Clinical and Experimental Ophthalmology 2011; 39: 386–392 doi: 10.1111/j.1442-9071.2010.02479.

Original Article

Amniotic membrane transplantation for

Mooren’s ulcer
Nguyen D Ngan MD1 and Hoang TM Chau PhD2
1
Department of Ophthalmology, Vietnam Military Medical University, Hanoi, and 2Department of Cornea and External Diseases,
Vietnam National Institute of Ophthalmology, Hanoi, Vietnam

ABSTRACT Conclusion: Amniotic membrane transplantation

may be a useful treatment for selected patients with
Background: To describe the outcome of surgery using
Mooren’s ulcer especially where systemic immuno-
amniotic membrane transplantation for Mooren’s
suppressive drugs are unavailable.
ulcer.
Key words: amniotic membrane, Mooren’s ulcer,
Design: A prospective interventional case series from
peripheral corneal ulcer.
the Vietnam National Institute of Ophthalmology.

Participants: Eighteen eyes of 14 patients with INTRODUCTION

Mooren’s ulcer. Seven eyes had recurrent episodes of
ulceration, and 11 were not responsive to medical
therapy or conjunctival resection.
Methods: All eyes were treated with amniotic mem-
brane grafts for Mooren’s ulcer (10 eyes with multi-
layer grafts; 8 with a single layer graft). Five eyes
with a 360° peripheral ulcer were treated with an
overlay amniotic membrane graft, and 13 eyes were
treated with a freehand graft tailored to fit the local-
ized defect.
Main Outcome Measures: Time to epithelial healing.
Visual acuity outcome.
Result: Sixteen of 18 eyes were treated by a single
surgery with amniotic membrane with rapid
healing of the epithelial defect (mean time to com-
plete epithelialization 12.4 days). Two eyes required
a second amniotic membrane graft: one eye
required regrafting following a subgraft haemor-
rhage and another eye required regrafting for a per-
sistent epithelial defect. Vision was stabilized in all
eyes with 10 of 18 eyes obtaining vision of 6/12 or
better.
Mooren’s ulcer is an idiopathic, non-infectious
painful, peripheral ulcerative keratitis with a charac-
teristic undermined opaque central edge. Typically,
the ulcer progressively enlarges both centrally and
circumferentially. It may also be recurrent in nature
and involve one or both eyes.1 Mooren’s ulcer is
thought to be an organ-specific autoimmune disease
but its exact pathogenesis remains unclear.2–4
The management aims to control corneal inflam-
mation and re-epithelialize the cornea. This may
be achieved with topical, periocular or systemic
corticosteroids, and other cases require systemic
immunosuppression.5–9 Epithelialization is pro-
moted with the use of topical non-preserved lubri-
cants or a bandage contact lens. Surgical treatments
such as tissue adhesive, for example cyanoacrylate
or fibrin glue, conjunctival resection,10 superfi-
cial lamellar keratectomy,11,12 keratoepithelioplasty,13
lamellar and penetrating keratoplasty14,15 may also
be required to control corneal inflammation and to
treat corneal perforation. Despite aggressive medical
and surgical therapy, some involved eyes develop
permanent loss of vision.1
Amniotic membrane (AM) is the inner layer of the
placenta and consists of a thick basement membrane
with an overlying avascular stroma. It has been used

䊏 Correspondence: Dr Hoang TM Chau, Vietnam National Institute of Ophthalmology, 85 Ba trieu street, Hanoi, Vietnam. Email:
minhchauvnio@gmail.com
Received 1 February 2010; accepted 31 October 2010.

© 2011 The Authors

Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists
Amniotic membrane for Mooren’s ulcer
on the ocular surface as a patch or graft to promote
corneal re-epithelialization, reduce ocular surface
inflammation, and as a tectonic graft to the conjunc-
tiva and cornea.16–18 There have also been small case
series reporting the use of AM in patients with acute
Mooren’s ulceration.19–21 In this study, we report a
prospective case series of patients from Vietnam
treated with AM grafting for Mooren’s ulcer.
METHODS
Patients
Patients with Mooren’s ulcer were recruited pro-
spectively from the Vietnam National Institute of
Ophthalmology between January 2005 and October
2006. Mooren’s ulcer was defined as an idio-
pathic painful ulceration of the peripheral cornea
with typical clinical features and absence of scleral
inflammation. Infection was excluded by clinical
assessment and microbiological investigations.
Other forms of peripheral ulcerative keratitis were
excluded on the basis of clinical assessment, review
of systems and directed laboratory investigations
where appropriate.
Amniotic membrane transplantation (AMT) was
used in patients that had failed medical therapy in
that their disease either progressed or failed to
respond. Additionally, patients with recurrent epi-
sodes of ulceration or corneal perforations smaller
than 2 mm in diameter were included in the study.
Medical therapy included topical corticosteroids,
systemic corticosteroids and, where considered nec-
essary, a trial of topical antibiotics. One patient was
treated with topical antiviral medication for possible
herpetic keratitis. No patients were treated with sys-
temic immunosuppressive therapy as this is largely
unavailable in Vietnam.
This study was approved by the institutional
review board of Vietnam National Institute of Oph-
thalmology, and informed consent was obtained
from all patients.
Human AM preparation
Amniotic membrane was obtained during cesarean
section in women seronegative for hepatitis B virus,
hepatitis C virus, syphilis and human immunodefi-
ciency virus. The method of AM preparation has
been previous described by Tsubota et al.22 AM was
cryopreserved for up to 3 months before use.
Preoperatively, the container of AM was thawed to
room temperature; the membrane was rinsed three
times in saline and then once in saline containing
1 mg/mL of gentamicin. The AM was separated
bluntly from the underlying chorion with forceps
before transplantation.
© 2011 The Authors
Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists
387
Amniotic membrane transplantation
Surgery was performed under peribulbar block. The
base of the ulcer and adjacent limbal tissue were
resected with up to 3 mm of hyperaemic, swollen
conjunctiva and underlying Tenon’s capsule being
typically debrided before normal tissue was rea-
ched. Once healthy corneal stroma and sclera were
exposed, an AM graft of similar size and shape, epi-
thelial surface up, was fashioned to cover the defect
and sutured with interrupted 10-0 nylon sutures.
Where needed, two or more AM grafts were sutured
in layers to restore normal corneal thickness. A soft
bandage contact lens covered the grafts until corneal
epithelialization occurred. When 360° of the periph-
eral cornea was involved, the remaining central
island of corneal stroma was removed as well as
debriding the ulcer bed. AM grafts were then placed
to cover the cornea and limbus, with the epithelial
side face up and anchored to the sclera with inter-
rupted 10-0 nylon sutures (overlay AMT).
Postoperative medications included topical
prednisolone acetate 1% (Predforte; Allergan, Irvine,
CA, USA) and ofloxacin 0.3% (Oflovid; Santen Phar-
maceutical Company, Osaka, Japan) eye drops four
times daily. Sodium hyaluronate 0.1% (Sanlein,
Santen Pharmaceutical Company) was instilled six
times a day. Patients were followed up daily after
surgery until complete corneal epithelialization
occurred and then monthly thereafter when possible.
After the corneal epithelium healed, antibiotics were
discontinued and the topical steroids were tapered
over a period of months.
RESULTS
Twenty-four patients with Mooren’s ulcer were seen
over the study period. Twelve eyes of 10 patients
responded to medical therapy or conjunctival resec-
tion and were therefore excluded from the study. In
two patients with bilateral disease, one of the eyes
responded to medical therapy and was excluded
from the study, and the fellow eye required AMT and
was included in the study. Therefore, 18 eyes of 14
patients (eleven men and three women) were eli-
gible for inclusion in the study (mean age ⫾ SD:
55.4 ⫾ 15.6 years, range 28–75 years)
Of the eyes treated with AM, 5 eyes had 360° of
corneal melting, 11 between 90° and 360° of melting
and 2 eyes had less than 90° of melting. Three eyes
also had a corneal perforation and one eye a
descemetocele. There were seven eyes with a recur-
rent episode of ulceration that had not responded to
medical therapy. The clinical features of the patient
group are detailed in Table 1. Ten eyes required mul-
tiple layers of AM to reconstitute the cornea. Of the
five eyes with 360° of corneal stromal involvement,
388 Ngan and Chau

Table 1. Clinical features of patients with Mooren’s ulcer

Case/No. eye Eye Age Sex Recurrent times Previous treatments Size of the ulcer Depth of the ulcer
(years) (in circumference)
1/1 OD 67 Female 1 CS, AB 180° >2/3
1/2 OS 67 Female 1 CS, AB, LKP 360° Perforation
2/3 OD 41 Male 2 CS, AB, LKP, CCR 120° ⱕ2/3
3/4 OD 67 Male 2 CS, AB, LKP 360° >2/3
3/5 OS 67 Male 2 CS, AB, LKP 360° >2/3
4/6 OD 29 Male 0 CS, AB 120° Perforation
5/7 OS 37 Male 3 CS, AB, LKP, CCR 180° >2/3
6/8 OD 28 Male 0 CS, AB 180° Descemetocele
7/9† OD 70 Male 0 CS, AB 120° ⱕ2/3
8/10 OS 55 Male 0 CS, AB 360° >2/3
8/11 OD 55 Male 0 CS, AB 360° ⱕ2/3
9/12 OS 57 Male 0 CS, AB, AVA 90° ⱕ2/3
10/13 OD 75 Male 0 CS, AB 150° ⱕ2/3
11/14 OS 56 Male 0 CS, AB 240° ⱕ2/3
11/15 OD 56 Male 0 CS, AB 210° ⱕ2/3
12/16† OS 70 Female 0 CS, AB 240° ⱕ2/3
13/17 OS 65 Male 0 CS, AB 90° ⱕ2/3
14/18 OD 59 Female 1 CS, AB 180° Perforation

360° ulcer means that the entire peripheral cornea is involved. Depth of the ulcer was compared with normal corneal thickness.
†
Both eyes were involved but the fellow eye was successfully treated with medical therapies. AB, antibiotic; AVA, antiviral agent;
CCR, conjunctival and corneal resection; CS, corticosteroid; LKP, lamella keratoplasty.

three had previously had a lamellar keratoplasty and
in the remaining two eyes, the residual central
corneal stroma was small and extremely oedemat-
ous making surgery that attempted to preserved
this tissue not feasible technically. All these eyes
required overlay grafts after excision of the central
island of the corneal stroma. Mean follow up was
12.0 ⫾ 5.7 months (range 1.5–20 months). Details of
the surgical procedure, follow up and visual results
are detailed in Table 2.
Visual outcomes are best considered into two
groups. Group 1, the five eyes with overlay grafts
had poor visual outcomes, with vision ranging from
hand movements to 6/60 vision. Vision was stabi-
lized in four of the five eyes and worse following
surgery in only one of these eyes. Three of the four
patients with bilateral Mooren’s ulcer had poor
vision in each eye. Group 2, the 13 eyes with local-
ized AM grafts had good visual outcomes. Nine
involved eyes had visual acuity improved by two or
more Snellen lines of visual acuity and in the
remaining four eyes visual acuity was stable. Ten of
the 13 eyes had a final visual acuity of 6/12 or better,
and only one eye had visual acuity of <6/60. None of
these patients had poor vision in both eyes.
Rapid healing of the epithelial defect occurred
in 16 of the 18 studied eyes following the AMT
(the mean time to complete epithelialization was
days ⫾ SD: 12.4 ⫾ 5.2 days, range 5–27 days) (Fig.
1a,b,d,e,g,h). One eye developed a large haematoma
under the AM graft 24 h postoperatively, and the AM
became necrotic despite draining the haematoma.
Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists
The patient was regrafted with a successful outcome.
Another eye had poor epithelial healing following
surgery, and the AM graft was destroyed by
ingrowth of pannus. Two months following surgery,
AMT was repeated with rapid corneal epithelializa-
tion postoperatively. There was a variable distur-
bance of the limbal vasculature postoperatively in all
eyes with localized AM grafts, but no progressive
ingrowth of pannus was observed (Fig. 1i,k). There
was reformation of a clinically distinct stable zone of
limbal vasculature in the five eyes with total replace-
ment of the corneal stroma by an overlay AM graft
(Fig. 1c,f). Limited superficial corneal pannus was
found in the palpebral fissure of all these eyes
without invading central corneal in follow-up time.
Topical steroid therapy was able to be progressively
tapered and ceased by 3 months following surgery in
all eyes.
DISCUSSION
Conjunctival resection removes inflamed conjunctiva
adjacent to the area of corneal ulceration is effective,
but there is a high recurrence rate.15,23,24 Systemic
therapy such as corticosteroids and additional immu-
nosuppressive therapy, although highly effective,7–9
are not used in the third world, because of the
high cost of immunosuppressive drugs. Keratoepi-
thelialoplasty is also highly effective,13 but is imprac-
tical in the third world, because of the shortage
of available donor material. Previous small
studies have shown that AMT can successfully heal
© 2011 The Authors
© 2011 The Authors
Table 2. Patient outcomes following AMT

Case/No. eye Follow-up time Size of AM Layers AM Begin epi. Completed epi. BCVA Outcome
(months) (days) (days)
Preoperation At last follow up
1/1 19 180° 2 3 14 6/60 6/30 Success
Amniotic membrane for Mooren’s ulcer

1/2 19 Overlay 2 2 13 HV 6/60 Success

2/3 20 120° 1 6 15 6/9 6/6 Success
3/4 20 Overlay (second AMT) 2 7 14 CF 4 m CF 4 m Success (2 procedure)
3/5 20 Overlay 2 4 18 CF 0.5 m CF 3 m Success
4/6 10 120° 2 3 11 6/9 6/6 Success
5/7 9 180° 2 2 9 6/60 6/9 Success
6/8 16 180° 2 2 11 6/60 6/6 Success
7/9 10 120° 1 4 15 6/12 6/9 Success
8/10 11 Overlay 2 2 27 CF 1 m 6/60 Success
8/11 10 Overlay 1 4 30 6/15 HV Success (2 procedure)
9/12 13 90° 2 2 5 CF 1.5 6/60 Success
10/13 7 150° 1 2 10 CF 4 m 6/15 Success
10/14 7 240° 1 2 10 6/30 6/6 Success
11/15 7 210° 1 2 9 6/30 6/6 Success
12/16 8 240° 1 2 10 6/60 6/15 Success
13/17 8 90° 1 2 6 6/15 6/6 Success
14/18 1.5 180° 3 4 15 HV HV Success

AMT, amniotic membrane transplantation; BCVA, best-corrected visual acuity; CF, counting fingers; epi., epithelialization; HV, hand motion; outcome success, ocular surface is
healed without inflammation.

Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists
389
390 Ngan and Chau

(a) (b)

(c) (d)

(e)
(f)

(g)
(h)

(i)
(j)

(k)

Figure 1. (a) 360° peripheral corneal ulcer of the right eye in a 67-year-old man (eye No. 4). (b) Postoperative appearance 2 weeks after
overlay amniotic membrane transplantation (AMT) shows complete corneal epithelialization. (c) The same eye with cloudy cornea
15 months after AMT. (d) 360° recurrent peripheral corneal ulcer after lamella keratoplasty of the left eye in a 67-year-old woman (eye
No. 2). (e) This eye 13 days after AMT combined with extracapsular cataract extraction + intraocular lens shows total corneal
re-epithelialization. (f) Transparent cornea 19 months after surgery. (g) 210° lower corneal melting of the right eye in a 56-year-old man
(eye No. 15). (h) Healed cornea, 7 days after AMT. (k) Stabilized corneal scar without pannus, 16 months postoperatively. (i) The third
recurrent 180° corneal ulcer of the left eye in 37-year-old man (eye No. 7). (j) The same eye with opacity scar and mild disturbance of the
limbal vasculature 8 months postoperatively.

© 2011 The Authors

Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists
Amniotic membrane for Mooren’s ulcer
non-responsive Mooren’s ulcers,19–21 and in the
current study AMT surgery has been shown to be
effective in eyes that do not respond to local medical
therapy and/or conjunctival resection. Treated eyes
rapidly became pain-free, the ocular surface inflam-
mation improved greatly and the epithelialization
occurred rapidly following surgery. Only one eye
remained severely inflamed following surgery and
following regrafting this eye healed rapidly.
Mooren’s ulcer is an autoimmune disease that targets
the corneal stroma,2–4 and the current study contrib-
utes more evidence that AMT therapy may help to
treat Mooren’s ulcer with a good visual outcome and
a low frequency of recurrence. Additionally, it is
likely that AMT downregulates inflammation
because of its expression of Fas ligand and HLA–G
antigens that reduce inflammation and activate sup-
pressor T-cell mechanisms.25–30
In this study 50% of the patients with Mooren’s
ulceration responded to relatively simple medical
and surgical treatment. The other 50% responded
well to AMT surgery. These are highly relevant
outcome data for ophthalmologists looking after
such patients in the developing world. This is
even more important given that the patient group in
this study is likely to be biased as patients with more
severe disease were more likely to be referred to a
tertiary referral centre. The strength of this study is
that it is a relatively large prospective series from a
tertiary referral ophthalmology unit serving a large
population in a developing country where systemic
immunosuppressive therapy is unavailable. The
major shortcoming of this study is the variable and
relatively short follow up. The nature of the study
population and the geographic location made it
impossible to obtain ongoing follow-up data.
The study was conducted in a country where the
prevalence of Mooren’s ulcer is high and expen-
sive immunotherapy is unavailable. A relatively
simple surgical intervention using AM graft is a
useful treatment that stabilizes and restores the
ocular surface. Vision is maintained or improved
with excellent short to medium-term outcomes and
no evidence of disease recurrence. AMT appears
to be a useful therapy for patients with Mooren’s
ulcer who progress following treatment with topical
corticosteroids and/or conjunctival resection, when
other therapies such as systemic immunosuppres-
sion are unavailable or contraindicated.
ACKNOWLEDGEMENTS
The authors thank Professor Peter McCluskey,
Dr Ravi Singh of University of Sydney, Sydney,
Australia and Dr Pham Trong Van of Hanoi Medical
University, Hanoi, Vietnam for their assistance with
this study and the preparation of the manuscript.
© 2011 The Authors
Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists
391
REFERENCES
1. Chow C, Foster CS. Mooren’s ulcer. Int Ophthalmol Clin
1996; 36: 1–13.
2. Gottsch JD, Liu SH, Minkovitz JB, Goodman DF,
Srinivasan M, Stark WJ. Autoimmunity to a cornea-
associated stromal antigen in patients with Mooren’s
ulcer. Invest Ophthalmol Vis Sci 1995; 36: 1541–7.
3. Kafkala C, Choi J, Zafirakis P, Baltatzis S, Livir-
Rallatos C, Rojas B, Foster CS. Mooren ulcer an immu-
nopathologic study. Cornea 2006; 25: 667–73.
4. Zelefsky JR, Srinivasan M, Kundu A et al. Hookworm
infestation as a risk factor for Mooren’s ulcer in South
India. Ophthalmology 2007; 114: 450–3.
5. Dinzis P, Mondino B. Management of non-infectious
corneal ulcers. Surv Ophthalmol 1987; 32: 94–110.
6. Frangieh T, Kenyon K. Mooren’s ulcer. In: Brightbill
FS, ed. Corneal Surgery: Theory, Technique, and Tissue, 2nd
edn. Saint Louis, MI: Mosby, 1993; 328–35.
7. Foster CS. Systemic immunosuppressive therapy for
progressive bilateral Mooren’s ulcer. Ophthalmology
1985; 92: 1436–9.
8. Wakefield D, Robinson LP. Cyclosporin therapy in
Mooren’s ulcer. Br J Ophthalmol 1987; 71: 415.
9. Zhao J, Jin X. Immunological analysis and treatment of
Mooren’s ulcer with cyclosporine A applied topically.
Cornea 1993; 12: 481–8.
10. Chihara E, Nishi R, Asayama K, Traukahara I. Treat-
ment of Mooren’s ulcer by conjunctival excision. Oph-
thalmology 1979; 179: 258–64.
11. Du NZ, Chen JQ, Gong XM, Xu HT. Mooren’s ulcer
treated by lamellar keratoplasty. Jpn J Ophthalmol 1979;
23: 257.
12. Martin N, Stark WJ, Maumenee AE. Treatment of
Mooren’s and Mooren’s-like ulcer by lamellar kerate-
ctomy: report of six eyes and literature review. Oph-
thalmic Surg 1987; 18: 564–9.
13. Kinoshita S, Koizumi N, Sotozono C, Inatomi B, Yokoi
N. The long term outcome of keratoepithelioplasty in
Mooren’s ulcer. Program and abstracts of the Cornea
Society and Eye Bank Association of America at the
American Academy of Ophthalmology and European
Society of Ophthalmology 2004 Joint Meeting;
October 23–26, 2004; New Orleans, Louisiana.
14. Brown SI, Mondino BJ. Penetrating keratoplasty. Am J
Ophthalmol 1980; 89: 255–8.
15. Chen J, Xie H, Wang Z et al. Mooren’s ulcer in China:
a study of clinical characteristics and treatment. Br J
Ophthalmol 2000; 84: 1244–9.
16. Kim JC, Tseng SCG. Transplantation of preserved
human amniotic membrane for surface reconstruction
in severely damaged rabbit corneas. Cornea 1995; 14:
473–84.
17. Dua HS, Gomes JAP, King AJ, Maharajan VS. The
amniotic membrane in ophthalmology. Surv Ophthalmol
2004; 49: 51–77.
18. Fernandes M, Sridhar MS, Sangwan VS, Rao GN.
Amniotic membrane transplantation for ocular surface
reconstruction. Cornea 2005; 24: 643–53.
19. Hanada K, Shimazaki J, Shimmura S, Tsubota K. Multi
layered amniotic membrane transplantation for severe
392
ulceration of the cornea and sclera. Am J Ophthalmol
2001; 131: 324–31.
20. Solomon A, Meller D, Prabhasawat P, John T, Espana
EM, Steuhl KP, Tseng SCG. Amniotic membrane grafts
for nontraumatic corneal perforations, descemetoco-
eles and deep ulcers. Ophthalmology 2002; 109: 694–
703.
21. Chen KH, Hsu WM, Liang CK. Relapsing Mooren’s
ulcer after amniotic membrane transplantation com-
bined with conjunctival autografting. Ophthalmology
2004; 111: 792–5.
22. Tsubota K, Toda I, Saito H, Shinozaki N, Shimazaki J.
Reconstruction of the corneal epithelium by limbal
allograft transplantation for severe ocular surface
disorders. Ophthalmology 1995; 102: 1486–96.
23. Brown SI, Mondino BJ. Therapy of Mooren’s ulcer. Am
J Ophthalmol 1984; 98: 1–6.
24. Stillma J. Mooren’s ulcer: conjunctival excision or
lamellar scleral auto graft in 38 Mooren’s ulcer from
Sierra Leon. Br J Ophthalmol 1983; 67: 475–8.
25. Shimmura S, Shimazaki J, Ohashi Y, Tsubota K. Anti-
inflammatory effect of amniotic membrane transplan-
Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists
Ngan and Chau
tation in ocular surface disorders. Cornea 2001; 20:
408–13.
26. Houlihan JM, Biro PA, Harper HM. The human
amnion is a site of MHC class Ib expression: evidence
for the expression of HLA-E and HLA-G. J Immunol
1995; 154: 5665–74.
27. Hammer A, Hutter H, Blaschitz A et al. Amnion epithe-
lial cells, in contrast to trophoblast cells, express all
classical HLA class I molecules together with HLA-G.
Am Reprod Immunol 1997; 37: 161–71.
28. Kubo M, Sonoda Y, Muramatsu R, Usui M. Immuno-
genicity of human amniotic membrane in experimen-
tal xenotransplantation. Invest Ophthalmol Vis Sci 2001;
42: 1539–46.
29. Griffith TS, Brunner T, Fletcher SM, Green DR, Fergu-
son TA. Fas ligand-induced apoptosis as a mechanism
of immune privilege. Science 1995; 270: 1189–92.
30. Riteau B, Menier C, Khalil-Daher I, Sedlik C, Dausset
J, Rouas-Freiss N, Carosella ED. HLA-G inhibits the
allogeneic proliferative response. J Reprod Immunol
1999; 43: 203–11.
© 2011 The Authors