Linear interstitial keratitis (LIK) is a rare corneal disease that causes linear opacities in the corneal stroma. It has been reported in young adults as early as 1923.
Previously, it was thought to be caused by syphilis infection. However, accumulated case reports have shown that anti-treponemal antibodies are generally negative. Positive serological tests are considered incidental findings. Histological examination of patch grafts in cases of corneal perforation has not yielded definitive findings.
Syphilitic interstitial keratitis has long been known as one of Hutchinson’s triad (Hutchinson teeth, interstitial keratitis, deafness) in congenital syphilis 1). However, LIK is positioned as an independent disease entity clinically distinct from syphilitic interstitial keratitis.
Main complaints are blurred vision, tearing, pain, and redness. Symptoms often occur unilaterally. The condition is characterized by recurrent episodes of remission and relapse.
Corneal Findings
Linear corneal opacity: Linear opacity within the corneal stroma. This is the most characteristic finding of LIK.
Corneal stromal edema: Stromal edema may be present around the opacity.
Corneal neovascularization: In chronic cases, corneal neovascularization may appear.
Central thinning: In advanced cases, thinning of the central cornea is observed.
Associated findings
Mild iritis: May be accompanied by mild inflammation in the anterior chamber.
Epithelial defect: Rarely, corneal epithelial defects may occur.
Corneal perforation: Although extremely rare, cases leading to perforation have been reported.
The etiology of LIK remains unknown.
Historically, associations with syphilis and Lyme disease have been suspected. However, serological test results are inconsistent and not all cases show clear positivity. Autoimmune involvement has been proposed but has not yet been proven.
Syphilitic interstitial keratitis typically presents as bilateral non-ulcerative corneal opacities in late childhood to young adulthood 1). Unlike LIK, it is characterized by tearing and photophobia, poor response to systemic penicillin, and responsiveness to steroids 1).
Historically, syphilis was suspected as a cause of LIK, but this is now considered unlikely. Serological tests in LIK patients generally do not show anti-treponemal antibodies. Syphilitic interstitial keratitis is a different disease presenting with bilateral non-ulcerative corneal opacities and has a different clinical picture from LIK.
The diagnosis of LIK is based on clinical findings. The linear appearance of corneal opacity is the most important diagnostic clue.
Key diagnostic points:
Differential diagnoses:
| Differential Diagnosis | Key Differentiating Features |
|---|---|
| Herpetic disciform keratitis | Round stromal edema, greasy keratic precipitates |
| Necrotizing keratitis | Severe inflammation, necrotic findings |
| Infectious keratitis | Infiltrates, positive culture |
In the differential diagnosis of corneal stromal opacity, it is important to distinguish and evaluate four elements: edema, infiltration, deposition, and scarring. In LIK, inflammatory edema and infiltration are predominant.
The most characteristic feature of LIK is that the corneal opacity shows a “linear” pattern. In herpetic keratitis, disciform edema is typical, and in infectious keratitis, infiltrative foci or positive culture findings are seen. LIK responds well to steroid eye drops, which is also useful for differentiation. However, it is important to rule out infectious keratitis, and culture tests should be performed as needed.
The main treatment for LIK is steroid eye drops.
Pharmacotherapy:
Surgical Treatment:
Prognosis: Recovery with steroid use is generally favorable. However, inflammation tends to recur, and the course may involve repeated relapses and remissions. Long-term prognosis varies by case.
LIK tends to recur and remit. Abrupt discontinuation of steroid eye drops can trigger recurrence, so it is important to gradually reduce the dose as directed by your doctor. Even if it recurs, restarting steroid eye drops can be expected to improve the condition.
The detailed mechanism of LIK remains unknown.
The corneal stroma is composed of regularly arranged collagen fibers, and this regularity maintains corneal transparency. In LIK, inflammation occurs in the stroma in a linear pattern, increasing the water content between collagen fibers and leading to loss of transparency.
Proposed mechanisms:
Comparison with syphilitic interstitial keratitis is useful for understanding the pathology. Syphilitic interstitial keratitis occurs as a late symptom of congenital syphilis and is one of Hutchinson’s triad 1). The corneal lesions are resistant to systemic penicillin but respond to steroids 1). This feature is shared with LIK’s steroid responsiveness, but LIK essentially lacks positive serological findings for syphilis.
Reports on LIK are limited, but recent advances in imaging diagnostics are deepening our understanding of the pathology.
Evaluation by confocal microscopy: Detailed histological observation of LIK using in vivo confocal microscopy has been reported. It allows non-invasive assessment of inflammatory cell infiltration and structural changes in the corneal stroma.
Evaluation by anterior segment OCT: Anterior segment optical coherence tomography (AS-OCT) can quantitatively assess the location, extent, and depth of corneal stromal opacities. It is also useful for objective evaluation of treatment effects.
Future challenges:
- Chauhan K, et al. Demystifying Ocular Syphilis: A Major Review. Ocul Immunol Inflamm. 2023.
