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Review
. 2025;13(1):8.
doi: 10.1007/s40135-025-00335-8. Epub 2025 Jun 21.

Subepithelial Lesions of the Ocular Surface: A Review

Wisam Najdawi  1 , Wendy J Li  1 , Sofia De Arrigunaga  1 , Mona M Amer  1 , Anat Galor  1   2 , Carol L Karp  1
Affiliations
Review

Subepithelial Lesions of the Ocular Surface: A Review

Wisam Najdawi et al. Curr Ophthalmol Rep. 2025.

Abstract

Purpose of review: Subepithelial lesions of the ocular surface represent a diverse group of pathologies which may be difficult to diagnose clinically. Some of these lesions are relatively uncommon, may result in systemic manifestations, or occur secondary to systemic disease. The purpose of this review is to summarize current approaches to the diagnosis and management of six subepithelial conjunctival lesions.

Recent findings: The standard for the diagnosis of subconjunctival lesions remains histopathologic evaluation; however, high-resolution anterior segment optical coherence tomography (HR-OCT) is a useful supplemental diagnostic tool that may facilitate diagnosis. Recent advancements in the management of subconjunctival lesions include targeted systemic therapies in conjunctival melanoma and ultra-low dose radiation radiotherapy in conjunctival lymphoma.

Summary: The development of HR-OCT has provided clinicians with valuable supplemental diagnostic information to guide the diagnosis of subepithelial lesions. Additionally, novel treatment modalities may provide an alternative to traditional surgical interventions in some pathologies.

Keywords: Benign reactive lymphoid hyperplasia; Conjunctival amyloidosis; Conjunctival lymphoma; Conjunctival melanoma; Conjunctival myxoma; Conjunctival neuroma; High-resolution optical coherence tomography.

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Conflict of interest statement

Competing InterestsThis work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences R&D (CSRD) I01 CX002015 (Dr. Galor), Biomedical Laboratory R&D (BLRD) Service I01 BX004893 (Dr. Galor), Department of Defense Gulf War Illness Research Program (GWIRP) W81XWH-20-1-0579 (Dr. Galor) and Vision Research Program (VRP) W81XWH-20-1-0820 (Dr. Galor), National Eye Institute R01EY026174 (Dr. Galor) and R61EY032468 (Dr. Galor), NIH Center Core Grant P30EY014801 (institutional), Research to Prevent Blindness Unrestricted Grant GR004596 (institutional), The Dr. Ronald and Alicia Lepke Grant, The Lee and Claire Hager Grant, The Robert Farr Family Grant, The Grant and Diana Stanton-Thornbrough, The Robert Baer Family Grant, The Roberto and Antonia Menendez Grant, The Emilyn Page and Mark Feldberg Grant, The Calvin and Flavia Oak Support Fund, The Jose Ferreira de Melo Grant, The Richard and Kathy Lesser Grant, The Honorable A. Jay Cristol Grant, The Michele and Ted Kaplan Grant, The Carol Soffer Grant, The Richard Azar Family Grant, The Mr. and Mrs. Irwin Friedman Grant, The Dr. Tim and Cammy Ioannides Grant, The Stephen Takach Grant, The Ragheb Family Grant, and The Zvi Levin Grant (institutional grants). Dr. Galor is a Section Editor for Current Ophthalmology Reports. All other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Conjunctival Melanoma. (a) Slit lamp examination of the left eye of a 68-year-old White female revealed an elevated, gelatinous, brown conjunctival lesion at 3:00 with an associated feeder vessel (arrow). (b) High resolution optical coherence tomography (HR-OCT) revealed a hyperreflective subepithelial lesion (asterisk) with overlying hyperreflective epithelium (above dashed line) of normal thickness (arrowheads). Findings were consistent with, and biopsy confirmed the diagnosis of malignant melanoma. Inset shows scan location
Fig. 2
Fig. 2
Conjunctival Lymphoma. (a) Slit lamp examination of the right eye of a 77-year-old White male revealed a superonasal, highly elevated “salmon patch” colored subepithelial conjunctival lesion. (b) High resolution optical coherence tomography (HR-OCT) revealed a subepithelial, homogeneous, hyporeflective infiltrate (asterisk) and a normal overlying epithelium (arrowheads). The border between the epithelium and subepithelial space is labeled (dashed line). Findings were consistent with, and biopsy confirmed the diagnosis of follicular lymphoma. Inset shows scan location
Fig. 3
Fig. 3
Conjunctival Benign Reactive Lymphoid Hyperplasia. (a) Slit lamp examination of the left eye of a 66-year-old Black female revealed a salmon-colored, elevated, nasal subepithelial conjunctival lesion. (b) High resolution optical coherence tomography (HR-OCT) revealed a subepithelial lesion (asterisk) with hyporeflective monomorphic infiltrate and a normal overlying epithelium (arrowheads). The border between the epithelium and subepithelial space is labeled (dashed line). Findings were consistent with a benign reactive lymphoid hyperplasia although a biopsy was needed to exclude a lymphoma diagnosis based on HR-OCT features. Biopsy confirmed diagnosis of reactive lymphoid hyperplasia with no morphologic or immunophenotypic evidence of lymphoma. Inset shows scan location
Fig. 4
Fig. 4
Conjunctival Myxoma. (a) Slit lamp examination of the right eye of a 67-year-old White male with a history of conjunctival myxoma status post surgical debulking revealed a residual salmon-colored conjunctival lesion along the nasal inferior fornix (arrows). (b) High resolution optical coherence tomography (HR-OCT) revealed a heterogeneous subepithelial lesion with medium to high reflectivity, hyperreflective linear features (arrow), and hypo-reflective intervening spaces (arrowheads) with a slightly hyperreflective, normal thickness overlying epithelium. The border between the epithelium and subepithelial space is labeled (dashed line). Findings were consistent with, and previous biopsy confirmed the diagnosis of conjunctival myxoma. Inset shows scan location
Fig. 5
Fig. 5
Conjunctival Neuroma. (a) Slit lamp examination of the left eye of an 18-year-old Black female with multiple endocrine neoplasia type 2b revealed a superior elevated globular conjunctival lesion with a serpentine appearance. (b) High resolution optical coherence tomography (HR-OCT) revealed a subepithelial lesion of mixed reflectivity with lobular components (arrows) and a hyperreflective overlying epithelium with normal thickness (arrowheads). The border between the epithelium and subepithelial space is labeled (dashed line). Findings were consistent with, and biopsy confirmed diagnosis of mucosal neuroma. Inset shows scan location
Fig. 6
Fig. 6
Conjunctival amyloidosis. (a) Slit lamp examination of the left eye of a 65-year-old White male revealed a pink and yellow-orange, fleshy conjunctival lesion extending inferotemporally into the fornix and left lower eyelid. The patient was initially thought to have conjunctival lymphoma based on clinical appearance. (b) High resolution optical coherence tomography (HR-OCT) revealed a subepithelial, heterogeneous conjunctival infiltrate with irregular borders, hyperreflective linear opacities (arrow), and a hyperreflective overlying epithelium with normal thickness (arrowheads). The border between the epithelium and subepithelial space is labeled (dashed line). Findings were consistent with, and biopsy confirmed the diagnosis of amyloidosis. Inset shows scan location
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