Current concepts and techniques in pterygium treatment Ang , and Donald T.H. Tan

Current concepts and techniques in pterygium treatment
Leonard P.K. Anga,b,c, Jocelyn L.L. Chuaa,c and Donald T.H. Tana,b,c
Purpose of review
Pterygium is a common ocular disorder in many parts of the
world. At present, there is a wide variety of surgical methods
but very few clinical guidelines on the optimal treatment of
primary or recurrent pterygium. The purpose of this review is
to summarize the more recent and relevant studies on
pterygium treatment.
Recent findings
The primary aim is to excise the pterygium and prevent its
recurrence. As bare sclera excision is associated with a high
recurrence rate, pterygium excision is often combined with
conjunctival autograft, mitomycin C, beta-irradiation or other
adjunctive therapies to reduce recurrence rates. There is
currently, however, no consensus regarding the ideal
treatment for the disease. Comparability between studies is
also hampered by the various definitions of pterygium
recurrence.
Summary
This article reviews the current concepts and techniques
used for the treatment of pterygium. Conjunctival
autografting and mitomycin C application are the most
commonly used methods for preventing recurrences. The
use of mitomycin C and beta-irradiation should be used
judiciously because of the potential long-term risk of
sight-threatening complications. Additional clinical trials
should be performed to evaluate the relative efficacies and
long-term safety of the various treatment modalities.
Keywords
beta irradiation, conjunctival graft, excision, mitomycin,
pterygium
Curr Opin Ophthalmol 18:308–313. ß 2007 Lippincott Williams & Wilkins.
a
Singapore National Eye Centre, bDepartment of Ophthalmology,
Yong Loo Lin School of Medicine, National University of Singapore and
c
Singapore Eye Research Institute, Singapore
Correspondence to Leonard P.K. Ang, MD, Singapore National Eye Centre,
11 Third Hospital Avenue, Singapore 168751
Tel: +65 62277255; fax: +65 62277266; e-mail: leopk@pacific.net.sg
Introduction
Pterygium is a common disorder in many parts of the
world, with reported prevalence rates ranging from 0.3
to 29% [1,2]. Epidemiological studies [1,2] suggest an
association with chronic exposure to sunlight, with an
increased geographical prevalence within a peri-equatorial
‘pterygium belt’ of latitudes of 378 north and south of the
equator. The various treatments for pterygium are aimed
at reducing recurrence of the lesion. Over the years, many
surgical procedures to excise this recurrent disorder have
been described. An excellent and comprehensive review
of the existing literature by Hirst [3] demonstrated the
wide variation in the modern surgical techniques and
reported success rates for pterygium surgery today.
The purpose of this review is to present a summary of the
more recent literature, paying particular attention to
prospective randomized studies. We also included our
views and personal experience in the management of this
disease.
Current concepts in pterygium pathogenesis
The UV type B light in solar radiation has been found to be
the most significant environmental factor in pterygium
pathogenesis [1,2]. Recent studies [4–7] have suggested
that p53 and human papillomavirus may also be implicated
in pterygium pathogenesis. UV radiation can cause
mutations in genes such as the p53 tumor suppressor gene,
resulting in its abnormal expression in pterygial epithelium. These findings suggest that pterygium is not just
a degenerative lesion, but could be a result of uncontrolled
cell proliferation [6,7]. Matrix metalloproteinases (MMPs)
and tissue inhibitors of MMPs (TIMPs) at the advancing
pterygium edge may be responsible for the inflammation,
tissue remodeling, and angiogenesis that characterize
pterygia, as well as the destruction of Bowman’s layer
and pterygium invasion into the cornea [4–7]. Tseng
et al. [8] have also speculated that pterygium may represent
an area of localized limbal stem cell deficiency.
Current Opinion in Ophthalmology 2007, 18:308–313
ß 2007 Lippincott Williams & Wilkins
1040-8738
Pterygium recurrence
The definition of pterygium recurrence varies among
studies. Most ophthalmologists define pterygium recurrence as corneal recurrence, which include regrowth of
fibrovascular pterygium-like tissue crossing the limbus
onto the cornea, fibrovascular recurrence attaining the
same degree of corneal encroachment as the original
lesion, or regrowth exceeding 1 mm onto the cornea.
308
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Pterygium treatment Ang et al. 309
Treatment of pterygium
The main aims of surgery are to completely excise the
pterygium and to prevent its recurrence.
recurrence rates associated with intraoperative and postoperative mitomycin C use are not significantly different.
Intraoperative mitomycin C treatment
Pterygium excision
Removal of the pterygium involves surgical excision of
the head, neck and body of the pterygium. The body and
base of the pterygium are dissected with conjunctival
scissors, while the head and neck of the pterygium that
has invaded the cornea is often removed with a surgical
blade. 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 blade.
As 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 4–6 mm from the limbus,
as retraction of the surrounding conjunctiva results in
enlargement of the surgical defect.
If 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 [9–11].
As such, bare sclera excision alone is no longer recommended for the treatment of pterygium.
The concentration of intraoperative mitomycin C application used in most of the studies range from 0.01 to 0.04%,
with 0.02% applied for 3 min being the commonest dosage
used [9,10,12–14]. The reported recurrence rates associated with intraoperative mitomycin C use range from 3 to
37.9%. 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 0.02 and 0.04% 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 complications.
Postoperative mitomycin C treatment
Postoperative mitomycin C eyedrops have also been shown
to be effective, with 0.02% being the commonest concentration used (concentrations used range from 0.005 to
0.04%) [11,13–15]. 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% [11,13–15]. 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 complications.
Prevention of pterygium recurrence
Pterygium 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 methods
Intraoperative 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 treatment
Mitomycin C treatment has been shown to be effective in
preventing recurrence for primary and recurrent pterygium
[9–15]. 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 – the intraoperative application 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 [9–16]. Studies [11,13,14] have shown that the
Although mitomycin C has been shown to be an effective
treatment for pterygium, its use has been associated with
serious sight-threatening complications, which may present 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.
Other medical treatment
Several isolated studies have proposed alternative
methods of treatment. Dadeya and Kamlesh [18] demonstrated a statistically significant difference in the recurrence rate of patients who were treated with daunorubicin
and those that received water placebo. Treated eyes were
more chemotic (20%), however, with 6.7% having delayed
epithelialization, compared with the control eyes, which
did not have similar complications.
Sodhi et al. [19] reported comparable results with the use of
doxorubicin and mitomycin C. In a study that evaluated
the use of 5-fluorouracil, Maldonado et al. [20] reported that
this was not effective in preventing pterygium recurrence.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
310 Corneal and external disorders
A randomized controlled prospective study [21] comparing
5-fluorouracil to conjunctival autograft showed a marginal
reduction in recurrence rate with the former. Larger
randomized clinical trials with longer follow-up periods
would need to be performed to evaluate the efficacy and
long-term safety of each of these potential treatment
options.
Beta-irradiation
Various 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 [22–24]. Although this
modality of treatment has been used for decades, few
prospective studies have been described. The use of postoperative 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 eyedrops.
Beta-irradiation is a less popular procedure because of the
inconvenience of arranging its treatment and the longterm 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 methods
The surgical options available include the use of conjunctival autograft, limbal and limbal–conjunctival transplant,
conjunctival flap and conjunctival rotation autograft surgery, amniotic membrane transplant, cultivated conjunctival transplant, lamellar keratoplasty and use of fibrin glue.
Conjunctival autografts
Conjunctival autograft surgery is generally regarded as
the procedure of choice for the treatment of primary and
recurrent pterygium, because of its efficacy and longterm safety [26–32]. A free conjunctival graft is harvested
from the superior bulbar conjunctiva and is sutured in
place over the bare scleral defect [9–11,13,14]. 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 [29,33–39]. A retrospective noncomparative case series [40] has shown
that juxtalimbal narrow-strip conjunctival autograft with
posterior epithelized bare sclera zone is effective in
preventing pterygium recurrence.
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 [27,28]. Sharma
et al. [28] demonstrated that there was no statistically
significant difference in the recurrence rates between
conjunctival autografting and mitomycin C use. A combination of conjunctival autograft with low dose (0.2 mg/ml)
mitomycin C was shown in a prospective randomized
comparative study by Frucht-Pery et al. [41] to have
a significantly lower recurrence rate compared with
conjunctival graft alone.
ComparedwiththeuseofmitomycinC andbeta-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. Once the surgical technique is
mastered, however, conjunctival autografting is generally
considered to be a better option than the other treatment
modalities, because of its proven efficacy and its long safety
record.
Limbal and limbal–conjunctival transplantation
It has been suggested that including limbal stem cells in
the conjunctival autograft (limbal–conjunctival graft)
may act as a barrier to conjunctival cells migrating onto
the corneal surface and help prevent recurrence. The
limbal–conjunctival graft includes approximately 0.5 mm
of the limbus and peripheral cornea. The corneal limbal
side of the graft is sutured in place with interrupted 10/0
nylon sutures, and the conjunctival side is sutured with
10/0 absorbable sutures.
The recurrence rates after limbal–conjunctival autograft
surgery (ranging from 0 to 15%) are similar to that of
conjunctival autograft surgery [29,33–35], while some
authors suggest that limbal–conjunctival autografts are
more effective than conjunctival autografts for recurrent
pterygium [34]. Oguz et al. [42] demonstrated an overall
recurrence rate of 9.52% with limbal conjunctival miniautografting performed in 63 eyes. Young et al. [35]
prospectively compared mitomycin C and limbal–
conjunctival autograft surgery in preventing pterygial
recurrence, and showed that the mitomycin C group
was associated with a higher recurrence rate (15.9%)
compared with the limbal–conjunctival autograft group
(1.9%). A major drawback for limbal–conjunctival autograft 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–conjunctival autografts over conventional conjunctival autografts exists,
and the added risk of limbal damage at the donor site
deserves consideration.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Pterygium treatment Ang et al. 311
Conjunctival flap and conjunctival rotation autograft surgery
Lamellar keratoplasty
Two reports [36,37] 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 [38,39]. 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 conjunctival tissue for the autograft.
Lamellar 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.
Amniotic membrane transplantation
Fibrin glue
Amniotic membrane transplantation has recently been
proposed as a treatment option [43–46]. 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 conventional epithelized cryopreserved human amniotic
membrane, the efficacy of membranes that are alternatively prepared such as the de-epithelized [47] or freezedried 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 [44,45,50] 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 autograft. This result is also supported by Luanratanakorn
et al. [50].
Fibrin glue (or Tisseel) has been used as an alternative to
sutures for securing conjunctival grafts [53–56]. 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.
Cultivated conjunctival transplantation
A 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 membrane transplantation, operated eyes achieved almost immediate reepithelialization of the ocular surface, reduced
postoperative inflammation and faster ocular rehabilitation. This procedure may be particularly useful for closing
large surgical defects following excision of extensive
pterygium.
In a retrospective study, Koranyi et al. [54] demonstrated
a pterygium recurrence rate of 5.3% with glue versus
13.5% with sutures. The authors suggested that immediate adherence of the graft and the lack of postoperative
inflammation may inhibit fibroblast ingrowth and reduce
recurrence. 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 technique. 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 sequelae.
Of greater concern is the potentially serious sight-threatening complications that have been associated with the use
of adjunctive mitomycin C and beta-irradiation, such as
scleral necrosis, infectious scleritis, severe secondary glaucoma, iritis, cataract, corneal edema, corneal perforation,
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
312 Corneal and external disorders
and endophthalmitis [17,25]. Complications arising from
the use of beta irradiation have been reported in up to
13% of patients, with latency periods of up to 14.5 2.5 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.
Conclusion
Pterygium 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 methodology 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.
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