Corneal Leukoma

1. What is corneal leukoma?

Corneal leukoma is a scar-like white opacity that occurs in the corneal stroma. It is an irreversible opacity that remains after the active phase of various keratitis, trauma, or inflammation has subsided, characterized by a hard texture without edema or infiltration.

Corneal scars are classified into three grades based on severity.

Nubecula

A faint, cloud-like opacity.

It is difficult to see with the naked eye and may only be recognized under a slit-lamp microscope.

Often only mildly affects vision.

Macula

Moderate localized opacity.

Details of the iris become difficult to see through.

If it involves the pupillary area, it can cause decreased vision.

Leukoma

Dense white opaque opacity.

The iris and pupil become invisible.

If in the pupillary area, it causes severe visual impairment.

Since the cornea is a transparent tissue, even a small scar directly reduces optical function. Even mild scar opacity can significantly reduce visual function due to irregular astigmatism.

Q Does corneal leukoma heal on its own?

Corneal leukoma is a scar of the corneal stroma and in principle does not resolve spontaneously. However, mild opacity (nebula level) may improve to some extent as inflammation subsides. If the leukoma involves the pupillary area, it significantly affects vision, so consult an ophthalmologist.

2. Main symptoms and clinical findings

Alina Gabriela Gheorghe, Ana Maria Arghirescu, Andrei Coleașă, Ancuța Georgiana Onofrei The surgical management of a patient with Fuchs endothelial dystrophy and cataracts 2024 Jan-Mar Rom J Ophthalmol. 2024 Jan-Mar; 68(1):75-80 Figure 1. PMCID: PMC11007553. License: CC BY.

Clinical photograph showing the state one month after corneal transplant surgery in the right eye. In the central cornea, sutures for the transplanted cornea are visible.

Subjective Symptoms

Decreased vision/blurred vision: Becomes prominent when the opacity involves the pupillary area
Photophobia (glare): Caused by light scattering due to irregular corneal surface
Eye pain/foreign body sensation: Occurs when active inflammation persists or with epithelial defects
Redness/tearing: May be present due to inflammation of the underlying disease

Clinical Findings (Findings Confirmed by Physician Examination)

Corneal opacity: White to gray-white localized or diffuse opaque area
Irregular surface: Irregular astigmatism detected by corneal topography
Thinning: Stromal thinning in post-ulcer scars, sometimes with iris bulging (adherent leukoma)
Neovascularization: In severe or prolonged cases, vascular invasion from the limbus
Anterior chamber findings: Check for residual inflammation (hypopyon, keratic precipitates, etc.) that caused scar formation

3. Causes and Risk Factors

The causes of corneal leukoma are diverse.

Infectious Diseases

Infectious keratitis is one of the most common causes of corneal leukoma.

Bacterial keratitis: Streptococcus pneumoniae can cause serpiginous corneal ulcer after eye exposure¹⁾. Pseudomonas aeruginosa leads to severe ulcer with ring abscess and can rapidly progress to perforation¹⁾. Gram-positive cocci form round, localized abscesses, while gram-negative rods tend to form ring abscesses¹⁾.
Fungal keratitis: Plant-related trauma and long-term use of steroid eye drops are risk factors¹⁾. Filamentous fungi present with gray-white ulcers with feathery margins (hyphate ulcer), and endothelial plaque on the posterior corneal surface is characteristic¹⁾.
Viral keratitis: HSV and varicella-zoster virus cause immunologic corneal stromal infiltration. It progresses through geographic keratitis and disciform keratitis to scarring.
Acanthamoeba keratitis: Common in contact lens wearers¹⁾. Early radial keratoneuritis progresses to ring infiltration and leaves scars.

Trauma

Penetrating trauma: Scarring occurs during the wound healing process of the corneal stroma.
Chemical trauma: Alkali penetrates deep into the corneal stroma and tends to cause extensive scarring.
Birth trauma (during passage through birth canal): Forceps delivery, etc., can apply external force to the cornea, causing Descemet’s membrane rupture leading to corneal edema, and after several weeks to months, vertical linear opacities and high astigmatism remain.

Inflammatory diseases

Stevens-Johnson syndrome / Toxic epidermal necrolysis: In the acute phase, extensive keratoconjunctival epithelial defects occur. If corneal epithelial stem cells are lost, conjunctival tissue with connective tissue and blood vessels covers the cornea, causing severe opacity.
Ocular cicatricial pemphigoid: Symblepharon and conjunctival invasion progress gradually, leading to corneal opacity. Surgical intervention carries a risk of rapid deterioration.

Congenital and hereditary diseases

Congenital glaucoma: Corneal edema due to elevated intraocular pressure leads to opacity.
Congenital hereditary endothelial dystrophy (CHED): Bilateral corneal edema and opacity present from birth.
Congenital rubella syndrome: Corneal opacity due to intrauterine infection.

Corneal Dystrophy

Granular corneal dystrophy (type I and II): Caused by mutations in the TGFBI gene. Granular opacities increase with age; type II (Avellino type) causes diffuse opacities in the superficial cornea.
Lattice corneal dystrophy: Amyloid deposits cause linear or lattice-like opacities. In type 1, central opacities are more prominent.
Macular corneal dystrophy: Autosomal recessive inheritance. Diffuse ground-glass opacities spread throughout the entire corneal stroma, and vision loss is usually noticed between ages 10 and 30.
Fuchs endothelial corneal dystrophy: Degeneration of corneal endothelial cells leads to bullous keratopathy ³⁾. It tends to develop in middle-aged and older individuals, with a higher prevalence in women ³⁾.

Drug-Induced

Cases of diffuse white granular opacities from the subepithelium to the stroma have been reported after long-term oral administration of atovaquone ⁴⁾. Lipophilic drugs such as amiodarone and chloroquine can also cause corneal deposits due to their cationic amphiphilic structure ⁴⁾.

Q Can using contact lenses cause corneal leukoma?

Improper use of contact lenses is a risk factor for bacterial keratitis and Acanthamoeba keratitis. If these infections become severe, they can leave corneal scars (leukoma). Regular replacement of lens cases, correct use of disinfecting solutions, and adherence to wearing time are important for prevention.

4. Diagnosis and Examination Methods

Slit-lamp microscopy

This is the basic method for evaluating corneal opacities. The location (central, paracentral, peripheral), depth (subepithelial, superficial stromal, deep stromal), extent, and density of the opacity are observed. Fluorescein staining is used to check for epithelial defects.

In the differential diagnosis of corneal opacities, it is important to distinguish between infiltrative opacities due to infectious keratitis and scarred opacities. Infiltrative lesions are accompanied by surrounding edema and anterior chamber inflammation, suggesting activity ¹⁾. Ring infiltrates can be seen in both fungal keratitis and Acanthamoeba keratitis, but radial corneal neuritis and severe pain are characteristic of Acanthamoeba ²⁾.

Anterior segment optical coherence tomography (AS-OCT)

This allows objective evaluation of the depth of corneal lesions ¹⁾. Findings such as increased or decreased corneal thickness, anterior chamber inflammatory cells, keratic precipitates (KP), and endothelial plaque can also be observed. Treatment efficacy can be assessed by comparing before and after treatment.

Corneal topography

This is useful for evaluating irregular astigmatism ¹⁾. Even if the opacity due to corneal leukoma is mild, visual function may be significantly reduced due to irregular astigmatism.

In vivo confocal microscopy (IVCM)

This allows non-invasive observation of cells, nerve fibers, and microorganisms (fungal hyphae, Acanthamoeba cysts) within the cornea ¹⁾. It is also useful for evaluating the cellular composition of scar tissue, but requires skill to perform and interpret the results.

Scraping culture and smear microscopy

This is performed when active infectious keratitis is suspected ¹⁾. Gram staining is used to estimate the causative organism, and culture on blood agar and chocolate agar is used for definitive diagnosis.

Differential diagnosis

For the differential diagnosis of diseases causing corneal stromal opacities, the following should be considered.

Differential diagnosis	Characteristic findings	Examination
Drug-induced corneal deposits	History of medication, vortex-shaped deposits	Review medication history, in vivo confocal microscopy
Ascher ring	Bilateral symmetric ring-shaped stromal opacity	AS-OCT, diagnosis of exclusion⁶⁾
Metabolic deposits	LCAT deficiency, Tangier disease	Blood tests, lipid panel

Q Is corneal leukoma the same as cataract?

No. Corneal leukoma is an opacity of the cornea (the transparent membrane at the front of the eye), while cataract is an opacity of the lens (the lens behind the cornea). Both can cause vision loss, but their pathology and treatment differ. They can be easily distinguished with a slit-lamp microscope.

5. Standard Treatment

Treatment of corneal leukoma aims to address the underlying cause and restore visual function.

Treatment of the underlying disease

If the underlying disease causing corneal leukoma is still active, treatment of the cause is prioritized first.

Infectious keratitis: Frequent instillation of antibacterial agents (fluoroquinolones, cephalosporins, aminoglycosides) according to the causative bacteria is the basic treatment¹⁾. For fungal infections, antifungal agents are used; for viral infections, antiviral agents are used.
Inflammatory diseases: Anti-inflammatory treatment with steroid eye drops and immunosuppressive agents.

Optical Correction

Glasses and contact lenses: For mild opacities or irregular astigmatism, correction with hard contact lenses may be possible.
Scleral lenses and PROSE devices: For corneal opacity and neovascularization associated with Stevens-Johnson syndrome/toxic epidermal necrolysis, wearing a PROSE device has been reported to induce regression of corneal opacity and neovascularization⁷⁾. The back channel design of the device promotes tear exchange and improves the ocular surface environment⁷⁾.

Surgical Treatment

Therapeutic laser keratectomy: First choice for opacities confined to the superficial corneal layer. Effective for superficial opacities in granular corneal dystrophy type I and Avellino type. Usually can be performed up to about two times.
Deep anterior lamellar keratoplasty (DALK): Selected when the corneal endothelium is healthy but opacities extend into the stroma. Lower risk of rejection.
Penetrating keratoplasty (PKP): Indicated when the full thickness of the stroma or the endothelium is involved. Examples include advanced cases of macular corneal dystrophy.
Corneal endothelial transplantation (DSAEK/DMEK): Performed for opacities due to endothelial diseases such as Fuchs endothelial corneal dystrophy³⁾. First choice if stromal changes are minimal.
Artificial cornea (keratoprosthesis): For severe cases where conventional corneal transplantation is difficult (e.g., Stevens-Johnson syndrome/toxic epidermal necrolysis, ocular cicatricial pemphigoid), artificial corneas such as the Boston KPro are considered.

6. Pathophysiology and Detailed Mechanisms

Mechanisms of Corneal Scar Formation

Corneal transparency is maintained by the regular lattice arrangement of collagen fibers in the corneal stroma. Scar formation after corneal injury follows the following process.

Apoptosis of keratocytes: Following epithelial damage due to trauma or infection, keratocytes at the injury site undergo apoptosis.
Differentiation into myofibroblasts: TGF-β1 and TGF-β2 released from tears and epithelium infiltrate the corneal stroma and differentiate surviving keratocytes into myofibroblasts⁵⁾.
Production of abnormal extracellular matrix: Myofibroblasts produce disorganized collagen and extracellular matrix, leading to loss of transparency⁵⁾.
Damage to the epithelial basement membrane (EBM): Normal EBM controls the inflow of TGF-β into the stroma, but when this barrier is disrupted by injury, fibrosis persists⁵⁾.

Classification of Corneal Stromal Opacities

Corneal stromal opacities are classified into the following three types.

Inflammatory opacity (infiltrative lesion): Active infectious foci such as bacterial or fungal keratitis. Caused by accumulation of neutrophils and lymphocytes. When an abscess forms, tissue destruction progresses due to proteolytic enzymes, leaving a scar with thinning after healing¹⁾.
Edematous opacity: Increased water content in the stroma due to corneal endothelial dysfunction. In Fuchs endothelial corneal dystrophy, degenerated endothelial cells protrude abnormal collagen-like material on the posterior surface of Descemet’s membrane (guttae), and as the disease progresses, the pump and barrier functions of the endothelium decline, leading to bullous keratopathy³⁾.
Depositional opacity: Deposition of substances due to corneal dystrophies (granular, lattice, macular) or metabolic diseases. In macular corneal dystrophy, CHST6 gene mutation impairs sulfation of keratan sulfate, and hyposulfated keratan sulfate accumulates diffusely inside and outside corneal stromal cells.

Mechanisms of Drug-Induced Corneal Opacity

Drugs with a cationic amphiphilic structure, such as atovaquone, consist of a hydrophobic ring and a hydrophilic cationic amine side chain, and they cross cell membranes to cause accumulation of phospholipids⁴⁾. Amiodarone reaches the cornea via tears, aqueous humor, and limbal vessels, and drug-lipid complexes form within lysosomes⁴⁾.

7. Latest Research and Future Perspectives

Treatment of Corneal Scarring with Losartan Eye Drops

Dutra et al. (2025) reported three cases of corneal scarring due to HSV or varicella-zoster virus keratitis treated with 0.8 mg/mL losartan eye drops administered six times daily ⁵⁾. In a 40-year-old woman with HSV scarring (Case 1), BCVA improved from 20/60 to 20/25 after 16 weeks of treatment, and AS-OCT confirmed regression of stromal opacity. In a 15-year-old male with varicella-zoster virus scarring (Case 3), BCVA improved from 20/200 to 20/20 ⁵⁾.

Losartan is an angiotensin II receptor antagonist that induces apoptosis of myofibroblasts by inhibiting the non-canonical pathway of TGF-β (ERK-mediated signaling) ⁵⁾. After removal of myofibroblasts, corneal fibroblasts repopulate, leading to regeneration of the epithelial basement membrane and absorption/reorganization of disorganized collagen, thereby restoring transparency ⁵⁾. Treatment effects may take 6 to 9 months to manifest ⁵⁾.

Long-term Effects of PROSE Device for Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Liao et al. (2022) reported regression of corneal opacity and neovascularization in two cases (four eyes) of Stevens-Johnson syndrome/toxic epidermal necrolysis with continuous wear of a back-channel designed PROSE device ⁷⁾. In Case 1 (19-year-old female with Stevens-Johnson syndrome), corneal opacity in the left eye improved from grade 1 to 0, and BCVA improved from 20/40 to 20/15. In Case 2 (26-year-old male with toxic epidermal necrolysis), all prescribed eye drops were discontinued after 17 months of PROSE wear, with sustained improvement in corneal neovascularization and opacity ⁷⁾.

Corneal Stromal Opacity Due to Atovaquone

Ashizuka et al. (2025) reported a 15-year-old male who developed bilateral diffuse corneal stromal opacity after 14 months of oral atovaquone for aplastic anemia ⁴⁾. Anterior segment OCT showed uniform diffuse opacity without changes in corneal shape, and in vivo confocal microscopy confirmed pigment deposition in the corneal stroma. Corneal opacity persisted one year after discontinuation of atovaquone ⁴⁾.

Ascher Ring (Idiopathic Corneal Annular Opacity)

Megalla et al. (2021) reported a case of bilateral symmetric annular corneal stromal opacity (Ascher ring) in a 70-year-old male ⁶⁾. Ascher ring is an extremely rare idiopathic stromal opacity first described in 1964, characterized by bilaterality and no effect on visual function ⁶⁾. No genetic pattern or laboratory abnormalities have been identified, and it is diagnosed by exclusion ⁶⁾.

8. References

日本眼感染症学会. 感染性角膜炎診療ガイドライン（第3版）. 日眼会誌. 2023.
Rhee MK, Ahmad S, Amescua G, et al.; American Academy of Ophthalmology Preferred Practice Pattern Cornea/External Disease Panel. Bacterial Keratitis Preferred Practice Pattern®. Ophthalmology. 2024;131(4):P87-P133. PMID: 38349295. doi:10.1016/j.ophtha.2023.12.035.
Matthaei M, Hribek A, Clahsen T, Bachmann B, Cursiefen C, Jun AS. Fuchs Endothelial Corneal Dystrophy: Clinical, Genetic, Pathophysiologic, and Therapeutic Aspects. Annu Rev Vis Sci. 2019;5:151-175. PMID: 31525145. doi:10.1146/annurev-vision-091718-014852.
Ashizuka T, Uematsu M, Mohamed TM, et al. A case of corneal opacity caused by atovaquone administration. Am J Ophthalmol Case Rep. 2025;37:102235.
Dutra BAL, Drew-Bear LE, Herretes SP, et al. Topical Losartan Treatment of Herpes Simplex Virus- or Varicella-Zoster Virus-Induced Corneal Scarring: A Case Series. Case Rep Ophthalmol. 2025;16:281-289.
Megalla M, Li E, Branden P, Chow J. Bilateral idiopathic corneal opacity: A report of Ascher ring and a review of the literature. Am J Ophthalmol Case Rep. 2021;23:101176.
Liao J, Asghari B, Carrasquillo KG. Regression of corneal opacity and neovascularization in Stevens-Johnson syndrome and Toxic Epidermal Necrolysis with the use of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment. Am J Ophthalmol Case Rep. 2022;26:101520.

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