Corneal keloid is a benign, pearly gray-white elevated lesion on the corneal surface. It is characterized by abnormal proliferation of fibrous tissue and accumulation of disorganized collagen fibrils and glycoproteins. It is accompanied by corneal epithelial hyperplasia and destruction of Bowman’s layer.
It was first reported by Szokalski in 1865 2). Since then, fewer than 100 cases have been documented in the literature, making it extremely rare among corneal diseases.
There is a tendency for higher incidence in males 1)2). Unlike skin keloids, no racial difference in incidence has been shown.
A direct association between corneal keloid and skin keloids has not been established. Except for Rubinstein-Taybi syndrome, there is no evidence that individuals with a history of skin keloids have an increased risk of developing corneal keloid. In fact, long-term follow-up after LASIK surgery in patients with skin keloid tendency has not reported the development of corneal keloid.
A 69-year-old man presented with a pearl-like white elevated lesion and several intrastromal new vessels in the inferior cornea one year after a corneal burn from boiling vegetable oil1).
In a report of a 35-year-old man who developed a giant corneal keloid two years after DSAEK, UBM revealed a hyperechoic lesion measuring 1,300 μm in thickness extending from the surface to the superficial stroma2).
When the lesion is large, it may interfere with eyelid closure and cause exposure keratopathy. It may also make intraocular pressure measurement and fundus examination difficult because it covers most of the cornea.
Ocular trauma or corneal surgery can trigger keloid formation.
There are reports of keloid development 30 years after pterygium surgery and 3 years after cataract surgery, with the time from injury to onset ranging from several months to several decades 1).
Corneal keloid can develop even without a history of ocular trauma or systemic disease. One should not easily exclude keloid from the differential diagnosis of a shiny, gray-white raised corneal mass.
No definitive method to prevent corneal keloid has been established. However, appropriate wound management after corneal trauma or surgery is important. The use of mitomycin C or tranilast eye drops has been reported for preventing recurrence of corneal keloid, but complete prevention is not possible. Regular follow-up is recommended.
The definitive diagnosis of corneal keloid is made by histopathological examination. If keloid is clinically suspected, the standard approach is to perform surgical excision for both diagnosis and treatment, and then evaluate the excised specimen histologically.
The following findings are confirmed by H&E staining and peripheral anterior synechia staining 1)2).
Masson trichrome staining is useful for highlighting irregular collagen bundles in the stroma 2). Negative Congo red staining excludes amyloidosis 2).
| Disease | Key differentiating features |
|---|---|
| Hypertrophic corneal scar | Localized within the trauma area, appears immediately |
| Corneal inclusion cyst | Acellular eosinophilic material |
| Salzmann nodular degeneration | Well-defined semitransparent elevation |
Other diseases to include in the differential diagnosis: corneal dermoid, Peters anomaly, congenital hereditary endothelial dystrophy (CHED), squamous cell carcinoma, juvenile xanthogranuloma, and fibrous histiocytoma.
Observation is performed for small, asymptomatic lesions. Because surgical excision may worsen the keloid due to corneal damage, surgery should be limited to cases where the visual axis is significantly compromised. Drug therapy with steroids alone does not lead to regression of the lesion.
Superficial Keratectomy (SK)
Indications: First choice for lesions confined to the superficial layer.
Adjuvant therapy: Combination with mitomycin C (MMC) 0.02% applied for 1 minute has been reported.
Outcomes: In 2 cases of secondary keloid, no recurrence was observed for 6 months after SK + MMC1). Visual acuity improved to 20/20 and 20/25 at 7 days postoperatively1).
Corneal transplantation
Deep anterior lamellar keratoplasty (DALK): Removes the entire stroma, potentially preventing residual activated fibroblasts that cause recurrence.
Penetrating keratoplasty (PKP): Indicated for cases with endothelial dysfunction or extensive lesions2).
Note: Recurrence after DALK and PKP has been reported; surgical technique alone cannot completely prevent recurrence.
Recurrence is the greatest challenge in treating corneal keloids. Recurrence has been reported after SK, PTK, and PKP.
A giant corneal keloid that developed after DSAEK was treated with SK, but due to residual fibrosis and endothelial dysfunction, PKP was required 3 months later2).
Superficial keratectomy (SK) combined with mitomycin C has been reported to improve visual acuity, with some cases showing no recurrence for 6 months. However, keloids are prone to recurrence, and long-term postoperative follow-up is necessary. Depending on the depth and extent of the lesion, corneal transplantation may be required. Please consult your doctor to decide on a treatment plan.
The exact pathogenesis of corneal keloid remains unclear, but the mechanism by which keratocytes transform into fibroblasts and myofibroblasts and undergo excessive proliferation is considered likely.
Current data support the theory that cytokines released from damaged corneal epithelium disrupt normal corneal repair and cause excessive fibrovascular proliferation. This is supported by cases where keloids form without corneal perforation or iris involvement.
In two cases, one after pterygium surgery and one after corneal injury from boiling oil, it is inferred that excessive activation of residual fibroblasts led to keloid formation1). In a case after DSAEK, fibroblast activation due to transplant surgery and tube shunt repositioning is suspected as the cause2).
Pathological findings vary depending on the stage of the keloid.
Sharifi et al. (2024) performed SK + MMC 0.02% (1 minute) in two patients who developed corneal keloids after corneal burn from boiling oil and after pterygium surgery, respectively1). Visual acuity improved to 20/20 and 20/25 at 7 days postoperatively, with no recurrence at 6 months1).
Vera-Duarte et al. (2024) reported a case of a 35-year-old male who developed a giant corneal keloid 2 years after DSAEK, following a course of traumatic Ahmed glaucoma valve insertion → endothelial dysfunction → DSAEK 2). This is the first report of keloid development after corneal endothelial transplantation 2). UBM confirmed a 1,300 μm thick lesion, and SK was performed, but endothelial dysfunction persisted, so PKP was added 3 months later 2).
These reports indicate that corneal keloids can appear after any type of ophthalmic surgery and highlight the importance of long-term follow-up.
- Sharifi A, Mirshekari TR, Azh M, Sadeghi H, Akbari Z, Zand A. Secondary corneal keloid: a report of two cases. Oxford Med Case Rep. 2024;2024(9):omae105.
- Vera-Duarte GR, Eskenazi-Betech R, Garcia-Padilla LA, et al. Giant corneal keloid following Descemet stripping automated endothelial keratoplasty for the treatment of corneal decompensation secondary to trauma. BMC Ophthalmol. 2024;24(1):404.
