Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 26  |  Issue : 2  |  Page : 89-98

PTERYGIUM: Recent trends and perspectives—A review of pathogenesis and current management options


1 Lecturer Ebonyi State University Abakaliki Ebonyi State, Consultant Ophthalmologist/Glaucoma specialist, Department of Ophthalmology, Federal Teaching Hospital, Abakaliki, Nigeria
2 Senior Lecturer Ebonyi State University Abakaliki Ebonyi State, Consultant Ophthalmologist/Glaucoma specialist, Department of Ophthalmology, Federal Teaching Hospital, Abakaliki, Nigeria
3 Lecturer Ebonyi State University Abakaliki Ebonyi State, Consultant Ophthalmologist/Paediatric Ophthalmologist, Department of Ophthalmology, Federal Teaching Hospital, Abakaliki, Nigeria

Date of Web Publication13-Feb-2019

Correspondence Address:
Dr. Helen A Ginger-Eke
Lecturer Ebonyi State University Abakaliki Ebonyi State, Consultant Ophthalmologist/Glaucoma specialist, Department of Ophthalmology, Federal Teaching Hospital, Abakaliki
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njo.njo_5_18

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  Abstract 


Objectives: (1) To review literature on the current understanding of the nature and pathogenesis of pterygium. (2) To highlight the recent advances in the treatment of pterygium. Materials and Methods: Relevant subheadings were entered into PubMed search engine and 165 articles addressing our objectives were retrieved and reviewed. Results: Pterygium may be proliferative rather than degenerative in nature. There is a strong correlation with ultraviolet radiation. Genetic alterations occur, such as point mutations of proto-oncogenesis such as Kirsten-Ras and alterations in the expression of tumor suppressor genes (TSGs) (p53 or p63), alteration of matrix metalloproteinase in limbal and corneal tissues, ultraviolet radiation (UVR) genetically mediated expression of various cytokines, growth factors, and growth factor receptors. Oxidative stress may play a role, evidenced by the expression of certain proteins in pterygium tissues presumed to have a protective role against oxidative stress-induced apoptosis. High prevalence of human papilloma viruses (HPVs) in pterygium tissue samples suggests a possible role for HPV. Several techniques of surgery have evolved over time including the modified bare-sclera techniques, sliding, “merest sclera,” adjunctive therapies with mitomycin C, 5-fluorouracil, corticosteroids, conjunctival autograft, limbal autograft, amniotic membrane graft, use of fibrin glue, and subconjuctival injection of bevacizumab. Conclusion: Advances in the understanding of pterygium have led to emerging treatment options that may not only reduce recurrent rates, but may also enable the use of less invasive treatment methods. Recommendation: Ophthalmologists working in hot climates should update their knowledge on the current concepts in the pathogenesis and management of pterygium to obtain better results.

Keywords: Pathogenesis, pterygium, treatment


How to cite this article:
Ginger-Eke HA, Ogbonnaya CE, Ezisi CN. PTERYGIUM: Recent trends and perspectives—A review of pathogenesis and current management options. Niger J Ophthalmol 2018;26:89-98

How to cite this URL:
Ginger-Eke HA, Ogbonnaya CE, Ezisi CN. PTERYGIUM: Recent trends and perspectives—A review of pathogenesis and current management options. Niger J Ophthalmol [serial online] 2018 [cited 2021 Dec 3];26:89-98. Available from: http://www.nigerianjournalofophthalmology.com/text.asp?2018/26/2/89/252184




  Introduction Top


Pterygium is a wing-shaped fibrovascular growth.[1] It can be divided into three recognizable parts: apex (head), neck, and body. The raised triangular portion of the pterygium with its base toward the canthus is the body, the neck that includes the superficial limbus, whereas the head invades the cornea and forms the apex of the triangle.[2] A subepithelial cap or “halo” is present in front of the head of the pterygium[3] and is usually the first sign of pterygium.[4],[5] Pterygium threatens vision through various mechanisms, such as blocking the visual axis as well as inducing significant astigmatism.[6] Pterygium is widely regarded to be a degenerative condition arising from benign growth of the conjunctiva, characterized by fibrovascularization, conjunctival invasion, and elastic degeneration of collagen. However, some studies have shown that pterygium shares some similarities with cancers, because active cell proliferation occurs with minimal apoptosis.[7],[8] Pterygium also displays other tumor-like properties, such as invasion of cornea and its high recurrence after surgical excision. It also exists with secondary premalignant lesions.[7],[9],[10] These tumor-like properties suggest that pterygium is possibly a premalignant tissue.[10] Several studies also showed that the pathogenesis of pterygium is closely linked to the p53 gene mutation.[11],[12],[13],[14],[15] Thus, pterygium is considered the result of uncontrolled cellular proliferation, like a tumor.


  Epidemiology Top


Pterygium has a worldwide distribution and is common in areas that lie within a geographical latitude of 40° north and 40° south of the equator.[16] Prevalence can be as high as 22% in these equatorial areas and less than 2% in latitudes above 40°.[16],[17],[18] Findings from an Asian region,[18] as well as Nigeria,[19] corroborate this trend. However, within the same regions, prevalence rates vary widely.[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30] Achigbu and Ezepue[19] in Enugu, Nigeria, found a prevalence rate of 19.3%. Among motorcycle riders, whereas Ogbonnaya[20] in Abakaliki, Nigeria, found a lower prevalence rate of 7.6% among patients visiting a hospital eye clinic, which compares with some other studies from parts of Asia that reported lower prevalence rates ranging from 4.4% to 10.1%.[21],[22],[23],[24] Several other studies from parts of Africa, Europe, and Australia reported a lower prevalence rate ranging from 0.8% to 11.7%.[25],[26],[27],[28],[29],[30]

Various risk factors have been suggested, including race, age, social status, occupation, and educational background.[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40] A large North American study has reported pterygium to be 2.5 to 3 times higher in blacks than among whites, almost twice as frequent among persons who worked outdoors but was only one-fifth as likely among those who always used sunglasses outdoors.[31] This study also found a positive association between pterygium and age and people of lesser educational background. Racial differences in pterygium has also been reported by many studies.[29],[32] Outdoor work as a risk for pterygium development has also been reported by other studies.[32],[33] Sunlight exposures (on an average of 1 h or more daily) were strongly associated with a higher risk of developing pterygium in people working outdoors.[34],[35],[36],[37] However, a study did not find a strong association between sun exposure and pterygium.[28] Ultraviolet (UV) light exposure may not be the only factor associated with the development of pterygium. Dust and sand may contribute to the development of pterygium. This could be explained by the fact that the normal flow of tears is from out inwards carrying with them any dust particles or fine foreign bodies as sandy dust is coarse than fine dust thereby exciting the inflammatory response with consequent formation of pterygium. Educational interventions to modify these potential exposures may assist in preventing pterygium. Older age, male sex, lower educational level, rural habitation, and nonsmoking have been reported by other studies as independent risk factors for pterygium.[21],[23],[30],[32] Some studies reported a preponderance of female gender,[25],[38] whereas some others reported no significant difference in gender in development of pterygium.[39]


  Clinical Presentation Top


Pterygium arises in the interpalpebral fissure as an elevated, fleshy mass on the bulbar conjunctiva near the limbus in its early stage. Engorged radial vessels may appear over the pterygium and adjacent conjunctiva and usually signal a period of rapid growth. The bulbar conjunctiva may become increasingly taut as the pterygium enlarges toward the limbus. Symptoms of burning, irritation, lacrimation, and foreign body sensation may accompany the growth of a pterygium onto the cornea. Significant astigmatism may be induced either with or against the rule as sectoral corneal steepening occurs.[41],[42] The astigmatism is often irregular and may lead to decreased vision. As the apex approaches the visual axis, glare and decreased contrast sensitivity appear. In severe cases, symblepharon formation may limit ocular motility and result in diplopia. The lesion may remain quiescent for the remainder of the patient’s life or resume growth again at a later time. Older, static lesions are often associated with an arcuate line of iron deposition in the superficial cornea immediately central to the cap known as Stocker’s line.


  Pathogenesis Top


The knowledge regarding the pathogenesis of pterygium has expanded vastly. Before now, early theories have proposed that pterygium development was associated with specific lifestyles such as outdoor working, exposure to sunshine, or dust. This led to the idea that chronic ocular surface irritation by such environmental factors might be the cause of the condition.[43],[44] It was also proposed that pterygium arises from other sunshine-related conditions, such as pingueculum. Pingueculum has no growth potential per se but may become inflamed and can evolve into a true pterygium.[45] Conjunctival vascular congestion frequently seen at the area of pterygium growth nasally was also believed to be caused by medial rectus activity that led to disturbance of the blood flow. This was suggested to be associated with pterygium growth.[43],[44] Other early reports such as pooling of tears, lacrimal composition, and unspecified local effects of lactic acid secreted by periocular sweat glands have all been implicated in the pathogenesis of pterygium.[46],[47],[48]

Pterygium is now accepted as a distorted wound-healing response and dysregulated cell proliferation disease rather than a degenerative lesion.[10] Antiapoptotic mechanisms,[49] cytokines,[50] growth and angiogenic factors,[51] viral infections,[52],[53],[54] and heredity[55],[56],[57] have been proposed as current causative agents in its pathogenesis.


  Current Concepts Top


Role of ultraviolet rays

The direct pathogenetic role of solar radiation in pterygium development has been reported by many studies.[23],[35],[36],[37] UV rays are the shorter wavelengths of nonionizing radiation (wavelength 100–400 nm) lying below the visible spectrum. Ultraviolet radiation (UVR) has been subdivided into three bands: UV-A (400–320 nm), UV-B (320–290 nm), and UV-C (290–100 nm).[37] UV-A, or near UVR, produces tanning (the browning of the skin due to an increase in the skin content of melanin) and photosensitivity reactions. UV-B causes sunburn (painful erythema and blistering), and increased exposure to UV-B is associated with an increased rate of skin cancer. UV-C is germicidal and may also cause skin cancer.[58],[59],[60] The eyes are normally protected and shielded from UVR by a number of factors, such as the normal horizontal alignment of the eyes, the orbits, and eyebrows which significantly reduces ocular exposure to whole-sky irradiation.[61] Further anatomical protection is provided by the nose, and the cheeks, as studies have shown that the cornea acts as a side on lens, focusing light incident on the temporal cornea unto the opposite side of the eye. The anatomy of the nose and cheek prevents this effect from occurring in the opposite direction, that is, light incident at the nasal limbus is not of such a peripheral angle as to allow a focusing effect unto the temporal limbus.[61] The eyelids provide protection that is further enhanced by squinting, a common reflex in bright sunlight.[62],[63],[64],[65] The eyes are relatively unprotected laterally (albedo),[16] although the transmission of UVR by internal reflection in the cornea may lead to a concentration of UV irradiation at the nasal limbus, hence the high incidence of nasal pterygium, an indication of the pathogenetic role of solar light. Scattered light might also follow alternative (transcameral) optical paths when entering the eye, thus hitting limbal stem cells from their inner surface.[16] The theory of transcameral pathway proposed that light scattered in the anterior chamber may deviate from the transpupillary course and be directed towards the limbus. The ab interno irradiation of limbal stem cells may cause genetic destabilization, eventually leading to development of pterygium. UV light is believed to cause pterygium[66] by inducing chronic inflammatory cells in the conjunctiva[67] or damage limbal stem cells.[68] However, the study by Anguria et al.[69] suggests that inflammation may not be crucial for pterygium to be present or to be opaque (i.e., a late stage of pterygium that appears clinically as a thick opaque vascular growth extending to the visual axis). Findings from the same report show chronic pterygium inflammation is not important for pterygium to recur after surgery, which is consistent with a previous report.[70] It looks as if the severity of chronic inflammation is independent of the degree of exposure to sunlight.[70],[71] Some reports have shown that damaged limbal stem cells are not a factor in pterygium occurrence[69],[72] unlike contrary report by Pelit et al.[73] Excessive exposure to sunlight has also been correlated with collagen degeneration. However, collagen degeneration has been discredited as a mechanism of pterygium pathogenesis.[74] Some primary pterygia may not show collagen degeneration histologically.[75],[76] This degeneration is not manifested in recurrent pterygia, suggesting short durations of exposure to UV light,[74],[77] supporting the belief that level of sunlight exposure may not be important for pterygium to occur or to recur.

The role of genetically altered limbal stem cells

Immunohistochemical studies have found conjunctival, limbal, and corneal cells to immunostain primarily for matrix metalloproteinase-I (MMP-I). Limbal basal epithelial cells (pterygium cells) were found in immunostain for multiple types of MMPs (MMP-1, MMP-2, MMP-3, MMP-9, membrane type 1-MMP, and membrane type 2-MMP).[78] MMPs have been detected in the fibroblasts and stroma of pterygium samples[79]; this suggests that these MMPs were remodeling the pterygium stroma,[80] but this was attributed to damaged limbal basal epithelial cells.[79] It is believed that the altered MMP expression of limbal basal epithelial cells (pterygium cells) enables them to invade and dissolute Bowman’s layer leading to firm adhesion of the lesion on the corneal surface.[77],[78] However, some studies did not find MMP expression in the pterygium fibroblasts or stroma yet the limbal basal epithelial cells were damaged.[69],[81] These suggest that matrix remodeling observed in pterygia is unlikely to be due to MMPs. Rather, sunlight damage has been implicated.[82],[83]

Oxidative stress

Generation of reactive oxygen species (ROS) by UV radiation has been suggested as initiating events in the development of pterygia.[84] Stocker line, an area of excess iron deposition at the advancing edge of a pterygium has provided further evidence for the importance of ROS in pterygium formation. Expression of certain proteins in pterygium tissues that are presumed to have a protective role against oxidative stress-induced apoptosis has been identified by a recent study.[85] In this study, aldehyde dehydrogenase dimeric nicotinimide adenosine dinucleotide phosphate (NADP)-preferring (ALDH3A1), protein disulfide-isomerase A3, and peroxiredoxin II were found to be significantly upregulated in pterygium and further increased in recurrent pterygium. A previous study also found peroxiredoxin I and II both to be upregulated in pterygium.[85] Immunohistochemistry and western blot analysis were both used in these studies to confirm that these proteins were mainly detected in the basal epithelial layer, and their expression was significantly increased in the pterygium compared to normal conjunctiva.

Hence, future study directions could include topical antioxidant therapy as a first-line treatment for pterygium lesions.

Molecular genetic alterations

TSGs and proto-oncogenes (POGs) have been implicated in the pathogenesis of pterygium. Using proteomic approach, 77 proteins were upregulated in pterygia.[85] Mitotic proteins were seen to be among the proteins significantly affected.[85] Large TSGs (large tumor suppressor kinase 1 (LATS1) and large tumor suppressor kinase 2 (LATS2)) are the common TSGs in the UV-induced DNA damage response signaling pathways. DNA methylation in the promoter regions are the main cause of TSG silencing and can result in tumor development. A recent study confirmed the significant relationship between reduced expression of the LATS1 and LATS2 through methylation and the risk of pterygium formation.[86] Other reports have showed aberrant DNA methylation and decreased expression of P16, E-cadherin, TGM 2, MMP2, and CD24 genes in pterygium damage.[87],[88],[89] LATS2 also interacts with a negative regulator of p53 and may function in a positive feedback loop with p53 that responds to the cytoskeleton damage. Levels of p53 have also been reported to be increased in pterygia by some studies.[78],[90],[91] The levels of p53 expression in pterygia have been found to differ between epithelial layers being higher in basal cells, compared to more superficial layers.[78],[92],[93] This finding could reflect increased exposure to UVR according to the proposed theory of transcameral exposure of limbal basal (stem) cells to solar light.

POG sequences may also be affected by UVR.[94],[95] LATS1 is activated by Ras-association domain family 1 isoform A that stimulates response to DNA damage. Mutations in genes of the ras family POGs, including Harvey-Ras, Kirsten-Ras (K-ras), and Neuroblastoma-Ras, have been detected in cultured cells of mouse skin tumors following exposure to near-UVR.[94] Restriction fragment length polymorphism and sequencing analysis of primary and recurrent pterygia have revealed K-ras mutations at codon 12 in 10% of pterygia. The above findings pave the road for discovering drugs with the regulation of methylation characteristic that will lead to better therapy in treatment of pterygium.

Role of growth factors and cytokines

The expression of various cytokines, growth factors, and growth factor receptors may be triggered by UVR genetic mediated trauma.[81] Immunohistochemical and Enzyme-linked immunosorbent assay (ELISA) techniques have revealed the presence or altered expression of this factors in pterygium.[96] UVR-inducible cytokines include the interleukin-1 (IL-1) system,[97],[98] the IL-6,[99],[100] and IL-8.[101],[102] Growth factors involved in pterygium according to previous reports include the epidermal growth factor (EGF) and heparin-binding EGF, vascular endothelial growth factor (VEGF), basic fibroblast growth factor, platelet-derived growth factor, transforming growth factor-ß, and insulin-like growth factor binding proteins.[81] However, some growth factors were expressed in controls as in cases, which suggests that overexpression of angiogenic growth factors is not the reason for vibrant fibroblast mitosis or for pterygium to occur,[103],[104] rather the upregulation of fibrogenic growth factors is most likely to be the reason for pterygium to occur.[103],[104],[105] VEGF has also been detected in increased amounts in pterygium epithelium, compared with normal conjunctiva using immunohistochemistry.[106] However, Bevacizumab (Avastin®; Genentech Inc., South San Francisco, California, USA), which is anti-VEGF, did not abolish pterygium recurrence after surgery.[107]

Role of viruses

Studies have revealed a high prevalence of oncogenic human papilloma viruses (HPVs) in tissue samples, suggesting a possible role for HPV in the pathogenesis of pterygia. Type 18 was the most prevalent genotype, followed by type 16, whereas less common genotypes were types 58 and 59.[108]

Role of heredity

Although existing reports indicate that sunlight exposure is the main factor in pterygium occurrence, studies on factors in pterygium occurrence and recurrence have identified heredity to be a crucial factor for pterygium development, and that sunlight is only a triggering factor.[109]


  Treatment of Pterygium Top


The treatment of pterygium can be conservative, medical, or surgical.

Conservative treatment is indicated when symptoms are mild and usually involves avoidance of smoke and dust-filled environment. Use of ultraviolent blocking glasses has been advocated by some authors in preventing progression.[110]

Medical treatment is used to relieve symptoms and involves use of topical, preservative-free lubricants, vasoconstrictors, and mild corticosteroids.

Surgical treatment is indicated when there is disturbance of visual function, significant discomfort, and for cosmetic reasons. The first report of a surgical treatment of pterygium is more than 3000 years old.[111] Many variations of this procedure since that time have been published.[112],[113] Only the current surgical techniques, with adjunctive therapies, are discussed in this review.


  Current Surgical Techniques Top


Bare sclera technique: This is the most popular method for the removal of primary pterygium and was first described by D’Ombrain.[112] This technique involved the complete excision of the pterygium head and removal of some of the adjacent normal nasal bulbar conjunctiva along with excision of the underlying Tenon’s capsule tissue, which then resulted in a bare sclera. The remaining conjunctival rim was then sutured onto the bare sclera surface at a variable distance from sclerocorneal limbus. This technique was associated with a high recurrence rate (30%–80%),[112] and there is a higher risk of recurrence after re-excision of a recurrent pterygium compared to a primary pterygium.[114] Therefore, this technique has been modified to reduce the recurrence rate.

Modified bare sclera technique: This technique was based on the understanding of the important role of normal conjunctiva in blocking pterygium regrowth on the corneal surface. These techniques include

Sliding conjunctival flaps: Sliding conjuctival flaps from both inferior and superior limbus is used for primary closure of a pterygium excision. A 1-year recurrence rate of only 5% has been reported using this technique.[115]

“Merest sclera” technique: In this technique, the head and midbody of the pterygium are excised and a tenonectomy is extended beneath the conjunctiva to the adjacent rectus muscle, particularly in young patients or large lesions. Relaxing conjunctival incisions are made both superiorly and inferiorly along the limbus, and the conjunctiva is closed primarily and meticulously. A recurrences of only 2.1% is reported.[116]

Bare sclera technique with partial sclerectomy: In this technique, the head of the pterygium was shaved off the cornea, and its body was dissected from conjunctiva above by blunt dissection until orbital fat was exposed. The pterygium was bluntly dissected from underlying sclera and muscle and then excised. A third partial thickness sclera flap 5 mm vertically by 3 mm horizontally was raised from the sclera bed measuring from limbus, this sclera was excised and cautery applied minimally. The conjunctiva was then anchored to the edge of the sclera using 8/0 silk suture while leaving the sclerectomy bare. A recurrence rate of 9.1% is reported.[117] It is postulated that removal of the superficial sclera with the episcleral tissue may remove with it the factor responsible for recurrence of pterygium.

Conjunctival autograft

The transplantation of free autografts of superotemporal bulbar conjunctiva from the same eye to close wounds after the excision of advanced or recurrent pterygium was described by Kenyon et al.[118],[119] Cautery spots are used to delineate the involved area of conjunctiva to be excised. Sharp, superficial excision of the head of the pterygium from the involved cornea to the limbus is performed. The conjunctiva and Tenon’s capsule are bluntly and meticulously dissected from the horizontal rectus muscle, leaving behind the bare sclera and exposed rectus muscle. Conjunctiva is secured to the sclera with absorbable suture (e.g., 8-0 Vicryl) on a spatulated needle. Calipers are used to determine the size of conjunctival graft required to resurface exposed sclera and horizontal rectus muscle. The globe is rotated inferomedially to expose an area of uninvolved superior bulbar conjunctiva. Dimensions are marked with several cautery spots, as large as 15 mm by 15 mm and extending to the limbus. Free grafts are dissected as thinly as possible, taking minimal subconjunctival tissue. The graft is excised such that cautery marks remain with the graft tissue margins, then the epithelial surface can be readily identified when the graft is repositioned. The donor site does not require suturing, but the conjunctival margins can be advanced to the limbus with two interrupted sutures. The free graft is transferred into the recipient bed and secured to adjacent conjunctiva and episclera with interrupted sutures of 8-0 Vicryl; 10-0 nylon is used for the limbal edge of the graft.[118],[119]

A recurrence rate of 21% was reported.[120] Other authors have reported a recurrence rate of 12.1%.[121]

Limbal autograft, a variation of free conjuctival autograft, has been described. This was based on the understanding that corneal epithelial stem cells are located at the limbus. Limbal epithelial stem cells generate new corneal epithelial cells in addition to inhibiting conjunctival epithelial invasion of the cornea. However, there are little data supporting its efficacy.

Amniotic membrane grafts

Following a pterygium excision, the bare sclera area is covered with either fresh or preserved amniotic membrane tissue with basement membrane side up. However, there is need to exclude infections such as human immunodeficiency virus and hepatitis when using fresh amniotic membrane.[122] The amniotic membrane is sutured through the episcleral tissue to the adjacent healthy conjunctiva using 8 to 10 size 8.0 Vicryl sutures. A recurrence rate of 6%, 7.9%, 25%, and 28.1%,[123],[124],[125],[126] respectively, has been reported by many studies. Its efficacy in reducing recurrence of pterygium is based on the understanding that amniotic membrane promotes conjunctival epithelial wound healing, suppresses fibroblasts, and reduces extracellular matrix production.[127] Of recent, fibrin glue is now been used to replace or augment sutures when attaching conjunctival grafts or amniotic membrane. Fibrin glues has been useful in shortening operating time and decreasing postoperative discomfort, as well as decreasing recurrence rates.[122]


  Adjunctive Therapy Top


Various adjunctive therapies have been used with pterygium surgery to decrease the risk of recurrence after its surgical removal. However, these adjuctive therapies have their drawbacks.

Cautery

Extensive use of intraoperative cautery with bare sclera, particularly at the limbus, to augment the surgical removal of the pterygium has been used by many surgeons. This was based on the knowledge that blood vessel growth at the operative site contributes to the recurrence of a pterygium.[128] Some authors believe that cautery can lead to the formation of hypertrophic scar tissue and discourage its intraoperative use.[129]

Mitomycin C

Mitomycin C is an antineoplastic/antibiotic agent isolated from the soil bacterium Streptomyces caespitosus. It inhibits the synthesis of DNA, cellular RNA, and proteins in rapidly growing cells.[130] Mitomycin C was first used topically at a concentration of 0.04% (doses of 0.4 mg/ml) three times daily for 1 to 2 weeks after pterygium surgery, with no recurrences by Kunimoto and Mori.[131] Other reports have confirmed the usefulness of mitomycin C in pterygium surgeries with a recurrence rate ranging from 2% to 16%.[132],[133],[134]

However, mitomycin C has been shown to be associated with vision-threatening complications such as iritis, severe secondary glaucoma, corneal edema, corectopia, sudden-onset mature cataracts, scleral calcification, and corneal perforation.[135]

Consequently, this motivated the use of a more dilute concentrations (0.02%) of mitomycin C. Some reports have described good results with no serious complications using 0.2 mg/ml of mitomycin C.[136],[137],[138] Presently, two approaches have been developed for applying mitomycin C: postoperative use of topical eye drops and intraoperative use of mitomycin C-soaked sponges. Both have similar recurrence rates. A recent report found pterygium surgery with intraoperative mitomycin C to have similar recurrent rate when compared with conjuctival autograft alone.[139] Hence, adjuvant role of mitomycin C should be studied further.

5-Fluorouracil

5-Fluorouracil (5-FU) is a fluorinated pyrimidine that inhibits the proliferation of fibroblasts. 5-FU is used intraoperatively at a dose of 50 mg/ml for 3 to 5 min by most surgeons, because 5-FU is cheaper than mitomycin C and is associated with fewer side effects.[140] The recurrence rate of 11.4% to 14% has been reported by Bekibele et al.[121] and 25% by Akarsu et al.,[140] respectively, has been reported. 5-FU was also found to be marginally superior to conjunctiva autograft in the prevention of pterygium.[121]

Corticosteroids

Several authors have advocated their use four times daily for 2 weeks after the healing of the corneal epithelial defect.[141],[142] This is based on the understanding of the direct antiangiogenic and their anti-inflammatory effects.[143] Given the chronic nature of topical steroid needs in pterygium management, a recent report has advocated the use of loteprenol etabonate ointments in the preoperative and postoperative management of pterygium surgery based on its potency and safety profile.[144]

Bevacizumab

Subconjunctival injections of Bevacizumab provide another strategy to manage primary and recurrent pterygium. This is based on the fact that vascular growth factors such as VEGF have been detected in pterygium.[145],[146] Subconjunctival injection of 0.2 ml (5 mg) of Bevacizumab (100 mg/4 ml Roche) following the injection of 0.2-ml lidocain 2% in subconjunctival area of pterygium body using a 1-ml syringe with 29-gauge needle, showed marked reduction in the size of pterygium and regression of blood vessels.[147],[148],[149] Subconjunctival injection of bevacizumab has also been shown by studies to be safe.[148],[149] Subconjuctival bevacizumab benefit the complex treatment of pterygium by reducing subjective complaints and delaying surgical intervention. However, a preliminary report[150] has found subconjuctival bevacizumab not useful in treating primary pterygium and also rather harmful. Further studies are required in this area.

Topical bevacizumab therapy is also advocated.[151] One study used it 1 month after surgical excision of recurrent pterygium and found it to be well tolerated and effective in preventing neovascularization.[152] There was no significant difference in the recurrence rate in the study group; further studies are required to support this result.

Laser therapy

The use of the argon laser in selected postoperative cases has been described. In one report, argon laser was applied at 50-µm spots to early neovascular fronds. The power settings were limited to minimize conjunctival epithelial damage[153]; the recurrence rate was unknown in this report.

Beta irradiation

The most common use of beta radiation has been in the management of pterygium, with local application of a Strontium-90 source to prevent recurrence. Initially a high dose of beta radiation was applied without surgical excision, the aim being to induce regression of the lesion. This was associated with a high recurrent rate that was attributed to the high levels of UV. Recently, administration after surgery, particularly for recurrent pterygia, became widely adopted, with subsequent reports, indicating a low recurrence rate ranging from 0% to 16%.[154],[155],[156],[157],[158]

A recent study[159] recommends a total combined dose of 2000 to 3000 cGy delivered in three fractions every other day starting on the 6th day postsurgery. Adverse effects with beta radiation for pterygium, such as lens opacity, scleral necrosis, punched out ulcers have been widely reported.[160]

Consequently, use of beta radiation for pterygium has diminished, with conjunctival autografting and topical mitomycin C now being widely used. Conjunctival autografting is reasonably effective and appears to be safe; however, it is considerably more time consuming than other methods.[161] Comparative data for beta radiation and mitomycin C are conflicting: one study found mitomycin C to be more effective[162]; another study suggested the converse,[163] a Dutch study suggested equivalence[164]; and a randomized controlled study suggested that beta radiation was more effective than either conjunctival autografting or mitomycin C.[165]


  Conclusion Top


Recently, there have been significant advances in the understanding of nature of pterygium, the molecular and biochemical events underlying pterygium pathogenesis, and recent advances in its treatment. Recent advances in the treatment have not only continued to reduce recurrent rate but also may enable the use of less invasive treatment methods other than surgery.

Recommendation

Pterygium is a very common eye disorder, particularly in the tropics; thus, there is need for ophthalmologists, working in hot climates to update their knowledge on the current concepts in the understanding of the nature of pterygium as well as the current treatment options to obtain better results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Introduction
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