Ocular Surface and Tear Film Management in Pterygium Surgery

A pterygium is usually a triangular encroachment of the nasal bulbar conjunctiva onto the cornea and is derived from the Greek word for “little wing.” 1,​2,​3 It is a degenerative and hyperplastic process with invasion of the peripheral cornea to the level of Bowman’s membrane. 1 Pterygium is a worldwide external disease problem and is especially common in the “pterygium belt,” 10 to 30 degrees above and below the equator. 1,​2 This geographic area is characterized by greater exposure to sunlight and ultraviolet (UV) radiation, as well as to dry, dusty, and strong winds, which are thought to be integral to pterygium pathogenesis. 1,​2,​3,​4 Although more common in men, in areas with equal sun exposure (e.g., Aruba), the incidence for men and women is similar. 1 In the northern climes, pterygium is much less common and mostly limited to patients with vocations that are exclusive to outdoor work. 1,​2 Dry eye disease and ocular surface inflammation are thought to be adjunctive factors. 1,​5,​6 There is no well-defined inheritance pattern, but the tendency toward pterygia appears to be autosomal dominant with low penetrance. 1,​7 The growth of the pterygia is toward the center of the cornea and can, though rarely, cross the visual axis. 1,​2,​6,​8 Extensive growth of a pterygium up to and partially through the visual axis is shown in ▶ Fig. 5.1.



Extensive pterygium crossing through the visual axis.


Fig. 5.1 Extensive pterygium crossing through the visual axis.



The tendency for the nasal conjunctiva being involved in the vast majority of cases is thought to be secondary to increased UV damage (possibly from reflection off the nose or the passage of light through the anterior chamber). 1,​9 When temporal and nasal pterygia coexist in one eye (“double headed”), the temporal pterygium usually forms later. 1,​2,​6,​8 An example of a double-headed pterygium is shown in ▶ Fig. 5.2.



“Double-headed” (nasal and temporal) pterygium.


Fig. 5.2 Double-headed” (nasal and temporal) pterygium.



A conservative, non-surgical approach may be taken with small pterygia that do not involve much of the cornea. 2 However, for larger pterygia causing visual disturbances, restriction of eye movement, unacceptable cosmesis, occurrence of secondary degenerative changes, or persistent irritation, the standard of care regarding pterygium management is surgical excision. 1,​2,​5 Different techniques have been developed in the realm of pterygium surgery, all with different indications, risks, and recurrence rates. 1,​2,​3,​4,​5,​6,​8,​9,​10,​11,​12,​13,​14,​15,​16,​17 Of interest are factors that lead to, and that importantly, can prevent pterygium recurrence, saving the patient additional surgery as well as cost to the healthcare system. 1,​2,​3,​5,​6,​8,​9,​10,​11,​12,​13,​14,​15,​18,​19,​20,​21,​22,​23,​24,​25,​26


There is extensive literature citing increased levels of ocular surface inflammation in the formation, growth, and recurrence of pterygia. 5,​6,​20,​21,​27,​28,​29,​30 Several inflammatory markers found in dry eye disease are also found in eyes with primary and recurrent pterygia. 5,​6,​27,​28,​29,​30 Thus, it is important to understand the pathogenesis of dry eye and ocular surface disease as it relates to the formation of pterygia, in order to properly manage these patients postoperatively, improve comfort, and prevent recurrences. Too often, common sense approaches, such as wearing a hat or polarized lenses outdoors, are ignored.


5.2 Pterygium Anatomy and Histology


There are three distinct parts of the pterygium. The cap or leading edge consists of a flat gray zone on the cornea, consisting mainly of fibroblasts—this area invades and destroys Bowman’s membrane. 1,​31 An iron line (Stocker’s line) may be seen anterior to the cap; there may be a dellen anterior to the cap. 1 The pterygium head is immediately behind the cap and consists of a whitish, thickened vascular area firmly attached to the cornea. 1,​31 The body (“tail”) is a fleshy, mobile vascular area of bulbar conjunctiva and serves as an important landmark for surgical dissection. 1 Tan et al developed an anatomically based grading system for pterygia, which was predictive of recurrence. 2,​32 The three types they identified were T1 (atrophic; episcleral vessels underlying pterygium are unobscured), T2 (intermediate; episcleral vessels are partially obscured), and T3 (fleshy; thick pterygium in which episcleral vessels underlying the body of the pterygium are totally obscured by fibrovascular tissue), T3 being the variant with the highest recurrence risk. 2,​32 Examples of the clinical types of pterygia are shown in ▶ Fig. 5.3, ▶ Fig. 5.4, ▶ Fig. 5.5.



Atrophic (T1), thin, small pterygium.


Fig. 5.3 Atrophic (T1), thin, small pterygium.



Intermediate (T2) pterygium.


Fig. 5.4 Intermediate (T2) pterygium.



Large, thickened (T3) pterygium.


Fig. 5.5 Large, thickened (T3) pterygium.



The histopathology of pterygia has been compared to that of pinguecula inasmuch as both lesions are characterized by elastotic degeneration of the stroma. 1,​31 However, when compared to pterygia, pinguecula tend to be relatively poorly vascularized. 1,​31 Both lesions originate from activated fibroblasts thought to occur from actinic stimulation and are more common on the nasal surface of the limbal conjunctiva in the interpalpebral area. 1,​2 On histologic evaluation, the stroma shows increased fibroblasts, pockets of inflammatory cells, and prominent hyalinization of stromal fibrils with increased amounts of twisted fibers that stain positively for elastic tissue, but resist digestion with elastase, hence the term elastotic degeneration. 1,​31 In some areas, there may be eosinophilic and basophilic changes that can simulate concretions. 1,​2,​31 The epithelium can transform into an acanthotic pattern that may have mild dysplastic areas and eventually in rare cases can lead to squamous cell carcinoma. 1,​2,​33,​34 Other areas in the epithelium may present with hyperkeratosis or goblet cell proliferation. 1,​2 The head of the pterygia has a fibrovascular frond that invades Bowman’s membrane. The pterygium body has mostly basophilic areas that represent damaged fibroblasts and altered stromal fibrils (i.e., elastotic degeneration). 1,​31


5.3 Etiologies and Growth of Pterygia


The prevalence of pterygia has been reported to range from 0.3 to 29%. 9 Many theories are suggested in the etiology and pathogenesis of pterygia (UV light exposure and chronic irritation from dust/wind). 9 They may present as a visual disturbance due to induction of astigmatism or by its growth extending onto the cornea to occlude the visual axis. 9 It may cause ocular irritation/recurrent inflammation and be cosmetically unsightly. 9


Pterygia typically grow in two stages: (1) the initial and progressive disruption of limbal corneal-conjunctival epithelial barrier and (2) progressive active “conjunctivalization” of the cornea by tissue characterized by extensive cellular proliferation, connective tissue remodeling, inflammation, and angiogenesis. 6 These factors can be managed individually and, if done successfully, can lead to excellent clinical and surgical outcomes in patients with pterygia.


As pterygia are thought to result from actinic damage and form from submucosal growth of fibrovascular connective tissue that migrates onto the cornea, they are viewed by some as aggressive growths with concern for dysplastic degeneration. 31 Additionally, impression cytology of surface cells directly overlying a pterygium has been shown to be abnormal, with increased goblet cell density and squamous metaplasia. 1,​21,​31


Fortunately, most pterygia are entirely benign; it is worthwhile sending the excised tissue for pathologic examination, because occasionally, precursors of actinic-induced neoplasms (e.g., squamous cell carcinoma and melanoma) are detected. 1,​31


5.4 Surgical Management


The main consideration with pterygia is regarding treatment, when to operate and how to best manage patients postoperatively. Historically, the initial treatment has been simple removal (“bare sclera technique”). Unfortunately, this has been associated with a recurrence rate of 40 to 90%. 7 This unacceptable recurrence rate has led to dozens of surgical techniques and the use of adjunctive agents such as mitomycin C (MMC), 5-fluorouracil (5-FU), and others. 2 Through the research of Friend and Thoft, the concept of conjunctival transplantation was born. 1,​2,​35,​36 This change in therapy led to an increase in success rate, decreased recurrences and obviates for the most part, and the use of dangerous adjunctive alkylating agents. 1,​2,​35,​36


Some of the therapies that have been popular include bare sclera technique with and without beta-radiation, pterygium excision with a mobile flap, mucous membrane graft, skin graft, misdirection of the head of the pterygium, lamellar scleral grafts, amniotic membrane, limbal conjunctival autografts, and free conjunctival autografts. 1,​2 Many surgeons have incorporated the use of tissue transplantation (i.e., amniotic membrane and conjunctival grafts) after pterygium excision in an effort to reduce recurrence. These grafts may be sutured in place or glued (e.g., fibrin glue and autologous blood). 10


5.5 Surgical Techniques


Herein, we briefly describe past and current techniques for pterygium excision. From bare sclera to the pterygium-extended removal followed by extended conjunctival transplant (PERFECT) technique, the techniques listed below are in order of increasing success rate and decreasing recurrence rate, as defined by the literature. 2,​4,​5,​8,​9,​11,​12,​13,​14,​16,​26,​37,​38


5.5.1 Bare Sclera


D’ombrian introduced the Bare Sclera technique in 1948; this technique is generally considered inadequate secondary to high recurrence rates. 2 Pterygium is excised in toto, and the sclera is left bare without graft or primary closure.


5.5.2 Lamellar Keratectomy


Lamellar keratectomy is mainly reserved for recurrent pterygia with scarred or thin corneal tissue. 9 After surgery for recurrent pterygium, there may be significant residual scarring and thinning of the cornea. 13 In this case, lamellar corneal graft tissue can be used to replace thin or scarred portions of the cornea. 13


5.5.3 Primary Conjunctival Closure and Sliding/Rotational Conjunctival Flaps


Primary conjunctival closure and sliding/rotational conjunctival flaps has also been used, but recurrence rates do not appear to be significantly better than the bare sclera technique (29–37%). 2,​5,​9 Here, either sliding conjunctival flaps from both the superior and inferior limbus, or a rotation of a flap of superior conjunctiva is sutured or glued into place. 2,​5,​9


5.5.4 Amniotic membrane grafts


Amniotic membrane grafts have been shown to be more efficacious than bare sclera technique, but have higher recurrence rates than conjunctival autografts (approximately 14–28%). 5,​8,​11 However, amniotic membrane may be preferable in patients who do not have adequate tissue available for transplantation (e.g., multiple prior surgeries with conjunctival scarring, those with filtering blebs, or those who may need glaucoma filtration surgery in the future). 5 Amniotic membrane is thought to promote healing and to reduce rates of recurrence through its anti-inflammatory properties. 8 Amniotic membrane may help suppress transforming growth factor-beta (TGF-β), and thus act as an antifibrotic agent. 5 It also acts as a basement membrane substance that allows epithelium to grow over it, perhaps speeding the healing process. 3,​6 We have seen its successful use in severe ocular surface disease, ocular burns, and forniceal reconstruction in limbal stem cell deficiency. 8 As some feel that the etiology of pterygium is related to localized limbal stem cell deficiency, and that this condition may be exacerbated by dry eye, amniotic membrane is a logical choice for use during pterygium excision. 8 Additionally, amniotic membrane has been shown to inhibit inflammation by releasing anti-inflammatory cytokines from its epithelium and stroma (interleukin [IL]-10 and IL-1 receptor antagonists). 8 In concert with these findings, amniotic membrane has been shown to decrease postoperative pain and rarely has problems with tissue rejection, as it does not express human leukocyte antigen (HLA) surface proteins (i.e., HLA-A, HLA-B, and HLA-D-rerated [HLA-DR]). 6


5.5.5 Conjunctival Limbal Autograft


Conjunctival limbal autograft is a useful technique in pterygium surgery, as one of the proposed etiologies of pterygium is focal limbal stem cell deficiency. 2 The procedure is similar to that of obtaining a conjunctival autograft; however, the limbal edge of the donor graft is extended to include limbal epithelium, either by superficial keratectomy or superficial lamellar dissection. 2,​3,​6 The graft is then secured in place with glue or sutures.


5.5.6 Free Conjunctival Autografts


Free conjunctival autografts provide the lowest rate of recurrence and have even been shown to be successful when split in half for use with double-headed pterygia. 5,​13 Typically, the free graft is obtained from the superotemporal conjunctiva and is placed over the bare scleral bed following pterygium excision. 2 Many studies have shown this technique to be superior to amniotic membrane transplantation, among others. 2,​5,​6,​8,​9,​11,​12,​14,​26 Conjunctival autografting is widely used as a tissue replacement after pterygium excision as it is readily available and has been shown to have excellent anatomical and functional results. 2,​5 The autograft provides a source of healthy conjunctival epithelium and may act by contact inhibition on the residual abnormal tissue to prevent recurrence. 5,​26 In addition, placing the conjunctival autograft in a limbus-to-limbus orientation may yield a better result by acting as a barrier against fibrovascular invasion of the cornea and supplying stem cells to the corneal epithelium. 2,​5 Bare sclera at the site of pterygium excision has been suggested to serve as a scaffold for pterygium regrowth and recurrence, either by induction of a dellen, or by expression of inflammatory cytokines. 5


5.5.7 Pterygium-Extended Removal Followed by Extended Conjunctival Transplant


PERFECT, developed by Hirst, is a very successful, although extensive procedure for pterygium excision. 2,​4,​16,​37 In this technique, there is wide excision of Tenon’s capsule above and below and over the corresponding rectus muscle (e.g., medial rectus for nasal pterygium and lateral rectus for temporal pterygium). 2,​4,​16,​37 For a nasal pterygium, there is subsequent excision of the semilunar fold, which leaves a very large defect. 2,​4,​16 The defect is then covered by an extensive, thin, free conjunctival graft. 2,​4,​16,​37 This technique has been shown to be extremely successful with close to zero recurrence rates, even in double-headed pterygia. 2,​4,​16,​37


5.6 Adjunctive Therapies for Pterygium Excision


In high-risk cases (increased risk of recurrence or surgery for recurrent pterygium), adjunctive therapy may be used to help prevent recurrence. 2,​5,​8,​11 These therapies include use of alkylating agents (MMC and 5-FU), anti-vascular endothelial growth factor (anti-VEGF), alcohol, and others. 2,​8,​9,​14 Adjunctive therapy may be employed preoperatively, intraoperative, or postoperatively to enhance pterygium surgery success. 2,​8,​9,​13,​36 Unfortunately, the majority of these therapies may lead to late serious ocular sequelae. 2,​3,​9,​10,​17,​36


5.6.1 Beta-Irradiation


Beta-irradiation (Strontium-90) has reportedly reduced recurrence rates, via reducing the rate of proliferating cells in the wound bed. 3 However, there are a plethora of possible late complications, such as scleral melts, infectious scleritis, endophthalmitis, corneal perforation, cataract, iris atrophy, secondary glaucoma, calcific scleral plaque, conjunctivitis, keratitis, ptosis, and limbal stem cell deficiency (and resultant severe ocular surface disease). 2,​9 This treatment has largely fallen out of favor in the United States, but is still in use in other countries.


5.6.2 Thiotepa


Thiotepa is a nitrogen mustard-alkylating agent with antimitotic properties that is thought to be able to obliterate proliferating vascular endothelial cells. 3 It was originally used in Japan in conjunction with the bare sclera technique, decreasing recurrence rates to approximately 12 to 16%. 3 However, this compound is also associated with adverse effects, such as prolonged conjunctival hyperemia, irritation, allergy, bacterial corneoscleritis, and permanent eyelid depigmentation. 3


5.6.3 Corticosteroids


Corticosteroids, either given as a drop or via subconjunctival injection, have been found to be a useful adjunct in some cases in preventing recurrence. 8 Use of corticosteroids is thought to inhibit the inflammatory reaction induced by pterygium surgery and therefore reduces neovascularization at the operative site. 3 The dosing frequency and duration of treatment varies; corticosteroids may be used both preoperatively and/or postoperatively. 3


5.6.4 Mitomycin C


MMC is an antibiotic derived from the bacteria Streptomyces caespitosus, and acts as an alkylating agent that inhibits cell division by inhibiting DNA, cellular RNA, and protein synthesis. 2,​8,​17 It is most commonly used intraoperatively, applied to bare sclera, but has also been used pre- and postoperatively. 2,​8,​9,​17 MMC has a strong antiproliferative effect, owing to action on both fibroblasts and VEGF. 18 Research has shown that its adjunctive use has led to decreased recurrence rates with bare sclera, amniotic membrane graft, and conjunctival autograft techniques. 8,​17


5.6.5 5-Fluorouracil


5-FU is a pyrimidine analog that interferes with DNA and RNA synthesis. 2 It induces apoptosis of Tenon’s fibroblasts, has anti-fibroblast activity, and may be used intraoperatively. 2,​9 This medication is relatively affordable and is readily available compared to some other adjunctive therapies (e.g., anti-VEGF). 9 Although efficacious, it should be remembered that side effects of chemotherapeutic agents (e.g., MMC and 5-FU) are potentially serious and mimic those seen with beta-irradiation, including punctate epitheliopathy, increased intraocular pressure, and delayed onset scleral melt. 2,​8,​9


5.6.6 Alcohol


Alcohol has been used as an adjunctive therapy, secondary to its ability to denature cytokines and growth factors, which may be involved in pterygium formation. 9 In addition, there have been studies demonstrating a decreased rate of recurrence and fewer postoperative complications comparing alcohol versus MMC as adjunctive therapy. 9


5.6.7 Anti-VEGF


Anti-VEGF therapy has been employed as adjunctive treatment for pterygia and pterygia recurrence. 9 This therapy is of interest as pterygia exhibit significantly higher levels of VEGF than normal cornea and conjunctiva. 13 Thus, blocking VEGF may halt the vascularity and growth of pterygia. 13 In addition, anti-VEGF also reduces inflammation and thus may reduce pterygium symptoms (e.g., redness and irritation). 14 Bevacizumab (Avastin, Genentech Inc., San Francisco, CA) is an anti-VEGF recombinant humanized murine monoclonal IgG1 that inhibits the VEGF-A isoform, the predominant stimulant of angiogenesis. 13 Recently, a randomized clinical trial reported the use of subconjunctival bevacizumab in conjunction with primary pterygium excision with conjunctival autograft to be safe and well tolerated, as well as capable of preventing recurrence when compared to control. 9,​13 There may also be a dose-dependence inhibitory effect of bevacizumab on cultured Tenon’s fibroblasts, as studies have shown positive results with increased frequency of dosing, either via subconjunctival injection or topical eye drop administration. 13


5.7 Role of Ocular Surface Health


In addition to induced astigmatism, potential limitation of extraocular motility, and binocular diplopia, pterygia can also impair vision through an altered tear film and epiphora. 6 The combination of pterygium and dry eye (either in coexistence or one exacerbating the other) can perpetuate the symptomatology and growth of pterygium, as well as its recurrence after surgery. 6,​15,​18 This fact leads us to perform a detailed dry eye evaluation in all our pterygia patients. It becomes obvious that maintenance of a healthy ocular surface and tear film is essential in these patients for optimal anatomical, clinical, and surgical outcomes.


In a study by Kampitak et al, it was determined that eyes that were post-pterygium excision with amniotic membrane who received lubrication therapy with artificial tears had a significantly lower recurrence rate (16%) compared to the control group (33%). 18 Additionally, double-headed pterygia have been found to be associated with dry eye. 15 These findings and others lead us to aggressively treat our patients for their associated dry eye disease.


Multiple studies have examined different dry eye symptoms and parameters (tear osmolarity [TOT]), tear breakup time (TBUT), Schirmer’s testing, corneal staining, and their relation to pterygium growth, symptomatology, and recurrence. 19,​20,​21,​22,​23,​24,​25,​29,​30 Schirmer’s and TBUT scores in pterygium patients are significantly reduced compared to those in controls, suggesting that both aqueous and mucin deficiency of the ocular surface may be inciting factors for pterygium growth. 19,​20,​21,​29,​30 In addition, improvement in TBUT, tear ferning tests and goblet cell densities have been shown post pterygium excision, demonstrating that tear function in patients with pterygium has a close relationship to dry eye, and that the presence of pterygium may initiate or exacerbate its symptoms. 21,​25 In most cases, there is evidence of surface irritation on examination, as seen in ▶ Fig. 5.6, ▶ Fig. 5.7, ▶ Fig. 5.8.



Lissamine green staining on the surface of a pterygium.


Fig. 5.6 Lissamine green staining on the surface of a pterygium.

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Mar 22, 2020 | Posted by in OPHTHALMOLOGY | Comments Off on Ocular Surface and Tear Film Management in Pterygium Surgery

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