Background
Mooren’s ulcer is a relentless, painful, and chronic ulcerative keratitis that was first described by Bowman in 1849 and later by Mooren in 1867 [
1‐
3]. It is a rare and potentially blinding ocular disease that is more commonly observed in the African, China and India [
4]. Although its underlying etiology remains unclear, it is widely accepted that Mooren’s ulcer is an idiopathic autoimmune disease [
4‐
6]. A typical Mooren’s ulcerative lesion is characterized by an overhanging edge and stromal melting. The ulceration begins in the peripheral cornea and tends to progress circumferentially or centrally, whereas rarely progressing to involve the entire cornea [
6,
7]. The natural progression of Mooren’s ulcer varies substantially, and corneal melting may cause descemetoceles or, in severe cases, corneal perforations [
8]. Conventional interventions for Mooren’s ulcer include the local or systematic use of steroids or non-steroidal immunosuppressants, conjunctival resection, lamellar keratoplasty (LKP), penetrating keratoplasty (PKP), epikeratoplasty or amniotic membrane transplantation [
3,
4,
8‐
11]. Conjunctival flap has been confirmed to be a simple, well-supported, short-term treatment for managing corneal perforation or impending perforation in infective corneal ulcers [
12‐
14]. However, it is not recommended for the Mooren’s ulcer, a peripheral autoimmune-related ulcerative corneal diseases. In the current report, we present two patients with Mooren’s ulcer who were incorrectly subjected to conjunctival flap to prevent corneal perforation. In each of these two cases, a rapid deterioration was observed in the ulceration following conjunctival flap.
Discussion and conclusions
Mooren’s ulcer is an idiopathic, progressive, and painful peripheral ulcerative keratitis that occurs in the absence of any other associated systematic diseases [
6]. To our knowledge, the etiology of Mooren’s ulcer remains unclear, but there is a general consensus that it may have an immunological basis [
4‐
6,
15‐
17].
Most experts advocate “the stepladder approach” for managing Mooren’s ulcer [
4,
6,
18]. Representative studies in the literature that describe interventions for Mooren’s ulcer are listed in Table
1 [
3,
8,
11,
19‐
27]. Conventional therapies involve the topical or Systematic application of steroids (such as dexamethasone and prednisolone) and immunosuppressive reagents (such as cyclosporin A and tacrolimus (FK506)) [
8,
19,
28,
29], and surgical treatments (such as conjunctival resection, freezing or thermocoagulating) [
4,
6,
11]. Occasionally, Mooren’s ulcers respond poorly to the conventional therapies that have been described here, and these patients may be at risk of corneal perforation [
8]. In these cases, LKP or PKP should be introduced [
8,
23,
24]. However, currently, the lack of donated corneas remains a major issue all over the world, especially in some Asian and African counties [
30‐
32]. In case of numerous other corneal diseases, including corneal perforation, infectious keratitis and resistant corneal ulcers, the conjunctival flap can been used as an alternate procedure. Conjunctival flaps are helpful for maintaining ocular integrity, reducing corneal pain, reducing inflammatory processes, arresting corneal ulceration and preventing secondary infection [
12,
33]. However, can the conjunctival flap procedure be applied in patients with Mooren’s ulcers?
Table 1
Representative studies describing interventions for Mooren’s ulcers
| Case series | Conjunctival resection + systemic immunosuppression | √ |
| Case series | Topic cyclosporin A + LKP | √ |
| Case series | Modified LKP + immunosuppressive therapy | √ |
| Case series | Topic tacrolimus alone or + KP | √ |
| Case series | AMT | √ |
Schallenberg et al. (2013) [ 27] | Case series | AMT alone or + conjunctival excision | × |
Alhassan et al. (2014) [ 4] | Systematic review | Conjunctival flap | N/A |
Brightbill et al. (2008) [ 21] | Textbook | Conjunctival flap | N/A |
| Case report (One case) | Conjunctival flap + AMT (excised from opposite healthy eye) | Caused replasing |
Our observation | Case report (Two cases) | Conjunctival flap (excised from the same diseased eye) | Caused rapid deterioration |
A search of databases revealed that a few studies and textbooks mentioned conjunctival flap being used to treat Mooren’s ulcers [
4‐
6,
21,
34]. However, probably because it was performed very rarely and chosen only in some extenuating circumstances, we were not able to retrieve the rate of successful treatment. In our study, we describe two cases of Mooren’s ulcer in which conjunctive flap (excised form the same diseased eye) was performed for management of corneal perforation since donor corneas were not available at the time. However, conjunctive flap appeared to cause a rapid ulceration deterioration and a subsequent expansion to the entire cornea. Our report lends further supportive to the findings of Chen [
22]. Chen and associates previously observed a Mooren’s ulcer that relapsed in one patient after amniotic membrane grafting was combined with conjunctival flap (excised from the opposite healthy eye).
There is evidence suggesting that Mooren’s ulcer is an autoimmune disease that is probably directed against a specific antigen in the corneal stroma and triggered by specific risk factors, including a history of ocular surgery or trauma and exposure to viral or parasitic infections [
4‐
6,
15‐
17]. Both cell-mediated and humoral immune components were shown to be directly involved in the pathogenesis of Mooren’s ulcer [
5,
6]. First, immunological aberrations in Mooren’s ulcers appear to involve a subpopulation of T lymphocytes that are known as suppressor T cells (T
S cells) [
5]. Second, studies have also found circulating IgG antibodies in the cornea and conjunctiva of patients with Mooren’s ulcers [
35]. Finally, high levels of serum IgA/IgM and circulating immune complexes have also been detected in patients with Mooren’s ulcers [
5,
17].
These alterations in systemic immunity cause a local immune response. The conjunctiva is a blood vessel-enriched tissue. A histopathological study of Mooren’s ulcers revealed that the conjunctival tissues adjacent to the ulcerative cornea housed a large amount of immune effect cells and circulating corneal-associated autoantibodies [
6,
26]. The triggering of local autoimmune processes further induced the conjunctiva to produce cornea-destroying enzymes, including collagenase and proteolytic enzymes [
15]. Therefore, the conjunctiva serves as a nest for immune mediators and proteases during the pathogenesis of Mooren’s ulcers, which may explain why Mooren’s ulcers always begin in the peripheral cornea. This may also explain why Mooren’s ulcer can be successfully treated using conjunctival resection, freezing and thermocoagulation: because these therapies move activated inflammatory components and proteases away from the cornea, which consequently arrests the progression of the ulceration. However, conjunctival flap, especially when the flap is excised from the same diseased eye, as was performed in the cases described in this study, are in direct opposition to conjunctival resection. Bring the conjunctiva to cover the ulcer will lead to inflammatory mediators and proteases increasing, resulting in ulcer deterioration and progression.
In the two case studies reported here, both patients ultimately underwent keratoplasty and obtained a final cure. Currently, LKP has become the dominant surgical treatment of choice for Mooren’s ulcer [
8,
36]. However, in cases such as the second patient in our report in whom corneal perforation has occurred, PKP should be performed instead. Because immunological memory is a hallmark of immune system functions, keratoplasty should be combined with the concurrent administration of topical or systemic immunosuppression to avoid recurrence and graft failure, even when the active disease has been arrested [
4,
6]. The reported final healing rate in Mooren’s ulcers that were treated using LKP plus topical immunosuppressive reagents (including 1% cyclosporin A and 0.05%/0.1% Tacrolimus) varied from 89.0% to 100% [
8,
29].
In light of our findings, keratoplasty combined with immunosuppression is effective in arresting Mooren’s ulcer and prevent its recurrence. Conversely, conjunctival flap could activate autoimmune process and result the deterioration and progression of ulceration, especially when inflammation has not been controlled. However, it remains unclear whether conjunctival flap could be recommended to treat corneal perforation due to other immune-mediated corneal melting diseases, such as rheumatoid arthritis-associated corneal ulcers and Wegener’s granulomatosis [
37].
Acknowledgements
We are grateful to all the stuff involved in the care of the patients included in this case report.