Corneal keloid are not a common disease in the clinic, which mainly manifested as white lesion that protrude from the corneal surface and involve the entire corneal stroma(4). The differential diagnosis of corneal keloid mainly include dermatoid tumor, myxoma and fibrous histiocytoma. Corneal dermoid is a congenital disease with yellowish white lesions involving the bulbar conjunctiva and corneal stroma(5). It characteristically occurs near the corneoscleral limbus and has hair tissue on the surface. Corneal dermoid may occur as an isolated lesion or accompany with Goldenhar’s syndrome(6). HE staining showed that the corneal surface was covered with stratified squamous epithelium. A large amount of collagen fiber tissue and adipose tissue were seen in the lesion(7). Corneal myxoma appears as avascular translucent subepithelial mass white within the stroma(8). Histopathology examination reveal subepithelial myxomatous tissue. Electron microscope show spindle shaped and stellate cells embedded in a loose stroma(9). Corneal fibroma can also appear as white tumors with intralesional blood vessels. The histopathological examination reveal the corneal epithelium was intact over the mass and subepithelial spindle cells in “featherstitched” or storiform pattern(10). However, some scholars have classified fibroma, keloid, and hypertrophic cicatrix as fibrous tumors of the ocular surface, which maybe represent different nodes of corneal tissue healing(11). In addition, it should be distinguished from the following diseases: sclerocornea, Salzmann’s nodular degeneration, Peter’s anomaly, congenital hereditary endothelial dystrophy, congenital glaucoma, familial band-shaped keratopahy, spheroidal degeneration, squamous cell carcinoma, juvenile xantogranuloma, birth trauma, infection and metabolic disease(12, 13).
Histopathology is the gold standard for confirmed diagnosis(14). Epithelium hyperplasia, absence of the Bowman layer, irregular collagen fibers are considered to be a characteristic pathological manifestation(4), which is consistent with our inspection results. The histogenesis of keloid can be divided into four stages of early inflammatory, fibroblastic, fibrous and hyaline stages(12). In the early stages, there is a predominance of type III collagen, abundant fibroblasts, and new vessel formations. In the later hyaline stages, there is a predominance of disordered type I collagen with involution of blood vessels, giving a whitish rigid scar appearance(2, 4, 12, 15). Immunohistochemical studies of keloids showed vimentin was positive staining in active fibroblasts and SMA was positive staining in myofibroblasts(4, 13). Our result revealed vimentin was staining in keloid lesion subject and SMA only in vascular wall, which was consistent with Palko JR’s study(16). Light and electron microscopy are also important for discovering hyalinized collagen, activated fibroblasts and myofibroblasts(3). The younger fibroblasts contain rough endoplasmic reticulum, numerous mitochondria and prominent nucleoli(2). The mature myofibroblast showing numerous thin filaments and fusiform densities(13). But not every patient has the conditions to do electron microscopy and immunohistochemistry, so HE staining is still the main method for the diagnosis of disease.
Corneal keloid can be divided into primary and secondary according to the etiology(2). Primary keloid are more common in congenital diseases, such as Lowe’s syndrome and Rubinstein-Taybi syndrome (RTS)(17, 18). In Lowe’s syndrome, increased levels of amino acids such as tyrosine leaking from abnormal new corneal vessels or the anterior chamber through defective endothelium,which stimulate fibroblast proliferation(17). Other ocular anomalies associated with congenital keloid include peripheral iridocorneal adhesions, anterior segment mesenchymal dysgenesis, aniridia and cataract with anophthalmia(2). Secondary corneal keloid are mostly caused by inflammation, trauma or surgery. Unlike a hypertrophic scar, a keloid outgrows its initial boundaries from several months to a many years after the initial injury(19). In our case, the formation of the lesion took thirty years after initial corneal trauma. The previous view was that when corneal perforation with iris incarceration, the keloids originated from stromal cells of the iris. However, Mejia and O’Grady believe that excessive hypertrophy of the scar is due to corneal epithelial damage releasing too many cytokines(20, 21). Dhooge et al further research found the high levels of BMP4 inhibit the normal activation of TGF-β, leading to overstimulating fibroblastic growth during corneal wound healing(22). In addition, new vessel growth or partial limbal stem cell deficiency might be involved in the pathogenesis of corneal keloid development or recurrence(23).
Because corneal keloid are benign lesions and are prone to recurrence after surgery, if the lesions are small, they may not be treated temporarily. However, surgical treatment is necessary when the appearance is affected or the eyelids cannot be closed. Surgical methods currently reported include superficial keratectomy, lamellar keratoplasty, penetrating keratoplasty and enucleation(16). Enucleation is considered only when the eyeball is non-functional, painful or unsightly(12).It is reported that superficial keratectomy combined with amniotic membrane transplantation can easily remove the lesion and control the recurrence of the disease, which maybe due to its antifibrotic and anti-inflammatory properties(14, 24). But Lee HK et al found the lesion recurred in three of four cases treated with superficial keratectomy and amniotic membrane. And then the mitomycin C (MMC) was applicated to suppress activated fibroblasts and keratocytes in the residual stroma during secondary surgery without lesion recurrent(23). Because residual aberrant nerves and myofibroblasts in the corneal stroma maybe cause it, the lesion is considered to be removed completely by penetrating keratoplasty (PK). In 2012, Alkatan HM reported a patient with corneal keloid underwent a PK. The graft remained clear and vision outcome was satisfactory at 6 months after surgery. However, the recurrent epithelial breakdown or persistent epithelial defect can easily lead to the failure of graft after PK(18). In recent years, deep anterior lamellar keratoplasty is considered to be a better choice, with a lower rejection rate than PK. Bakhtiari P reported that no recurrence of corneal stromal opacification is noted in a 21-year-old child 8 months after the deep anterior lamellar keratoplasty (25). In our case, the lesion involved the entire corneal layer during the operation, which can also be confirmed by postoperative AS-OCT. However, the surgical method of deep lamellar corneal transplantation is adopted, and the thickness of stroma left about 100 µm during the operation. On the one hand, we considered that oversize graft can easily lead to rejection after surgery. On the other hand, we have exposed enough central optical areas during the surgery to ensure vision recovery. If necessary, we can do another central PK in the second phase. Fortunately, the lesion has not recurred so far, and the patient is satisfied with his vision.