randomized trial of intraoperative mitomycin c in surgery for pterygium

Randomized Trial of lntraoperative Mitomycin C in Surgery for Pterygium

ANITA PANDA, MD, GOPAL K. DAS, MD, SUHAS W. TULI, MD, AND A. KUMAR

l PURPOSE: To report the efficacy and safety of

intraoperative application of mitomycin C in sur-

gery for pterygium.

l METHODS: In a prospective randomized and double-blind study done within a span of 2.5 years

in 50 eyes (50 patients) with primary progressive

pterygium, mitomycin C in a concentration of

0.02 mg/ml soaked in a sterile 5 x 5-mm sponge

was applied over the bare sclera intraoperatively as

an adjuvant therapy in 25 eyes after pterygium

excision. These cases were compared with another

25 similar eyes that underwent the same procee dure but in which gentamicin solution 0.3% was

used instead of mitomycin C solution.

l RESULTS: Three eyes (12%) in the mitomycin C

group showed recurrence within 7 months of

surgery compared with eight eyes (32%) of the

gentamicin control group within 3 to 5 months.

Mild side effects, such as pain, photophobia, and

delayed wound healing, were observed within the

first 1 to 2 weeks postoperatively in both groups. In the mitomycin C-treated group, cornea1 chang-

es in the form of superficial punctate keratitis

(three eyes) and limbal avascularity (two eyes)

subsided within 2 weeks postoperatively. Follow-

up time for these cases ranged from 18 to 2 1

months.

l CONCLUSIONS: A diluted solution of mitomycin

C, 0.02 mg/ml, with an accurate size of sterile sponge applied to bare sclera after primary pterygi-

urn excision decreases the rate of recurrence to a

Accepted for publication May 6, 1997. From the Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All

India Institute of Medical Sciences, New Delhi, India. Reprint requests to Anita Panda, MD, Dr. Rajendra Prasad Centre for

Ophthalmic Sciences, 412, Howa Singh Block, Asiad Village, New Delhi-110049, India; fax: 91-11-6852919.

greater extent than does gentamicin solution and is

not associated with severe complications.

B ECAUSE THE RECURRENCE RATE OF PTERYGIA

after surgical removal is very high, a major problem in the treatment of pterygium is to

prevent recurrence after surgical excision. The postoperative recurrence rate varies from 5.3% to 69%,le3 although antimitotic agents have been shown to reduce the recurrence rate.3.9

We conducted a prospective, randomized, double- blind study to evaluate the effectiveness of, and the complications encountered with, intraoperative mitomycin C in a concentration of 0.02 mg/ml for 3 minutes in primary pterygium and to compare its use with that of gentamicin in a control group of patients.

PATIENTS AND METHODS

FIFTY CONSECUTIVE PATIENTS (50 EYES) WITH PRIMARY

pterygia who attended the outpatient department of our eye institute between February 1993 and July 1995 were included in this study. All patients had recurrent ocular irritation or a rapid growth encroach- ing toward the pupillary area. Only those patients with progression of the disease process as evidenced by increased size of the pterygium and who were not previously operated on were included in this study.

A complete ocular examination, including photo- graphic documentation and tear film examination, was performed on each patient. A complete hematologic examination was performed in all. All surgical excisions of the pterygium were performed by one surgeon (one of us, A.P.) on an outpatient basis using local anesthesia. All patients were given an explana-

VOL. 125, No. 1 @ AMERICAN JOURNAL OF OPHTHALMOLOGY 1998;125:59-63 59

tion of the procedure, and informed consent was obtained from all.

A drop of lidocaine 4% was instilled twice, with a 2-minute interval, on the eye to undergo surgery. After applying an eyelid speculum, 0.4 ml of lidocaine 2% was injected under the pterygium to elevate it from its attachment to the cornea. With the help of toothed forceps, the head of the pterygium was grasped, and the excision was done with a Bard Parker no. 15 surgical blade, starting from the cornea1 side. A complete resection of the mass was done, leaving 3 mm or more of the bare sclera exposed. At this point in each surgery, each patient was randomly assigned in a masked fashion to one of two groups. Patients assigned to group I received a 3-minute scleral application of a 5 X 5-mm sterile sponge soaked in a solution of 0.02 mg/ml mitomycin C. After removal of the sponge, the application site was irrigated with an isotonic saline solution for 5 minutes. Patients assigned to group II underwent the same procedure with the 5 x 5-mm sterile sponge except that, in a coded manner, gentamicin solution 0.3% was applied instead of mitomycin C. In both groups, no conjunctival sutures were placed. Instillation of one drop each of topical dexamethasone 0.1% and gentamicin 0.3%, followed by eye patching, completed the surgery.

Postoperatively in both groups of patients, dexamethasone and gentamicin eyedrops were instilled three times a day for 1 week, reduced to twice daily for 1 more week, then discontinued. All patients were examined postoperatively with a slit lamp on days 1, 7, 15, and 30, and then at monthly intervals, by two of us (G.K.D. and S.W.T.), masked to each patient’s treatment, to evaluate any recurrence of pterygium and complications. All of the patients were followed up for a minimum of 1.5 years. All patients had a repeat hematologic checkup at the end of the second postoperative week. Recurrence was considered as having taken place when a fibrovascular growth similar to that present preoperatively, crossing the corneoscleral limbus and extending into the cornea for any distance, had occurred.

RESULTS

OF THE 25 PATIENTS IN GROUP I, 19 WERE MEN AND SIX

were women, and in group II, 17 were men and eight

were women. The mean age in group I was 41.44 years (range, 22 to 59 years) and in group II was 41.64 years (range, 23 to 61 years). All of the pterygia were nasally located, with a mean cornea1 encroachment of 3.5 mm (range, 2 to 4.5 mm) in group I and 3.3 mm (range, 2 to 4.6 mm) in group II. The preopera- tive clinical findings in both the groups were compa- rable. The mean postoperative follow-up period was 18.8 months (range, 18 to 21 months).

Three recurrences (12%) were observed in the mitomycin C-treated group, whereas eight recurrent es (32%) were observed in the gentamicintreated group (Tables 1 and 2). The difference between the groups was statistically significant (P < .OOl). All recurrences in the gentamicin control group occurred within 3 to 5 months, compared with 7 months in the mitomycin C group.

Complications and side effects were observed only during the first 2 weeks of follow-up. Although such side effects as photophobia and mild ocular pain occurred in both the groups, in the mitomycin C group, three patients experienced mild superficial keratitis and two developed minimal limbal avascularity (Tables 1 and 2). No scleral necrosis was observed in any of the patients, even after 1.5 years.

DISCUSSION

PRIMARY PTERYGIUM IS ONE OF THE MOST COMMON

cornea1 disorders in a tropical country such as India. Exposure to ultraviolet light is presumed to be the most important risk factor.” A wide range of surgical maneuvers for removal of pterygia have been reported.“J* However, recurrence after excision has been reported to be as high as 30% to 88%.6J’-‘5 Various adjuvant therapies, such as postoperative beta radiation,16 argon laser therapy,17 topical thiotepa,” and conjunctival autograft transplantation,* have been used to reduce recurrence after pterygium excision. However, none of these procedures is free of complications. Also, different systems of classification of pterygium have been adopted to assist in deciding which type of surgery is needed in a particular case. 13,14 The classification that we used in the present study, although not an exact fit with any one of them, still is close to that of Youngson” in that we empha- sized the involvement of the cornea.

60 AMERICAN JOURNAL OF OPHTHALMOLOGY JANUARY i 998

TABLE 1, Mbmydn G Group

Patient No.,

Age (yrs), Sex

1,33, M

2, 22, M

3,41, F

4, 46, M

5, 22, M

6, 50, M 7153, I=

8, 22, M

9, 49, M 10, 46, F

11, 54, M

12, 51, M

13, 40, F

14, 37, M

15, 59, M 16, 39, M

17, 27, M

18, 50, M

19, 52, F

20, 45, M 21, 48, M

22, 39, M

23, 36, F

24, 39, M

25, 49, M

Best-corrected Visual Acuity

Pretreatment Posttreatment

2W-3 W61 20/20 (6/6)

20/20 (6/6) 20/20 (6/6)

20/20 (S/S) w20 W)

20/40 (6/l 2) 20/40 (6/l 2)

20/20 (S/S) 20/20 (S/6)

20/20 (6/6) 20/20 (6/6) 20/30 (6/Q) 20/30 (6/Q)

20/30 (6/Q) 20/30 (6/Q)

20/20 (6/6) .w20 @/6) 20/20 (6/6) 20/20 (6/6)

20/20 (6/6) 20130 (S/9)

20/20 (6/6) 20/20 (6/6)

20/20 (6/6) w20 @/W 20/30 (6/9) 20/30 (6/9)

20/20 (S/S) 20120 (6/6) 20/20 (6/6) 20/20 (6/6)

20/30 (619) 20/30 (6/9)

20/30 (6/9) 20/30 (6/9)

20/40 (6/l 2) 20/40 (a/12)

20/40 (6/l 2) 20/30 (6/9) 20/30 (6/Q) 20/20 (616)

20/20 (6/6) 20/20 (6/6)

20/20 (S/S) 20120 (S/S)

20/20 (6/6) 20/20 (6/6)

20/30 (6/Q) 2OJ30 (6/9)

Complications

-

-

Delayed wound healing {l-2 wks) -

Recurrence (7 mos)

Conjunctival granuloma -

Recurrence (7 mos)

-

Astigmatism >5 D

Superficial keratitis punctate


Limbal avascularities

Anterior chamber reaction -

Recurrence (5 mos)


Pain

Delayed wound healing -

-

-

-

Limbal avascularities

Frequent application of topical mitomycin C leads

to a large cumulative dose, which is thought to be a

common factor in causing toxic side effects.4 Consid-

ering the untoward effect of a large cumulative dose of postoperative topical eyedrops, a single intraoperative

application of mitomycin C has been tried.4J Howev-

er, mild side effects in the form of low-grade ocular

pain, photophobia, superficial punctate keratitis, and

conjunctival granuloma have been reported.4*8 Cano- Parra and associates in 19954 commented about

delayed conjunctival wound healing of up to 1 to 2 weeks, which was a significant occurrence in their

intraoperatively treated mitomycin C group.4 Such

use may predispose to future scleral ulceration. Singh

and associates in 198g3 postulated the correlation of

ulceration to damaged sclera and episclera. Complica-

tions such as delayed healing, superficial punctate keratitis, and conjunctival granuloma were less in our

study than in another study reported earlier4; howev-

er, the recurrence rate in our series of patients was

much greater than in that of Cano-Parra and associ-

ates4-12.0% compared with 3.3%, respectively (Ta-

ble 3).

In 1964, Kumitomo and Mori2’ reported the effect of postoperative instillation of mitomycin C 0.04%

eyedrops to prevent pterygium recurrence after its

excision. Since that initial report, many studies have

been carried out using mitomycin C eyedrops postop-

eratively at different concentrations to reduce the recurrence of pterygium after its excision.6a7,9*15 How-

ever, many reports have also appeared on various complications of topical mitomycin C therapy, such as

symblepharon, scleral ulceration, and cornea1 perfo-

ration.‘3*2’ We agree with Mastropasqua and associ-

ates8 that mitomycin C is less effective in preventing

fibrovascular reactions in younger patients, for all three mitomycin C patients reported here who showed

recurrence were aged 22 to 27 years. However, the

eight patients in the gentamicin control group who showed recurrence were aged from 26 to 52 years.

VOL. 125, No. 1 MITOMYCIN C AND PTERYGIUM 61

TABLE 2. Gentamicin (Control) Group

Patient No..

Age (yrs), Sex

I, 49, F

Best-corrected Visual Acuity

Pretreatment Posttreatment Complications

20/20 (S/S) 20/20 (6/6)

2, 27, M 20/20 (S/S) 20/20 (6/6)

3, 52, M 20/20 (S/S) 20/20 (6/6)

4, 49, M 20/30 (6/9) 20/30 (6/9)

5, 25, F 20/40 (6/l 2) 20/20 (S/6)

6, 46, F 20/20 (6/6) 20/20 (S/S)

7, 42, M 20/30 (6/9) 20/30 (S/9)

6, 23, M 20/30 (6/9) 20/30 (6/9)

9, 32, M 20/20 (6/6) 20/20 (6/S)

IO, 36, F 20/20 (6/6) 20/20 (6/6)

11, 61, M 20/30 (6/9) 20130 (6/9)

12, 37, M 20/20 (6/6) 20/20 (6/6)

13, 41, M 20/20 (6/6) 20/20 (6/6)

14, 50, F 20/20 (6/6) 20/20 (S/S)

15, 53, M 20/30 (6/9) 20/30 (6/9)

16, 48, M 20/20 (6/6) 20/20 (S/S)

17, 37, M 20/30 (6/9) 20/30 (6/9)

18, 36, F 20/40 (6/l 2) 20/30 (6/9)

19, 46, M 20/30 (6/9) 20f30 (6/9)

20, 49, M 20/30 (6/9) 20/30 (6/9)

21, 51, M 20/20 (6/6) 20/40 (6/l 2)

22, 52, F 20/20 (6/6) 20/20 (6/6)

23, 32, M 20/20 (6/6) 20120 (S/S)

24, 39, M 20/20 (6/6) 20/20 (6/6)

25, 26, F 20/40 (6/l 2) 20/80 (6/24)

Delayed wound healing

Recurrence (3 mos)

Recurrence (4 mos)

Conjunctival granuloma

Recurrence (3 mos) -

- -

Recurrence (5 mos)


Astigmatism >5 D -

Recurrence (4 mos)

Conjunctival granuloma - -


Delayed wound healing

Conjunctival granuloma

Recurrence (4 mos)

TABLE 3. Mitomycin C Therapy and Pterygium (Comparative Study)

Study (year published) No. of Eyes

Type of

Pterygium Therapy

Recurrence

Rate

Hayasaka et aIs (1988)

Mahar and Nwokora’ (1993)

Rachmeil et al9 (1995)

Chen et alis (1995)

Cano-Parra et al4 (1995)

Mastropasqua et al* (1996)

Present study (1997)

29

31

12

14

38

24

17

30

36

45

45

25

25

Primary Postoperative

Primary None


Primary None



Primary None

Primary Intraoperative

Primary None

Recurrent lntraoperative

Recurrent None

Primary lntraoperative

Primary Placebo

7% 32%

None

57.14%

2.6%

36%

88%

3.33%

38.8%

12.5%

35.6%

12.0%

32.0%

The period of recurrence after surgery has been our groups within 7 months of surgery, and no

reported to be within 6 months.4 Therefore, a close recurrence was seen thereafter during the follow-up follow-up during this period is mandatory. Our study period of 18 months. also suggests that all the recurrence occurred in both Thus, we conclude that a diluted solution of

62 AMERICAN JOURNAL OF OPHTHALMOLOGY JANUARY i 998

mitomycin C, 0.02 mg/ml, applied intraoperativeiy with an accurately sized sterile sponge for 3 minutes to the bare sclera after excision of the pterygium, reduces the rate of recurrence of pterygium and minimizes corneoscleral toxicity.

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7. Mahar F’S, Nwokora GE. Role of mitomycin C in pterygium surgery. Br J Ophthalmol 1993;77:433-435.

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randomized trial of intraoperative mitomycin c in surgery for pterygium

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