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Mitomycin C-Associated Scleral Stromalysis After
Mitomycin C-Associated Scleral Stromalysis After
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Cornea Volume 34, Number 4, April 2015 Scleral Stromalysis After Pterygium Surgery
surgery for recurrent pterygium. Patients were treated with and/or ocular surface lubrication alone in 8/13 (62%) and
varying concentrations and routes of administration of MMC scleral patch graft in 4/13 (31%) with 1/13 (8%) requiring an
using multiple surgical techniques with no standardization. AMT. One patient required multiple patch grafts (Fig. 1). The
When known, the concentration of MMC in all cases was treatment endpoint was cessation of inflammation and
0.02%; MMC was given as an intraoperative application in 12 stabilization of the overlying ocular surface.
eyes and used topically after surgical excision in 1 eye. The
MMC was applied directly to bare sclera in 5 eyes and to the DISCUSSION
Tenon capsule in 3 eyes. In 1 patient, MMC 0.02% drops were We identified 13 eyes of 12 patients with scleral
administered postoperatively 4 times daily for 2 weeks. The stromalysis attributable to the use of MMC during pterygium
length of intraoperative MMC application ranged from 30 surgery. Patients in whom stromalysis was observed had a range
seconds to 3 minutes. The surgical technique included bare of MMC application times and surgical techniques for excision,
sclera excision in 7 eyes, conjunctival autograft (CAG) in 1 as well as a range in severity of scleral stromalysis. All patients
eye, AMT in 5 eyes, and the exact technique was unknown in 4 for whom the MMC dose was known had a concentration and
eyes. Individual treatment regimens are listed in Table 1. application time that has been widely accepted and deemed safe
Four basic types of scleral stromalysis were identified: in the peer-reviewed literature.7,8,18–27
(1) corneoscleral dellen (3 eyes), (2) scleral stromalysis with Although MMC use as a surgical adjunct after ptery-
overlying calcific plaque (3 eyes), (3) chronic scleral gium excision has shown decreased recurrence rates in the
stromalysis with underlying scleromalacia (5 eyes), and (4) literature,2,7,8,18–26 it has also been associated with a number of
active scleritis with episcleral ischemia (2 eyes) (Fig. 1). None cited complications.10–17 Increased safety is thought to occur
of the cases were infectious in etiology. Patients had no other using a lower dose of MMC, a shorter duration of application,
known cause of stromalysis, such as rheumatologic disease or and a controlled intraoperative application to the Tenon
infectious scleritis. capsule as opposed to postoperative topical application. We
Time from initial pterygium surgery to presentation of found that even short intraoperative applications of low-dose
scleral stromalysis ranged from 1 month to 10 years, with MMC can result in scleral stromalysis. In this study, an MMC
a mean time of 4 years. Eight of 13 eyes (62%) presented application of the lowest commonly used dose (0.02%) for 30
more than 3 years after their initial pterygium surgery. Patient seconds was enough to result in stromalysis in 1 case. It is
age and race were varied and can be seen in Table 1. important to note that there was a range in the severity of
Treatment after scleral stromalysis consisted of observation 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
mild stromalysis that was inactive and controlled with MMC is an alkylating agent that inhibits synthesis of
lubrication alone. However, a large number (39%) of patients DNA, RNA, and protein and is a potent inhibitor of fibroblast
presented with more significant active stromalysis that proliferation.7,8,18–27 The pathophysiology of scleral stromal-
required surgical intervention. The surgical technique and ysis after pterygium surgery is not well understood, but the
method of MMC application varied in these more severe presence of a bare scleral defect, possibly caused by the use of
cases, which limits our ability to make conclusions regarding antimetabolites preventing conjunctival regrowth, has been
cause and effect. However, we note that in the more severe suggested to play a role.2,14 In this study, scleral stromalysis
cases, the surgical technique consisted of either bare sclera or occurred not only with bare sclera excision but also when
adjunctive AMT, and MMC technique included application to conjunctival autograft or AMT were used as adjuvants,
the Tenon capsule only or to bare sclera. We also demonstrate although the latter were associated with mild stromalysis.
that scleral stromalysis may occur years after initial applica- More severe stromalysis was associated with either a bare
tion of MMC, as 3 of our cases presented for management sclera surgical technique or MMC application to sclera
beyond 9 years after initial surgery. Although several studies (instead of Tenon) in 80% of cases. We wish to emphasize
claim safety of MMC when used for pterygium removal, most that the bare sclera technique is not recommended because it
have limited follow-up times.23–27 We therefore suggest that lends a higher rate of recurrence and a greater chance of
scleral stromalysis may be an underreported complication of stromalysis.2,3 Likewise, if MMC is used, it is to be applied to
MMC use in pterygium surgery. the Tenon capsule and not to the scleral bed. Certainly, the
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Cornea Volume 34, Number 4, April 2015 Scleral Stromalysis After Pterygium Surgery
etiology of scleral stromalysis is multifactorial, and although 10. Carrasco MA, Rapuano CJ, Cohen EJ, et al. Scleral ulceration after
this study focuses on MMC, other factors such as surgical preoperative injection of mitomycin C in the pterygium head. Arch
Ophthalmol. 2002;120:1585–1586.
technique could be a contributing factor. 11. Dadeya S, Fatima S. Comeoscleral perforation after pterygium excision
In comparison, CAG as a surgical adjunct has shown and intraoperative mitomycin C. Ophthalmic Surg Lasers Imaging. 2003;
adequate safety and low recurrence rates with little to no 34:146–148.
increased complication risk.1,2,28 Its main limitations are increased 12. Dougherty PJ, Hardten DR, Lindstrom RL. Corneoscleral melt after
pterygium surgery using a single intraoperative application of mitomycin-C.
surgical time, prolonged patient discomfort, and increased Cornea. 1996;15:537–540.
surgical skill required to complete the procedure.2,28 Recurrence 13. Safianik B, Ben-Zion I, Garzozi HJ. Serious corneoscleral complications
rates with conjunctival autograft are equal to or better than those after pterygium excision with mitomycin C. Br J Ophthalmol. 2002;86:
with MMC in many studies.1,2,20,28 Three studies suggest that 357–358.
MMC combined with CAG may be more effective than autograft 14. Rubinfeld RS, Pfister RR, Stein RM, et al. Serious complications of
topical mitomycin-C after pterygium surgery. Ophthalmology. 1992;99:
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debatable. The PERFECT technique recently described by Hirst1 15. Peponis V, Rosenberg P, Chalkiadakis SE, et al. Fungal scleral keratitis
reports a recurrence rate of 0.1% with conjunctival autograft and endophthalmitis following pterygium excision. Eur J Ophthalmol.
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16. Wan Norliza WM, Raihan IS, Azwa JA, et al. Scleral melting 16 years
none of the risk associated with the use of MMC. after pterygium excision with topical Mitomycin C adjuvant therapy.
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mined. This study highlights vision-threatening complications pterygium surgery. Jpn J Ophthalmol. 1997;41:192–195.
that may be associated with MMC use during pterygium 18. Fujitani A, Hayasaka S, Shibuya Y, et al. Corneoscleral ulceration and
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surgery. Because a safe and seemingly equally effective therapy. Ophthalmologica. 1993;207:162–164.
alternative exists, that of conjunctival autograft, we recom- 19. Frucht-Pery J, Raiskup F, Ilsar M, et al. Conjunctival autografting
mend that MMC be used with extreme caution in the setting combined with low-dose mitomycin C for prevention of primary
of primary pterygium removal. pterygium recurrence. Am J Ophthalmol. 2006;141:1044–1050.
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