CLINICAL SCIENCE
Mitomycin C-Associated Scleral Stromalysis After
Pterygium Surgery
T. Peter Lindquist, MD, and W. Barry Lee, MD
Purpose: To describe complications after use of mitomycin C
(MMC) as a surgical adjuvant in pterygium surgery.
Methods: This is a retrospective chart review of patients presenting
to a tertiary referral center over a 7-year period with a diagnosis of
scleral stromalysis after previous pterygium removal.
Results: Sixteen eyes of 15 patients were identified with scleral
stromalysis after pterygium surgery with the use of adjuvant MMC.
Three eyes were excluded because of insufficient chart information or
previous beta-irradiation treatment. Twelve of 13 eyes underwent
surgical treatment for primary pterygium, and 1 eye was treated for
recurrent pterygium. Time from initial pterygium surgery to pre-
sentation ranged from 1 month to 10 years. Dosage and routes of MMC
administration included 0.02% intraoperative application to either the
bare sclera or Tenon capsule with a range of 30 seconds to 3 minutes or
topical administration 4 times daily for 2 weeks. In some cases, the
dose and route of MMC administration were unknown. Four of 13
patients (31%) required a scleral patch graft with 1 patient (8%)
requiring multiple patch grafts.
Conclusions: Use of MMC in various forms and concentrations can
cause devastating complications including scleral stromalysis. Scleral
stromalysis may present anywhere from months to years after
application. We suggest that MMC should be used with extreme
caution when used as a surgical adjuvant for pterygium surgery.
Patients must be urged to continue long-term follow-up after MMC use
because of the potential for future anterior segment complications.
Key Words: mitomycin C, stromalysis, pterygium, pterygium surgery,
amniotic membrane, conjunctival graft, scleral melt
(Cornea 2015;34:398–401)
M edical and surgical treatments for pterygia have been
described for over 5000 years. Despite centuries of
experience, numerous publications, and innumerable scientific
meeting presentations, no consensus has emerged on the gold
standard for surgical removal of pterygia. Outcomes continue
to remain imperfect and lack standardization.1,2 Simple
Received for publication July 10, 2014; revision received November 26,
2014; accepted December 28, 2014. Published online ahead of print
February 19, 2015.
From the Division of Ophthalmology, Piedmont Hospital; Cornea Service, Eye
Consultants of Atlanta, Atlanta, GA.
The authors have no funding or conflicts of interest to disclose.
Reprints: W. Barry Lee, MD, Eye Consultants of Atlanta, 3225 Cumberland
Boulevard, Suite 900, Atlanta, GA 30339 (e-mail: wblee@mac.com).
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surgical excision of pterygia, leaving only bare sclera, has been
shown to result in recurrence rates of up to 88% in some
populations and is not recommended.2,3 A number of adjuvants
have been used in attempts to reduce recurrence rates and improve
postoperative cosmesis. These adjuvants include beta-irradiation,
thiotepa, 5 fluorouracil (5-FU), cauterization, conjunctival or
limbal autograft (CAG), amniotic membrane graft (AMT), and
mitomycin C (MMC).2–9 Each of these adjuvants has advantages
and disadvantages.
The use of MMC as a surgical adjuvant has proven
effective in reducing recurrence rates after pterygium excision
when used alone or in combination with a grafting technique,
but complications after MMC use have been reported.10–17
Vision-threatening complications including scleral melting,
corneal perforation, infectious scleritis, and endophthalmitis
have occurred with MMC use.10–17 The purpose of this study
was to present multiple cases of a vision-threatening compli-
cation after use of MMC during pterygium excision and to
discuss its negative role as an adjuvant in pterygium surgery.
This relatively large case series is important given that the
American Academy of Ophthalmology position paper on
pterygium surgery, and its adjuvants was unable to comment
on long-term complications of MMC use after pterygium
surgery because of its study design.
METHODS
A retrospective review was performed for patients present-
ing to 1 specialist at a single tertiary referral center over a 7-year
period for management of MMC-associated scleral complications
after pterygium surgical excision. A search was conducted in the
medical record database for diagnoses of scleromalacia or
scleritis, and charts were reviewed systematically. The inclusion
criteria were a clinical diagnosis of scleral stromalysis and
a history of pterygium excision with the use of MMC. Primary
and recurrent pterygia were included. Patients were excluded if
most relevant surgical data were missing from the medical
record, scleral stromalysis was not related to pterygium surgery
alone, or if radiotherapy was performed.
RESULTS
Sixteen patients were identified with a clinical diagnosis
of scleral stromalysis after pterygium surgery with adjuvant
MMC. Three were excluded because of insufficient medical
records or previous treatment with radiotherapy. After
exclusion, 13 eyes of 12 patients were analyzed.
Twelve of 13 eyes (92%) were treated with surgical
excision for primary pterygium with 1 patient undergoing
Cornea  Volume 34, Number 4, April 2015
 Cornea  Volume 34, Number 4, April 2015 Scleral Stromalysis After Pterygium Surgery

surgery for recurrent pterygium. Patients were treated with
varying concentrations and routes of administration of MMC
using multiple surgical techniques with no standardization.
When known, the concentration of MMC in all cases was
0.02%; MMC was given as an intraoperative application in 12
eyes and used topically after surgical excision in 1 eye. The
MMC was applied directly to bare sclera in 5 eyes and to the
Tenon capsule in 3 eyes. In 1 patient, MMC 0.02% drops were
administered postoperatively 4 times daily for 2 weeks. The
length of intraoperative MMC application ranged from 30
seconds to 3 minutes. The surgical technique included bare
sclera excision in 7 eyes, conjunctival autograft (CAG) in 1
eye, AMT in 5 eyes, and the exact technique was unknown in 4
eyes. Individual treatment regimens are listed in Table 1.
Four basic types of scleral stromalysis were identified:
(1) corneoscleral dellen (3 eyes), (2) scleral stromalysis with
overlying calcific plaque (3 eyes), (3) chronic scleral
stromalysis with underlying scleromalacia (5 eyes), and (4)
active scleritis with episcleral ischemia (2 eyes) (Fig. 1). None
of the cases were infectious in etiology. Patients had no other
known cause of stromalysis, such as rheumatologic disease or
infectious scleritis.
Time from initial pterygium surgery to presentation of
scleral stromalysis ranged from 1 month to 10 years, with
a mean time of 4 years. Eight of 13 eyes (62%) presented
more than 3 years after their initial pterygium surgery. Patient
age and race were varied and can be seen in Table 1.
Treatment after scleral stromalysis consisted of observation
and/or ocular surface lubrication alone in 8/13 (62%) and
scleral patch graft in 4/13 (31%) with 1/13 (8%) requiring an
AMT. One patient required multiple patch grafts (Fig. 1). The
treatment endpoint was cessation of inflammation and
stabilization of the overlying ocular surface.
DISCUSSION
We identified 13 eyes of 12 patients with scleral
stromalysis attributable to the use of MMC during pterygium
surgery. Patients in whom stromalysis was observed had a range
of MMC application times and surgical techniques for excision,
as well as a range in severity of scleral stromalysis. All patients
for whom the MMC dose was known had a concentration and
application time that has been widely accepted and deemed safe
in the peer-reviewed literature.7,8,18–27
Although MMC use as a surgical adjunct after ptery-
gium excision has shown decreased recurrence rates in the
literature,2,7,8,18–26 it has also been associated with a number of
cited complications.10–17 Increased safety is thought to occur
using a lower dose of MMC, a shorter duration of application,
and a controlled intraoperative application to the Tenon
capsule as opposed to postoperative topical application. We
found that even short intraoperative applications of low-dose
MMC can result in scleral stromalysis. In this study, an MMC
application of the lowest commonly used dose (0.02%) for 30
seconds was enough to result in stromalysis in 1 case. It is
important to note that there was a range in the severity of
stromalysis. The majority (62%) of patients presented with

TABLE 1. Summary of Cases With Scleral Melting After Pterygium Excision and Adjunctive MMC Use
Time Final Visual
Surgical (Surgery to Acuity Clinical Findings on
Patient Age Race Adjunct MMC % MMC Route/Dose Presentation) (Snellen) Presentation/Treatment
1 71 C Bare sclera 0.02 Topical/4 times a day 10 yrs 20/60 Active stromalysis with epi defect,
· 2 wk scleritis/scleral patch graft
2 42 H AMT 0.02 Intraoperative/3 min 4 yrs 20/20 Quiet scleromalacia + calcific plaque and
to sclera diplopia/repeat AMT
3 81 C Bare sclera Unknown Intraoperative/? 9 yrs 20/25 Calcific plaque/observed with lubrication
4 61 AA CAG Unknown Intraoperative/2 min 6 yrs 20/40 Corneoscleral dellen/observed with
to sclera lubricants
5 30 AA AMT 0.02 Intraoperative/30 sec 3 mo 20/30 Mild, quiet scleromalacia/observed with
to sclera lubricants
6 73 Asian Bare sclera Unknown Intraoperative/? 3 yrs 20/40 Active stromalysis with epi defect/scleral
patch graft
7 53 C Bare sclera 0.02 Intraoperative/2 min 10 yrs 20/40 Quiet scleromalacia/observed with
to sclera lubricants
8 67 Asian AMT 0.02 Intraoperative/3 min 2 yrs 20/30 Active stromalysis with epi defect/scleral
to Tenon patch graft · 3 (recurrent melts)
9 87 AA Bare sclera Unknown Intraoperative/? 5 yrs 20/50 Quiet scleromalacia/observed with
lubricants
10 82 AA Bare sclera Unknown Intraoperative/? 4 yrs 20/50 Quiet scleromalacia/observed with
lubricants
11 41 H AMT 0.02 Intraoperative/2 min 1 mo 20/30 Episcleral ischemia/observed with
to Tenon lubricants
12 34 H Bare sclera 0.02 Intraoperative/3 min 1 yr 20/50 Active stromalysis with epi defect/scleral
to Tenon patch graft
13 45 C AMT 0.02 Intraoperative/2 min 1 yr 20/40 Quiet scleromalacia/observed with
to sclera lubricants
AA, African American; C, Caucasion; Epi, epithelium; H, Hispanic; ?, unknown.

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 Lindquist and Lee Cornea  Volume 34, Number 4, April 2015

FIGURE 1. A, A slit-lamp photograph

with a calcific plaque overlying
chronic, yet quiet scleral stromalysis
(case 2). B, A corneoscleral dellen
formed years after pterygium excision
with MMC and bare sclera (case 4). C,
Scleromalacia after pterygium excision
with adjuvant MMC and a conjuncti-
val autograft (case 7). D, Episcleral
ischemia with surrounding episcleral
inflammation after MMC application
with pterygium surgery and AMT
(case 10). E, A well-healed scleral graft
placed to treat severe scleral stromal-
ysis after MMC-related ischemia and
scleritis (case 1). F, Recurrent stromal-
ysis in a scleral graft in a patient after
pterygium excision with MMC and
AMT (case 8).

mild stromalysis that was inactive and controlled with
lubrication alone. However, a large number (39%) of patients
presented with more significant active stromalysis that
required surgical intervention. The surgical technique and
method of MMC application varied in these more severe
cases, which limits our ability to make conclusions regarding
cause and effect. However, we note that in the more severe
cases, the surgical technique consisted of either bare sclera or
adjunctive AMT, and MMC technique included application to
the Tenon capsule only or to bare sclera. We also demonstrate
that scleral stromalysis may occur years after initial applica-
tion of MMC, as 3 of our cases presented for management
beyond 9 years after initial surgery. Although several studies
claim safety of MMC when used for pterygium removal, most
have limited follow-up times.23–27 We therefore suggest that
scleral stromalysis may be an underreported complication of
MMC use in pterygium surgery.
MMC is an alkylating agent that inhibits synthesis of
DNA, RNA, and protein and is a potent inhibitor of fibroblast
proliferation.7,8,18–27 The pathophysiology of scleral stromal-
ysis after pterygium surgery is not well understood, but the
presence of a bare scleral defect, possibly caused by the use of
antimetabolites preventing conjunctival regrowth, has been
suggested to play a role.2,14 In this study, scleral stromalysis
occurred not only with bare sclera excision but also when
conjunctival autograft or AMT were used as adjuvants,
although the latter were associated with mild stromalysis.
More severe stromalysis was associated with either a bare
sclera surgical technique or MMC application to sclera
(instead of Tenon) in 80% of cases. We wish to emphasize
that the bare sclera technique is not recommended because it
lends a higher rate of recurrence and a greater chance of
stromalysis.2,3 Likewise, if MMC is used, it is to be applied to
the Tenon capsule and not to the scleral bed. Certainly, the

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 Cornea  Volume 34, Number 4, April 2015
etiology of scleral stromalysis is multifactorial, and although
this study focuses on MMC, other factors such as surgical
technique could be a contributing factor.
In comparison, CAG as a surgical adjunct has shown
adequate safety and low recurrence rates with little to no
increased complication risk.1,2,28 Its main limitations are increased
surgical time, prolonged patient discomfort, and increased
surgical skill required to complete the procedure.2,28 Recurrence
rates with conjunctival autograft are equal to or better than those
with MMC in many studies.1,2,20,28 Three studies suggest that
MMC combined with CAG may be more effective than autograft
alone,2,19,20 yet the benefit of MMC as an adjuvant remains
debatable. The PERFECT technique recently described by Hirst1
reports a recurrence rate of 0.1% with conjunctival autograft
alone in the largest reported series, and this technique carries
none of the risk associated with the use of MMC.
When considering adjuvants in pterygium surgery, like
any medical decision, the risk–benefit ratio must be deter-
mined. This study highlights vision-threatening complications
that may be associated with MMC use during pterygium
surgery. Because a safe and seemingly equally effective
alternative exists, that of conjunctival autograft, we recom-
mend that MMC be used with extreme caution in the setting
of primary pterygium removal.
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