Int Ophthalmol
DOI 10.1007/s10792-016-0358-5
REVIEW
Developments and current approaches in the treatment
of pterygium
Dilek Hacıoğlu . Hidayet Erdöl
Received: 14 March 2016 / Accepted: 18 September 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract
Purpose To assess and compare the studies conducted
in the literature with recurrence rates and the summary
of the justified treatment approaches be presented.
Method Pterygium, a fibrovascular tissue that pro-
ceeds from the bulbar conjunctiva towards the cornea,
is quite a commonly seen ocular surface deterioration.
The treatment is performed through a surgical exci-
sion, and the frequent recurrence of this disorder,
despite the developments of today, is the major
problem experienced in the wake of the surgery.
There are various treatment methods applied for the
prevention of recurrence; yet, there is no definite view
as to what treatment is the most effective one. Since
the recurrent pterygium cases are more aggressive
than the primary pterygium, it is of great importance to
determine the treatment method in which recurrence
rate is the lowest. In different studies seen in the
literature, there is difficulty in comparing the results
due to the fact that the follow-up periods, recurrence
criteria and the doses and durations of the medications
administered differ from one another.
D. Hacıoğlu
The State Hospital of Iğdır, Kışla Neighborhood,
Melekli Mainstreet, Iğdır, Turkey
e-mail: dilenkh@hotmail.com
H. Erdöl (&)
Department of Ophthalmology, Medical Faculty,
Karadeniz Technical University, Trabzon, Turkey
e-mail: erdolhidayet@yahoo.com
Conclusion When the literature is reviewed, the bare
sclera technique is not used due to the high rate of
recurrence, whereas successful results can be achieved
through the conjunctival autograft technique. Lower
recurrence rates have been reported along with the
administration of mitomycin C, 5-FU and other agents
that were used as an adjuvant treatment.
Keywords Pterygium
Treatment
Surgery

Antineoplastics
Radiotherapy
Introduction
Pterygium, which is defined as the triangular fibrovas-
cular tissue that proceeds from the bulbar conjunctiva
towards the cornea, is a commonly seen eye disorder.
It is often localized in the nasal side but can still be
seen in the temporal side, as well. Its etiopathogenesis
has not been precisely clarified, and UV rays in
particular [1, 2]. In a study conducted by Cameron
et al. in 1965, it was reported that pterygium had been
frequently seen between the 37th parallel north and the
37th parallel south and that the incidence of this
disorder had increased in the areas closer to the
equator [3]. These latitudes are defined as the ptery-
gium region, and it was argued that the angle of UV
rays in reaching the earth had played a role in the
aetiology of pterygium [3]. The fact that pterygium is
also seen in different regions supports the fact that
there are also other factors in its aetiology, apart from
123

UV rays [4]. Hot and dry weather and environmental
conditions such as a dusty atmosphere as well as the
period of exposure to such conditions play an impor-
tant role in the development of pterygium. The reason
why it is more commonly seen in males compared to
females is identified with the fact that the males work
for longer periods outdoors than females [5].
Within the pterygium tissue, the collagen fibres lose
their normal structure, the normal elastogenesis is
interrupted and an elastic material formation of
anomalous structure occurs. It was shown that the
mast cells found at a lower rate in the conjunctival
tissue had increased in the pterygium tissue and that
these cells had multiplied in the stroma within the
perivascular and elastoid degeneration areas [6]. In
addition, it was shown that various cytokines, such as
interleukin, tumour necrosis factor and vascular
endothelial growth factor, had increased, as well [7, 8].
It was also considered that genetic factors might
also have played a role in pterygium, and it was
demonstrated in the studies conducted that genetic
transition had an autosomal dominant and low pene-
tration [9]. It was also shown in the studies that UV
rays caused mutation in p53, a tumour suppressor
gene, which, then, led to the formation of abnormal
pterygium epithelial cells [10, 11].
The primary treatment for pterygium is the surgical
excision; yet, there is still no definite view as to which
surgical interventions are most effective one [12, 13].
In different studies seen in the literature, there is
difficulty in comparing the results due to the fact that
the follow-up periods, recurrence criteria and the
doses and durations of the medications administered
differ from one another. Various treatment modalities
have been developed due to the high rate of post-
surgical recurrences, and adjuvant treatment methods
are performed if required [14, 15]. Since the recurrent
pterygium cases are more aggressive than the primary
pterygium, it is of great importance to determine the
treatment method with the lowest recurrence rate.
Today, the pterygium tissue is regarded as a tumour
rather than a degenerative lesion, and in the treatment
of this disorder, the medications used in the treatment
tumour are increasingly used as the adjuvant treat-
ment. In this article, it was aimed that the studies
conducted in the literature be revised and the summary
of the justified treatment approaches be presented.
Table 1 summarizes the recurrence rates for different
surgical procedures and adjuvant therapies.
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Int Ophthalmol
Surgical treatments
Bare sclera technique
One of the oldest methods used in the surgical
treatment of pterygium, bare sclera technique is the
method of leaving the scleral area open after the
excision of the pterygium tissue so as to allow for a
spontaneous closure by the conjunctiva surrounding
the scleral area. High rate of recurrences was reported
to be seen between 38 and 88 % in various publica-
tions [15, 16]. Since it has a high recurrence rate,
applying the bare sclera method not alone but along
with additional therapies, such as intraoperative
mitomycin C, postoperative mitomycin C and 5-FU
and thiotepa, yields more successful results.
Kareemet et al. [17], in a study they conducted,
evaluated the recurrence rate as 32 % when applied
with bare sclera technique, 8 % when applied along
with intraoperative mitomycin C and as 18 % when
applied along with intraoperative 5-FU. Yanyaliet al.
[18], in their study, evaluated the recurrence rate as
57.8 % when applied with bare sclera technique and as
21 % when applied with intraoperative mitomycin C;
on the other hand, Demirok et al. [19] evaluated this
rate as 40 % along with the bare sclera technique and
as 5.9 % when applied with intraoperative mitomycin
C. Vermaet et al. [20], however, reported the recur-
rence rate as 48 % when applied together with the bare
sclera technique on the cases with recurrent pterygium
and as 3 % with the use of intraoperative mitomycin
C, while Mastropasquaet et al. [21] reported it as
Table 1 Summary recurrence rate by surgical technique and
adjuvant therapies
Techniques Recurrence
rate (%)
Bare sclera 38–88
Conjunctival autograft 5–30
Conjunctival autograft with fibrin glue 5.5–11.9
Limbal conjunctival autograft 0–15
Amniotic membrane graft 6–40
Adjuvant therapies
MMC 0–40
5-FU 5–25
Anti-VEGF 66.7
Radiotherapy 0–50
Int Ophthalmol
35.6 % after the application of bare sclera technique
and as 12.5 % with the administration of intraopera-
tive mitomycin C. Bare sclera technique must be used
along with the adjuvant treatment because of the high
recurrence rates seen when applied alone.
Conjunctival autograft
Conjunctival autograft technique was first performed
by Kenyon et al. in 1985 [22]. Conjunctival autograft
suturing procedure is performed on the location of the
pterygium tissue excised by being removed from the
upper temporal part of the bulbar conjunctiva within
the same eye or in the other eye. In the study conducted
by Kenyon et al., the recurrence rate was reported to be
at a lower rate like 5.3 % [22]. In the succeeding
studies, the recurrence rate may vary between 5 and
30 % [23–31]. Lewallenet al. reported the recurrence
rate, when applied with conjunctival autograft, as
21 % in the tropical region [23], whereas Allan et al.
reported it as 6.5 % [24].
In the study conducted by Tiet al., it was found that
the recurrence rate in the cases with primary ptery-
gium proved to be 20.8 %, whereas it proved to be
31.2 % in the cases with recurrent pterygium [25]. It
was stated that the recurrence rates had varied between
5 and 82 % in the conjunctival autograft technique
performed by different surgeons, which was also said
to be probably due to the experiences of the surgeons
and the differences in the methods they used [25].
In other studies performed through the use of this
technique, Kmihaet al. reported the recurrence rate as
10 % [26], while Seid et al. found it as 6.2 % [27]; on
the other hand, Chaidaroon et al. found this rate as 5 %
[28]; Huerva et al. found it as 11.76 % [29], whereas
Varssano et al. reported it as 11.4 % [30] and
Kocamışet al. reported it as 8 % [31]. Conjunctival
autograft technique is a procedure that takes longer
time and requires experience. Today, in the conjunc-
tival autograft technique, the duration of the surgery
takes shorter time along with the use of fibrin glue or
autologous blood instead of suturation. The patient
comfort gets better during the postoperative period
since no suture is used. It was shown in various
publications that the duration of the operation took
shorter time when fibrin glue was used and that the
patient comfort during the postoperative period got
better when compared with the surgery performed by
means of suture [32–39]. It was reported in some of the
studies performed in terms of recurrence that there
were more recurrences with the use of fibrin tissue
glue, while in some others, there was a higher
recurrence rate in the procedure performed by means
of suture. Koryani et al. reported the recurrence rate
after the use of fibrin glue as 5.3 % and after the
application of suture as 13.5 % [32]. On the other
hand, Bahar et al. reported that the recurrence rate with
the use of fibrin glue was 11.9 %, while it was 7.7 %
after the use of suture [36]. Since fibrin tissue glue is
costly and it has the risk of causing infection, today the
use of autologous blood fibrin has come to the others
the alternative. Successful results have also been
reported with respect to the use of autologous blood
fibrin in conjunctival grafting procedure [40–43].
In the wake of the conjunctival grafting procedure,
complications such as corneoscleral dellen, graft
oedema, epithelial cysts, suture granuloma, flap
retraction and necrosis can be seen. In the light of
the studies conducted in recent years, the conjunctival
autograft technique can be preferred as the primary
treatment in pterygium surgery due to the low
complication and recurrence rates.
Limbal conjunctival autograft
Since, in the etiopathogenesis of pterygium, there is
the view that the progression of conjunctival cells
towards the cornea cannot be hindered as the result of
the insufficiency of limbal stem cells, the elimination
of limbal insufficiency by including limbus in the
conjunctival autograft has come to the fore [44].
Limbal conjunctival autograft contains approxi-
mately 0.5 mm of limbal and peripheral corneal tissue.
A better anatomic and functional result will be
achieved by including limbus epithelium in the
conjunctival graft, and thus, the barrier function in
the limbus will have been ensured once again, and the
pterygium recurrence will be minimized. In the
conducted studies, the application of limbal conjunc-
tival autograft was reported to have been effective in
preventing the pterygium recurrence. The recurrence
rate in the wake of limbal autograft varies between 0
and 15 % [45–49]. Malik et al. reported the recurrence
rate after limbal conjunctival autograft as 2.5 % [47],
whereas Al fayez et al. reported it as 1 % [48] and
Masters et al. reported it as 2.14 % [49]. The
recurrence rates after the conjunctival autograft and
limbal conjunctival autograft show similarity to one
123

another. Apart from the fact that including the limbal
tissue in the grafting procedure in limbal conjunctival
graft technique extends the duration of the surgery,
this process requires more experience than the
conjunctival autograft technique.
Application of amniotic membrane
Amniotic membrane is the innermost layer of the
placental foetal membrane. It has anti-inflammatory,
antiangiogenic and neurotrophic effects. It poses an
inflammation-reducing effect with the protease inhi-
bitors it contains [IL-1 receptor antagonist and lacto-
ferrin] [50, 51]. It also reduces neovascularization
with the antiangiogenic proteins it contains [50, 51]. It
poses a neurotrophic effect since it synthesizes various
neurotransmitters and neuropeptides. The amniotic
membrane regulates the levels of cytokines and
growth factors. It provides advantages in wide-area
defects or in the cases such as scars on which
conjunctival grafts cannot be performed and also in
the patients on which no graft can be performed in
terms of glaucoma surgery afterwards. In various
studies conducted so far, it has been reported that the
recurrence rate had varied between 6 and 40 % after
the application of amniotic membrane [52–59]. Okoy-
eet al., in their study, reported the recurrence rate as
6 % after the amniotic membrane practice [53],
whereas Arain et al. reported it as 12.9 % [54],
Solomonet al. as 15.6 % [55] and Essex et al. reported
a high recurrence rate like 64 % [56].
Lianget al., on the other hand, found the recurrence
rate as 7.4 % when conjunctival autograft was
performed, whereas the recurrence rate they found
after the application of amniotic membrane was
19.2 % [57]. Tananuvat et al. found that the recurrence
rate in the conjunctival autograft technique was
4.76 %; yet, it proved to be 40.9 % in the amniotic
membrane transplantation technique [58].
Again, in the same way, Luanratanakorn et al.
stated that the recurrence rate after the conjunctival
autograft was 13.1 %; however, it proved to be 28.1 %
in the wake of applying amniotic membrane [59].
Since the recurrence rates after the application of
amniotic membrane are higher than those in the
conjunctival autograft practice, it seems more appro-
priate for the amniotic membrane application to be
performed particularly in the cases with recurrent
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Int Ophthalmol
pterygium for whom no conjunctival autograft can be
provided, in those in need of a glaucoma surgery and
also in wide-area defects.
Adjuvant treatments
These treatments are performed along with surgical
treatments in order to prevent recurrence. Although
they often accompany bare sclera and primary
conjunctival closure methods, they can be combined
with all the surgical methods.
Antineoplastics
Mitomycin C[MMC] This is an alkylating agent
which destroys the DNA synthesis and inhibits mitosis
and protein synthesis. It is used in pterygium surgery to
stop subconjunctival tissue proliferation and the
fibroblastic activity. It is also used both intraopera-
tively and postoperatively in pterygium surgery. After
the pterygium tissue has been intraoperatively excised,
the sponge pieces impregnated with mitomycin in
0.01–0.05 % concentration are kept on the exposed
sclera for 3–5 min, after which the surgery is continued.
Mitomycin C, which is turned into the form of drop by
being diluted postoperatively in 0.01–0.05 %
concentration, is used twice or four times a day from 5
to 14 days in accordance with different treatment
protocols. When the publications regarding pterygium
excisions including the use of Mitomycin C are
reviewed, quite different recurrence rates attract the
attention. While in some practices, the recurrence rate
drops down to 0 %, it is stated in the literature to have
reached up to 40 % when applied along with the bare
sclera technique in particular [19, 20, 60].
While there is still no consensus as regards for how
long and at what doses MMC should be used, the
success rate goes up with high dose and concentration
practices, whereas the incidence of the risk of
complications due to a given dose increases.
In a study conducted by Paracha et al., the uses of
conjunctival autograft and intraoperative MMC were
compared, and the recurrence rate in the autograft
technique proved to be 8 %, whereas in the use of
intraoperative MMC, it was reported to be 16 % [61].
In the study conducted by Young et al., which
involved a 10-year observation, the uses of intraoper-
ative MMC and the limbal conjunctival autograft
Int Ophthalmol
technique were evaluated; eventually, the recurrence
rate in the group to which 0.02 % MMC was
intraoperatively administered proved to be 25.5 %,
whereas it was found to be 6.9 % in the application of
limbal conjunctival autograft technique [62].
Maledeet al. reported the recurrence rate after the
conjunctival autograft as 3.33 %, and with the use of
intraoperative MMC, it proved to be 23.3 % [63].
Again, in the studies comparing the conjunctival
autograft performed in the same way with the use of
MMC, the conjunctival autograft technique was
evaluated to have been more successful. However, in
the publications in which the conjunctival autograft
technique was stated to have been used along with
MMC, the recurrence rate was reported to have varied
between 0.02 and 4.6 % [64–67].
When the use of MMC is performed alone, a high
rate of recurrence is seen; yet, when it is performed in
combination with the conjunctival autograft tech-
nique, more successful results are achieved. Due to the
use of MMC, some complications such as scleral
necrosis [68–72], corneal perforation, cataract, glau-
coma, photophobia and pain may develop. The risk of
the development of a complication increases in the
high dose and long-term use of MMC [70]. When the
studies within the literature are reviewed, it is seen that
the conjunctival autograft technique is more efficient
than the use of MMC. When serious complications
that develop due to the use of MMC are also taken into
consideration, it is seen that administering MMC to
the cases with recurrent pterygium in particular is
more appropriate than administering it to the cases
with primary pterygium.
Thiotepa This is an alkylating agent analogous with
nitrogen mustard. It inhibits mitosis and division
within the rapidly multiplying tissues. After the
surgical excision of pterygium, it is used four times
a day for 6–8 weeks in the form of a drop in 0.05 %
concentration. The recurrence rates observed in the
wake of this procedure have been reported to be
between 0 and 28 %.
Ngoy et al. reported a recurrence rate by 28 % with
the use of thiotepa [73], whereas Tassy et al. reported
recurrence as 3 % [74] and Wu et al. reported the
recurrence rates as 10 % [75]. Thiotepa is not
preferred for use today since it causes black pigment
deposits on the eyelids and hyperpigmentation of the
skin as well as allergic reactions and local irritations.
Fluorouracil This antimetabolite, which is a
pyrimidine analogue, inhibits the thymidylate
synthetase and prevents fibroblast proliferation.
After the excision of pterygium, it is usually kept on
the bare sclera for 3–5 min by being impregnated with
sponge pieces in 25 mg/ml concentration. In the
literature were recurrence rates varying between 5
and 25 % reported. Akarsuet al. reported recurrence
by 25 % [76], while Bekilebe et al. reported a
recurrence rate by 11.4 and 8.7 % [77, 78] in two
separate studies they conducted; on the other hand,
Salustana et al. reported a recurrence rate by 5.83 %
[79]. The fact that it has local irritant effects, though
not as much as Mitomycin, restricts its applicability.
Anti-VEGF agents
The fact that VEGF level in the pterygium tissue was
found to be higher than normal conjunctiva suggests
that the use of anti-VEGF drugs during the treatment
could be effective [80, 81]. Ranibizumab and Beva-
cizumab, as the anti-VEGF drugs, are applied on the
eye in the form of a subconjunctival or topical drop.
Tenget al. showed that vascularization in the
pterygium tissue had diminished after the subcon-
junctival Bevacizumab injection [80]. Kocabora et al.,
in their study in which the uses of subconjunctival
Bevacizumab and MMC were compared, found that
the recurrence rate within the group to which beva-
cizumab was administered proved to be 66.7 %,
whereas the recurrence rate within the group to which
MMC was administered was found as 26.7 % [82].
Again, in various studies conducted so far, it was
shown that subconjunctival practice had not prevented
the development of recurrence [83–85]. Kasetsuwan
et al., on the other hand, demonstrated that the use of
topical bevacizumab had prevented the recurrence of
pterygium [86]. Again, in the same way, there have
been studies showing that the postoperative topical
bevacizumab minimizes the recurrence of pterygium
[87–89], and it seems that there is the need to conduct
more extensive studies to determine the long-term
efficiency and reliability of anti-VEGF drugs.
Radiotherapy
This is the method of treatment in which high-energy,
beta-emission radioactive substances are used. The
radiation formed poses an effect by suppressing the
123

obliteration of arterioles as well as the fibroblast
proliferation. It is the oldest method used as an
adjuvant therapy in the treatment of pterygium, and
Ruthenium 106 and Sr 90 are more frequently used as
the radioactive substances. It is almost always used
along with the bare sclera technique. After the
excision of pterygium, the radioactive plaque is
sutured on the sclera and is kept there until the desired
dose is reached. There are numerous treatment proto-
cols and dose schemes recommended for this method,
as well. The recurrence rates reported in the literature
vary between 0 and 50 % [90–92]. In this practice, rare
but serious complications such as scleral necrosis,
cataract, corneal perforation and endophthalmitis may
develop [93, 94]. When the challenges in its applica-
tion, high costs and possible serious complications are
taken into consideration, radiotherapy is not com-
monly used as the adjuvant treatment.
Conclusion
Although there are different approaches in the treat-
ment of pterygium, they have some advantages and
disadvantages. Therefore, these should be taken into
account in the treatment of pterygium. It should be
decided according to the clinic of pterygium which
treatment would be implemented. Here, surgeon’s
experience and clinic of pterygium is important.
Compliance with ethical standards
Conflict of Interest The authors declare that they have no
conflict of interest.
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