Topographic Changes After Excision Surgery of Primary Pterygia ...

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ARTICLE Topographic Changes After Excision Surgery of Primary Pterygia and the Effect of Pterygium Size on Topograpic Restoration Ryohei Nejima, M.D., Ayami Masuda, M.D., Keiichiro Minami, Ph.D., Yosai Mori, M.D., Yumi Hasegawa, M.D., and Kazunori Miyata, M.D. Ph.D. Objective: To assess the effect of pterygium size on time-course change of corneal topography after excision surgery of primary pterygium. Methods: Retrospective case series included eyes that underwent excisions of primary pterygium. Pterygium size was graded according to the advancing edge position: less than one third of corneal diameter (grade 1), outside the pupil (grade 2), and within the pupillary area (grade 3). Time-course changes in corneal refractive power, astigmatism, and irregularity (surface regularity and asymmetry indices) in corneal top- ographies over 12 months postoperatively were compared between the pterygium size grades. Results: Pterygium excision was performed on 562 eyes, consisting of 119, 338, and 105 eyes with grades 1 to 3, respectively. Grade 1 did not change in corneal irregularity, and there was no difference between grades 1 and 2, except for corneal astigmatism at 6 months. Grade 3 showed signicantly higher corneal refractive power and irregularity than grade 1 until 3 and 6 months, respectively, whereas corneal astigmatism was higher over 12 months. Conclusions: Topographic changes after primary pterygium excision were associated with pterygium size. Pterygium advancing over the pupillary area required 6 to 12 months for corneal topography restoration, resulting in slow recovery of visual acuity. Key Words: PterygiumTopographyIrregular astigmatism. (Eye & Contact Lens 2015;41: 5863) P terygium is a brovascular overgrowth of bulbar conjunctiva and Tenon membrane onto the cornea, 1 and the etiology re- mains unknown. Advancing of pterygium toward the corneal cen- ter induces change in topographic refractive power and increases irregular astigmatism, resulting in impaired visual acuity. 27 Ptery- gium excision surgery can restore corneal topography and improve visual acuity. Postoperative change in corneal astigmatism increases with the size of pterygium excised, although corneal disorder may persist. 4,6,7 It has been anticipated that excision of larger pterygium results in larger residual astigmatism and slow restoration of corneal topography. However, there were no previous studies that evaluated time-course changes in postoperative corneal topography regarding different pterygium size. In addition, previous studies assessing corneal topography evaluated with limited number of subjects. 812 In-depth analysis of the size effect would require sufcient number of subjects. The purpose of this retrospective study is to evaluate time-course changes in corneal topography after primary pterygium excision and the effect of pterygium size in postoperative restoration of corneal topography. METHODS This retrospective study reviewed medical records of eyes that underwent primary pterygium excision on the nasal side at Miyata Eye Hospital and were followed up during 12 months after the excision. Eyes with history of corneal trauma, corneal scarring, or ocular surgery were excluded. This study followed the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of Miyata Eye Hospital. Written consent for the procedure and for utilization of clinical data for scientic purposes was obtained from all patients. Subjects were divided into three groups according to the position of the advancing pterygium edge with respect to corneal diameter: extension of the edge to one third of the corneal diameter (grade 1), between one third of the corneal diameter and the pupil (grade 2), and within the pupillary area (grade 3). Representative cases are shown in Figure 1. All excision surgeries were performed using the same procedure. Pterygium was removed bluntly, subconjuctival brous tissue was removed, and abnormal scarring tissue on the cornea was polished. After administrating 0.04% mitomycin C (MMC) for 1 min, the bare sclera was covered by sliding adjacent superior or inferior conjunctiva. Postoperative medication until 6 months included 0.5% levooxacin eye drop (Cravit, Santen, Osaka, Japan) 4 times per day, and 0.1% betamethasone sodium phosphate (Rinderon, Shionogi, Osaka, Japan) that was replaced with 0.1% uorome- tholone (Flumetholon, Santen) shortly afterward. Recurrence was diagnosed when the extended tissue was found within the cornea. Best-corrected distance visual acuity (BCVA) and corneal topography was measured preoperatively, and 1, 3, 6, and 12 months postoperatively. Corneal topography was measured using TMS-2 Corneal Topographer (Tomey, Nagoya, Japan). Refractive power of the corneal surface was calculated based on simulated keratometry (SimK) provided by the topographer. 5 Corneal refrac- tive power was obtained by averaging SimK values at the steepest and attest meridians, and corneal astigmatism as the difference between SimK values. Surface regularity index (SRI) and surface asymmetry index (SAI) were used to evaluate corneal irregularity. From the Miyata Eye Hospital, Miyazaki, Japan. The authors have no funding or conicts of interest to disclose. Presented at the ARVO Annual Meeting, Seattle, WA, 2013. Address correspondence to Ryohei Nejima, M.D., Miyata Eye Hospital, 6-3 Kurahara-cho, Miyakonojo, Miyazaki, 885-0051 Japan; e-mail: [email protected] Accepted June 10, 2014. DOI: 10.1097/ICL.0000000000000065 58 Eye & Contact Lens Volume 41, Number 1, January 2015 Copyright @ Contact Lens Association of Opthalmologists, Inc. Unauthorized reproduction of this article is prohibited.

Transcript of Topographic Changes After Excision Surgery of Primary Pterygia ...

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ARTICLE

Topographic Changes After Excision Surgery of Primary Pterygiaand the Effect of Pterygium Size on Topograpic Restoration

Ryohei Nejima, M.D., Ayami Masuda, M.D., Keiichiro Minami, Ph.D., Yosai Mori, M.D., Yumi Hasegawa, M.D.,and Kazunori Miyata, M.D. Ph.D.

Objective: To assess the effect of pterygium size on time-course change ofcorneal topography after excision surgery of primary pterygium.Methods: Retrospective case series included eyes that underwent excisionsof primary pterygium. Pterygium size was graded according to theadvancing edge position: less than one third of corneal diameter (grade1), outside the pupil (grade 2), and within the pupillary area (grade 3).Time-course changes in corneal refractive power, astigmatism, andirregularity (surface regularity and asymmetry indices) in corneal top-ographies over 12 months postoperatively were compared between thepterygium size grades.Results: Pterygium excision was performed on 562 eyes, consisting of 119,338, and 105 eyes with grades 1 to 3, respectively. Grade 1 did not changein corneal irregularity, and there was no difference between grades 1 and 2,except for corneal astigmatism at 6 months. Grade 3 showed significantlyhigher corneal refractive power and irregularity than grade 1 until 3 and 6months, respectively, whereas corneal astigmatism was higher over 12months.Conclusions: Topographic changes after primary pterygium excision wereassociated with pterygium size. Pterygium advancing over the pupillaryarea required 6 to 12 months for corneal topography restoration, resulting inslow recovery of visual acuity.

Key Words: Pterygium—Topography—Irregular astigmatism.

(Eye & Contact Lens 2015;41: 58–63)

P terygium is a fibrovascular overgrowth of bulbar conjunctivaand Tenon membrane onto the cornea,1 and the etiology re-

mains unknown. Advancing of pterygium toward the corneal cen-ter induces change in topographic refractive power and increasesirregular astigmatism, resulting in impaired visual acuity.2–7 Ptery-gium excision surgery can restore corneal topography and improvevisual acuity. Postoperative change in corneal astigmatism increaseswith the size of pterygium excised, although corneal disorder maypersist.4,6,7 It has been anticipated that excision of larger pterygiumresults in larger residual astigmatism and slow restoration of cornealtopography. However, there were no previous studies that evaluatedtime-course changes in postoperative corneal topography regardingdifferent pterygium size. In addition, previous studies assessing

corneal topography evaluated with limited number of subjects.8–12

In-depth analysis of the size effect would require sufficient numberof subjects. The purpose of this retrospective study is to evaluatetime-course changes in corneal topography after primary pterygiumexcision and the effect of pterygium size in postoperative restorationof corneal topography.

METHODSThis retrospective study reviewed medical records of eyes that

underwent primary pterygium excision on the nasal side at MiyataEye Hospital and were followed up during 12 months after theexcision. Eyes with history of corneal trauma, corneal scarring, orocular surgery were excluded. This study followed the tenets of theDeclaration of Helsinki and was approved by the InstitutionalReview Board of Miyata Eye Hospital. Written consent for theprocedure and for utilization of clinical data for scientific purposeswas obtained from all patients.Subjects were divided into three groups according to the position

of the advancing pterygium edge with respect to corneal diameter:extension of the edge to one third of the corneal diameter (grade 1),between one third of the corneal diameter and the pupil (grade 2),and within the pupillary area (grade 3). Representative cases areshown in Figure 1.All excision surgeries were performed using the same procedure.

Pterygium was removed bluntly, subconjuctival fibrous tissue wasremoved, and abnormal scarring tissue on the cornea was polished.After administrating 0.04% mitomycin C (MMC) for 1 min, thebare sclera was covered by sliding adjacent superior or inferiorconjunctiva. Postoperative medication until 6 months included0.5% levofloxacin eye drop (Cravit, Santen, Osaka, Japan) 4 timesper day, and 0.1% betamethasone sodium phosphate (Rinderon,Shionogi, Osaka, Japan) that was replaced with 0.1% fluorome-tholone (Flumetholon, Santen) shortly afterward. Recurrence wasdiagnosed when the extended tissue was found within the cornea.Best-corrected distance visual acuity (BCVA) and corneal

topography was measured preoperatively, and 1, 3, 6, and 12months postoperatively. Corneal topography was measured usingTMS-2 Corneal Topographer (Tomey, Nagoya, Japan). Refractivepower of the corneal surface was calculated based on simulatedkeratometry (SimK) provided by the topographer.5 Corneal refrac-tive power was obtained by averaging SimK values at the steepestand flattest meridians, and corneal astigmatism as the differencebetween SimK values. Surface regularity index (SRI) and surfaceasymmetry index (SAI) were used to evaluate corneal irregularity.

From the Miyata Eye Hospital, Miyazaki, Japan.The authors have no funding or conflicts of interest to disclose.Presented at the ARVO Annual Meeting, Seattle, WA, 2013.Address correspondence to Ryohei Nejima, M.D., Miyata Eye

Hospital, 6-3 Kurahara-cho, Miyakonojo, Miyazaki, 885-0051 Japan;e-mail: [email protected]

Accepted June 10, 2014.

DOI: 10.1097/ICL.0000000000000065

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Eyes with pterygium recurrence during 12 months were notexcluded.Results are expressed as mean6standard deviation. Time-

course changes in topography after surgery were examined witheach grade using paired analysis of variance (ANOVA) andBonferroni multiple comparison. Restoration in corneal refrac-tive power, astigmatism, and irregularities were also comparedusing one-way ANOVA. Best-corrected visual acuity wascompared using the Kruskal–Wallis test and the Steel–Dwassmultiple comparison. P,0.05 was considered as statisticallysignificant.

RESULTSThis study included 562 eyes of 464 patients (170 men, 294

women; mean age, 66.269.1 years). Pterygia were developed in254 right and 308 left eyes. Mean BCVA was 0.05360.219 log-MAR preoperatively and20.03060.211 logMAR 12 months post-operatively. Mean preoperative corneal refractive power andastigmatism were 43.5961.66 and 3.0062.70 diopters (D), respec-tively. Mean corneal irregularities were 0.90960.586 in SRI and0.86960.881 in SAI. The numbers of eyes in each size grade were119, 338, and 105 of grades 1 to 3, respectively. Demographic datafor the three grades are shown in Table 1. Preoperative BCVAdegraded with a higher size grade (P,0.0013). Corneal refractivepower decreased significantly with the grade (P,0.001), whereascorneal astigmatism, SRI, and SAI increased (P,0.001). Postop-erative BCVA in grade 3 was significantly worse than in grades 1and 2 (P,0.006). There were recurrences in 22 eyes (3.9%) from 2to 8 months (mean: 4 months).

Change in Corneal Refractive Powerand AstigmatismChanges in corneal refractive power and astigmatism of the 3 grades

are shown in Figure 2. During 12 months, grade 1 was relatively stablewith 20.18% of change in the corneal refractive power and 27.70%in astigmatism, whereas there were significant differences between 1and 12 months and 1 and 6 months, respectively. Corneal astigmatismin grade 2 did not change (27.85% of change in 12 months), althoughthe corneal refractive power (20.40% of change) showed significantdifferences until 6 months. In contrast, changes in grade 3 were20.94% and229.2% in the corneal refractive power and astigmatism,respectively, that were approximately 2 and 4 times larger than grades1 and 2. Continuous changes were observed during 12 months withsignificant differences between 1 month and 3 to 12 months in cornealrefractive power and astigmatism (P#0.005).In comparison of pterygium sizes (Fig. 3), corneal refractive

power in grades 2 and 3 showed a significant difference from thatin grade 1 until 3 months. In corneal astigmatism, there weresignificant differences until 6 months in grade 2, whereas grade3 retained higher than grade 1 over 12 months.

Change in Corneal IrregularitiesFigure 4 shows changes in corneal irregularities, SRI, and SAI.

Changes in grade 1 during 12 months were 212.1% in SRI and28.19% in SAI with no significant difference. In grade 2, SRI andSAI changed 226.4% and 215.1%, respectively. There were signif-icant differences between all points except for between 3 and 6 monthsin the SRI, and between 1 and 6–12 months in the SAI. Change ratesin grade 3 were229.0% and229.1%, respectively. Surface regularityindex and SAI in grade 3 continued to decrease over 12 months.

FIG. 1. Representative cases of each pterygium sizegrade.

TABLE 1. Demographic Data of Each Pterygium Size Grade

Pterygium Size Grade 1 Grade 2 Grade 3 P

N (eye) 119 338 105Sex, male/female (eye) 28/91 123/215 43/62Age, y 65.369.1 66.068.7 68.868.9 0.005a

Preoperative BCVA, logMAR 20.0160.19 0.0560.22 0.1560.20 ,0.001b

Preoperative corneal refraction (D) 44.5161.29 43.5461.66 42.7161.54 ,0.001a

Preoperative corneal astigmatism (D) 0.8260.49 2.7562.13 6.2062.79 ,0.001a

Preoperative SRI 0.6360.37 0.7860.42 1.6360.70 ,0.001a

Preoperative SAI 0.4860.30 0.7060.42 1.8661.50 ,0.001a

Postoperative BCVA, 12 months, logMAR 20.0560.16 20.0460.21 0.0260.26 ,0.021b

Recurrence rate, % 3.4 3.8 4.8Recurrence duration, mo 4.061.2 3.861.6 4.563.0

The data are expressed as the mean6standard deviation.aOne-way analysis of variance.bKruskal–Wallis test.

BCVA, best-corrected visual acuity; SAI, surface asymmetry index; SRI, surface regularity index.

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FIG. 2. Postoperative changes in cornealrefractive power (� with the left axis) andastigmatism (B with the right axis) of thethree pterygium size grades. P value denotesa significant difference over time.

FIG. 3. Comparison of the pterygium size regarding changes of corneal refractive power (A) andastigmatism (B). P value denotes a significant difference between grades.

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Comparison of the pterygium size is shown in Figure 5. Surfaceregularity index of grade 2 reduced to the level of grade 1 until 6months, whereas grade 3 required more than 6 months. In the SAI,grade 2 was reduced to the level of grade 1 from 1 month post-operatively; however, grade 3 was significantly higher than othergrades until 6 months.

DISCUSSIONSeveral studies that assessed topographic changes after ptery-

gium excision reported that corneal spherical refraction increasedand the corneal cylindrical refraction and irregular astigmatismdecreased postoperatively.8–12 In previous studies, the number ofsubjects was limited to 16 to 120, whereas investigation of therecurrent rate was analyzed in hundreds of subjects.13,14 This studyassessed postoperative topographic changes using over 460 sub-jects. Comparisons in the previous studies were performed betweenthe preoperative and one point of postoperative visit without anobservation of the time-course change. The effect of pterygium sizewas not examined as well. Ozdemir and Cinal9 evaluated changesat 2 weeks and 3 months postoperatively, demonstrating that majorchanges were induced in the early period, although a longer periodrequired for the restoration of corneal topography coincided wellwith the results in this study: pterygium of grade 1 or 2 could

restore corneal topography in 1 to 3 months, whereas that of grade3 required 6 to 12 months for restoration.Advanced pterygium induces decreasing corneal spherical

refraction by flattening the corneal surface and increasing thecorneal astigmatism,2,4,5 and excision surgery restores the cornealchange because of pterygium.3,5,8,11 Eye with a large pterygiumneed a longer period to recover to the normal shape. Tomidokoroet al.5 revealed that the pterygium size was correlated with post-operative changes in the corneal refractive power, which was alsofound in this study. Furthermore, a major change in corneal refrac-tive power was observed until 1 month postoperatively in allgrades, and there was a slow change afterward in grades 2 and3. It was speculated that large pterygium covering the pupil couldinduce critical changes in the corneal shape and deformation onBowman membrane, therefore the restoration of corneal topogra-phy required more time. Comparison of the four surgical techni-ques found that the use of conjunctival autograft and MMCinduced less corneal refractive changes postoperatively than thebare sclera technique.10 Even so, the current excision surgery forgrade 3 pterygium required a longer time for the restoration ofcorneal topography.Best-corrected visual acuity is degraded with corneal irregular-

ity.15,16 An SRI exceeding 1.3 would result in a BCVA of 0.0logMAR or worse in normal and keratoconus eyes.16 Although

FIG. 4. Postoperative changes in surfaceregularity index (� with the left axis) andsurface asymmetry index (B with the rightaxis) of the three pterygium size grades.P value denotes a significant difference overtime.

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the SRI in grade 3 was not significantly worse than those in grades1 and 2 at 12 months, the BCVA (0.02260.256 logMAR) wasworse than the others. It was considered that other factors in-fluence the postoperative BCVA. Fourier17 or high-order aberrationanalyses6,7 of corneal topography would be necessary for furtherinvestigation.Several techniques of pterygium excision surgery have been

developed. The literature analysis suggested that the use ofconjunctival autograft or MMC significantly reduced recurrencerate compared with bare sclera technique.13 While the bare scleratechnique resulted in the least postoperative topographic irregular-ity in the comparison by Yilmaz et al.,12 there was no significantdifference between techniques using conjunctival autograft orMMC. Therefore, the current excision surgery using intraoperativeMMC and conjunctival autograft was considered as acceptablefor minimizing recurrence and promoting recovery of visualimpairment.Placido topographer used in this study effectively captured mires

on the corneal surface. Pterygium extension might disturb theimages of the mires because of high irregularity of the pterygiumsurface. Therefore, analysis of the central 6-mm area was notappropriate. This study measured extension of pterygia withrespect to the pupil area, while mean pupil diameters in a 60-yearJapanese were 2.3 and 4.1 mm under mesopic and photopicilluminations, respectively.18 In grade 3, preoperative indices thatwere obtained from approximately central 3-mm area15 could beaffected. Although all images of the mires were confirmed, artifi-cial feature was not reported, and the preoperative indices coin-cided with previous studies.8–12 Therefore, the influence ofdisturbance in the mires was not significant. Previous studiesshowed that the corneal surface after excision surgery wouldbe within a range where the placido topographer properlymeasured.4,12

There were some limitations to this study. First, because of theretrospective design, demographics of each grade could not bematched between groups. Larger pterygia could be found in older

patients. It would be also anticipated that corneal surface restorationcould be slower in older patients; however, the difference of 3.5 yearswas not considered as significant. Second, the pupil diameter and high-order aberration were not examined. Grade 3 was diagnosed regardingthe pupil diameter; however, there was no record of the pupil diametermeasurement. Third, best-corrected visual acuity impairment was alsocaused by increase of ocular high-order aberration.6,7 Prospectiveassessment is required for further assessments.In conclusion, change in corneal refractive power, astigmatism,

and irregularity after excision surgery varied with pterygium size.Time for restoration should be 1 to 3 months when the pterygium didnot reach the pupil; a case with a larger pterygium would require 6 to12 months for restoration of the corneal refractive power andirregularity, and over 12 months for corneal astigmatism, whichresulted in slow recovery of visual acuity impairment. The restorationduration in each pterygium size indicated about when cataract orrefractive surgery should be conducted to obtain a preferableoutcome. In cataract surgery, the power of an intraocular lens shouldbe determined after the corneal refractive power and astigmatism arestable. Wavefront-guided laser in situ keratomileusis would beeffective when the corneal irregularity is in a stable condition.

REFERENCES

1. Hirst LW. The treatment of pterygia. Surv Ophthalmol 2003;48:145–180.2. Lin A, Stern G. Correlation between pterygium size and induced corneal

astigmatism. Cornea 1998;17:28–30.3. Stern GA, Lin A. Effect of pterygium excision on induced corneal topo-

graphic abnormalities. Cornea 1998;17:23–27.4. Tomidokoro A, Oshika T, Amano S, et al. Quantitative analysis of regular

and irregular astigmatism induced by pterygium. Cornea 1999;18:412–415.5. Tomidokoro A, Miyata K, Sakaguchi Y, et al. Effect of pterygium

on corneal spherical power and astigmatism. Ophthalmology 2000;107:1568–1571.

6. Gumus K, Topaktas D, Goktas A, et al. The change in ocular high-orderaberrations after pterygium excision with conjunctival autograft: A 1-yearprospective clinical trial. Cornea 2012;31:1428–1431.

7. Pesudovs K, Figueiredo FC. Corneal first surface wavefront aberrationsbefore and after pterygium surgery. J Refract Surg 2006;22:921–925.

FIG. 5. Comparison of pterygium size regarding changes of surface regularity index (A) and surfaceasymmetry index (B). P value denotes a significant difference between the size grades.

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8. Bahar I, Loya N, Weinberger D, et al. Effect of pterygium surgery oncorneal topography: A prospective study. Cornea 2004;23:113–117.

9. Ozdemir M, Cinal A. Early and late effects of pterygium surgery on cornealtopography. Ophthalmic Surg Lasers Imaging 2005;36:451–456.

10. Yagmur M, Ozcan AA, Sari S, et al. Visual acuity and corneal topographicchanges related with pterygium surgery. J Refract Surg 2005;21:166–170.

11. Errais K, Bouden J, Mili-Boussen I, et al. Effect of pterygium surgery oncorneal topography. Eur J Ophthalmol 2008;18:177–181.

12. Yilmaz S, Yuksel T, Maden A. Corneal topographic changeafter four types of pterygium surgery. J Refract Surg 2008;24:160–165.

13. Kaufman SC, Jacobs DS, Lee WB, et al. Options and adjuvants in surgeryfor pterygium: A report by the American Academy of Ophthalmology.Ophthalmology 2013;120:201–208.

14. Al Fayez MF. Limbal-conjunctival vs conjunctival autograft transplant forrecurrent pterygia: A prospective randomized controlled trial. JAMA Oph-thalmol 2013;131:11–16.

15. Wilson SE, Klyce SD. Quantitative descriptors of corneal topography.A clinical study. Arch Ophthalmol 1991;109:349–353.

16. Shiotani Y, Maeda N, Inoue T, et al. Comparison of topographic indices thatcorrelate with visual acuity in videokeratography. Ophthalmology 2000;107:559–564.

17. Oshika T, Sugita G, Tanabe T, et al. Regular and irregular astigmatism aftersuperior versus temporal scleral incision cataract surgery. Ophthalmology2000;107:2049–2053.

18. Nakamura K, Bissen-Miyajima H, Oki S, et al. Pupil sizes in differentJapanese age groups and the implications for intraocular lens choice.J Cataract Refract Surg 2009;35:134–138.

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Original Article

Randomized, controlled trial of conjunctivalautografting combined with subconjunctivalbevacizumab for primary pterygium treatment:1-year follow-upAngel Nava-Castañeda MD MSc,1,2 Osiris Olvera-Morales MD,2 Cynthia Ramos-Castellon MD,2

Lilia Garnica-Hayashi MD2 and Yonathan Garfias MD PhD1,3

1Research Unit, 2Oculoplastics Department, Institute of Ophthalmology Conde de Valenciana and 3Biochemistry Department, Faculty

of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico

ABSTRACT

Background: To investigate the efficacy and safetyof subconjunctival bevacizumab application as anadjuvant therapy for primary pterygium.

Design: This study was a clinical randomized trialperformed at the Institute of Ophthalmology ‘Condede Valenciana’.

Participants: Forty-nine patients with primary ptery-gium were enrolled in the study.

Methods: Each primary pterygium patient was ran-domized after pterygium excision and a conjunc-tival autograft to receive either a single 2.5 mg/0.1 mL dose of subconjunctival bevacizumab im-mediately after surgery (group 1); a double 2.5 mg/0.1 mL injection of subconjunctival bevacizumab,one immediately after surgery and the second15 days after surgery (group 2); or no injection(group 3).

Main Outcome Measures: Autoconjunctival graftpresence or absence of ischaemia, necrosis, infectionor detachment; surgical bed appearance; and

pterygium recurrence at 1-year follow-up periodwere determined.

Results: Forty-nine eyes of 49 patients were included.Sixteen patients were assigned to group 1, 17 togroup 2 and 16 to group 3. Patients from groups 1and 2 showed conjunctival autograft ischaemia at24 h postoperative (37.5% and 58.8%, respectively,P > 0.05), which disappeared by the first posto-perative month. No significant difference in themain outcome measures was found among singleversus double-dose of subconjunctival bevacizumabinjection patients. At the end of the study, ptery-gium recurrences were observed only in group3 (P < 0.04).

Conclusions: A single 2.5 mg/mL subconjunctivalbevacizumab injection in conjunction with primarypterygium surgery accomplishing a conjunctivalautograft procedure is safe and well tolerated, and iscapable of preventing pterygium recurrences whencompared with a control group.

Key words: clinical trial, conjunctival allograft, ptery-gium, subconjunctival bevacizumab.

� Correspondence: Dr Yonathan Garfias, Instituto de Oftalmología Fundación Conde de Valenciana, Chimalpopoca 14, 06800 Mexico City, Mexico.

Email: [email protected]

Received 11 November 2012; accepted 7 June 2013.

Competing/conflicts of interest: No stated conflict of interest.

Funding sources: This work was supported by Consejo Nacional de Ciencia y Tecnología grant numbers CONACyT-SALUD-C01-160286 and

CVU: 172996.

The study was registered at Clinical Trials with number: NCT01686529.

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Clinical and Experimental Ophthalmology 2014; 42: 235–241 doi: 10.1111/ceo.12140

© 2013 Royal Australian and New Zealand College of Ophthalmologists

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INTRODUCTION

Pterygium is an ocular surface disease; this conditioninvolves invasive centripetal growth with associ-ated inflammation and neovascularization.1 Althoughseveral theories have been postulated for the patho-genesis of pterygium, including ultraviolet exposi-tion, immunological mechanisms and infections,2–4

the precise cause of pterygium is still under study.It has been shown that the ultraviolet expositioninduces the expression of cytokines and growthfactors from pterygium cells.5,6 Histologically, thepterygium is composed of epithelium and a highlydeveloped vascular neoformation network consist-ing of arterioles, venules and a very large numberof capillaries found in the connective tissue.7 Ithas been demonstrated that angiogenesis-relatedfactors such as CD31 and vascular endothelial growthfactor (VEGF) are highly expressed in pterygiumcompared with normal conjunctiva.8,9 The VEGFinduces mitosis and cell migration in endothelialcells, enhances vascular permeability, and stimulatesthe proteases secretion; all these actions are exertedthrough VEGF specific receptors.10,11

Bevacizumab is a neutralizing recombinanthumanized monoclonal antibody against all theVEGF isoforms; although bevacizumab was initiallyused in colon cancer treatment, it is used in age-related macular degeneration in ophthalmology aswell.12 Bevacizumab has not only been used to treatretinal diseases because of neoangiogenesis, but ithas also been used in eye surface diseases such ascorneal neovascularization resulting in most casesin vessel regression.13,14 Recently, bevacizumab hasbeen used as an adjuvant therapy in combinationwith surgery to treat pterygium; however, there arestill controversies related to the doses, frequencyand timing of bevacizumab application to treat thispathology.15–18 The present study was designed toinvestigate the efficacy and safety of bevacizumabsubconjunctival application as an adjuvant therapyin primary pterygium.

METHODS

Study design

The current study was a simply randomized, single-centre trial. The method of ensuring allocation con-cealment was sequentially numbered. We enrolledpatients with primary pterygium who visited TheInstituto de Oftalmologia Conde de Valencianabetween March 2010 and February 2011. The studyadhered to the tenets of the Declaration of Helsinkiand was approved by the Institutional Ethics Com-mittee Board (Registration Number: CC-008–2010)and registered at Clinical Trials with number:NCT01686529. All patients included were from

Mexico City. The pterygia lesions included in thepresent study were in an active and progressivestage; all the lesions were Stocker’s line-free and didnot present Fuchs’ patches.

The patients were included in the study anddivided into three groups. In group 1, bevacizumab(2.5 mg/0.1 mL) was applied once after surgery;in group 2 the bevacizumab (2.5 mg/0.1 mL) wasapplied after surgery, with another same dose 15days after surgery; and in group 3, the controlgroup, surgery was performed without bevacizu-mab application. Patients with diabetes mellitus,colagenopathies, previous ocular surgeries, andpregnant or lactating patients were excluded fromthe study.

Pterygia measurements

The measurements of the pterygia were performedaccording to Welch et al. modified technique as fol-lowing: the distance in millimetres from the limbusto the apex of the lesion on the cornea (horizontallength) and the distance in millimetres between theinferior and superior crossing points of the lesion atthe limbus (vertical length) were performed usingthe slit-lamp beam (BQ 900, Haag-Streit, Koeniz,Switzerland). A standard magnification of 16 wasused, and the variable aperture was focused from thelimbus to the apex, as well as the inferior and supe-rior crossing points of the lesion at the limbus.19

Bevacizumab subconjunctival injectionand surgical technique

All the surgeries were performed on an outpatientbasis at The Instituto de Oftalmología Conde deValenciana. In order to reduce the intersurgeon bias,all the surgeries were performed by one surgeon(ANC). The eye was prepared and draped in theusual sterile fashion. The procedure included topicalanaesthesia using 0.5% tetracaine hydrochloride(Ponti-Ofteno, Laboratorios Sophia, Jalisco, Mexico)and 0.3 mL subconjunctival 2% lidocaine, and1/100 000 epinephrine (AstraZeneca, Mexico City,Mexico) injection under the area of pterygium. Thepterygium head was lifted off the corneal surface byblunt dissection. The pterygium body was dissectedfrom the underlying sclera and thereafter excised. Athorough removal of Tenon’s capsule was performedin an area much greater than the pterygium body.Any abnormal scarred tissue on the corneal surfacewas polished with a corneal burr (Algerbrush II).Free conjunctival autografting after pteryigum exci-sion was performed as follows: the desired size ofthe conjunctiva under the upper eyelid was marked(according to the size of the bare sclera defect),

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inflated with 0.5 mL of 2% lidocaine and 1/100 000epinephrine (AstraZeneca) and excised. No limbaltissue was included in the graft. The excised tissuewas placed on the bare sclera and tightly sutured tothe sclera and the limbal area with 10-0 nylonstitches (Ethicon, Johnson&Johnson, Sommerville,New Jersey, USA). Finally, the autograft edges weresutured to the conjunctiva all around with 10-0 nylonstitches (Ethicon, Johnson&Johnson). The subcon-junctival injection of bevacizumab (F-Hoffmann-LaRoche, Basel, Switzerland) was applied adjacent tothe site of pterygium separation inside the healthyconjunctiva. The half of the dose (1.25 mg/0.05 mL)was applied in the nasal inferior quadrant, and theother half of the dose was applied in the nasal supe-rior quadrant. Fifteen days after the pterygiumsurgery, a second dose was applied only to thosepatients enrolled in group 2. The second subconjunti-val injection was applied similarly as describedearlier (Fig. 1). The patients in group 3 were treatedsimilar to the other two groups; however, they had nobevacizumab injections. Topical antibiotics and corti-costeroids (Trazidex, Laboratorios Sophia, Jalisco,Mexico) were instilled and followed by eye pressurepatching.

Following the surgery, each patient was treatedwith topical eye drops of 0.3% tobramycin and 0.1%dexamethasone (Trazidex, Laboratorios Sophia) and0.5% carboxymethylcellulose lubricating eye drops(Refresh Tears, Allergan, Irving, California, USA)four times daily, corticosteroids and antibiotics eyedrops were tapered and discontinued after 3 months.Patients were examined at days 1, 15, 30, 90, and

then at 6th and 12th month. The ophthalmologist(CRC) who assessed the outcomes was masked tothe treatment.

Outcome measures

Demographic data, slit-lamp biomicroscopic exami-nation and slit-lamp photography were performedat baseline and at every follow-up visit. The mainoutcome measurements in this study were the pres-ence or absence of ischaemia, necrosis, infection anddetachment in the autoconjunctival graft; the appear-ance of the operated-on site; and pterygium recur-rence, as reported previously.20

Statistical analysis

Statistical analyses were performed using the SPSSversion 18.0 (Chicago, IL, USA). The demographicvariables were analysed using descriptive statistics.In order to determine differences of the variablesamong groups, Mann–Whitney, Kruskall–Wallis, c2

and Cochran tests were used. P < 0.05 was consid-ered statistically significant.

RESULTS

Forty-nine eyes of 49 patients were enrolled in thisstudy. Thirty-three patients were treated with beva-cizumab subconjunctival injection (BSI) and the sur-gical removal of pterygium. From those 33 patients,16 patients received only one BSI (2.5 mg/0.1 mL)after surgery (group 1); meanwhile, 17 patientsreceived two BSI (2.5 mg/0.1 mL), the first doseapplied after surgery, and the second dose (2.5 mg/0.1 mL) applied 15 days after surgery (Group 2).Sixteen patients, who served as a control group(Group 3), had only the surgical procedure and noBSI. The demographic data of all the participantsin the study are summarized in Table 1. The age ofthe patients ranged from 29 to 66 years with a meanage of 48.8 � 15.5 years. There were 11 men and 38women with similar distribution in the three groups.Data on preoperative pterygium morphology werealso reviewed; all the pterygia were located nasally.The horizontal pterygia length, which was measuredas the greatest distance from the limbus to the apexof the lesion, varied from 1.98 to 4.63 mm with amean size of 3.34 � 1.14 mm. The vertical length ofthe pterygia varied from 3.22 to 5.97 mm with amean size of 4.56 � 1.39 mm. All patients were fol-lowed for 12 months. In the present study, there wasno loss of patients during the experimental time.

The graft ischaemia was observed in the groupswhere bevacizumab was subconjunctivally applied;in contrast, ischaemic events in the group withoutbevacizumab treatment were not observed. As

Figure 1. Slit-lamp group 2 patient photograph at 2 weeksfollow-up showing bevacizumab injection. Half of the dose(1.25 mg/0.05 mL) was applied in the nasal inferior quadrant, andthe other half of the dose was applied in the nasal superior quad-rant (green arrows), within the healthy conjunctiva.

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described in Table 2, both groups that receivedbevacizumab treatment presented a similar per-centage of ischaemic events at 24 h postoperative;likewise, there were no statistical differences whencomparing both groups at 15 days postoperative(P > 0.05). Moreover, there was not red eye appear-ance after BSI. The normal conjunctiva in thenasal region did not present any ischaemia changes.Interestingly, the second subconjunctival applica-tion in group 2 did not increase the percentage ofischaemia. The graft ischaemia was totally resolvedin both groups at 1 month postoperative. Theabsence of the ischaemic events was clinically cor-roborated with the disappearance of the graft, whitecoloration and the presence of blood vessels all overthe conjunctival graft. Ischaemic events did not influ-ence in the conjunctival cicatrization; moreover,there were not suture dehiscence after bevacizumabinjection.

The appearance of the operated-on site was meas-ured at 12 months after surgery, according to a pre-viously reported scale.20 As shown in Table 3, themajority of the cases in the three groups at the end of

the study (group 1, 87.5%; group 2, 83%; group 3,69%) scored low (grades I and II) on the scale. Inter-estingly, when the recurrence rate was analysedamong groups, there was a recurrence in two controlgroup patients, whereas the patients treated witheither one or two doses of bevacizumab presented norecurrence; this difference was statistically signifi-cant (P = 0.04) (Fig. 2).

DISCUSSION

Our results have shown that the recurrence rate isdiminished when pterygia are treated with eitherone or two doses of bevacizumab in comparisonwith the control group treated with autograft alonewithout bevacizumab injection. Although both beva-cizumab treatments caused ischaemic events, thesewere transient and self-resolved incidents at 1 monthpostoperative. These findings support in part thehypothesis in which angiogenic factors such asVEGF is increased in pterygium. Hosseini et al. hasproposed the use of an antiangiogenic as an adjuncttherapy in the management of pterygia.21 Accordingto this proposal, the bevacizumab has been used asan adjuvant to treat pterygium.

It has been documented that a single intraopera-tive subconjunctival bevacizumab injection in com-bination with a rotational conjunctival flap had noeffect on recurrence rate or early postoperative con-junctival erythema following pterygium excision.22

Moreover, Banifatemi et al. reported that the use oftwo consecutive bevacizumab doses had no adverseeffects on early postoperative wound healing ofexcised primary pterygium.23 In addition, Shenasiet al. stated that subconjunctival injection of bevaci-zumab immediately after surgical excision of primarypterygium is well tolerated, but it did not signifi-cantly prevent the recurrence of this condition.18

Table 1. Demographic data of the patients and pterygia

Group 1 Group 2 Group 3 P

Number of patients 16 17 16Sex (male/female) 4/12 4/13 3/13 0.30Age (years) 51.8 � 14.5 45.7 � 16.3 47.8 � 15.6 0.36Horizontal length (mm) 3.21 � 1.23 3.38 � 1.02 3.45 � 1.18 0.36Vertical length (mm) 4.58 � 1.39 4.55 � 1.40 4.56 � 1.34 0.41

Table 2. Ischaemic postoperative evolution

Ischaemia Group 1 Group 2 P

+ - + -

24 h 6 (37.5%) 10 (62.5%) 10 (58.8%) 7 (41.2%) 0.7215 days 7 (43.8%) 9 (56.3%) 9 (52.9%) 8 (47.1%) 0.651 month 0 16 (100%) 0 17 (100%)

Table 3. Results of final appearance grading

Grading Group 1 Group 2 Group 3 P

1 8 (50%) 9 (52.9%) 6 (37.5%) 0.172 6 (37.5%) 5 (29.4%) 5 (31.25%) 0.113 2 (12.5%) 3 (17.6%) 3 (18.75%) 0.444 0 0 2 (12.5%) 0.04

Grade 1: normal appearance of the operative site; grade 2:presence of some fine episcleral vessels, without any fibroustissue in the excised area extending up to but beyond the limbus;grade 3: presence of additional fibrous tissues in the excised areawithout invading the cornea; grade 4: true recurrence with afibrovascular tissue invading the cornea.20

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Unlike these studies, our results showed that theinjections are well tolerated and have positive effectson the treatment of primary pterygium, reducingthe recurrence rate. The bevacizumab dose used byShenasi et al., as well as the surgical technique theyhave reported are possible factors to be consideredto explain the different outcomes reported in thepresent manuscript compared with the reported bythem.18

By the other hand, our results are in accordance tothose reported by Galor et al. in which a single doseof 0.5 mg/0.05 mL of ranibizumab was administeredsubconjunctivally, either prior to the pterygiumsurgery or at the end of the pterygium excision sur-gery.24 Although the antiangiogenic molecule differsfrom the one used in our study, the surgical tech-nique employed was similar to that performed anddocumented by Galor et al. in which they did notreport any case of necrosis, infection or ischaemia inthe surgical bed area. In the present study, weobserved that conjunctival autograft ischaemia wasa major finding present in almost 50% of thebevacizumab-treated patients. This ischaemia eventwas topographically situated adjacent to the site ofbevacizumab injection, involving nearly 30% of thearea of the conjunctival autograft. Interestingly, theischaemia gradually disappeared over time and wastotally absent in the first follow-up month in allbevacizumab-treated patients. It has been describedthat subconjunctival bevacizumab injection inducesischaemia at the site of injection after penetrating

keratoplasty;25 however, the revascularization pro-cess could be determined by the vessels from thesurrounding healthy conjunctiva as well as from thenon-ischaemic portion of the graft,26 avoiding graftnecrosis. In contrast with our original hypothesis,the second bevacizumab injection at day 15 did notgenerate any additional positive or negative effectson either ischaemia or recurrence rate. This resultsuggests that single intraoperative subconjunctivalbevacizumab injection is sufficient as an adjuvant totreat primary pterygium. The possibility that the firstbevacizumab injection diminished the vessels in anactive growth phase cannot be ruled out. To thisrespect, it has been hypothesized that the use ofanti-VEGF agents is effective only in cases in whichthere are vessels in an active growth phase, whichare dependent on the action of VEGF.27 Similar tothe results reported by Galor et al., most of thebevacizumab-treated patients showed a more pro-nounced quiescence on the conjunctival autograftbed.24

For the present study, we chose a 2.5 mg/0.1 mLBSI because several studies have shown that bev-acizumab dosages lower than 2.5 mg/0.1 do notproduce any significant changes in ocular surfaceneovascularization regression when injected inaffected eye areas.28 In addition, this particular beva-cizumab dose has been proven to be well-toleratedwithout local or systemic side-effects.29

It is believed that early anti-VEGF therapy canprevent limbal-conjunctival neovascularization by

Group 1

Preoperative Postoperative Day 1 Postoperative Day 15 Postoperative Month 1 Postoperative Month 6 Postoperative Year 1

Group 2

Group 3

Figure 2. Slit-lamp photographs of representative patients of all groups before and after treatment. The study started with patientswith similar pterygium characteristics. There is a remarkably well-defined white ischaemic region adjacent to the site of subconjunctivalbevacizumab injection that is more evident at 15th postoperative day in both groups 1 and 2. In both groups, the ischaemia was fadingover time and had completely disappeared at first-month postoperative, and the entire graft appeared covered with vessels. Morepronounced quiescence of the surgical bed was seen in bevacizumab patients. In contrast, proper irrigation is observed in group 3 in allperiods.

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blocking access to the nutrients necessary for fibrob-last proliferation and fibrous tissue growth.30 Aspterygium excision is often combined with variousadjunctive measures to prevent recurrence of thedisease, we evaluated the anti-VEGF properties ofbevacizumab as a novel adjunctive therapy. In thisrandomized clinical study, there were no statisticallysignificant differences in the patients’ demographicdata, and the beneficial effects between a single versusdouble dose of BSI were similar. The outcomes of ourstudy are encouraging. First, we observed a goodtolerability and safety between the combination of asingle or double 2.5 mg/0.1 mL BSI at the end of aconjunctival autograft procedure, meaning that theconjunctival graft’s survival and integration to thesurgical bed is not compromised by the antiang-iogenic properties of bevacizumab. Second, only thebevacizumab-treated patients remained pterygium-recurrence-free at the end of the study. Recurrence-free surgery for pterygium continues to present achallenge. A number of surgical techniques havebeen described as methods for pteryigium treatment,including bare sclera resection,31 bare sclera resec-tion followed by mitomycin C application at dif-ferent time points, doses and concentrations,32–34

and pterygium excision plus conjunctival auto-graft placement.35,36 Recurrence rates are influencedby several factors, being the surgical techniqueemployed, the only factor that can be fully controlledby the ophthalmic surgeon. For pterygium resectionwith conjunctival graft placement, the surgical tech-nique used in the present study, the recurrencerate ranges from 2% and 39%.35,37,38 Among ptery-gium surgical techniques, conjunctival autograftingis more technically demanding and more time-consuming to perform. Intersurgeon variability interms of surgical technique, skill and experiencecontributes to the wide variation in recurrence ratesthat have been reported.39 Devereaux et al. pointedout that a surgical expertise based randomized, con-trolled trial must ensure satisfactory competenceamong the surgeons doing each procedure.40 In thepresent study, all the surgeries were performed by asingle qualified surgeon who has attained properpost-training experience in pterygium surgery, par-ticularly in conjunctival autografting (ANC). Thesimilarities between the lowest 2% recurrence ratereported in the literature and the recurrence rateachieved in the present study’s control group makeus think that choosing this strategy, the intersurgeonbias has been reduced. The strength of our study isbased on its long follow-up period. Nevertheless, westrongly suggest increasing the sample size forfurther studies. As outcomes of pterygium surgerydepend on several factors, mainly ultraviolet lightexposure, we must consider including patients fromdifferent latitudes, as well as high-risk patients

(young patients, those with recurrent pterygia).However, to our knowledge, this is the first clinicaltrial evaluating the role of a single versus double BSIas an adjunct therapy to surgical removal of pterygiawith conjunctival autograft compared with a controlgroup. The understanding of the role of anti-VEGFagents in the treatment of pterygium is evolving.Whether bevacizumab must be considered as anadjunctive therapy in order to prevent pterygiumrecurrence in pterygium patients deserves morestudies.

In conclusion, the findings of the present studysuggest that one single 2.5 mg/mL BSI in conjunc-tion with pterygium surgery using conjunctivalautograft procedure is safe and well tolerated, andwas able to prevent pterygium recurrence whencompared with a control group.

REFERENCES

1. Bradley JC, Yang W, Bradley RH et al. The science ofpterygia. Br J Ophthalmol 2010; 94: 815–20.

2. Gallagher MJ, Giannoudis A, Herrington CS, HiscottP. Human papillomavirus in pterygium. Br J Ophthal-mol 2001; 85: 782–4.

3. Garfias Y, Bautista-De Lucio VM, Garcia C et al. Studyof the expression of CD30 in pterygia compared tohealthy conjunctivas. Mol Vis 2009; 15: 2068–73.

4. Nolan TM, DiGirolamo N, Sachdev NH et al. The role ofultraviolet irradiation and heparin-binding epidermalgrowth factor-like growth factor in the pathogenesis ofpterygium. Am J Pathol 2003; 162: 567–74.

5. Jin J, Guan M, Sima J et al. Decreased pigmentepithelium-derived factor and increased vascularendothelial growth factor levels in pterygia. Cornea2003; 22: 473–7.

6. Di Girolamo N, Wakefield D, Coroneo MT. UVB-mediated induction of cytokines and growth factors inpterygium epithelial cells involves cell surface recep-tors and intracellular signaling. Invest Ophthalmol Vis Sci2006; 47: 2430–7.

7. Golu T, Mogoanta L, Streba CT et al. Pterygium: histo-logical and immunohistochemical aspects. Rom JMorphol Embryol 2011; 52: 153–8.

8. Aspiotis M, Tsanou E, Gorezis S et al. Angiogenesis inpterygium: study of microvessel density, vascularendothelial growth factor, and thrombospondin-1. Eye2007; 21: 1095–101.

9. Marcovich AL, Morad Y, Sandbank J et al. Angiogen-esis in pterygium: morphometric and immunohisto-chemical study. Curr Eye Res 2002; 25: 17–22.

10. Kajdaniuk D, Marek B, Borgiel-Marek H, Kos-KudlaB. Vascular endothelial growth factor (VEGF) – part 1:in physiology and pathophysiology. Endokrynol Pol2011; 62: 444–55.

11. Unemori EN, Ferrara N, Bauer EA, Amento EP. Vascu-lar endothelial growth factor induces interstitial colla-genase expression in human endothelial cells. J CellPhysiol 1992; 153: 557–62.

240 Nava-Castañeda et al.

© 2013 Royal Australian and New Zealand College of Ophthalmologists

Page 13: Topographic Changes After Excision Surgery of Primary Pterygia ...

12. Magdelaine-Beuzelin C, Pinault C, Paintaud G, WatierH. Therapeutic antibodies in ophthalmology: old isnew again. MAbs 2010; 2: 176–80.

13. Gueudry J, Richez F, Tougeron-Brousseau B et al.Subconjunctival bevacizumab for corneal neovascu-larization. J Fr Ophtalmol 2010; 33: 630–6.

14. Dastjerdi MH, Al-Arfaj KM, Nallasamy N et al. Topicalbevacizumab in the treatment of corneal neovasculari-zation: results of a prospective, open-label, noncom-parative study. Arch Ophthalmol 2009; 127: 381–9.

15. Besharati MR, Manaviat MR, Souzani A. Subconjunc-tival bevacizumab injection in treatment of pterygium.Acta Med Iran 2011; 49: 179–83.

16. Enkvetchakul O, Thanathanee O, Rangsin R et al. Arandomized controlled trial of intralesional bevacizu-mab injection on primary pterygium: preliminaryresults. Cornea 2011; 30: 1213–8.

17. Lekhanont K, Patarakittam T, Thongphiew P et al.Randomized controlled trial of subconjunctival beva-cizumab injection in impending recurrent pterygium: apilot study. Cornea 2012; 2: 155–61.

18. Shenasi A, Mousavi F, Shoa-Ahari S et al. Subconjunc-tival bevacizumab immediately after excision ofprimary pterygium: the first clinical trial. Cornea 2011;30: 1219–22.

19. Welch MN, Reilly CD, Kalwerisky K et al. Pterygiameasurements are more accurate with anterior seg-ment optical coherence tomography – a pilot study.Nepal J Ophthalmol 2011; 3: 9–12.

20. Prabhasawat P, Barton K, Burkett G, Tseng SC. Com-parison of conjunctival autografts, amniotic membranegrafts, and primary closure for pterygium excision.Ophthalmology 1997; 104: 974–85.

21. Hosseini H, Nejabat M, Khalili MR. Bevacizumab(Avastin) as a potential novel adjunct in the manage-ment of pterygia. Med Hypotheses 2007; 69: 925–7.

22. Razeghinejad MR, Hosseini H, Ahmadi F et al.Preliminary results of subconjunctival bevacizumab inprimary pterygium excision. Ophthalmic Res 2010; 43:134–8.

23. Banifatemi M, Razeghinejad MR, Hosseini H,Gholampour A. Bevacizumab and ocular woundhealing after primary pterygium excision. J Ocul Phar-macol Ther 2011; 27: 17–21.

24. Galor A, Yoo SH, Piccoli FV et al. Phase I study ofsubconjunctival ranibizumab in patients with primarypterygium undergoing pterygium surgery. Am J Oph-thalmol 2010; 149: 926–31 e922.

25. Bhasin P, Gujar P. A case of recipient bed melt andwound dehiscence after penetrating keratoplasty and

subconjunctival injection of bevacizumab. Cornea 2012;31: 1342–3.

26. Calcagni M, Althaus MK, Knapik AD et al. In vivovisualization of the origination of skin graft vascula-ture in a wild-type/GFP crossover model. Microvasc Res2011; 82: 237–45.

27. Bahar I, Kaiserman I, McAllum P et al. Subconjunc-tival bevacizumab injection for corneal neovasculari-zation in recurrent pterygium. Curr Eye Res 2008; 33:23–8.

28. You IC, Kang IS, Lee SH, Yoon KC. Therapeutic effectof subconjunctival injection of bevacizumab in thetreatment of corneal neovascularization. Acta Ophthal-mol 2009; 87: 653–8.

29. Doctor PP, Bhat PV, Foster CS. Subconjunctival beva-cizumab for corneal neovascularization. Cornea 2008;27: 992–5.

30. Wu PC, Kuo HK, Tai MH, Shin SJ. Topical bevacizu-mab eyedrops for limbal-conjunctival neovasculariza-tion in impending recurrent pterygium. Cornea 2009;28: 103–4.

31. D’Ombrain A. The surgical treatment of pterygium. BrJ Ophthalmol 1948; 32: 65–71.

32. Hayasaka S, Noda S, Yamamoto Y, Setogawa T. Post-operative instillation of low-dose mitomycin C in thetreatment of primary pterygium. Am J Ophthalmol 1988;106: 715–8.

33. Mahar PS, Nwokora GE. Role of mitomycin C in ptery-gium surgery. Br J Ophthalmol 1993; 77: 433–5.

34. Singh G. Postoperative instillation of low-dose mito-mycin C in the treatment of primary pterygium. Am JOphthalmol 1989; 107: 570–1.

35. Kenyon KR, Wagoner MD, Hettinger ME. Con-junctival autograft transplantation for advanced andrecurrent pterygium. Ophthalmology 1985; 92: 1461–70.

36. Said A, Fouad AR, Mostafa MS, Abbas S. Surgicalmanagement of recurrent pterygium by an operationof transposition. Bull Ophthalmol Soc Egypt 1975; 68:81–4.

37. Lewallen S. A randomized trial of conjunctivalautografting for pterygium in the tropics. Ophthalmology1989; 96: 1612–4.

38. Sebban A, Hirst LW. Treatment of pterygia in Queens-land. Aust N Z J Ophthalmol 1991; 19: 123–7.

39. Ang LP, Chua JL, Tan DT. Current concepts and tech-niques in pterygium treatment. Curr Opin Ophthalmol2007; 18: 308–13.

40. Devereaux PJ, Bhandari M, Clarke M et al. Need forexpertise based randomised controlled trials. BMJ2005; 330: 88–91.

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Recurrence and Complications after 1000Surgeries Using Pterygium ExtendedRemoval Followed by Extended ConjunctivalTransplant

Lawrence W. Hirst, MD, MPH1,2,3

Objective: To document the recurrence rate and complication rate of pterygium extended removal followedby extended conjunctival transplant.

Design: An open, prospective study of consecutive pterygium patients undergoing pterygium extendedremoval followed by extended conjunctival transplant.

Participants and Controls: The study included 1000 consecutive patients undergoing pterygium surgerybetween August 2001 and September 2009.

Interventions: All patients underwent pterygium extended removal followed by extended conjunctivaltransplant by the author with attempted follow-up for 1 year.

Main Outcome Measures: Recurrence and complication rates.Results: Follow-up of �1 year was obtained in 99% of patients. There was 1 recurrence in the 1000

surgeries (0.1%) with 95% confidence intervals of 0.003%–0.56% (Fischer exact test). Seven patients requiredfurther surgery: 3 had graft replacements, and 1 each for recurrence, strabismus, inclusion cyst, and granuloma.One patient lost 4 lines of vision from a corneal ulcer.

Conclusions: Pterygium extended removal followed by extended conjunctival transplant results in one of thelowest recurrence rates reported in the world’s literature and an acceptable complication rate.

Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.Ophthalmology 2012;119:2205–2210 © 2012 by the American Academy of Ophthalmology.

Pterygium surgery has been described as far back as 3000BC.1 Over the last 50 years, a variety of methods have beenused to try to reduce the commonest complication of ptery-gium surgery,2–21 namely recurrence. However, there is stillno uniformity of opinion as to the technique with the lowestrecurrence rate.22

Pterygium Extended Removal Followed by Extended Con-junctival Transplantation (P.E.R.F.E.C.T. for PTERYGIUM)has been reported to have virtually no recurrences in a seriesof primary and recurrent pterygia removal.23,24 This pro-spective study examines the recurrence rate and complica-tion rate in the largest single-surgeon, single-technique se-ries in the literature.

Methods

PatientsThis research was conducted under Human Research Ethics Com-mittee approval and conformed to the tenets of the Declaration ofHelsinki. All patients in whom either a primary or recurrentpterygium was to be removed by the author between August 2001and September 2009 were entered into a prospective trial ofsurgery using pterygium extended removal followed by extendedconjunctival transplant examining specifically the endpoints ofrecurrence rates and complication rates.

All patients were referred to the author by general practitioners,optometrists, or other ophthalmologists for evaluation and possiblesurgery for primary or recurrent pterygia. The most commonindication for surgery was an absolute size of �3 mm onto thecornea, that is, half way to the visual axis and where further growthwas likely to perturb vision. The next most common indication wassymptoms of irritation and redness not alleviated by lubricants orrequiring �1 drop of vasoconstrictor per day for �2 years. Avariety of over-the-counter, nonprescription drops incorporatingphenylephrine or antihistamines are frequently used in Australiaby patients with pterygium to alleviate the symptoms of rednessand irritation. After this, cosmetic concerns, actual visual loss,documented growth, restriction of movement, and unusual mor-phology were other reasons to recommend excision of the ptery-gium. All patients, even those with irritative symptoms only, hadan established pterygium.

Recurrence was defined as any new fibrovascular tissue cross-ing the limbus.

Surgery

The surgery for both primary and recurrent pterygia was essen-tially the same, but important distinguishing details are noted at theend of this summary description of the technique. Complete de-scription of the technique has been published.23 Almost all sur-geries were performed under peribulbar anesthesia apart from asmall number requiring general anesthesia because of age orsymptoms such as claustrophobia.

2205© 2012 by the American Academy of Ophthalmology ISSN 0161-6420/12/$–see front matterPublished by Elsevier Inc. http://dx.doi.org/10.1016/j.ophtha.2012.06.021

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Stage 1. The Tenon’s and conjunctival components of thepterygium were transected at the limbus after marking the limbaltissue with a pen. The pterygium was stripped from the limbustoward the central cornea. Then the Tenon’s layer, almost to thesuperior and inferior recti and back to the caruncle, was isolated byundermining between Tenon’s and conjunctiva, and Tenon’s andsclera. After identifying and protecting the medial rectus insertion,Tenon’s was excised by a hand-over-hand maneuver. Suturesunder the medial rectus and the lateral rectus provided traction andexposure. The semilunar fold was excised leaving an absolutelybare sclera usually measuring about 14�14 mm with only themedial rectus remaining in this area.

Stage 2. The eye was rotated downward using the medial andlateral rectus sutures and an appropriate sized quadrilateral graftoutlined with a marking pen. Approximately 2 ml of balanced saltsolution was injected just under the conjunctiva to raise this layeraway from Tenon’s. The conjunctiva was dissected off the under-lying Tenon’s capsule in an attempt to maintain a pristine Tenon’ssurface with an almost transparent conjunctival graft with noadherent Tenon’s and minimal bleeding. Care was taken to leave1–2 mm of limbal conjunctiva.

Stage 3. The graft was sutured with 2 interrupted 9-0 polyg-lactin 910 sutures to the sclera and the free conjunctival edges nearthe cornea, recessing the graft back about 1 mm from the limbus.The 2 posterior corners of the graft were sutured into superficialsclera about 12–15 mm from the limbus above and below themedial rectus and then the superior and inferior edges sutured intosclera and the free conjunctival edges with a further 3 interruptedsutures, and to the paracaruncular edge sutured with a runningsuture.

Recurrent Pterygia. Although the same technique was used asdescribed, the scarring inherent in these cases made the identifi-cation of the medial rectus insertion problematic with an increasedrisk of medial rectus damage and frequently twenty minutes mightbe required to correctly locate and protect the insertion. Theinsertion at times seem to be drawn to within 2–3 mm of thelimbus requiring early identification otherwise inadvertent damagemay occur, and after multiple previous removals, the muscle maybe encased in a thickened fascia with restriction on forced duction.In these cases the fascia was removed. The orbital fat may be seento be drawn forward into the operative area and over the sclerabefore any Tenon’s resection is undertaken and during the proce-dure without any undue traction on Tenon’s membrane, and rarelysome excision of orbital fat may be required although generally itcould be reposited into a more posterior position by the graft/scleral sutures.

Recurrent Pterygia with Loss of Fornices. Surgery was un-dertaken as above, but every attempt to preserve all conjunctivaltissue was essential if the fornices are to be reformed without theuse of additional grafts or amniotic membrane. This may mean notexcising any conjunctiva from the pterygium head, but ratherrecessing the pterygium head back toward the caruncle, or har-vesting the conjunctiva from the pterygium head for later re-construction, not removing the semilunar fold, harvesting alarger superior graft, and occasionally also harvesting inferiorconjunctiva. The free edge of the recessed existing conjunctivais sutured firmly to sclera just short of the fornix, therebyrecreating the fornix and the additional graft tissue covering theresultant bare sclera.

Temporal Pterygia. These were removed in exactly the samemanner as for nasal pterygia, except that the temporal free edge ofconjunctiva is only trimmed slightly, maintaining as much con-junctiva as possible, and the surgery is performed from the head ofthe operating table.

Monocular Nasal and Temporal Pterygia. The largest ptery-gium is removed first and then the remaining pterygium is re-moved 6–12 months later, harvesting the graft from the samesuperior area both times.

During these thousand removals, the graft size has been de-creased slightly from approximately 15 to 13 mm from the limbusto the sutured paracaruncular edge, whereas the width remainsunchanged, but no other changes have been made.

Patients were seen on postoperative day 1, at month 1, months3–4, and then year 1 after the surgery. Prednisolone acetate 1%was used second hourly for 3 weeks during normal waking hoursand then 4 times a day for a further 6 weeks, and chloramphenicol0.5% drops used 4 times a day for 1 week.

Results

A thousand consecutive pterygium surgeries were included intothis study, and where more than 1 pterygium was removed from apatient, these were considered as separate entries. These includethe previously reported 250 primary pterygium removals23 and the111 recurrent pterygium removals.24 There were a total of 806primary pterygium removals and 194 recurrent pterygium remov-als. The biographical details of the population are listed in Table 1.

Nine hundred ninety-two of the pterygium surgeries were fol-lowed for �1 year with a loss to follow-up of 0.8%. Three of these8 were seen only immediately after the surgery and 2 patients diedbefore the completed follow-up of 1 year. The mean follow-up was616�523 days (range, 1–3495). Table 2 details the completenessof follow-up. Distribution of the number of previous removals inthe 194 recurrent pterygia is outlined in Table 3.

Table 1. Pterygium Details

Details Results

Primary pterygium, n (%) 806 (80.6%)Recurrent pterygium, n (%) 194 (19.4%)Male:female, n (%) 656:344 (65.6%:34.4%)Average age, yrs (range) 50 (14–88)Follow-up, days (range) 616�523 (1–3495)Vertical size of pterygium, mm (range)* 8.7�2.0 (4–15)Horizontal size of pterygium, mm (range)† 3.7�0.89 (0.5–7)Size of defect (horizontal), mm (range)‡ 13.7�1.82 (4.5–17)Size of defect (vertical), mm (range)§ 12.8�1.9 (5–20)

*Chord length at limbus.†From limbus to apex of pterygium.‡From limbus to paracaruncular suture line.§From inferior to superior suture line measured halfway from limbus toparacaruncular suture line.

Table 2. Follow-up

Follow-up Period Number of Surgeries

0–6 months 57–12 months 31–2 years 7692–3 years 1253–4 years 244–5 years 215–6 years 126–7 years 147–8 years 128–9 years 10�9 years 5

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There was only 1 recurrence in this series resulting in a recur-rence rate of 0.1% (95% confidence intervals [Fischer exact] of0.003%–0.56%), with this patient having a further removal at 8months after the first unsuccessful surgery and remaining free ofpterygium for a further 3 years of follow-up.

Further surgery was required in another 6 patients for reasonslisted in Table 4. Special note should be made of 3 patients inwhom the graft remained unduly inflamed, but with no sign ofrecurrence, and these were replaced for cosmetic reasons at ap-proximately 6 months after initial surgery with a good final cos-metic result and no recurrences.

Other complications, which resolved without the need for fur-ther surgery, included 3 granulomas, 1 inclusion cyst, and 3vascularized corneas after dellen, and 5 patients had slight diplopiain extreme gaze, which did not bother them. One patient, in whomthe diagnosis of concomitant corneal anesthesia was not noted onpreoperative examination, developed a persistent epithelial defect,which was resistant to multiple medical and surgical therapies witha subsequent corneal infection, which caused a corneal scar andreduced vision by 4 Snellen lines. This was the only patient withany visual loss in the series, attributable to the surgery.

Two patients had unrelated ocular events causing visual loss, 1with a severe traumatic corneoscleral laceration and another withherpes zoster ophthalmicus scleritis.

It is this author’s impression that patients had moderate pain for1–2 days controlled with oral analgesia and some diplopia for afew days to 1 week.

It is interesting to note that re-epithelialization of the baresclera in front of the graft, the limbus, and the corneal epithelialdefect occurred from the corneal epithelium and not from the graftand was complete usually by 3–4 days. Re-epithelialization of thedonor site was complete in 10–14 days with remodeling to anormal-appearing conjunctiva in most cases within 6 months.

Discussion

Pterygium removal has always been associated with a vari-able recurrence rate with most scientific reports describingexisting or new techniques that purport to reduce the rate atwhich the pterygium returns.2–21 There seems to be a con-sensus that simply excising the pterygium and leaving baresclera or simply closing the resultant conjunctival defectresults in a recurrence rate of up to 82%.2,3 If these findingsare replicated by other surgeons, then it would be reasonableto suggest that this method should no longer be used. Theadvantage of these outdated methods was simplicity andspeed, which are also the principal advantages of the meth-ods that have generally replaced these, namely, bare scleratechnique with adjunctive radiotherapy4,5 or cytotoxicagents,6–12 both of which reduce the unacceptable recur-rence rate of bare scleral closure, to �15%. However,adjunctive radiotherapy has been demonstrated to result in a

high rate of scleral thinning or necrosis, which is usuallyseen only after 10–20 years of postoperative follow-up.4

This complication leaves the eye at risk of endophthalmitis,which has been reported in the literature.4 Complications ofmitomycin have also been reported in the literature, with notonly late-onset scleral necrosis,25 similar to that seen afterthe administration of radiotherapy, but also acute scleritis,26

both of which may result in loss of all vision. It is difficultto rationalize the use of these agents for a disease that canbe successfully treated with extremely low complicationrates with a conjunctival autograft, when the reason for theiruse is speed and simplicity only.

The other commonly used method is amniotic grafting,which results in a wide range of recurrence rates, from 5%to 64%.12–21 Researchers who promote this method havefound it necessary to combine the amniotic membrane graftwith mitomycin, extensive tenonectomy, and a variablenumber of postoperative injections of steroids to achieve thelowest recurrence rate reported for amniotic membrane.14,19

It would seem reasonable to postulate that the lowered recur-rence rate may be because of the mitomycin or the tenonec-tomy and not the amniotic membrane. The same researchershave been unable to provide consistent cosmetic results andreport a very high rate of granuloma formation.13,14,19

In the 1980s, conjunctival grafting gained favor as asurgical method with a low recurrence rate and few com-plications, although it required more surgical finesse andoperative time. In general this technique results in a recur-rence rate of between 5% and 15%.8,13,16–18,20 It was thismethod that was the starting point for the development ofthis new technique of P.E.R.F.E.C.T. for PTERYGIUM23,24

and over a period of approximately 10 years evolved intothe technique used in this series. The basic component ofthis technique, which is thought to reduce recurrence, hasbeen reported in the literature �40 years ago (extensivetenonectomy)27 and this has been combined with a muchlarger graft than is normally used in conjunctival autograft-ing to provide this exceptionally low recurrence rate.

The other aspect of this surgery that is different, at leastin association with a conjunctival autograft, is the excisionof the semilunar fold, which is designed to hide the nasalscar and provide a superior cosmetic result. It is worthnoting that direct conjunctival to conjunctival edge apposi-tion such as this paracaruncular suture line, however care-fully it is undertaken, always results in some scarring, andsuturing a conjunctival edge to the sclera, such as that at thesuperior and inferior edge of the graft, can oftentimes leavevirtually no perceptible scar.

There are a number of other modifications associatedwith this surgery that are worth highlighting and are prin-

Table 4. Requirement for Further Surgery

Reason for Further Surgery Number of Patients

Hyperemic grafts 3Exotropia 1Granuloma 1Inclusion cyst 1Recurrence 1

Table 3. Number of Previous Removals

No. of Previous Removals No. of Eyes

1 1462 273 144 4

�4 3

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cipally designed to enhance the final cosmetic appearancethat, in a previous study,28 was such that graders could notdifferentiate normal eyes from eyes that had undergone thisprocedure, and resulted in almost 95% of eyes having anacceptable cosmetic appearance. These include the largegraft that is, at an average square area of 176 mm2, about 7times the size of an average conjunctival autograft measur-ing 6�4 mm. The careful dissection of the graft at the donorsite leaves the underlying Tenon’s layer as pristine as pos-sible and enables a subsequent harvesting of another graft.This also suggests that this graft retrieval is unlikely toimpede subsequent glaucoma drainage procedures.

Leaving a fringe of 1–2 mm of limbal conjunctiva supe-riorly guarantees that this area will not be made limballydeficient by this surgery and reaffirms that limbal stem celltransplantation is unnecessary and potentially dangerous inthe long term. Recessing the graft 1–2 mm from the limbusat the pterygium site permits re-epithelialization of any baresclera by corneal epithelium, rather than from the graft, andresults in the long-term appearance of a normal limbus,except after multiple pterygium removals where the limbusmay often be ragged and indistinct. Because of the almostuniversal diplopia from medial rectus underaction that hasaffected patients for a few days to up to 2 weeks, somemodifications have been made to the surgery since thisseries. The graft has not been sutured back to the sclera asfar posteriorly as previously, so that now the limbus toposterior corner is usually at 13 mm rather than the previous14–15 mm, and specific attention is paid to making theanastomosis of the paracaruncular suture line quite lax overthe belly of the medial rectus, thereby avoiding creating anew fulcrum of movement for the muscle, which wasthought to be the cause of the longer lasting transientdiplopia early in the series. Otherwise, the operative proce-dure has not changed over the course of these 1000 surger-ies. The intensive postoperative steroid administration isdesigned to reduce postoperative inflammation as rapidly aspossible, although whether 9 weeks of treatment is requiredremains to be determined. Transient diplopia is now notuniversal and usually resolves within 3–5 days and probablyis a result of the manipulation of the muscle by the suture toobtain adequate exposure.

The complications reported in this series are lower thanmost other series apart from the residual diplopia. Granu-loma formation using other methods such as amniotic mem-brane grafting, can result in rates of up to 20%14 comparedwith 1 in 250 in this series. The replacement of 3 grafts forcosmetic reasons is probably a result of grafts to which toomuch Tenon’s remained attached and highlights the needfor very transparent, thin grafts. The most sensitive indica-tor that the graft is thin enough is that there should be noneed for cautery in the donor bed because Tenon’s and thevasculature will not have been violated. This also meansthat small button holes in the graft are not infrequent butthey do not cause any problems.

Only 1 patient lost vision from a corneal infection andthis can be explained by the failure of the author to appre-ciate that the patient also had a totally anesthetic cornea.

This study represents the largest single-surgeon, single-technique series reported in the literature. There is also an

unparalleled follow-up of 1 year in almost all the patients,which is required to reliably identify a recurrence.29 The onlyobserved recurrence occurred in a primary pterygium removalwith no recurrences in 194 recurrent pterygia. These patientsreflect, for the most part, tertiary referrals and as such are notpreselected for small, inactive pterygia as can be seen by theirmean size of 3.7 mm, so that these results are not obtainedbecause of the “trivial” nature of these pterygia. In fact, a resultof no recurrence in 194 recurrent pterygia which had a sumtotal of 273 previous removals showcases the success of thisprocedure as most other series report recurrence rates from5%8,13,19 to �50%.17

Although this series has no control group, the results ofa near-zero recurrence rate in the preparatory and develop-mental pilot series of �200 surgeries made it difficult forthe author to ethically undertake a subsequent randomized,controlled trial of this new method against the “gold stan-dard” method of conjunctival autografting where the aver-age recurrence rate is almost 10 times that of this newmethod. The principal limitation in this series is that it is asingle surgeon’s experience, with results evaluated in anunmasked fashion, which is yet to be replicated by othersurgeons and reported in the literature.

This operative technique may not be practical in demo-graphic situations where only limited resources, time, andskills are available.

P.E.R.F.E.C.T. for PTERYGIUM provides an unprece-dented result with a recurrence rate close to zero and anacceptable complication rate. Despite the acronym, thisprocedure is far from perfect and hopefully over time willevolve into a procedure that is easier to perform and havingfewer complications. For the first time, there seems to be 1operative technique that warrants ophthalmologists’ accep-tance, especially if the results reported here are replicated byother surgeons. The potentially sight-threatening complica-tions of radiotherapy4 and cytotoxic drugs25,26 make thesemethods of removal problematic at the best, especially whentheir recurrence rates do not match this series. Because thissurgery for symblephara release and forniceal reconstruc-tion in combination with the pterygium removal could beachieved in all of the 194 recurrent pterygia, amnioticmembrane transplantation13–21 is at the very least unneces-sary and does not seem to offer a superior cosmetic resultand has a much higher recurrence rate and a much higherrate of granuloma formation. It is also quite clear as a resultof this procedure that the removal of limbal stem cells30–33

with the graft and transplantation of these limbal stem cellsare unnecessary to achieve a low recurrence rate and shouldbe discarded as a method of grafting for pterygium to avoidlater superior limbal deficiency.

I undertook �200 surgeries to develop the surgery to theprocedure described herein. During this series of develop-mental surgeries, a variety of variables changed, such as thesize of the graft, the amount of Tenon’s excised, and thesuturing technique. Although these surgeries are not in-cluded in this series of standardized surgeries, the recur-rence rate and complication rates were not different fromthe rates described in this series of 1000.

Each of the 3 components of the operative techniquerequires meticulous attention to detail and the method is

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unforgiving if not performed fastidiously and error free, notunlike the escalation of problems that may occur duringphacoemulsification if the capsulorhexis is imperfectlycompleted. Therefore, there is a steep learning curve for thisprocedure and it should be undertaken only on primarypterygia until it is mastered. Using this procedure on mul-tiply recurrent pterygia provides a challenge that is equal toundertaking a surgeon’s initial phacoemulsification on asubluxed brunescent cataract. It also takes up to an hour forprimary pterygium surgery, and it requires a surgical assis-tant and a peribulbar or general anesthetic, and the patientmust be prepared for some pain and for transient diplopiaafter surgery.

Although the current literature seems to emphasize speedand simplicity for pterygium surgery,34–39 in most of thesepublications this is given inordinate weight over the recur-rence rate and complications. Attention should once morebe turned to the principal complications of pterygium sur-gery, which are recurrence and a poor cosmetic result, andoperative techniques selected on the basis of success inthese measures rather than on how quickly and simply thesurgery can be undertaken. Patients are not interested inhow long the surgeon takes in completing the pterygiumsurgery or if it takes consummate skill. The patients, forwhom we remain advocates, are only interested in theoutcomes of nonrecurrence, low complication rates, and thecosmetic appearance.

References

1. Hirschberg J. The History of Ophthalmology. vol. 1. Antiq-uity. Blodi FC, trans. Bonn, Germany: Wayenborgh; 1982:47,57,87,190,203,239,288,345.

2. Tan DT, Chee SP, Dear KB, Lim AS. Effect of pterygiummorphology on pterygium recurrence in a controlled trialcomparing conjunctival autografting with bare sclera excision.Arch Ophthalmol 1997;115:1235–40.

3. Sánchez-Thorin JC, Rocha G, Yelin JB. Meta-analysis on therecurrence rates after bare sclera resection with and withoutmitomycin C use and conjunctival autograft placement insurgery for primary pterygium. Br J Ophthalmol 1998;82:661–5.

4. MacKenzie FD, Hirst LW, Kynaston B, Bain C. Recurrencerate and complications after beta irradiation for pterygia. Oph-thalmology 1991;98:1776–80.

5. Mourits MP, Wyrdeman HK, Jurgenliemk-Schulz IM, BidlotE. Favorable long-term results of primary pterygium removalby bare sclera extirpation followed by a single 90Strontiumapplication. Eur J Ophthalmol 2008;18:327–31.

6. Yanyali AC, Talu H, Alp BN, et al. Intraoperative mitomycinC in the treatment of pterygium. Cornea 2000;19:471–3.

7. Cheng HC, Tseng SH, Kao PL, Chen FK. Low-dose intraop-erative mitomycin C as chemoadjuvant for pterygium surgery.Cornea 2001;20:24–9.

8. Mutlu FM, Sobaci G, Tatar T, Yildirim E. A comparativestudy of recurrent pterygium surgery: limbal conjunctival au-tograft transplantation versus mitomycin C with conjunctivalflap. Ophthalmology 1999;106:817–21.

9. Young AL, Leung GY, Wong AK, et al. A randomised trialcomparing 0.02% mitomycin C and limbal conjunctival au-tograft after excision of primary pterygium. Br J Ophthalmol2004;88:995–7.

10. Avisar R, Weinberger D. Pterygium surgery with mitomycinC: how much sclera should be left bare? Cornea 2003;22:721–5.

11. Young AL, Tam PM, Leung GY, et al. Prospective study onthe safety and efficacy of combined conjunctival rotationalautograft with intraoperative 0.02% mitomycin C in primarypterygium excision. Cornea 2009;28:166–9.

12. Ma DH, See LC, Hwang YS, Wang SF. Comparison ofamniotic membrane graft alone or combined with intraopera-tive mitomycin C to prevent recurrence after excision ofrecurrent pterygia. Cornea 2005;24:141–50.

13. Prabhasawat P, Barton K, Burkett G, Tseng SC. Comparisonof conjunctival autografts, amniotic membrane grafts, andprimary closure for pterygium excision. Ophthalmology 1997;104:974–85.

14. Kheirkhah A, Casas V, Sheha H, et al. Role of conjunctivalinflammation in surgical outcome after amniotic membranetransplantation with or without fibrin glue for pterygium.Cornea 2008;27:56–63.

15. Essex RW, Snibson GR, Daniell M, Tole DM. Amnioticmembrane grafting in the surgical management of primarypterygium. Clin Experiment Ophthalmol 2004;32:501–4.

16. Li M, Zhu M, Yu Y, et al. Comparison of conjunctivalautograft transplantation and amniotic membrane transplanta-tion for pterygium: a meta-analysis. Graefes Arch Clin ExpOphthalmol 2012;250:375–81.

17. Luanratanakorn P, Ratanapakorn T, Suwan-Apichon O,Chuck RS. Randomised controlled study of conjunctival au-tograft versus amniotic membrane graft in pterygium excision.Br J Ophthalmol 2006;90:1476–80.

18. Tananuvat N, Martin T. The results of amniotic membranetransplantation for primary pterygium compared with conjunc-tival autograft. Cornea 2004;23:458–63.

19. Solomon A, Pires RT, Tseng SC. Amniotic membrane trans-plantation after extensive removal of primary and recurrentpterygia. Ophthalmology 2001;108:449–60.

20. Küçükerdönmez C, Akova YA, Altinörs DD. Comparison ofconjunctival autograft with amniotic membrane transplanta-tion for pterygium surgery: surgical and cosmetic outcome.Cornea 2007;26:407–13.

21. Kucukerdonmez C, Karalezli A, Akova YA, Borazan M.Amniotic membrane transplantation using fibrin glue in ptery-gium surgery: a comparative randomised clinical trial. Eye(Lond) 2010;24:558–66.

22. Hirst LW. The treatment of pterygium. Surv Ophthalmol2003;48:145–80.

23. Hirst LW. Prospective study of primary pterygium surgeryusing pterygium extended removal followed by extended con-junctival transplantation. Ophthalmology 2008;115:1663–72.

24. Hirst LW. Recurrent pterygium surgery using pterygium ex-tended removal followed by extended conjunctival transplant:recurrence rate and cosmesis. Ophthalmology 2009;116:1278–86.

25. Ti SE, Tan DT. Tectonic corneal lamellar grafting for severescleral melting after pterygium surgery. Ophthalmology 2003;110:1126–36.

26. Rubinfeld RS, Pfister RR, Stein RM, et al. Serious complica-tions of topical mitomycin-C after pterygium surgery. Oph-thalmology 1992;99:1647–54.

27. Barraquer JI. Etiology, pathogenesis, and treatment of thepterygium. In: Symposium on Medical and Surgical Diseasesof the Cornea. Transactions of the New Orleans Academy ofOphthalmology (28th: 1979). St. Louis: Mosby; 1980:167–78.

28. Hirst LW. Cosmesis after pterygium extended removal fol-lowed by extended conjunctival transplant as assessed by a

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new, web-based grading system. Ophthalmology 2011;118:1739–46.

29. Hirst LW, Sebban A, Chant D. Pterygium recurrence time.Ophthalmology 1994;101:755–8.

30. Kheirkhah A, Hashemi H, Adelpour M, et al. Randomizedtrial of pterygium surgery with mitomycin C application usingconjunctival autograft versus conjunctival-limbal autograft.Ophthalmology 2012;119:227–32.

31. Soliman Mahdy MA, Bhatia J. Treatment of primarypterygium: role of limbal stem cells and conjunctival autografttransplantation. Eur J Ophthalmol 2009;19:729–32.

32. Ozer A, Yildirim N, Erol N, Yurdakul S. Long-term results ofbare sclera, limbal-conjunctival autograft and amniotic mem-brane graft techniques in primary pterygium excisions. Oph-thalmologica 2009;223:269–73.

33. Ozdamar Y, Mutevelli S, Han U, et al. A comparative study oftissue glue and vicryl suture for closing limbal-conjunctivalautografts and histologic evaluation after pterygium excision.Cornea 2008;27:552–8.

34. Pan HW, Zhong JX, Jing CX. Comparison of fibrin glueversus suture for conjunctival autografting in pterygiumsurgery: a meta-analysis. Ophthalmology 2011;118:1049–54.

35. Caccavale A, Romanazzi F, Imparato M, et al. Ropivacainefor topical anesthesia in pterygium surgery with fibrin glue forconjunctival autograft. Cornea 2010;29:375–6.

36. Karalezli A, Kucukerdonmez C, Akova YA, et al. Fibrin glueversus sutures for conjunctival autografting in pterygiumsurgery: a prospective comparative study. Br J Ophthalmol2008;92:1206–10.

37. Bahar I, Weinberger D, Dan G, Avisar R. Pterygium surgery:fibrin glue versus vicryl sutures for conjunctival closure. Cor-nea 2006;25:1168–72.

38. Marticorena J, Rodríguez-Ares MT, Touriño R, et al. Ptery-gium surgery: conjunctival autograft using a fibrin adhesive.Cornea 2006;25:34–6.

39. Uy H, Reyes JM, Flores JD, Lim-Bon-Siong R. Comparisonof fibrin glue and sutures for attaching conjunctival autograftsafter pterygium excision. Ophthalmology 2005;112:667–71.

Footnotes and Financial Disclosures

Originally received: March 1, 2012.Final revision: June 14, 2012.Accepted: June 14, 2012.Available online: August 11, 2012. Manuscript no. 2012-301.1 Queensland Eye Institute, Brisbane, Australia.2 University of Queensland, Brisbane, Australia.3 The Australian Pterygium Centre, Brisbane, Australia.

Presented in part at: the World Cornea Congress, April 2010.

Supported in part by the Prevent Blindness Foundation, Brisbane, Austra-lia, which had no role in the design or conduct of the research.

Financial Disclosure(s):The author has made the following disclosures:Lawrence Hirst owns the trademark P.E.R.F.E.C.T. for PTERYGIUM.

Correspondence: Lawrence Hirst, MD, MPH. The Australian PterygiumCentre, 232 Oxley Road, Graceville, Australia, 4075. E-mail: [email protected].

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