Fuchs’ superficial marginal keratitis (FSMK) is a rare inflammatory disease characterized by recurrent infiltration and progressive stromal thinning of the peripheral cornea.
It was first reported by Ferdinand Von Arlt in 1881. In 1895, Ernst Fuchs described the disease in more detail, and it has since been named after Fuchs 1).
It commonly occurs in young to middle-aged adults in their 20s to 40s 1). It develops bilaterally, but the severity is often asymmetric between the eyes. It follows a chronic course, progressing over several years with repeated relapses and remissions. The etiology is unknown, and in many cases, no cause is identified even after thorough investigation for systemic autoimmune diseases.
Terrien marginal degeneration (TMD) and FSMK share overlapping clinical features, suggesting they may be different phenotypes of the same pathological process 1)2).
Both are rare diseases characterized by peripheral corneal thinning, and there is a theory that they are different phenotypes of the same disease. However, FSMK is distinguished from TMD by the absence of lipid deposition, the presence of a gray linear border, and the presence of epithelial defects. A definitive conclusion has not been reached at this time.
Recurrent redness and eye pain are the most common complaints. Episodes usually resolve spontaneously within a few days, but may persist 1).
Corneal findings in FSMK change with progression. The following characteristic findings are observed.
Pterygium is a disease in which conjunctival tissue spontaneously proliferates across the corneal limbus onto the cornea. Pseudopterygium is a secondary extension of conjunctival tissue covering the thinned area resulting from corneal thinning in conditions such as FSMK. Because highly thinned cornea exists beneath the pseudopterygium, careless resection carries the risk of perforation.
The underlying cause of FSMK is unknown. Even after thorough investigation for systemic autoimmune diseases, the cause remains unidentified in the majority of cases.
The following hypotheses and associated factors have been reported:
The corneal limbus is an area where vascular, immune, and nervous systems are densely packed, making it prone to immune-related keratoconjunctival diseases. The predilection of FSMK near the limbus may be related to this anatomical specificity.
There is no specific test to definitively diagnose FSMK. Diagnosis is made by evaluating clinical findings and excluding other diseases.
The following tests are performed to rule out other diseases 2).
The main diseases to differentiate from FSMK are listed below.
| Differential disease | Main differences from FSMK |
|---|---|
| Terrien marginal degeneration | Lipid deposition present, inflammatory findings scarce |
| Mooren ulcer | Severe inflammation, rapid progression, epithelial defect |
| Catarrhal corneal ulcer | Clear zone present, blepharitis associated |
There is no specific definitive diagnostic test for FSMK. Clinical diagnosis is made by confirming typical peripheral infiltration, thinning, pseudopterygium, and gray linear border on slit-lamp microscopy, and absence of lipid deposits. Additionally, blood tests are performed to rule out systemic diseases such as collagen vascular disease.
FSMK is extremely rare, and no established treatment protocol exists. In many reported cases, the disease progresses despite medical therapy. Treatment is based on two axes: inflammation control and structural repair.
Acute Phase Treatment
Steroid eye drops: Used to calm acute inflammatory episodes. Intraocular pressure monitoring is necessary with long-term use.
Artificial tears: Aim to lubricate and protect the ocular surface.
Antibiotic eye drops: Used concurrently to prevent secondary infection.
Maintenance and Chronic Phase Treatment
Oral doxycycline: Inhibits matrix metalloproteinase (MMP) activity and suppresses stromal melting 1).
Oral vitamin C: Promotes collagen synthesis 1).
Oral cyclosporine: Managed with trough levels of 70–100 ng/mL 1).
Steroid eye drops are effective in the acute phase, but many cases relapse upon tapering or discontinuation 2). Long-term steroid eye drops may be effective in suppressing disease progression, but management of side effects such as glaucoma remains a challenge 1).
In Terrien marginal degeneration, low-concentration steroid eye drops such as fluorometholone 0.1% are used when conjunctival injection or episcleritis occurs. A similar approach is also useful for managing inflammation in FSMK.
FSMK may recur even after transplantation 1).
Surgery combining superficial keratectomy and conjunctival autograft is possible, but the cornea under the pseudopterygium is extremely thin, with a high risk of perforation. Corneal thickness should be evaluated preoperatively with AS-OCT, and the procedure must be performed carefully by an experienced corneal specialist. Postoperative recurrence can occur.
The following histopathological features of FSMK have been reported.
Ellis examined two cases of bilateral FSMK and reported the presence of epithelioid giant cells in the corneal stroma. Acute inflammatory cells were concentrated directly beneath the ulcer, and degeneration of the conjunctiva and limbus resembled that of pterygium 1).
The exact pathogenesis of FSMK remains unknown, but the following hypotheses have been proposed.
The corneal limbus is located at the border between the corneal epithelium and conjunctival epithelium, and is an area rich in vascular, immune, and neural systems. Antigen-presenting cells such as Langerhans cells are abundant, making it prone to immune-related keratoconjunctival diseases. The predilection of FSMK lesions near the limbus is thought to be related to the unique immunological environment.
Arnalich-Montiel reported a 55-year-old man with features of both TMD and FSMK who was treated with mycophenolate mofetil (1 g twice daily), resulting in reduced frequency and severity of relapses 2). This is the first report in the literature of using mycophenolate mofetil for TMD/FSMK, suggesting the potential of targeting immune/inflammatory pathways.
Harada et al. reported two cases of FSMK at Nagasaki University 1). In case 1 (47-year-old woman), early pseudopterygium excision + mitomycin C + pedicled conjunctival flap transplantation was performed, followed by postoperative oral cyclosporine, resulting in a stable course without recurrence for 1.5 years. In contrast, case 2 (28-year-old woman) had delayed treatment, underwent repeated surgeries (6 times in the right eye, 3 times in the left eye) but experienced repeated recurrences, and final visual acuity decreased to 0.01 in both eyes. These contrasting two cases suggest the importance of early surgical intervention and inflammation control.
In the same cases, it was suggested that excision of the pseudopterygium itself may have an effect of suppressing recurrence of inflammatory episodes 2). In the eye that underwent superficial keratectomy and conjunctival autograft, recurrence disappeared, while in the contralateral unoperated eye, marked enlargement and thinning of the pseudopterygium were observed. This suggests that the conjunctiva may be involved in the inflammatory process.
The hypothesis that TMD and FSMK are different phenotypes of the same disease is supported by several reports1)2). If both diseases originate from a common vasculitis, systemic immunosuppressive therapy and conjunctival resection similar to that for Mooren’s ulcer may be effective2). Further accumulation of cases is expected to elucidate the pathophysiology.
