [Crossref] [PubMed]
18. Sangwan VS, Zafirakis P, Foster CS. Mooren's ulcer: current concepts in management. Indian J Ophthalmol 1997;45:7-17.
19. Taylor CJ, Smith SI, Morgan CH, et al. HLA and Mooren's ulceration. Br J Ophthalmol 2000;84:72-5. [Crossref] [PubMed]
20. Cohn H, Mondino BJ, Brown SI, et al. Marginal corneal ulcers with acute beta streptococcal conjunctivitis and chronic dacryocystitis. Am J Ophthalmol 1979;87:541-3. [Crossref] [PubMed]
21. Moshirfar M, Somani SN, Tingey MT, et al. Marginal Keratitis with Secondary Diffuse Lamellar Keratitis After Small Incision Lenticule Extraction (SMILE) After Initiation of Continuous Positive Airway Pressure (CPAP) Therapy. Int Med Case Rep J 2020;13:685-9. [Crossref] [PubMed]
22. Scarabosio A, Surico PL, Singh RB, et al. Thyroid Eye Disease: Advancements in Orbital and Ocular Pathology Management. J Pers Med 2024;14:776. [Crossref] [PubMed]
23. Cabrera-Aguas M, Khoo P, Watson SL. Infectious keratitis: A review. Clin Exp Ophthalmol 2022;50:543-62. [Crossref] [PubMed]
24. Wang S, Gong Y, Huang K, et al. Peripheral ulcerative keratitis secondary to tuberculosis: A case report and literature review. Medicine (Baltimore) 2024;103:e39482. [Crossref] [PubMed]
25. Vignesh AP, Srinivasan R, Vijitha S. Ocular syphilis masquerading as bilateral peripheral ulcerative keratitis. Taiwan J Ophthalmol 2016;6:204-5. [Crossref] [PubMed]
26. Praidou A, Androudi S, Kanonidou E, et al. Bilateral herpes simplex keratitis presenting as peripheral ulcerative keratitis. Cornea 2012;31:570-1. [Crossref] [PubMed]
27. Ding Y, Murri MS, Birdsong OC, et al. Terrien marginal degeneration. Surv Ophthalmol 2019;64:162-74. [Crossref] [PubMed]
28. Moshirfar M, Villarreal A, Ronquillo Y. Furrow Degeneration. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2025 [cited 2025 Oct 6]. Available online: http://www.ncbi.nlm.nih.gov/books/NBK557532/
29. Rodriguez-Garcia A, Ruiz-Lozano RE, Barcelo-Canton RH, et al. The etiologic and pathogenic spectrum of exposure keratopathy: Diagnostic and therapeutic implications. Surv Ophthalmol 2025;70:882-99. [Crossref] [PubMed]
30. Scarabosio A, Surico PL, Patanè L, et al. The Overlooked Floppy Eyelid Syndrome: From Diagnosis to Medical and Surgical Management. Diagnostics (Basel) 2024;14:1828. [Crossref] [PubMed]
31. Gurnani B, Feroze KB, Patel BC. Neurotrophic Keratitis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2025 [cited 2025 Oct 6]. Available online: http://www.ncbi.nlm.nih.gov/books/NBK431106/
32. Semeraro F, Forbice E, Romano V, et al. Neurotrophic keratitis. Ophthalmologica 2014;231:191-7. [Crossref] [PubMed]
33. Branisteanu DC, Stoleriu G, Branisteanu DE, et al. Ocular cicatricial pemphigoid Exp Ther Med 2020;20:3379-82. (Review). [Crossref] [PubMed]
34. Stan C, Diaconu E, Hopirca L, et al. Ocular cicatricial pemphigoid. Rom J Ophthalmol 2020;64:226-30.
35. Ramos-Dávila EM, Ruiz-Lozano RE, Rodríguez-García A, et al. Childhood-onset ocular mucous membrane pemphigoid presenting with peripheral ulcerative keratitis: a case report and review of the literature. J Ophthalmic Inflamm Infect 2025;15:47. [Crossref] [PubMed]
36. Ghanbari H, Rahimi M, Momeni A, et al. Challenges and advances in ocular mucous membrane pemphigoid (OMMP); from pathogenesis to treatment strategies. Graefes Arch Clin Exp Ophthalmol 2025;263:1489-502. [Crossref] [PubMed]
37. Akgun Z, Palamar M, Egrilmez S, et al. Severity Classification of Limbal Stem Cell Failure Due to Steven Johnson Syndrome in the Light of the Classification Consensus of Limbal Stem Cell Deficiency. Eye Contact Lens 2024;50:159-62. [Crossref] [PubMed]
38. Isawi H, Dhaliwal DK. Corneal melting and perforation in Stevens Johnson syndrome following topical bromfenac use. J Cataract Refract Surg 2007;33:1644-6. [Crossref] [PubMed]
39. Soleimani M, Mahdavi Sharif P, Cheraqpour K, et al. Ocular graft-versus-host disease (oGVHD): From A to Z. Surv Ophthalmol 2023;68:697-712. [Crossref] [PubMed]
40. Singh RB, Cho W, Liu C, et al. Immunopathological mechanisms and clinical manifestations of ocular graft-versus-host disease following hematopoietic stem cell transplantation. Bone Marrow Transplant 2024;59:1049-56. [Crossref] [PubMed]
41. Dietrich-Ntoukas T, Cursiefen C, Westekemper H, et al. Diagnosis and treatment of ocular chronic graft-versus-host disease: report from the German-Austrian-Swiss Consensus Conference on Clinical Practice in chronic GVHD. Cornea 2012;31:299-310. [Crossref] [PubMed]
42. Rigas B, Huang W, Honkanen R. NSAID-induced corneal melt: Clinical importance, pathogenesis, and risk mitigation. Surv Ophthalmol 2020;65:1-11. [Crossref] [PubMed]
43. Aslan Bayhan S, Bayhan HA, Adam M, et al. Marginal keratitis after intravitreal injection of ranibizumab. Cornea 2014;33:1238-9. [Crossref] [PubMed]
44. Calvo-Río V, Sánchez-Bilbao L, Álvarez-Reguera C, et al. Baricitinib in severe and refractory peripheral ulcerative keratitis: a case report and literature review. Ther Adv Musculoskelet Dis 2022;14:1759720X221137126.
45. Smith VA, Cook SD. Doxycycline-a role in ocular surface repair. Br J Ophthalmol 2004;88:619-25. [Crossref] [PubMed]
46. Cho YW, Yoo WS, Kim SJ, et al. Efficacy of systemic vitamin C supplementation in reducing corneal opacity resulting from infectious keratitis. Medicine (Baltimore) 2014;93:e125. [Crossref] [PubMed]
47. Yagci A. Update on peripheral ulcerative keratitis. Clin Ophthalmol 2012;6:747-54. [Crossref] [PubMed]
48. Stodola E. Peripheral ulcerative keratitis diagnosis and management. 2024. Available online: https://www.eyeworld.org/2024/peripheral-ulcerative-keratitis-diagnosis-and-management/
49. Krysik K, Dobrowolski D, Lyssek-Boron A, et al. Differences in Surgical Management of Corneal Perforations, Measured over Six Years. J Ophthalmol 2017;2017:1582532. [Crossref] [PubMed]
50. Sabhapandit S, Murthy SI, Sharma N, et al. Surgical Management of Peripheral Ulcerative Keratitis: Update on Surgical Techniques and Their Outcome. Clin Ophthalmol 2022;16:3547-57. [Crossref] [PubMed]
51. Vote BJ, Elder MJ. Cyanoacrylate glue for corneal perforations: a description of a surgical technique and a review of the literature. Clin Exp Ophthalmol 2000;28:437-42. [Crossref] [PubMed]
52. Tuli S, Gray M. Surgical management of corneal infections. Curr Opin Ophthalmol 2016;27:340-7. [Crossref] [PubMed]
53. Solomon A, Meller D, Prabhasawat P, et al. Amniotic membrane grafts for nontraumatic corneal perforations, descemetoceles, and deep ulcers. Ophthalmology 2002;109:694-703. [Crossref] [PubMed]
54. Parmar UPS, Surico PL, Scarabosio A, et al. Amniotic Membrane Transplantation for Wound Healing, Tissue Regeneration and Immune Modulation. Stem Cell Rev Rep 2025;21:1428-48. [Crossref] [PubMed]
55. Meller D, Pauklin M, Thomasen H, et al. Amniotic membrane transplantation in the human eye. Dtsch Arztebl Int 2011;108:243-8. [Crossref] [PubMed]
56. Prabhasawat P, Tesavibul N, Komolsuradej W. Single and multilayer amniotic membrane transplantation for persistent corneal epithelial defect with and without stromal thinning and perforation. Br J Ophthalmol 2001;85:1455-63. [Crossref] [PubMed]
57. Chan E, Shah AN, O'Brart DP. "Swiss roll" amniotic membrane technique for the management of corneal perforations. Cornea 2011;30:838-41. [Crossref] [PubMed]
58. Mead OG, Tighe S, Tseng SCG. Amniotic membrane transplantation for managing dry eye and neurotrophic keratitis. Taiwan J Ophthalmol 2020;10:13-21. [Crossref] [PubMed]
59. Wilson FM 2nd, Grayson M, Ellis FD. Treatment of peripheral corneal ulcers by limlial conjunctivectomy. Br J Ophthalmol 1976;60:713-9. [Crossref] [PubMed]
60. Zemba M, Stamate AC, Tataru CP, et al. Conjunctival flap surgery in the management of ocular surface disease Exp Ther Med 2020;20:3412-6. (Review). [Crossref] [PubMed]
61. Sharma A, Sharma R. Customized therapeutic deep anterior lamellar keratoplasty in perforated Mooren's ulcer: A novel technique. Indian J Ophthalmol 2024;72:130-133. [Crossref] [PubMed]
62. Bernauer W, Ficker LA, Watson PG, et al. The management of corneal perforations associated with rheumatoid arthritis. An analysis of 32 eyes. Ophthalmology 1995;102:1325-37. [Crossref] [PubMed]
63. Ang M, Mehta JS, Sng CC, et al. Indications, outcomes, and risk factors for failure in tectonic keratoplasty. Ophthalmology 2012;119:1311-9. [Crossref] [PubMed]
64. Kim CY, Jeong C, Lee H, et al. Corneal Endothelium Regeneration with Decellularized Porcine Corneal Extracellular Matrix Scaffolds. Tissue Eng Regen Med 2025;22:735-46. [Crossref] [PubMed]
65. Koulikovska M, Rafat M, Petrovski G, et al. Enhanced regeneration of corneal tissue via a bioengineered collagen construct implanted by a nondisruptive surgical technique. Tissue Eng Part A 2015;21:1116-30. [Crossref] [PubMed]
66. Basu S, Mohamed A, Chaurasia S, et al. Clinical outcomes of penetrating keratoplasty after autologous cultivated limbal epithelial transplantation for ocular surface burns. Am J Ophthalmol 2011;152:917-924.e1. [Crossref] [PubMed]
67. Tseng SC. Concept and application of limbal stem cells. Eye (Lond) 1989;3:141-57. [Crossref] [PubMed]
68. Song QS, Fan HY, Chen ZL. Clinical observation of the corneal limbus stem cell transplantation on treating amniotic membrane dissolving after pterygium resection with amniotic membrane transplantation. Int J Ophthalmol 2016;16:365-366.
69. Yoon JJ, Ismail S, Sherwin T. Limbal stem cells: Central concepts of corneal epithelial homeostasis. World J Stem Cells 2014;6:391-403. [Crossref] [PubMed]