ORIGINAL ARTICLE

Effect of Pterygium Morphology on Recurrence with

Preoperative Subconjunctival Injection of Mitomycin-C
in Primary Pterygium Surgery
Faisal Aziz Khan and Shafaq Pervez Khan Niazi

ABSTRACT
Objective: To investigate the effect of pterygium morphology on recurrence with preoperative subconjunctival injection of
mitomycin-C in primary pterygium surgery.
Study Design: Quasi-experimental study.
Place and Duration of Study: Eye Department, Combined Military Hospital, Malir Cantt, Karachi, from February 2017 to
February 2018.
Methodology: On the basis of pterygium morphology, 165 eyes of 165 patients were equally divided into three equal
groups of atrophic, intermediate and fleshy pterygia. In each morphology group, length was graded into three groups using
limbus, pupil margin and midiris as landmarks. All pterygia received 0.1 ml of mitomycin-C injection in a concentration of
0.15 mg/ml at 24 hours prior to undergoing a bare sclera surgical excision technique in all cases. All patients were followed
up for 12 months. The recurrence rate was recorded in each morphology group. Pearson Chi-Square test was used to
compare recurrence rate and morphology group. Fisher's exact test was applied to compare recurrence rate with length
and age in each type of morphology.
Results: Among the three morphology groups, the recurrence rate was statistically significant between fleshy and atrophic
pterygia (p=0.01) and no significant association was found among other morphology comparisons. Age less than 40 years
had a significant effect on recurrence in all morphology groups. Length did not affect the recurrence rate in any of
morphology types.
Conclusion: Recurrence of primary pterygium is related to fleshiness of the pterygium and is a significant risk factor for
recurrence after preoperative subconjunctival injection of mitomycin-C given at 24 hours before sclera excision.

Key Words: Mitomycin-C, Pterygium morphology, Pterygium surgery, Recurrence, Subconjunctival injection.

INTRODUCTION The preoperative use of MMC as a subconjunctival

Recurrence of pterygium is a frequent source of dis- injection into the body of pterygium before surgical
satisfaction for the operating surgeon as well as for the excision is another modality in which the recurrence rate
patient.1 Preoperative risk factors for recurrence of primary is similar to the intraoperative application of MMC.7 The
pterygium include younger age of less than 50 years,2 incidence and severity of postoperative complications of
higher grade of corneal involvement,3 pterygium preoperative subconjunctival injection are comparable to
morphology,4 operating surgeon’s skill and experience.5 the intraoperative application of MMC.8 Compared to
intraoperative application of MMC, the preoperative sub-
Amidst these factors, the morphology of the pterygium conjunctival injection into the body of pterygium is
has been associated with higher recurrence rate, with advantageous as its concentration does not get diluted
fleshy pterygia producing higher recurrence rate than in the tear film, there is limited intraocular penetration
atrophic ones.3 Previous studies have correlated the since the corneal epithelium is intact; and as a result
morphology of the pterygium with recurrence by there is more prolonged contact time with the sub-
employing various techniques in dealing with the bare conjunctival tissue.8
sclera after surgical excision. These modalities are
conjunctival autograft,4,6 amniotic membrane graft, Preoperative injection has been given either at one month
intraoperative and postoperative Mitomycin-C (MMC) or 24 hours prior to pterygium removal with neither
application.6 offering advantage over the other in terms of recurrence
and corneoscleral complications.9 The one month
Department of Eye, Combined Military Hospital, Malir Cantt, waiting time adds to the patient discomfort as it becomes
Karachi, Pakistan a two-stage procedure.9
Correspondence: Dr. Faisal Aziz Khan, Department of Eye, After reviewing the published data, we found that
Combined Military Hospital, Malir Cantt, Karachi, Pakistan research work on the influence of pterygium morphology
E-mail: faisaleyecare@gmail.com and recurrence with the preoperative use of MMC as a
Received: November 07, 2018; Revised: December 21, 2018; subconjunctival injection into the body of pterygium is
Accepted: December 21, 2018 lacking. Consequently, the rationale of this study was to

Journal of the College of Physicians and Surgeons Pakistan 2019, Vol. 29 (7): 639-643 639
Faisal Aziz Khan and Shafaq Pervez Khan Niazi

determine whether morphology of the pterygium have an noting the location of the apex; and graded according to
effect on the recurrence of pterygium with the pre- the classification into grade I (between limbus and a
operative use of MMC as a subconjunctival injection point midway between limbus and pupillary margin),
given at 24 hours prior to the removal of pterygium; grade II (between pupillary margin and a point midway
considering recurrence as the most serious post- between limbus and pupillary margin) and grade III
operative complication of pterygium surgery. (crossing pupillary margin).11 Intraocular pressure was
The objective of this study was to investigate the effect checked.
of pterygium morphology on recurrence with pre- All patients received an injection of MMC into the
operative subconjunctival injection of MMC in primary pterygium at approximately 24 hours before the surgical
pterygium surgery. excision of the pterygium. The surgical modality utilised
for all the pterygia was bare sclera technique after
METHODOLOGY excision. Using a 30G insulin needle, 0.1 ml of 0.15
This quasi-experimental study was conducted at the Eye mg/ml concentration of MMC was injected into the body
Department of Combined Military Hospital, Malir Cantt, of pterygium after instilling a drop of proparacaine under
Karachi, from February 2017 to February 2018. The the operating microscope. The needle was inserted
study was approved by the Ethical Review Board approximately 1.5 mm away from the limbus into the
Committee of the Hospital. Patients attending the body of pterygium under aseptic condition. A drop of
outpatient unit of the department were selected for the 0.3% ofloxacin eye drop was placed after the injection.
study. The inclusion criteria was primary pterygium for The patients were examined under the slitlamp
which surgery was indicated, considering the presence examination just preceding surgery. At the slitlamp, the
of one of the following criteria: (i) minimal length equal to conjunctiva and cornea were stained for epithelial
a point midway between limbus and pupillary margin; defects and intraocular pressure was checked. All
(ii) pterygium induced corneal astigmatism; and/or surgeries were performed by one surgeon. The surgery
(iii) chronic symptomatic pterygia. The other inclusion was performed under topical anaesthesia using
criteria were age between 20 and 80 years, male or proparacaine and local infiltration of 0.1% lignocaine HCl
female gender, nasal or temporal pterygium. Patients with 1:100000 adrenaline into the body of the pterygium.
having a pseudopterygium, recurrent pterygium, dry The pterygium head was dissected from its corneal edge
eyes syndrome and ocular cicatricial diseases were using No.15 Bard Parker blade till the limbus. The
excluded from the study. On the basis of morphology pterygium was separated with blunt dissection from the
of pterygium proposed by Tan et al,10 patients were underlying sclera till the insertion of the medial rectus
divided into three equal groups labelled based on its muscle and also separated from the overlying bulbar
translucency as atrophic (grade T1), intermediate (grade conjunctiva. Then the pterygium was excised alongwith
T2) and fleshy (grade T3). A grade T1 (atrophic) pteygium its accompanying tenon's fascia. The bare scleral defect
was defined as the grade in which the episcleral vessels was left as such. A tobramycin / dexamethasone
underlying the body of pterygium were unobscured and ointment was applied and the eye was padded. The eye
clearly distinguished, while grade T3 (fleshy) was the pad was removed on the first postoperative day and
pterygium in which the underlying episcleral vessels tobramycin/dexamethasone eye drops, three times
were totally obscured by the fibrovascular tissue of the daily, was prescribed for four weeks. All the patients
pterygium; and a pterygium was labelled as grade T2 were examined at one week and then monthly for 12
(intermediate) when its morphology did not fall in grade months. At each examination, the eyes were examined
T1 or T3 categories.10 A sample size of 53 patients in for epithelial defects, corneoscleral thinning, dellen,
each group was calculated using the WHO calculator so secondary glaucoma, granuloma and pterygium
as to detect a significant difference in the recurrence rate recurrence. The recurrence was defined as fibrovascular
between the groups with 90% power (=0.10), a (two- growth of conjunctival tissue extending for more than
sided) level of significance of 95% (=0.05) and 1mm past the limbus.
anticipated population proportion P1 for grade T3 was Statistical analysis was performed using SPSS version
0.33 and anticipated population proportion P2 for grade 20.0. Descriptive statistics were calculated for age.
T1 was 0.08. Frequencies and percentages were calculated to
A total of 165 eyes of 165 patients were included in the describe gender distribution. Normality tests were
study. A written informed consent was obtained from all applied for age. Patients were divided into two age
the patients. After obtaining ocular and systemic history, groups, one less than 40 years and other 40 years and
ocular examination was done which included Snellen above, within each morphology group. Recurrence of
visual acuity, manifest refraction, automated keratometry, pterygium was described as frequency and percentage.
During slitlamp anterior segment examination, the length The recurrence rate of pterygium in each morphology
of corneal involvement of pterygium was recorded by group was calculated.

640 Journal of the College of Physicians and Surgeons Pakistan 2019, Vol. 29 (7): 639-643
Pterygium morphology and recurrence in pterygium surgery with preoperative use of mitomycin-C

Pearson Chi-square test was used to compare the point midway between limbus and pupillary margin) in
recurrence rate and morphology type. Fisher's exact test each morphology group depicted a statistically insigni-
was used to compare the recurrence rate between age ficant association in the atrophic (p=1.0), intermediate
groups in each type of morphology group. Similarly, morphology (p=0.09), and fleshy pterygia group (p=0.39).
Fisher's exact test was also applied to compare the
recurrence rate between length groups in each type of DISCUSSION
pterygium morphology. The tests were 2-tailed and Pterygium is a highly invasive, inflammatory, fibro-
a p-value <0.05 was considered to be statistically vascular growth.12 Clinically, fleshiness of the pterygium
significant. is a significant risk factor for recurrence if bare sclera
excision is performed.10 Han et al. precisely quantified
RESULTS the pterygium vascularity preoperatively using automated
The median (IQR) age of the patients were 44 (23) years. image analysis and applied a limbal-conjunctival
Male to female ratio was 3:1. The overall recurrence rate autograft. They found a significantly higher recurrence
was 18.2%. No intraoperative complications were noted. rate among pterygia whose vascularity index was
high (p<0.001) despite the autograft.13 At immuno-
Postoperatively, out of the 165 patients, one (0.6%)
histochemistry level, it has also been found that active
patient developed scleral thinning, Tenon's granuloma
pterygia with thick bodies might be at increased risk of
was seen in three (1.8%) patients, and two (1.2%) patients
recurrence.14 On the contrary, Ha et al. determined the
developed conjunctival avascularity.
role of pterygium morphology and recurrence by
The recurrence rate of the pterygium in atrophic group subdividing the morphology using a grading system
was 9% (5 out of 55 eyes), in pterygia with intermediate proposed by Oh and Kim,15 into fibrous thickness and
morphology 10 eyes out of 55 developed recurrence vascularity features and separately analyzed each
(18%), and in those with fleshy pterygia the recurrence feature with recurrence using digital image acquisition
rate was 27.3% (15 out of 55 eyes). The difference in and software image processing. An amniotic membrane
recurrence rate between atrophic and fleshy pterygia graft or conjunctival autograft was sutured in all their
group was statistically significant (p=0.01). However, the cases. Their results depicted that neither the fibrous
difference in recurrence rate between atrophic pterygia thickness nor the vascularity affected the recurrence
and intermediate morphology pterygia group was not rate.16 Similarly in another study by Kwon and Kim, it
statistically significant (p=0.16). Similarly, no statistically was reported that the severity of preoperative pterygium
significant difference in the recurrence rate of pterygium morphology, which was based on the same grading
was found between pterygia of intermediate and fleshy system as used by Ha et al., did not affect the
morphology (p=0.25, Table I). recurrence rate after applying a conjunctival graft in all
Comparison of the recurrence rate and age in each their cases and selectively applying MMC intra-
morphology group showed a statistically significantly operatively.17
higher recurrence rate of pterygium in patients whose Dzunic and his colleagues applied the identical grading
age was less than 40 years in atrophic, intermediate system of pterygium morphology, as used in our study;
morphology and fleshy pterygium group (Table II). but found no significant association between morpho-
Comparative analysis of the recurrence rate between logy and recurrence. In their technique, the bare sclera
grade III (pterygium length crossing pupillary margin) was covered by directly suturing the conjunctival wound
and grade I (pterygium length between limbus and a edges together after excising the pterygium till the

Table I: Comparison of pterygium morphology and recurrence rate (n=165).

Recurrence Atrophic vs Fleshy Atrophic vs Intermediate Intermediate vs Fleshy
n=55 n=55 n=55 n=55 n=55 n=55
Yes 5 (9%) 15 (27.3%) 5 (9%) 10 (18%) 10 (18%) 15 (27.3%)
No 50 (91%) 40 (72.7%) 50 (91%) 45 (82%) 45 (82%) 40 (72.7%)
p-value 0.01 0.16 0.25

Table II: Age group and recurrence rate comparison in each morphology group (n=165).
Age group Recurrence Age-wise distribution of recurrence rate in each morphology group
Atrophic (n=55) Intermediate (n=55) Fleshy (n=55)
Age less than 40 years Yes 4 (28.5%) 7 (33.3%) 14 (35.8%)
No 10 (71.5%) 14 (66.7%) 25 (64.2%)
Age 40 years and more Yes 1 (2.4%) 3 (8.8%) 1 (6.2%)
No 40 (97.6%) 31 (91.2%) 15 (93.8%)
p-value 0.01 0.03 0.04

Journal of the College of Physicians and Surgeons Pakistan 2019, Vol. 29 (7): 639-643 641
Faisal Aziz Khan and Shafaq Pervez Khan Niazi

caruncle.18 On the other hand with the identical grading graft is used or MMC is applied intraoperatively or
system for morphology as the present, Tan et al. subconjunctivally or a direct closure is performed to
reported that those pterygia whose sclera was left bare cover the bare sclera.
after excision, in them morphology was significantly Age is an important variable that can influence wound
associated with recurrence.10 The present results are in healing.19 In young subjects, there is rapid re-epithelia-
agreement with Ha et al.16 despite the fact that their lisation, aggressive collagen synthesis and angiogenesis
morphology assessment differed from ours as theirs was as compared to the aged ones.20 It was, therefore, included
based on the degree of pterygium vascularity and they in the analysis as a risk factor in causing recurrence. In
only placed a conjunctival autograft without any a multivariate analysis using logistic regression model,
adjunctive treatment. The results of Ha et al. and Kwon two identical studies by Kwon et al. and Ha et al. found
contradict with the present findings.16,17 This may be due
that age less than 40 years was a significant risk factor
to the fact that both utilised a grading system that was
for pterygium recurrence.16,17 Both authors have even
based on precise quantification of pterygium vascularity
suggested that early pterygium excision should not be
as well as on its thickness for comparing the morphology
performed in young age rather the surgical indication
with recurrence which was different from grading criteria
should be adjusted according to the patient’s age.16,17
for morphology. With identical grading system as the
Likewise, using a conjunctival graft after pterygium
present, Tan et al. results are in agreement and Dzunic
excision in all case, it was found that less than 45 years
et al. findings disagree with the present findings.10,18
of age was an important element in affecting the
These disagreements reported in the previous research
recurrence.21 On the contrary, Han et al. reported that
work and in our study in the context of morphology; and
age had no significant association with recurrence after
recurrence may also be due to the fact that each study
applying a graft in all his cases and with bare sclera
has used different techniques in dealing with the wound
excision technique. Tan also found that age was not a
defect after excision which might have affected the
risk factor.13,10 In this study, the cutoff limit for young age
relationship between morphology and recurrence.
was less than 40 years on the basis of previous studies.
Length of corneal involvement of pterygium is another Past studies had simply analysed the effect of young
risk factor that has been considered to be related to age on recurrence. Compared to the previous studies,
pterygium recurrence. In this contexts a study by Han et al. this study is unique of the fact that we analysed the role
showed that relative length did affect the recurrence rate of age in each morphology grade and found that younger
when its role was analysed in a univariate manner; but age does affect recurrence significantly, irrespective of
in a multivariate analysis, the length had no effect on the type of morphology. Additionally, this study also
recurrence rate.13 Likewise, two identical studies which enlightens the point that even with preoperative sub-
included both primary and recurrent cases found no conjunctival use of MMC, young age still affects the
difference in recurrence rate among pterygia whose recurrence rate.
length was greater than 1mm from the limbus, and
pterygia with length within 1mm from the limbus after The overall recurrence rate in this study with the pre-
placing a conjunctival graft in all cases and applying operative subconjunctival injection of MMC given at 24
MMC in selective cases intraoperatively.16,17 Dzunic and hours before surgery was 18.4%. The recurrence rate
his colleagues covered the bare sclera after excision reported in previous research work on the use of MMC
with direct closure of conjunctival wound. They reported as a subconjunctival injection given at one month before
that the recurrence was higher in medium sized surgery in cases of primary pterygium shows wide range
pterygium with length between 3-4 mm rather than with no recurrences,22,23 to 2.9%,24 3.3%,9 and 4.2%
pterygia with length ranging from 5-6 mm; and hence, no recurrences.25 The failure rate for primary pterygium that
correlation existed between size and recurrence in their receives MMC just 24 hours before surgery has been
study.18 With regard to previous studies, this study is reported in the literature to be upto 6.7%. 9 The presently
unique in this respect that we analysed the role of reported recurrence rate differs widely and is on the
pterygium length in causing recurrence by comparing higher side from the previous researched data on the
among each morphology grading system so as to basis that previous studies did not analyse the impact of
eliminate the role of variation of morphology as a the morphology and have not mentioned the proportion
confounding variable and controlling it from affecting the of cases having fleshy, highly vascularised pterygia that
recurrence rate. These findings depicted that the can adversely affect the overall recurrence rate of a
anatomical position of the pterygium on the cornea research work.
between fleshy and atrophic pterygia did not affect the
recurrence rate with preoperative subconjunctival CONCLUSION
injection of MMC. These results and those of previous Recurrence of primary pterygium is related to fleshiness
studies support the fact that length is not significantly of the pterygium; and is a significant risk factor for
associated with recurrence irrespective of whether a recurrence after preoperative subconjunctival injection

642 Journal of the College of Physicians and Surgeons Pakistan 2019, Vol. 29 (7): 639-643
Pterygium morphology and recurrence in pterygium surgery with preoperative use of mitomycin-C

of MMC given at 24 hours before sclera excision. In 13. Han SB, Jeon HS, Kim M, Lee SJ, Yang HK, Hwang JM, et al.
addition, young age significantly affects recurrence Risk factors for recurrence after pterygium surgery: An image
analysis study. Cornea 2016; 35:1097-103.
among all morphological types of pterygium.
14. Kim KW, Park SH, Wee SW. Overexpression of angiogenin in
REFERENCES pterygium body fibroblasts and its association with proliferative
potency. Invest Ophthalmol Vis Sci 2013: 54:6355-62.
1. Chow CY, Dunn SP, Heidemann DG. Pterygium. In: Brightbill FS,
McDonnel PJ, McGhee CNJ, Farjo AA, Serderavic O (Eds.) 15. Oh JH, Kim HK. The effect of preoperative subconjunctival
Corneal surgery theory technique and tissue. ed 4th. China: injection of mitomycin C and triamcinolone in recurrent
Mosby Elsevier; 2009:p194. pterygium. J Korean Ophthalmol Soc 2009; 50:1005-14.
2. Mahar PS, Manzar N. Risk factors involved in pterygium recurrence 16. Ha SW, Park JH, Shin IH, Kim HK. Clinical analysis of risk
after surgical excision. Pak J Ophthalmol 2014; 30:73-7. factors contributing to recurrence of pterygium after excision
and graft surgery. Int J Ophthalmol 2015; 8:522-7.
3. Mahar PS, Manzar N. Pterygium recurrence related to its size
and corneal involvement. J Coll Phy Surg 2013; 23:120-3. 17. Kwon SH, Kim HK. Analysis of recurrence patterns following
pterygium surgery with conjunctival autografts. Medicine
4. Sandra S, Zeljka J, Zeljka VA, Kristian S, Ivana A. The
(Baltimore) 2015; 94:e518.
influence of pterygium morphology on fibrin glue conjunctival
autografting pterygium surgery. Int Ophthalmol 2014; 34:75-9. 18. Dzunic BN, Jovanovic P, Petrovic A. Comparative analysis of
pterygium clinical characteristics. Acta Facultatis Medicae
5. Karalezli A, Kucukerdonmez C, Akova YA, Koktekir BE. Does
Naissensis 2009; 26:77-83.
topical bevacizumab prevent postoperative recurrence after
pterygium surgery with conjunctival autografting? Int J 19. Engeland CG, Bosch JA, Cacioppo JT, Marucha PT. Mucosal
Ophthalmol 2014; 7:512-6. wound healing: The roles of age and sex. Arch Surg 2006;
141:1193-7.
6. Kaufman SC , Jacobs DS, Lee WB, Deng SX, Rosenblatt MI,
Shtein RM. Options and adjuvants in surgery for pterygium: 20. Gosain A, DiPietro LA. Review aging and wound healing.
A report by the American Academy of Ophthalmology. World J Surg 2004; 28:321-6.
Ophthalmology 2013; 120:201-8.
21. Aidenloo NS, Motarjemizadeh Q, Heidarpanah M. Risk factors
7. Martins TGS, Costa ALFA, Alves MR, Chammas R, Schor P. for pterygium recurrence after limbal-conjunctival autografting:
Mitomycin C in pterygium treatment. Int J Ophthalmol 2016; 9: A retrospective, single-centre investigation. Jpn J Ophthalmol
465-8. 2018; 62:349-56.
8. Zaky KS, Khalifa YM. Efficacy of preoperative injection versus 22. Avisar R, Bar S, Weinberger D. Preoperative injection of
intraoperative application of mitomycin in recurrent pterygium mitomycin C in combined pterygium and cataract surgery.
surgery. Indian J Ophthalmol 2012; 60:273-6. Cornea 2005; 24:406-9.
9. Khan FA, Niazi SPK, Awais M, Ishaq M, Akhter N. Effective- 23. Khakshoor H, Razavi ME, Daneshvar R, Shakeri MT, Ghate MF,
ness of preoperative subconjunctival injection of Mitomycin-C Ghooshkhanehi H. Preoperative subpterygeal injection vs
in primary pterygium surgery. J Coll Physicians Surg Pak 2017: intraoperative mitomycin C for pterygium removal: comparison
27:88-91. of results and complications. Am J Ophthalmol 2010; 150:
10. Tan DT, Chee SP, Dear KB, Lim AS. Effect of pterygium 193-8.
morphology on pterygium recurrence in a controlled trial 24. Ishtiaq O, Iqbal Z, Naz MA, Ameen SS. Comparison of
comparing conjunctival autografting with bare sclera excision. preoperative and intraoperative Mitomycin C in prevention of
Arch Ophthalmol 1997; 115:1235-40. pterygium recurrence and postoperative complications.
11. Maheshwari S. Pterygium-induced corneal refractive changes. Pak Armed Forces Med J 2011; 3:210-12.
Indian J Ophthalmol 2007; 55:383-6. 25. Mandour SS, Farahat HG, Mohamed HM. Preoperative sub-
12. Di Girolamo N, Coroneo MT, Wakefield D. Active matrilysin pterygial mitomycin C injection versus limbal conjunctival auto-
(MMP-7) in human pterygia: Potential role in angiogenesis. graft transplantation for prevention of pterygium recurrence.
Invest Ophthalmol Vis Sci 2001; 42:1963-8. J Ocul Pharmacol Ther 2011; 27:481-5.

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