---
title: "Severity-based surgical algorithm for refractory Mooren’s ulcer preserves globe integrity"
id: "plos-one-12-evaluation-of-a-severity-based-surgical-strategy-for-refractory-mooren-s-ulcer"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-12-evaluation-of-a-severity-based-surgical-strategy-for-refractory-mooren-s-ulcer"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359413"
published_at: "2026-09-30T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Severity-based surgical algorithm for refractory Mooren’s ulcer preserves globe integrity
## Provenance & Clinical Metadata
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- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359413)
- **Published At:** 2026-09-30T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This retrospective series reviewed 24 eyes with **refractory Mooren’s ulcer** treated surgically after failing maximal medical therapy and adjunctive conjunctival resection, using a predefined severity-based algorithm (AMT, LK, PK). - Inclusion required progressive disease despite at least 3 weeks of maximal medical therapy or rapid melting with impending/actual perforation; systemic autoimmune and infectious causes were excluded by laboratory and microbiological testing. - Surgical allocation: **AMT** for ulcers 4 mm or when LK was infeasible. - All patients received standardized postoperative topical and systemic immunosuppression (topical prednisolone acetate tapered over months; oral prednisolone and cyclosporine A), and long-term maintenance topical fluorometholone for keratoplasty cases as indicated. - Primary healing rates were high: 100% for AMT and PK groups and 93.3% for LK (overall 95.8%). - Visual outcomes: BCVA improved or stabilized in 71.4% of AMT and 86.7% of LK eyes; functional vision (BCVA ≥ 0.3) was reached in 71.4% of AMT eyes but only 13.3% of LK eyes. PK eyes had poor functional outcomes (hand motion to no light perception). - Recurrence rates differed by procedure: 28.6% for AMT, 64.3% for LK, and 100% for PK. Median recurrence-free survival for LK was 36 months by Kaplan–Meier analysis. - Final anatomic success (globe preservation without phthisis, enucleation, or evisceration) was achieved in 85.7% of AMT, 93.3% of LK, and 50.0% of PK eyes, yielding an overall globe preservation rate of 87.5% (21/24). - Authors conclude a severity-graded surgical approach can effectively preserve globe integrity in refractory cases; keratoplasty-level disease reflects more aggressive biology and higher recurrence risk, necessitating vigilant long-term follow-up and sustained immunomodulation. - Study limitations inherent to the report: retrospective design, single-center series, and small numbers — details of these limitations were presented within the source manuscript.
## Clinical Analysis & Structured Key Points
Evaluation of a severity-based surgical strategy for refractory Mooren’s ulcer: A retrospective series with long-term follow-up | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Reader Comments Figures Figures Abstract Objective To evaluate the clinical outcomes of a Severity-Based Surgical Algorithm for treating refractory Mooren’s ulcer. Methods We retrospectively reviewed consecutive patients with Mooren’s ulcer who underwent surgical intervention between February 2016 and January 2024 after failing medical therapy. A predefined severity-based surgical algorithm was applied: amniotic membrane transplantation (AMT) for ulcers involving 4 mm or technical infeasibility of LK. All patients received postoperative systemic and local immunosuppression. Primary outcomes included primary healing, changes in best-corrected visual acuity (BCVA), recurrence, and anatomical success. Results The cohort comprised 24 patients (24 eyes) with a mean follow-up of 30 months (range 12–84). Seven eyes underwent AMT, 15 LK, and 2 PK. Primary healing rates were 100% for AMT and PK, and 93.3% for LK (overall 95.8%). Although BCVA improved or stabilized in 71.4% of AMT and 86.7% of LK eyes, functional acuity (BCVA ≥ 0.3) was achieved in 71.4% (5/7) of the AMT group compared to only 13.3% (2/15) of the LK group. Conversely, PK outcomes were poor (HM to NLP). Recurrence rates were 28.6% (2/7) for AMT, 64.3% (9/14) for LK, and 100% (2/2) for PK. Kaplan-Meier analysis showed a median recurrence-free survival of 36 months for the LK group. Crucially, final anatomical success was achieved in 85.7% of AMT, 93.3% of LK, and 50.0% of PK eyes, resulting in an overall globe preservation rate of 87.5% (21/24). Conclusion A severity-graded surgical approach effectively preserves globe integrity in refractory Mooren’s ulcer. While AMT provides excellent outcomes for less-severe cases, cases requiring keratoplasty demonstrate more aggressive disease biology with higher recurrence risks. Therefore, vigilant long-term follow-up and sustained immunomodulation are mandatory for severe cases. Citation: Huang M, Wu Z, Wei D, Nong J, Zhang Z, Hoang T, et al. (2026) Evaluation of a severity-based surgical strategy for refractory Mooren’s ulcer: A retrospective series with long-term follow-up. PLoS One 21(9): e0359413. https://doi.org/10.1371/journal.pone.0359413 Editor: Vaitheeswaran Ganesan Lalgudi, University at Buffalo Jacobs School of Medicine and Biomedical Sciences: University at Buffalo School of Medicine and Biomedical Sciences, UNITED STATES OF AMERICA Received: February 12, 2026; Accepted: September 13, 2026; Published: September 30, 2026 Copyright: © 2026 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All relevant data are within the manuscript and its Supporting information files. Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Introduction Mooren’s ulcer is a rare, painful, and idiopathic peripheral ulcerative keratitis characterized by progressive stromal melting and undermining of the corneal epithelium and stroma [ 1 – 3 ]. Although the precise etiology remains elucidated, converging evidence implicates an autoimmune basis. The clinical course is notoriously aggressive; without timely intervention, the disease can rapidly progress to descemetocele, frank perforation, and catastrophic loss of vision or globe integrity. Management of Mooren’s ulcer is strictly time-sensitive. Standard first-line therapy involves intensive topical corticosteroids, conjunctival resection, and often systemic immunosuppression. However, a significant subset of cases proves resistant to these measures. In this study, we defined “refractory Mooren’s ulcer” as disease that persists or progresses despite comprehensive conservative therapy (specifically, maximal tolerated medical therapy combined with adjunctive conjunctival resection. For these patients, surgical escalation is not merely an option but a globe-saving necessity. While various surgical techniques—ranging from amniotic membrane transplantation (AMT) to lamellar keratoplasty (LK) and penetrating keratoplasty (PK)—have been described, the optimal surgical timing and choice of procedure remain controversial [ 4 , 5 ]. Current literature largely focuses on the outcomes of individual techniques in isolation, offering limited guidance on how to match specific surgical interventions to the severity of the ulceration. This lack of consensus often leads to heterogeneous, experience-based decision-making, potentially resulting in undertreatment of severe perforations or overtreatment of superficial melting. To address this therapeutic conundrum, we implemented a standardized, severity-based surgical algorithm that stratifies interventions according to ulcer depth, perforation size, and extent. The purpose of this study is to evaluate the long-term clinical outcomes of this algorithmic approach in a consecutive series of refractory cases, specifically analyzing its efficacy in achieving anatomical stability, minimizing recurrence, and preserving visual function. Materials and methods Study design This retrospective cohort study was conducted at Nanning Aier Eye Hospital, China. We analyzed surgical outcomes in patients with refractory Mooren’s ulcer who underwent severity-based surgical interventions between February 2016 and January 2024. The study was approved by the Medical Ethics Committee of Nanning Aier Eye Hospital (ID: NNAIER-2024-08) and adhered to the tenets of the Declaration of Helsinki. Written informed consent forms were obtained from all participants. The data used in this retrospective study were accessed for research purposes on 02 April 2024. All data were de-identified before analysis.Investigators did not have access to information that could identify individual participants at any time. Eligibility criteria Medical records of all patients diagnosed with Mooren's ulcer at our institution from February 2016 to January 2024 were reviewed. Inclusion criteria: Clinical diagnosis of Mooren's ulcer, defined by a characteristic peripheral, crescentic corneal ulcer with overhanging edge, in the absence of scleritis or systemic autoimmune disease; Failure to respond to comprehensive medical therapy and adjunctive conjunctival resection (see protocol below). Our step-up conservative management protocol was tailored to disease severity. Topical 1% prednisolone acetate was initiated at a frequency of 4 times daily and escalated up to hourly as needed. If the response was inadequate after 1 week, adjunctive conjunctival resection was performed, followed by oral prednisolone (1 mg/kg/day) if clinical stabilization was not achieved within 3–7 days. Severe cases (e.g., bilateral involvement or extensive circumferential ulceration without impending perforation) received immediate concurrent topical and systemic corticosteroids. Oral cyclosporine A (5 mg/kg/day) was added as a steroid-sparing agent for refractory cases. To ensure objective assessment, “refractory Mooren’s ulcer”—which was defined as the failure of comprehensive medical therapy and adjunctive conjunctival resection, and served as the absolute indication for reconstructive surgery (AMT, LK, or PK)—was strictly defined as: (1) progressive ulceration and corneal thinning despite at least 3 weeks of the aforementioned maximum tolerated medical therapy and adjunctive conjunctival resection, or (2) rapid corneal melting with impending or actual perforation at any time during active therapy. 3.Underwent surgical intervention with AMT, LK, or PK. Exclusion criteria: Clinical or laboratory evidence of alternative causes of peripheral ulcerative keratitis (e.g., rheumatoid arthritis, granulomatosis with polyangiitis, collagen vascular diseases); Ocular infection or concomitant scleritis; Incomplete clinical data or follow-up 4 mm or when LK was technically infeasible. Technique: Under general anesthesia, the full-thickness recipient cornea was excised by manual dissection extending 0.25 mm beyond the ulcer margin. A full-thickness donor corneal button, oversized by 0.25 mm relative to the excised recipient bed and including a 1–2 mm lamellar scleral rim, was fashioned to match the contour of the excised cornea and secured to the host bed with interrupted 10−0 nylon sutures. The anterior chamber was reconstituted with balanced salt solution. Postoperative management All patients received a standardized postoperative regimen. Topical therapy included 0.5% levofloxacin four times daily and tobramycin–dexamethasone ointment nightly for 1 month. In addition, 1% prednisolone acetate was administered four times daily for the first month, then tapered gradually over 6–12 months. Systemic immunosuppression consisted of oral prednisolone (1 mg/kg/day, tapered gradually over 1–2 month) combined with cyclosporine A (5 mg/kg/day in two divided doses, tapered gradually over 3–6 month). Specifically for patients who underwent LK or PK, topical therapy was transitioned to 0.1% fluorometholone once daily after 1 year for long-term maintenance, individualized according to recurrence risk. Recurrences were first managed by reapplying and intensifying the initial therapeutic approach—up to hourly topical 1% prednisolone acetate, conjunctival resection, and reinitiation of systemic immunosuppression as indicated. Persistent or progressive disease despite this regimen (i.e., refractory per our predefined criteria) was subsequently re-evaluated for surgery using the same severity-based surgical algorithm. Follow-up and outcome measures Patients were followed for 12–84 months. Serial evaluations included visual acuity testing, intraocular pressure measurement (non-contact or iCare tonometry), slit-lamp biomicroscopy, and fluorescein staining. Ancillary tests—including anterior segment optical coherence tomography, in vivo confocal microscopy, and microbiological cultures—were performed as clinically indicated. Specifically, in vivo confocal microscopy was employed to rapidly exclude opportunistic infectious etiologies (such as fungal hyphae and Acanthamoeba cysts) in cases of suspected corneal superinfection, and to evaluate subbasal/stromal dendritic cell density and morphology to provide objective microstructural guidance during the initiation and subsequent tapering of immunosuppressiv therapy. Outcomes assessed comprised: Primary outcomes: Primary Healing: Defined as complete corneal epithelialization (negative fluorescein staining) combined with the cessation of stromal thinning. Recurrence: Defined as the re-emergence of marginal ulceration, infiltration, or progressive stromal thinning in the host cornea, graft or at the graft-host junction after initial primary healing had been achieved. This was strictly differentiated from immunological graft rejection based on clinical signs. Anatomic Success: Defined as the preservation of globe integrity without the need for evisceration or enucleation, and the absence of phthisis bulbi at the final follow-up, regardless of graft clarity. Secondary outcomes: Secondary outcomes included best-corrected visual acuity (BCVA), and postoperative complications such as complicated cataract, secondary glaucoma, and allograft rejection. Statistical analysis Descriptive statistics summarized demographic and clinical data (mean ± SD or median [IQR] for continuous variables; counts and percentages for categorical variables). Kaplan–Meier survival analysis estimated the cumulative recurrence-free probability following LK; only the first recurrence was analyzed as the endpoint. Statistical analyses were performed with IBM SPSS Statistics version 22 (IBM Corp., Armonk, NY, USA). Results Patient demographics and clinical characteristics Between February 2016 and January 2024, a total of 52 patients (66 eyes) with Mooren's ulcer were assessed for eligibility. Among them, 26 patients (26 eyes) with refractory disease underwent surgical reconstruction (AMT, LK, or PK). After excluding two patients due to insufficient follow-up (<12 months), the final cohort comprised 24 patients (24 eyes) ( Fig 2 ). To ensure data independence and avoid inter-eye correlation bias, only the eye requiring surgical intervention after failing conservative management was included for the 8 patients with bilateral disease; the contralateral eyes in these cases were successfully managed with conservative therapy alone. For the analyzed cohort, the median follow-up was 30.0 months (IQR, 23.5–48.0 months; range, 12–84 months). Download: PNG larger image TIFF original image Fig 2. Study flow diagram illustrating participant selection and treatment allocation based on the severity-based surgical algorithm. Abbreviations: AMT, amniotic membrane transplantation; LK, lamellar keratoplasty; PK, penetrating keratoplasty. https://doi.org/10.1371/journal.pone.0359413.g002 The baseline demographic and clinical characteristics of the cohort are detailed in Table 1 , and individual patient-level data are provided in S1 Table . Key overall indicators included a long median symptom duration prior to surgery (7.5 months), extensive peripheral involvement (≥6 clock hours in 66.7%), and a high rate of corneal perforation (45.8%). Preoperative best corrected visual acuity was correspondingly poor, with a median of 0.10 (logMAR 1.0; IQR, HM–0.45). Over half of the eyes (14/24, 58.3%) had a BCVA of 0.1 or worse, including 9 eyes with hand motion (HM) and 2 with finger counting (FC). Baseline characteristics differed logically across the surgical tiers, reflecting an individualized treatment strategy based on disease severity. Patients undergoing AMT generally presented with less severe, non-perforated ulcers and better preoperative vision. In contrast, those requiring lamellar keratoplasty (LK) and especially penetrating keratoplasty (PK) had more extensive circumferential involvement, deeper ulcers, and higher rates of perforation. Download: PNG larger image TIFF original image Table 1. Baseline demographics and preoperative severity by surgical tier. https://doi.org/10.1371/journal.pone.0359413.t001 Outcomes of surgical interventions Surgical outcomes for each group are summarized below; individual patient-level data are provided in S1 Table . Amniotic membrane transplantation (AMT) AMT was performed in 7 of 24 eyes (29.2%) for <2/3 CT, non-perforated ulcers, with a median follow-up of 25 months (IQR, 24–36 months) ( Table 1 ). This technique achieved universal initial healing and a high final anatomic success rate (85.7%); the integrated membrane provided robust tectonic support despite remaining opaque ( Fig 3A , a ), and a final BCVA of ≥0.3 was maintained in most eyes (71.4%). The primary adverse events were two ulcer recurrences (28.6%)—one controlled medically, the other requiring subsequent lamellar keratoplasty—and one case of postoperative cataract ( Table 2 ). Download: PNG larger image TIFF original image Fig 3. Representative preoperative (left) and postoperative (right) slit-lamp photographs illustrating surgical interventions selected according to the severity-based surgical algorithm for refractory Mooren’s ulcer. (A, a) AMT: The transplanted opaque amniotic membrane integrated with the recipient cornea, restoring structural integrity. (B, b) Partial LK: C-shaped LK for deep corneal ulcer presenting as descemetoceles, demonstrating graft transparency and restored corneal structural integrity. (C, c) Double-layer LK for a 4 mm corneal perforation with iris prolapse: A large D-shaped outer lamellar graft overlying a small, thin inner patch graft secured at the nasal perforation site, showing postoperative graft transparency and structural integrity. (D, d) Total LK for extensive peripheral corneal ulceration extending over 9 clock hours with central involvement,
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