Konsep Dan Teknik Terkini Dalam Penatalaksanaan PterigiumLeonard PK Angabc Jocelyn LL Chuaac and Donald TH Tanabc

Tujuan UlasanPterigium merupakan suatu gangguan ocular yang bsering ditemui di seluruh dunia Saat ini terdapat suatu keragaman metode pembedahan tetapi sangat sedikit panduan klinis untuk penatalaksanaan yang optimal pada pterigium primer atau rekuren Tujuan ulasan ini adalah untuk menyimpulkan penelitian terkini yang relevan mengenai penatalaksanaan pterigium Temuan TerkiniTujuan utama adalah untuk mengeksisi pterigium dan mencegah kekambuhan Eksisi bare sclera dihubungkan dengan rata ndash rata rekurensi yang tinggi eksisi pterigium sering dikombinasi autograph konjungtiva mitomycin C beta-irradiation atau terapi ajuvan lainnya untuk mengurangi angka kekambuhan Akan tetapi saat ini tidak terdapat konsensus berkenaan dengan penatalaksanaan ideal untuk penyakit ini Perbandingan antara penelitian ndash penelitian ini juga terhambat oleh berbagai definisi pterigium rekuren

KesimpulanArtikel ini mengulas konsep dan teknik terkini yang digunakan untuk penatalaksanaan pterigium Autograft konjungtiva dan penerapan mitomycin C adalah metode yang paling sering digunakan untuk mencegah kekambuhan Penggunaan mitomycin C dan beta-irradiation harus digunakan secara bijaksana karena potensi resiko jangka panjang komplikasi yang mengancam penglihatan Percobaan klinis tambahan harus dilakukan untuk mengevaluasi kemanjuran dan keamanan jangka panjang pada berbagai modalitas penatalaksanaan

Konsep terkini dalam pathogenesis pterigiumSinar UV tipe B dalam radiasi solar telah ditemukan sebagai factor lingkungan paling signifikan dalam pathogenesis pterigium Penetilitan terkini telah mengajukan bahwa p53 dan human papillomavirus kemungkinan juga telibat dalam pathogenesis pterigium Radiasi UV bisa menyebabkan mutasi pada gen seperti gen supresor p53 menyebabkan ekspresi abnormal pada epithelium pterigial Temuan ndash temuan ini menyatakan bahwa pterigium bukan hanya suatu lesi degeneratif tetapi bisa berupa hasil proliferasi sel yang tidak terkontrol Matrix metalloproteinases (MMP) dan tissue inhibitors MMP (TIMP) pada pinggir pterigium lanjut bertanggungjawab untuk inflamasi remodeling jaringan dan angiogenesis yang menunjukkan kekhasan pterigium serta kerusakan lapisan Bowman dan invasi pterigium ke kornea Tseng et al memperkirakan bahwa pterigium mewakili lokalisasi area defisiensi stem cell limbal

Rekurensi PterigiumDefinisi pterigium rekuren berbeda ndash beda di antara penelitian ndash penelitian Kebanyakan dokter spesialis mata mendefinisikan pterikium rekuren sebagai rekurensi corneal yang meliputi pertumbuhan kembali jaringan fibrovaskular mirip pterigium yang melintasi limbus hingga ke kornea fibrovaskular rekuren yang mencapai derajat yang sama pada gangguan corneal seperti lesi awal atau pertumbuhan kembali yang melewati 1mm hingga ke kornea

Penatalaksanaan PterigiumTujuan utama pembedahan adalah untuk mengeksisi pterigium seluruhnya dan untuk mencegah rekurensinya

Eksisi PterigiumPengangkatan pterigium melibatkan eksisi kepala leher dan badan pterigium Badan dan dasar pterigium dibedah dengan gunting konjungtiva sementara kepala dan leher pterigium yang menyerang kornea sering diangkat dengan pisau bedah

An attempt is made to identify the plane of dissection which facilitates removal of the pterygium while keeping the underlying corneal surface smooth Remnant stromal attachments may be smoothed out with the bladeAs the body of the pterygium has no clearly defined margin the extent of surgical excision of the pterygium and subconjunctival fibrovascular tissue varies between reports Our preferred method is to excise the base of the pterygium approximately 4 ndash 6 mm from the limbus as retraction of the surrounding conjunctiva results in enlargement of the surgical defectIf no additional measures are performed pterygium excision alone is commonly referred to as bare sclera excision The recurrence rates for bare sclera excision alone are unacceptably high (ranging from 30 to 80) when compared with other treatment modalities [9 ndash 11] As such bare sclera excision alone is no longer recom- mended for the treatment of pterygium

Prevention of pterygium recurrencePterygium excision is often combined with various adjunctive measures to prevent recurrence of the disease These may be broadly classified as adjunctive medical methods beta-irradiation and surgical methods

Medical methodsIntraoperative and postoperative mitomycin C remain the most commonly used medical adjunctive therapies for the prevention of pterygium recurrence Several other medical alternatives such as 5-fluorouracil and daunorubicin have also been tried

Mitomycin C treatmentMitomycin C treatment has been shown to be effective in preventing recurrence for primary and recurrent pterygium [9 ndash 15] The recurrence rates associated with mitomycin C treatment are significantly lower compared with bare sclera excision Essentially two forms of mitomycin C application are currently used ndash the intraoperative appli- cation of surgical sponges soaked in mitomycin C solution applied directly to the scleral bed after pterygium excision and the postoperative use of topical mitomycin C as eyedrops [9 ndash 16] Studies [111314] have shown that the recurrence rates associated with intraoperative and post- operative mitomycin C use are not significantly different

Intraoperative mitomycin C treatmentThe concentration of intraoperative mitomycin C application used in most of the studies range from 001 to 004 with 002 applied for 3 min being the commonest dosage used [91012 ndash 14] The reported recurrence rates associated with intraoperative mitomycin C use range from 3 to 379 In the study by Lam et al [10] intraoperative mitomycin C was associated with significantly reduced recurrence rates compared with cases where no adjunctive treatment was used It was further shown that application of 002 and 004 intraoperative mitomycin C for 3 min was less effective than application for 5 min Increasing the duration and concentration of mitomycin C however may lower the risk of recurrence but may lead to a higher risk of complicationsPostoperative mitomycin C treatmentPostoperative mitomycin C eyedrops have also been shown to be effective with 002 being the commonest concen- tration used (concentrations used range from 0005 to 004) [1113ndash15] These were generally prescribed at a frequency of four times a day with the duration of application varying from 5 to 14 days (mean duration of application 10 days) The reported recurrence rates range from 0 to 38 [1113 ndash 15] Cardillo et al [13] compared the use of mitomycin C postoperatively for 7 and 14 days and showed that there was no significant difference in the final outcome suggesting that the shorter period may be equally efficacious and may also reduce the risk of complicationsAlthough mitomycin C has been shown to be an effective treatment for pterygium its use has been associated with serious sight-threatening complications which may pre- sent many years after surgery such as scleral necrosis infectious scleritis perforation and endophthalmitis [17] Patients should be counseled regarding the potential for rare but serious long-term sight-threatening complications related to its use

Beta-irradiationVarious regimes of beta-irradiation have been used to treat pterygium including a single application of beta-irradiation several applications over consecutive days in the immediate postoperative period or several applications periodically over a 2-week period [22 ndash 24] Although this modality of treatment has been used for decades few prospective studies have been described The use of post- operative single dose irradiation was demonstrated to be similarly efficacious as consecutive days of postoperative application Chayakul [22] showed that beta-irradiation was associated with a significantly higher recurrence rate than postoperative mitomycin C eyedropsBeta-irradiation is a less popular procedure because of the inconvenience of arranging its treatment and the long- term risk of serious sight-threatening complications such as scleral necrosis infectious scleritis corneal perforation and endophthalmitis [25] Patients should therefore be counseled regarding the potential long-term complications arising from its use

Surgical methodsThe surgical options available include the use of conjunc- tival autograft limbal and limbal ndash conjunctival transplant conjunctival flap and conjunctival rotation autograft sur- gery amniotic membrane transplant cultivated conjunctival transplant lamellar keratoplasty and use of fibrin glueConjunctival autograftsConjunctival autograft surgery is generally regarded as the procedure of choice for the treatment of primary and recurrent pterygium because of its efficacy and long- term safety [26 ndash 32] A free conjunctival graft is harvested from the superior bulbar conjunctiva and is sutured in place over the bare scleral defect [9 ndash 111314] Variations in conjunctival autograft surgery include the use of narrow-strip conjunctival autograft limbal-conjunctival autografts limbal epithelial autografts conjunctival flaps or conjunctival rotation autografts [2933 ndash 39] Conjunctival autografts are associated with recurrence rates (ranging from 2 to 39) that are comparable to that of mitomycin C and beta-irradiation without the attendant risk of sight-threatening complications associated with mitomycin C or beta-irradiation usage [2728] Sharma et al [28] demonstrated that there was no statistically significant difference in the recurrence rates between conjunctival autografting and mitomycin C use Compared with the use of mitomycin C and beta-irradiation conjunctival autografting is more technically demanding and more time-consuming to perform Inter-surgeon variability in terms of surgical technique skill and experience contributes to the wide variation in recurrence rates that have been reported

Limbal and limbal ndash conjunctival transplantationIt has been suggested that including limbal stem cells in the conjunctival autograft (limbal ndash conjunctival graft) may act as a barrier to conjunctival cells migrating onto the corneal surface and help prevent recurrence The limbal ndash conjunctival graft includes approximately 05 mm of the limbus and peripheral cornea The corneal limbal side of the graft is sutured in place with interrupted 100 nylon sutures and the conjunctival side is sutured with 100 absorbable suturesThe recurrence rates after limbal ndash conjunctival autograft surgery (ranging from 0 to 15) are similar to that of conjunctival autograft surgery [2933ndash35] while some authors suggest that limbal ndash conjunctival autografts are more effective than conjunctival autografts for recurrent pterygium [34] Oguz et al [42] demonstrated an overall recurrence rate of 952 with limbal conjunctival mini- autografting performed in 63 eyes Young et al [35] prospectively compared mitomycin C and limbal ndash conjunctival autograft surgery in preventing pterygial recurrence and showed that the mitomycin C group was associated with a higher recurrence rate (159) compared with the limbal ndash conjunctival autograft group (19) A major drawback for limbal ndash conjunctival auto- graft transplantation is that it is technically more demanding and time-consuming to perform To date however it should be noted that no conclusive evidence regarding the superiority of limbal ndash conjunctival auto- grafts over conventional conjunctival autografts exists and the added risk of limbal damage at the donor site deserves consideration

Conjunctival flap and conjunctival rotation autograft surgery

Two reports [3637] have described the use of sliding conjunctival flaps harvested from the inferior or the superior bulbar conjunctiva to close the scleral defect with reported recurrence rates ranging from 1 to 5 Conjunctival rotation autografting involves removal of the pterygium and reversal of the removed conjunctiva so that the most nasal aspect is sutured at the limbus and vice versa [3839] This is a useful technique for cases in which it is not possible or desirable to use the superior conjunctiva as a donor source such as with excision of extensive pterygium which leaves insufficient conjunc- tival tissue for the autograft

Amniotic membrane transplantationAmniotic membrane transplantation has recently been proposed as a treatment option [43 ndash 46] Ma et al [44] compared the excision of recurrent pterygia followed by amniotic membrane alone and amniotic membrane graft combined with intraoperative mitomycin C and found no significant difference in the recurrence rates between the two groups Amniotic membrane possesses antiscarring antiangiogenic and anti-inflammatory properties which may be useful for treating pterygium Besides the con- ventional epithelized cryopreserved human amniotic membrane the efficacy of membranes that are alterna- tively prepared such as the de-epithelized [47] or freeze- dried sterilized ones [48] have also been studied Delayed vascularization of amniotic membrane demonstrated with an anterior segment indocyanine green angiography is thought to be responsible for the delayed recurrence after pterygium surgery [49] An additional advantage is that it removes the need for harvesting large autografts thereby minimizing iatrogenic injury to the rest of the conjunctiva surface Three prospective studies [44455011130901113090] have compared amniotic membrane transplantation with other conventional treatment modalities In a randomized prospective study by Tananuvat et al [45] amniotic membrane transplant is associated with an unacceptably high recurrence rate compared with conjunctival auto- graft This result is also supported by Luanratanakorn et al [5011130901113090]

Cultivated conjunctival transplantationA novel method of closing the surgical defect involves the use of an ex-vivo expanded conjunctival epithelial sheet on an amniotic membrane substrate Although the preliminary study [51] demonstrated no significant difference in the recurrence rate compared with denuded amniotic mem- brane transplantation operated eyes achieved almost im- mediate reepithelialization of the ocular surface reduced postoperative inflammation and faster ocular rehabilita- tion This procedure may be particularly useful for closing large surgical defects following excision of extensive pterygium

Lamellar keratoplastyLamellar keratoplasty has been used to act as a barrier against pterygium recurrence and to replace thinned and scared corneal tissue after pterygium excision [52] It does not appear to offer any special advantage in preventing pterygium recurrence with recurrence rates ranging from 6 to 100 [52] As such this is not a favored procedure for treating primary pterygium It has mostly been used to treat recurrent pterygium to restore corneal thickness in thinned scarred corneas The main limitations are the need for donor corneal tissue with the attendant risks of graft rejection and transmission of infection as well as the increased complexity of the procedure

Fibrin glueFibrin glue (or Tisseel) has been used as an alternative to sutures for securing conjunctival grafts [53 ndash 56] The use of fibrin glue shortens operating times significantly and is associated with less postoperative discomfort Fibrin glue also provides a more even attachment of the graft to the scleral bed Most cases performed with fibrin adhesive healed with minimal inflammation and there were only sporadic cases of graft dislodgment or loss Bahar et al [57] showed that the use of fibrin glue was associated with a significantly shorter operative time and greater patient acceptance compared with using sutures The major concerns that need to be addressed include the cost of Tisseel and the potential risk of transmitted infection Further studies are required to evaluate the long-term efficacy of fibrin glue in reducing recurrences

Complications of treatment

Operative complications related to pterygium excision are uncommon and are generally related to the surgical tech- nique This includes excessive bleeding button hole of the conjunctiva graft perforation of the globe with the suture needle and injury to the medial rectus muscle The main postoperative complication is recurrence Other complications such as pyogenic granuloma dellen persistent epithelial defects are not uncommon but these may be easily treated with no significant long-term sequelaeOf greater concern is the potentially serious sight-threat- ening complications that have been associated with the use of adjunctive mitomycin C and beta-irradiation such as scleral necrosis infectious scleritis severe secondary glau- coma iritis cataract corneal edema corneal perforationand endophthalmitis [1725] Complications arising from the use of beta irradiation have been reported in up to 13 of patients with latency periods of up to 1451113090 25 years [25] These serious complications represent cases in which surgery was performed some years back when relative therapeutic doses of both mitomycin C and beta irradiation were higher and it remains to be seen if the newer treatments with reduced therapeutic dosages are associated with similar complications

ConclusionPterygium excision combined with mitomycin C or conjunctival autograft surgery are currently the main methods used for treating pterygium As the clinical trials describing various surgical techniques often have differing method- ology and sometimes conflicting results additional large randomized clinical trials need to be performed to evaluate the relative efficacy and long-term safety of the various treatment options Issues that need to be addressed include developing a standardized method of grading pterygium and its recurrence as well as identifying risk factors for pterygium recurrence

An attempt is made to identify the plane of dissection which facilitates removal of the pterygium while keeping the underlying corneal surface smooth Remnant stromal attachments may be smoothed out with the bladeAs the body of the pterygium has no clearly defined margin the extent of surgical excision of the pterygium and subconjunctival fibrovascular tissue varies between reports Our preferred method is to excise the base of the pterygium approximately 4 ndash 6 mm from the limbus as retraction of the surrounding conjunctiva results in enlargement of the surgical defectIf no additional measures are performed pterygium excision alone is commonly referred to as bare sclera excision The recurrence rates for bare sclera excision alone are unacceptably high (ranging from 30 to 80) when compared with other treatment modalities [9 ndash 11] As such bare sclera excision alone is no longer recom- mended for the treatment of pterygium

Prevention of pterygium recurrencePterygium excision is often combined with various adjunctive measures to prevent recurrence of the disease These may be broadly classified as adjunctive medical methods beta-irradiation and surgical methods

Medical methodsIntraoperative and postoperative mitomycin C remain the most commonly used medical adjunctive therapies for the prevention of pterygium recurrence Several other medical alternatives such as 5-fluorouracil and daunorubicin have also been tried

Mitomycin C treatmentMitomycin C treatment has been shown to be effective in preventing recurrence for primary and recurrent pterygium [9 ndash 15] The recurrence rates associated with mitomycin C treatment are significantly lower compared with bare sclera excision Essentially two forms of mitomycin C application are currently used ndash the intraoperative appli- cation of surgical sponges soaked in mitomycin C solution applied directly to the scleral bed after pterygium excision and the postoperative use of topical mitomycin C as eyedrops [9 ndash 16] Studies [111314] have shown that the recurrence rates associated with intraoperative and post- operative mitomycin C use are not significantly different

Intraoperative mitomycin C treatmentThe concentration of intraoperative mitomycin C application used in most of the studies range from 001 to 004 with 002 applied for 3 min being the commonest dosage used [91012 ndash 14] The reported recurrence rates associated with intraoperative mitomycin C use range from 3 to 379 In the study by Lam et al [10] intraoperative mitomycin C was associated with significantly reduced recurrence rates compared with cases where no adjunctive treatment was used It was further shown that application of 002 and 004 intraoperative mitomycin C for 3 min was less effective than application for 5 min Increasing the duration and concentration of mitomycin C however may lower the risk of recurrence but may lead to a higher risk of complicationsPostoperative mitomycin C treatmentPostoperative mitomycin C eyedrops have also been shown to be effective with 002 being the commonest concen- tration used (concentrations used range from 0005 to 004) [1113ndash15] These were generally prescribed at a frequency of four times a day with the duration of application varying from 5 to 14 days (mean duration of application 10 days) The reported recurrence rates range from 0 to 38 [1113 ndash 15] Cardillo et al [13] compared the use of mitomycin C postoperatively for 7 and 14 days and showed that there was no significant difference in the final outcome suggesting that the shorter period may be equally efficacious and may also reduce the risk of complicationsAlthough mitomycin C has been shown to be an effective treatment for pterygium its use has been associated with serious sight-threatening complications which may pre- sent many years after surgery such as scleral necrosis infectious scleritis perforation and endophthalmitis [17] Patients should be counseled regarding the potential for rare but serious long-term sight-threatening complications related to its use

Beta-irradiationVarious regimes of beta-irradiation have been used to treat pterygium including a single application of beta-irradiation several applications over consecutive days in the immediate postoperative period or several applications periodically over a 2-week period [22 ndash 24] Although this modality of treatment has been used for decades few prospective studies have been described The use of post- operative single dose irradiation was demonstrated to be similarly efficacious as consecutive days of postoperative application Chayakul [22] showed that beta-irradiation was associated with a significantly higher recurrence rate than postoperative mitomycin C eyedropsBeta-irradiation is a less popular procedure because of the inconvenience of arranging its treatment and the long- term risk of serious sight-threatening complications such as scleral necrosis infectious scleritis corneal perforation and endophthalmitis [25] Patients should therefore be counseled regarding the potential long-term complications arising from its use

Surgical methodsThe surgical options available include the use of conjunc- tival autograft limbal and limbal ndash conjunctival transplant conjunctival flap and conjunctival rotation autograft sur- gery amniotic membrane transplant cultivated conjunctival transplant lamellar keratoplasty and use of fibrin glueConjunctival autograftsConjunctival autograft surgery is generally regarded as the procedure of choice for the treatment of primary and recurrent pterygium because of its efficacy and long- term safety [26 ndash 32] A free conjunctival graft is harvested from the superior bulbar conjunctiva and is sutured in place over the bare scleral defect [9 ndash 111314] Variations in conjunctival autograft surgery include the use of narrow-strip conjunctival autograft limbal-conjunctival autografts limbal epithelial autografts conjunctival flaps or conjunctival rotation autografts [2933 ndash 39] Conjunctival autografts are associated with recurrence rates (ranging from 2 to 39) that are comparable to that of mitomycin C and beta-irradiation without the attendant risk of sight-threatening complications associated with mitomycin C or beta-irradiation usage [2728] Sharma et al [28] demonstrated that there was no statistically significant difference in the recurrence rates between conjunctival autografting and mitomycin C use Compared with the use of mitomycin C and beta-irradiation conjunctival autografting is more technically demanding and more time-consuming to perform Inter-surgeon variability in terms of surgical technique skill and experience contributes to the wide variation in recurrence rates that have been reported

Limbal and limbal ndash conjunctival transplantationIt has been suggested that including limbal stem cells in the conjunctival autograft (limbal ndash conjunctival graft) may act as a barrier to conjunctival cells migrating onto the corneal surface and help prevent recurrence The limbal ndash conjunctival graft includes approximately 05 mm of the limbus and peripheral cornea The corneal limbal side of the graft is sutured in place with interrupted 100 nylon sutures and the conjunctival side is sutured with 100 absorbable suturesThe recurrence rates after limbal ndash conjunctival autograft surgery (ranging from 0 to 15) are similar to that of conjunctival autograft surgery [2933ndash35] while some authors suggest that limbal ndash conjunctival autografts are more effective than conjunctival autografts for recurrent pterygium [34] Oguz et al [42] demonstrated an overall recurrence rate of 952 with limbal conjunctival mini- autografting performed in 63 eyes Young et al [35] prospectively compared mitomycin C and limbal ndash conjunctival autograft surgery in preventing pterygial recurrence and showed that the mitomycin C group was associated with a higher recurrence rate (159) compared with the limbal ndash conjunctival autograft group (19) A major drawback for limbal ndash conjunctival auto- graft transplantation is that it is technically more demanding and time-consuming to perform To date however it should be noted that no conclusive evidence regarding the superiority of limbal ndash conjunctival auto- grafts over conventional conjunctival autografts exists and the added risk of limbal damage at the donor site deserves consideration

Conjunctival flap and conjunctival rotation autograft surgery

Two reports [3637] have described the use of sliding conjunctival flaps harvested from the inferior or the superior bulbar conjunctiva to close the scleral defect with reported recurrence rates ranging from 1 to 5 Conjunctival rotation autografting involves removal of the pterygium and reversal of the removed conjunctiva so that the most nasal aspect is sutured at the limbus and vice versa [3839] This is a useful technique for cases in which it is not possible or desirable to use the superior conjunctiva as a donor source such as with excision of extensive pterygium which leaves insufficient conjunc- tival tissue for the autograft

Amniotic membrane transplantationAmniotic membrane transplantation has recently been proposed as a treatment option [43 ndash 46] Ma et al [44] compared the excision of recurrent pterygia followed by amniotic membrane alone and amniotic membrane graft combined with intraoperative mitomycin C and found no significant difference in the recurrence rates between the two groups Amniotic membrane possesses antiscarring antiangiogenic and anti-inflammatory properties which may be useful for treating pterygium Besides the con- ventional epithelized cryopreserved human amniotic membrane the efficacy of membranes that are alterna- tively prepared such as the de-epithelized [47] or freeze- dried sterilized ones [48] have also been studied Delayed vascularization of amniotic membrane demonstrated with an anterior segment indocyanine green angiography is thought to be responsible for the delayed recurrence after pterygium surgery [49] An additional advantage is that it removes the need for harvesting large autografts thereby minimizing iatrogenic injury to the rest of the conjunctiva surface Three prospective studies [44455011130901113090] have compared amniotic membrane transplantation with other conventional treatment modalities In a randomized prospective study by Tananuvat et al [45] amniotic membrane transplant is associated with an unacceptably high recurrence rate compared with conjunctival auto- graft This result is also supported by Luanratanakorn et al [5011130901113090]

Cultivated conjunctival transplantationA novel method of closing the surgical defect involves the use of an ex-vivo expanded conjunctival epithelial sheet on an amniotic membrane substrate Although the preliminary study [51] demonstrated no significant difference in the recurrence rate compared with denuded amniotic mem- brane transplantation operated eyes achieved almost im- mediate reepithelialization of the ocular surface reduced postoperative inflammation and faster ocular rehabilita- tion This procedure may be particularly useful for closing large surgical defects following excision of extensive pterygium

Lamellar keratoplastyLamellar keratoplasty has been used to act as a barrier against pterygium recurrence and to replace thinned and scared corneal tissue after pterygium excision [52] It does not appear to offer any special advantage in preventing pterygium recurrence with recurrence rates ranging from 6 to 100 [52] As such this is not a favored procedure for treating primary pterygium It has mostly been used to treat recurrent pterygium to restore corneal thickness in thinned scarred corneas The main limitations are the need for donor corneal tissue with the attendant risks of graft rejection and transmission of infection as well as the increased complexity of the procedure

Fibrin glueFibrin glue (or Tisseel) has been used as an alternative to sutures for securing conjunctival grafts [53 ndash 56] The use of fibrin glue shortens operating times significantly and is associated with less postoperative discomfort Fibrin glue also provides a more even attachment of the graft to the scleral bed Most cases performed with fibrin adhesive healed with minimal inflammation and there were only sporadic cases of graft dislodgment or loss Bahar et al [57] showed that the use of fibrin glue was associated with a significantly shorter operative time and greater patient acceptance compared with using sutures The major concerns that need to be addressed include the cost of Tisseel and the potential risk of transmitted infection Further studies are required to evaluate the long-term efficacy of fibrin glue in reducing recurrences

Complications of treatment

Operative complications related to pterygium excision are uncommon and are generally related to the surgical tech- nique This includes excessive bleeding button hole of the conjunctiva graft perforation of the globe with the suture needle and injury to the medial rectus muscle The main postoperative complication is recurrence Other complications such as pyogenic granuloma dellen persistent epithelial defects are not uncommon but these may be easily treated with no significant long-term sequelaeOf greater concern is the potentially serious sight-threat- ening complications that have been associated with the use of adjunctive mitomycin C and beta-irradiation such as scleral necrosis infectious scleritis severe secondary glau- coma iritis cataract corneal edema corneal perforationand endophthalmitis [1725] Complications arising from the use of beta irradiation have been reported in up to 13 of patients with latency periods of up to 1451113090 25 years [25] These serious complications represent cases in which surgery was performed some years back when relative therapeutic doses of both mitomycin C and beta irradiation were higher and it remains to be seen if the newer treatments with reduced therapeutic dosages are associated with similar complications

ConclusionPterygium excision combined with mitomycin C or conjunctival autograft surgery are currently the main methods used for treating pterygium As the clinical trials describing various surgical techniques often have differing method- ology and sometimes conflicting results additional large randomized clinical trials need to be performed to evaluate the relative efficacy and long-term safety of the various treatment options Issues that need to be addressed include developing a standardized method of grading pterygium and its recurrence as well as identifying risk factors for pterygium recurrence

Beta-irradiationVarious regimes of beta-irradiation have been used to treat pterygium including a single application of beta-irradiation several applications over consecutive days in the immediate postoperative period or several applications periodically over a 2-week period [22 ndash 24] Although this modality of treatment has been used for decades few prospective studies have been described The use of post- operative single dose irradiation was demonstrated to be similarly efficacious as consecutive days of postoperative application Chayakul [22] showed that beta-irradiation was associated with a significantly higher recurrence rate than postoperative mitomycin C eyedropsBeta-irradiation is a less popular procedure because of the inconvenience of arranging its treatment and the long- term risk of serious sight-threatening complications such as scleral necrosis infectious scleritis corneal perforation and endophthalmitis [25] Patients should therefore be counseled regarding the potential long-term complications arising from its use

Surgical methodsThe surgical options available include the use of conjunc- tival autograft limbal and limbal ndash conjunctival transplant conjunctival flap and conjunctival rotation autograft sur- gery amniotic membrane transplant cultivated conjunctival transplant lamellar keratoplasty and use of fibrin glueConjunctival autograftsConjunctival autograft surgery is generally regarded as the procedure of choice for the treatment of primary and recurrent pterygium because of its efficacy and long- term safety [26 ndash 32] A free conjunctival graft is harvested from the superior bulbar conjunctiva and is sutured in place over the bare scleral defect [9 ndash 111314] Variations in conjunctival autograft surgery include the use of narrow-strip conjunctival autograft limbal-conjunctival autografts limbal epithelial autografts conjunctival flaps or conjunctival rotation autografts [2933 ndash 39] Conjunctival autografts are associated with recurrence rates (ranging from 2 to 39) that are comparable to that of mitomycin C and beta-irradiation without the attendant risk of sight-threatening complications associated with mitomycin C or beta-irradiation usage [2728] Sharma et al [28] demonstrated that there was no statistically significant difference in the recurrence rates between conjunctival autografting and mitomycin C use Compared with the use of mitomycin C and beta-irradiation conjunctival autografting is more technically demanding and more time-consuming to perform Inter-surgeon variability in terms of surgical technique skill and experience contributes to the wide variation in recurrence rates that have been reported

Limbal and limbal ndash conjunctival transplantationIt has been suggested that including limbal stem cells in the conjunctival autograft (limbal ndash conjunctival graft) may act as a barrier to conjunctival cells migrating onto the corneal surface and help prevent recurrence The limbal ndash conjunctival graft includes approximately 05 mm of the limbus and peripheral cornea The corneal limbal side of the graft is sutured in place with interrupted 100 nylon sutures and the conjunctival side is sutured with 100 absorbable suturesThe recurrence rates after limbal ndash conjunctival autograft surgery (ranging from 0 to 15) are similar to that of conjunctival autograft surgery [2933ndash35] while some authors suggest that limbal ndash conjunctival autografts are more effective than conjunctival autografts for recurrent pterygium [34] Oguz et al [42] demonstrated an overall recurrence rate of 952 with limbal conjunctival mini- autografting performed in 63 eyes Young et al [35] prospectively compared mitomycin C and limbal ndash conjunctival autograft surgery in preventing pterygial recurrence and showed that the mitomycin C group was associated with a higher recurrence rate (159) compared with the limbal ndash conjunctival autograft group (19) A major drawback for limbal ndash conjunctival auto- graft transplantation is that it is technically more demanding and time-consuming to perform To date however it should be noted that no conclusive evidence regarding the superiority of limbal ndash conjunctival auto- grafts over conventional conjunctival autografts exists and the added risk of limbal damage at the donor site deserves consideration

Conjunctival flap and conjunctival rotation autograft surgery

Two reports [3637] have described the use of sliding conjunctival flaps harvested from the inferior or the superior bulbar conjunctiva to close the scleral defect with reported recurrence rates ranging from 1 to 5 Conjunctival rotation autografting involves removal of the pterygium and reversal of the removed conjunctiva so that the most nasal aspect is sutured at the limbus and vice versa [3839] This is a useful technique for cases in which it is not possible or desirable to use the superior conjunctiva as a donor source such as with excision of extensive pterygium which leaves insufficient conjunc- tival tissue for the autograft

Amniotic membrane transplantationAmniotic membrane transplantation has recently been proposed as a treatment option [43 ndash 46] Ma et al [44] compared the excision of recurrent pterygia followed by amniotic membrane alone and amniotic membrane graft combined with intraoperative mitomycin C and found no significant difference in the recurrence rates between the two groups Amniotic membrane possesses antiscarring antiangiogenic and anti-inflammatory properties which may be useful for treating pterygium Besides the con- ventional epithelized cryopreserved human amniotic membrane the efficacy of membranes that are alterna- tively prepared such as the de-epithelized [47] or freeze- dried sterilized ones [48] have also been studied Delayed vascularization of amniotic membrane demonstrated with an anterior segment indocyanine green angiography is thought to be responsible for the delayed recurrence after pterygium surgery [49] An additional advantage is that it removes the need for harvesting large autografts thereby minimizing iatrogenic injury to the rest of the conjunctiva surface Three prospective studies [44455011130901113090] have compared amniotic membrane transplantation with other conventional treatment modalities In a randomized prospective study by Tananuvat et al [45] amniotic membrane transplant is associated with an unacceptably high recurrence rate compared with conjunctival auto- graft This result is also supported by Luanratanakorn et al [5011130901113090]

Cultivated conjunctival transplantationA novel method of closing the surgical defect involves the use of an ex-vivo expanded conjunctival epithelial sheet on an amniotic membrane substrate Although the preliminary study [51] demonstrated no significant difference in the recurrence rate compared with denuded amniotic mem- brane transplantation operated eyes achieved almost im- mediate reepithelialization of the ocular surface reduced postoperative inflammation and faster ocular rehabilita- tion This procedure may be particularly useful for closing large surgical defects following excision of extensive pterygium

Lamellar keratoplastyLamellar keratoplasty has been used to act as a barrier against pterygium recurrence and to replace thinned and scared corneal tissue after pterygium excision [52] It does not appear to offer any special advantage in preventing pterygium recurrence with recurrence rates ranging from 6 to 100 [52] As such this is not a favored procedure for treating primary pterygium It has mostly been used to treat recurrent pterygium to restore corneal thickness in thinned scarred corneas The main limitations are the need for donor corneal tissue with the attendant risks of graft rejection and transmission of infection as well as the increased complexity of the procedure

Fibrin glueFibrin glue (or Tisseel) has been used as an alternative to sutures for securing conjunctival grafts [53 ndash 56] The use of fibrin glue shortens operating times significantly and is associated with less postoperative discomfort Fibrin glue also provides a more even attachment of the graft to the scleral bed Most cases performed with fibrin adhesive healed with minimal inflammation and there were only sporadic cases of graft dislodgment or loss Bahar et al [57] showed that the use of fibrin glue was associated with a significantly shorter operative time and greater patient acceptance compared with using sutures The major concerns that need to be addressed include the cost of Tisseel and the potential risk of transmitted infection Further studies are required to evaluate the long-term efficacy of fibrin glue in reducing recurrences

Complications of treatment

Operative complications related to pterygium excision are uncommon and are generally related to the surgical tech- nique This includes excessive bleeding button hole of the conjunctiva graft perforation of the globe with the suture needle and injury to the medial rectus muscle The main postoperative complication is recurrence Other complications such as pyogenic granuloma dellen persistent epithelial defects are not uncommon but these may be easily treated with no significant long-term sequelaeOf greater concern is the potentially serious sight-threat- ening complications that have been associated with the use of adjunctive mitomycin C and beta-irradiation such as scleral necrosis infectious scleritis severe secondary glau- coma iritis cataract corneal edema corneal perforationand endophthalmitis [1725] Complications arising from the use of beta irradiation have been reported in up to 13 of patients with latency periods of up to 1451113090 25 years [25] These serious complications represent cases in which surgery was performed some years back when relative therapeutic doses of both mitomycin C and beta irradiation were higher and it remains to be seen if the newer treatments with reduced therapeutic dosages are associated with similar complications

ConclusionPterygium excision combined with mitomycin C or conjunctival autograft surgery are currently the main methods used for treating pterygium As the clinical trials describing various surgical techniques often have differing method- ology and sometimes conflicting results additional large randomized clinical trials need to be performed to evaluate the relative efficacy and long-term safety of the various treatment options Issues that need to be addressed include developing a standardized method of grading pterygium and its recurrence as well as identifying risk factors for pterygium recurrence

Two reports [3637] have described the use of sliding conjunctival flaps harvested from the inferior or the superior bulbar conjunctiva to close the scleral defect with reported recurrence rates ranging from 1 to 5 Conjunctival rotation autografting involves removal of the pterygium and reversal of the removed conjunctiva so that the most nasal aspect is sutured at the limbus and vice versa [3839] This is a useful technique for cases in which it is not possible or desirable to use the superior conjunctiva as a donor source such as with excision of extensive pterygium which leaves insufficient conjunc- tival tissue for the autograft

Amniotic membrane transplantationAmniotic membrane transplantation has recently been proposed as a treatment option [43 ndash 46] Ma et al [44] compared the excision of recurrent pterygia followed by amniotic membrane alone and amniotic membrane graft combined with intraoperative mitomycin C and found no significant difference in the recurrence rates between the two groups Amniotic membrane possesses antiscarring antiangiogenic and anti-inflammatory properties which may be useful for treating pterygium Besides the con- ventional epithelized cryopreserved human amniotic membrane the efficacy of membranes that are alterna- tively prepared such as the de-epithelized [47] or freeze- dried sterilized ones [48] have also been studied Delayed vascularization of amniotic membrane demonstrated with an anterior segment indocyanine green angiography is thought to be responsible for the delayed recurrence after pterygium surgery [49] An additional advantage is that it removes the need for harvesting large autografts thereby minimizing iatrogenic injury to the rest of the conjunctiva surface Three prospective studies [44455011130901113090] have compared amniotic membrane transplantation with other conventional treatment modalities In a randomized prospective study by Tananuvat et al [45] amniotic membrane transplant is associated with an unacceptably high recurrence rate compared with conjunctival auto- graft This result is also supported by Luanratanakorn et al [5011130901113090]

Cultivated conjunctival transplantationA novel method of closing the surgical defect involves the use of an ex-vivo expanded conjunctival epithelial sheet on an amniotic membrane substrate Although the preliminary study [51] demonstrated no significant difference in the recurrence rate compared with denuded amniotic mem- brane transplantation operated eyes achieved almost im- mediate reepithelialization of the ocular surface reduced postoperative inflammation and faster ocular rehabilita- tion This procedure may be particularly useful for closing large surgical defects following excision of extensive pterygium

Lamellar keratoplastyLamellar keratoplasty has been used to act as a barrier against pterygium recurrence and to replace thinned and scared corneal tissue after pterygium excision [52] It does not appear to offer any special advantage in preventing pterygium recurrence with recurrence rates ranging from 6 to 100 [52] As such this is not a favored procedure for treating primary pterygium It has mostly been used to treat recurrent pterygium to restore corneal thickness in thinned scarred corneas The main limitations are the need for donor corneal tissue with the attendant risks of graft rejection and transmission of infection as well as the increased complexity of the procedure

Fibrin glueFibrin glue (or Tisseel) has been used as an alternative to sutures for securing conjunctival grafts [53 ndash 56] The use of fibrin glue shortens operating times significantly and is associated with less postoperative discomfort Fibrin glue also provides a more even attachment of the graft to the scleral bed Most cases performed with fibrin adhesive healed with minimal inflammation and there were only sporadic cases of graft dislodgment or loss Bahar et al [57] showed that the use of fibrin glue was associated with a significantly shorter operative time and greater patient acceptance compared with using sutures The major concerns that need to be addressed include the cost of Tisseel and the potential risk of transmitted infection Further studies are required to evaluate the long-term efficacy of fibrin glue in reducing recurrences

Complications of treatment

Operative complications related to pterygium excision are uncommon and are generally related to the surgical tech- nique This includes excessive bleeding button hole of the conjunctiva graft perforation of the globe with the suture needle and injury to the medial rectus muscle The main postoperative complication is recurrence Other complications such as pyogenic granuloma dellen persistent epithelial defects are not uncommon but these may be easily treated with no significant long-term sequelaeOf greater concern is the potentially serious sight-threat- ening complications that have been associated with the use of adjunctive mitomycin C and beta-irradiation such as scleral necrosis infectious scleritis severe secondary glau- coma iritis cataract corneal edema corneal perforationand endophthalmitis [1725] Complications arising from the use of beta irradiation have been reported in up to 13 of patients with latency periods of up to 1451113090 25 years [25] These serious complications represent cases in which surgery was performed some years back when relative therapeutic doses of both mitomycin C and beta irradiation were higher and it remains to be seen if the newer treatments with reduced therapeutic dosages are associated with similar complications

ConclusionPterygium excision combined with mitomycin C or conjunctival autograft surgery are currently the main methods used for treating pterygium As the clinical trials describing various surgical techniques often have differing method- ology and sometimes conflicting results additional large randomized clinical trials need to be performed to evaluate the relative efficacy and long-term safety of the various treatment options Issues that need to be addressed include developing a standardized method of grading pterygium and its recurrence as well as identifying risk factors for pterygium recurrence

Operative complications related to pterygium excision are uncommon and are generally related to the surgical tech- nique This includes excessive bleeding button hole of the conjunctiva graft perforation of the globe with the suture needle and injury to the medial rectus muscle The main postoperative complication is recurrence Other complications such as pyogenic granuloma dellen persistent epithelial defects are not uncommon but these may be easily treated with no significant long-term sequelaeOf greater concern is the potentially serious sight-threat- ening complications that have been associated with the use of adjunctive mitomycin C and beta-irradiation such as scleral necrosis infectious scleritis severe secondary glau- coma iritis cataract corneal edema corneal perforationand endophthalmitis [1725] Complications arising from the use of beta irradiation have been reported in up to 13 of patients with latency periods of up to 1451113090 25 years [25] These serious complications represent cases in which surgery was performed some years back when relative therapeutic doses of both mitomycin C and beta irradiation were higher and it remains to be seen if the newer treatments with reduced therapeutic dosages are associated with similar complications

ConclusionPterygium excision combined with mitomycin C or conjunctival autograft surgery are currently the main methods used for treating pterygium As the clinical trials describing various surgical techniques often have differing method- ology and sometimes conflicting results additional large randomized clinical trials need to be performed to evaluate the relative efficacy and long-term safety of the various treatment options Issues that need to be addressed include developing a standardized method of grading pterygium and its recurrence as well as identifying risk factors for pterygium recurrence