nurbuanto


179

Pterygium: degeneration, exuberant wound healing
or benign neoplasm?

September-December, 2009September-December, 2009September-December, 2009September-December, 2009September-December, 2009                            Vol.28 - No.3                           Vol.28 - No.3                           Vol.28 - No.3                           Vol.28 - No.3                           Vol.28 - No.3

UNIVERSA MEDICINA

Nurbuanto Tradjutrisno*

*Department of Ophthalmology,
Gatot Subroto Central Military
Hospital, Jakarta

Correspondence
dr. Nurbuanto Tradjutrisno,SpM
Department of Ophthalmology,
Gatot Subroto Central Military
Hospital
Jl. Abdul Rahman Saleh No.24,
Jakarta Pusat
Phone: 021-3441008
Email:
ntradjutrisno@gmail.com

Univ Med 2009;28:179-87

ABSTRACT

Pterygium is a condition characterized by the encroachment of a fleshy triangle of
conjunctival tissue into the cornea. Despite various studies, the pathogenesis of
pterygium remains unclear. Chronic exposure to sun is the only factor of which the
role has been clearly documented by epidemiologic and in vitro studies. Recent
studies have provided data such as loss of heterozygosity and microsatellite
instability, decreased apoptosis, increased growth factors, increased p53 expression,
telomerase activity, and presence of oncogenic viruses, which support the concept
that pterygia can be considered a neoplastic condition. Some of results are
contradictory and some features were only found in a proportion of pterygia; this
may be due to differences in methodology and study population, but may also be
indicative of multiple causative factors. This implies that the pterygium should be
viewed as a final common outcome of various etiological factors, such as geography
and ethnicity, with ultraviolet radiation-induced damage as the main factor. Thus
the pterygium remains an enigma, having the features of an exuberant growth but
also those of a benign neoplasm. In this connection there is a need for a unifying
theory capable of explaining all of the characteristics of the pterygium.

Keywords: Pterygium, apoptosis, growth, neoplasm

INTRODUCTION

Pterygium is a chronic disease that is
characterized by an aggressive invasion of fibro-
vascular tissue into the cornea, and is one of the
most common ocular surface diseases in tropical
and subtropical zones.(1) Many suffer from this
aggressive disease and its prevalence in the

general population has been estimated to be 7–
13%.(2,3) Two frequently encountered lesions of
the conjunctiva are pterygia and pingueculae(4)

Pterygia have been known since antiquity and
theories about their pathogenesis have been
proposed for a comparable length of time. One
of the theories that should be mentioned is that
of Fuchs, described in 1892.(5) Fuchs postulated



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Tradjutrisno                                                                                                                                                                             Pterygium

that the pingueculum is the forerunner of the
pterygium. Modern ophthalmology usually
d e s c r i b e  p t e r y g i a  a s  d e g e n e r a t i o n s  o f  t h e
conjunctiva originating from pingueculae, which
have been considered as precursors of pterygia.
However, Kanski(4) is of the opinion that pterygia
may represent a response to chronic dryness and
ultraviolet exposure, and does not mention any
relationship with pingueculae.(4) The association
of pterygia with chronic exposure to sunlight and
dryness had also been noted.(6)

The term “pterygium” (pteron = a wing)
usually refers to a triangular lesion on the
conjunctiva, but may also designate winglike or
weblike structures in other locations, such as the
n e c k  o r  e l b o w s .  T h u s  t h e  p t e r y g i u m  o f
ophthalmology should properly be called “ocular
pterygium” or “ophthalmic pterygium”. Omission
of the label “ocular” may result in the inclusion
of non-ocular pterygia in Internet searches based
on the key word “pterygium”, eg. multiple
pterygium syndrome.(7)

In connection with recent advances in
research on pterygia, this mini-review aims to
summarize some of the current views on the
pathogenesis of pterygia.

Pterygium morphology
A pterygium is usually described as a fleshy

triangular growth located in the interpalpebral
fissure, most frequently on the nasal side. The
lesion starts growing from limbal (or corneal)
stem cells in the limbal epithelium and invades
the cornea centripetally, eventually covering the
pupil. A typical pterygium consists of the apex
or head, the collarette or collar, the body and
the edges. The apex is the part of the pterygium
that invades the cornea as a raised whitish growth
firmly adherent to the cornea. Behind the apex
is the collar, which represents the limbal portion
of the pterygium and is continuous with the apex.
The apex is preceded by a hood or cap, which is
a crescent-shaped grayish avascular patch on the

corneal epithelium around the apex. In front of
the hood under the corneal epithelium there are
small irregular areas of grayish opacity called
Fuchs’ patches, and a fine yellow-green crescent-
shaped line (Stocker ’s line) resulting from
hemosiderin (iron) deposits in Bowman’s layer.
Stocker’s line is a morphological marker of a
chronic inactive pterygium; in rapidly advancing
lesions there is no time for the accumulation of
the iron. The body is the main fleshy part of the
pterygium, trapezoidal in shape and highly
vascularized. It has winglike lateral extensions
(the edges) consisting of conjunctival folds that
demarcate the pterygium from the normal
conjunctiva.(6,8) The iron deposition in Stocker’s
line has also been said to originate from tear film
lactoferrin.(9)

T h e  m a i n  h i s t o l o g i c a l  f e a t u r e s  o f  a
pinguecula are elastotic degeneration of the
collagen fibers of the conjunctival stroma,
thinning of the overlying epithelium, and
occasionally calcification. A pterygium has
essentially the same features as a pinguecula, but
with more neovascularization and thickening of
the conjunctival epithelium. In addition, there
is also destruction of Bowman’s layer and the
superficial corneal lamellae.

An in vivo study of 20 primary pterygia
from 15 patients by confocal microscopy using
t h e  n e w l y  d e v e l o p e d  H e i d e l b e rg  re t i n a l
tomograph II (HRT-II) with cornea module. Their
observations showed that the vascularization of
the pterygium formed loops at the leading edge
of the head of the pterygium and did not extend
into the healthy cornea.(6) In front of the pterygial
h e a d  g r o u p s  o f  c e l l s  c o u l d  c o m m o n l y  b e
observed that were more refringent than the
corneal epithelial cells. These cell clusters had
indistinct outlines and corresponded to Fuchs’
patches (ilôts de Fuchs). Occasionally the region
in front of the head took the form of an irregular
refringent band, which was more marked in
active pterygia.



181

I n  t e r m s  o f  g r o w t h  c h a r a c t e r i s t i c s ,  a
pinguecula may occasionally enlarge very
slowly, but seldom requires surgical excision. In
contrast, a pterygium ultimately progresses
towards the visual axis, when surgical excision
is indicated. Recurrence of pterygia after surgical
removal is a particularly difficult problem, for
which may solutions have been proposed, such
as postoperative administration of beta-radiation,
thiotepa, or mitomycin, none of them being
completely satisfactory.(9)

Ocular surface biology
The normal ocular surface is composed of

two types of epithelia, conjunctival and corneal,
each with a distinct cellular phenotype. The non-
keratinized conjunctival epithelium contains
mucin-expressing goblet cells, whereas the
corneal epithelium is a non-keratinized stratified
epithelium expressing the cornea-specific

keratins K3 and K12 and has mucin-expressing
non-goblet superficial epithelial cells. The
l i m b u s  o r  c o r n e o s c l e r a l  j u n c t i o n  i s  t h e
transitional zone between the conjunctiva and
cornea, and contains corneal stem cells, also
known as limbal stem cells. This finding was a
major advance in ocular surface epithelial
biology, as this discovery led to many other
research studies.(10)

In 1997 it was proven conclusively that
corneal progenitor cells are localized in the
limbus, by culturing limbal cells from patients
w i t h  c o m p l e t e  l o s s  o f  t h e  c o r n e o - l i m b a l
epithelium into sheets of corneal cells and
subsequently restoring the patients damaged
cornea by grafting of autologous corneal sheets.(11)

Characteristics of pterygia
T h e  c o m m o n l y  a c c e p t e d  f e a t u r e s  o f

pterygia may be summarized as follows: Pterygia

Univ Med                                                                                                             Vol.28 No.3

Figure 1. Pterygium morphology(6)

Legend: T = head of pterygium; c = collar of pterygium; C = body of pterygium; arrow = progressive zone of Fuchs; arrowhead
= Fuchs’s patch



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Tradjutrisno                                                                                                                                                                             Pterygium

originate in the limbal epithelium from altered
limbal basal epithelial cells as a result of
ultraviolet (UV) radiation induced damage. The
limbal cells invade the cornea centripetally
followed by conjunctival epithelium. Bowman’s
layer is dissolved under the leading edge of the
pterygia, while vascularization occurs in the
conjunctiva adjacent to pterygia. It should also
be noted that pterygia have a high recurrence
rate.(12)

Pathogenesis of pterygium
Currently, theories on the pathogenesis of

pterygium cannot give a completely satisfactory
explanation of this enigmatic lesion. Theories
that have been proposed include inflammatory
influence, degeneration of connective tissue,
genetic instability, angiogenesis, redox related
toxicity, cellular proliferation, aberration of
apoptosis, exuberant wound healing, altered lipid
metabolism, mast cell infiltration, and stem cell
dysfunction.(13)

Dushku and Reid(14) found nuclear p53
expression without apoptosis in the limbal
epithelia of pterygia, limbal tumors, and most
pingueculae. A study also found overexpression

of p53 in 7 of 14 pterygia.(15) Subsequently
D u s h k u  e t  a l . ( 1 2 ) d e m o n s t r a t e d  e l e v a t e d
expression of matrix metalloproteinases (MMPs)
i n  p t e r y g i u m  c e l l s .  M M P s  a r e  u b i q u i t o u s
proteolytic enzymes that are controlled by
natural antagonists, the tissue inhibitors of
metalloproteinases (TIMPs). The MMPs modify
or degrade extracellular matrix components in
normal and remodeling tissues, and are found in
many diseases. These enzymes are secreted by a
variety of cell types including fibroblasts and
are categorized into five groups: collagenases
( M M P - 1 ,  M M P - 8 ,  M M P - 1 3 ) ,  g e l a t i n a s e s
(MMP-2, MMP-9), stromelysins (MMP-3,
MMP-10, MMP-21, MMP-22), membrane type
MMPs.(16) Proposed that pterygia actually consist
of two tumors, where the main tumor is the
pterygium itself, while the second tumor is
formed by a group of fibroblasts (the pinguecula)
within the pterygium.(12) This condition is also
seen in other ocular and skin tumors with
elastotic stromal degeneration. The pterygium
arises from UV-induced alterations in the p53
gene of limbal (corneal) basal epithelial cells,
whereas the pinguecula originate from mutations
in the elastin gene of limbal fibroblasts. The

 

Figure 2. Pterygium (arrow)



183

fibroblasts make abnormal elastotic material and
express multiple types of MMP, which are also
produced by the limbal epithelial cells.

T h e  p 5 3  g e n e  m u t a t i o n s  a r e  a c t i v e
mutations resulting in a damaged programmed
cell death mechanism (apoptosis), thus leading
to acquisition of mutations in other genes. This
allows for the multistep development of pterygia
from p53-expressing limbal basal epithelial cells.
T h e  p 5 3  m u t a t i o n s  m a y  a l s o  l e a d  t o
overproduction of TGF-b via the p53-Rb-TGF-
b pathway; thus pterygia may be considered to
be TGF-b secreting tumors. Excess secretion of
TGF-b results in elevated MMP expression by
pterygium cells (altered limbal basal epithelial
cells) as well as by activated normal fibroblasts
under the invading limbus epithelium, both
leading to dissolution of Bowman’s layer. Some
of these cytokine-activated fibroblasts migrate
anterior to the leading edges of pterygia between
Bowman’s layer and the basement membrane of
the corneal basal cells to form little islands of
fibroblasts (ilôts de Fuchs) that make MMPs,
again helping to dissolve Bowman’s layer.(12)

However, in a more recent study, the
investigator found no p53 gene mutations in
Caucasian pterygia. In their revised theory, the
accumulation of p53 protein without causing
apoptosis may be the result of inactivation of the
p53 protein.(17) In contrast, their molecular analysis
of p53 gene mutations in eight Chinese pterygia
detected mutations in all samples, with six
substitutions and two deletions.(18) Additionally, a
study showed statistically significant
overexpression of p53 in around 35% of 31
Ecuadorian pterygia, which were also 8-hydroxy
deoxyguanosine (8-OHdG) immunoreactive.(19)

Moreover, a study in Brazil found abnormal p53
expression in 14 of 36 pterygial specimens, and
HPV DNA in 21 of them.(20)

Support for Dushku’s statements on the role
of MMPs in pterygia may be found in the results
of a Chinese study, in which the investigators

reported overexpression of MMP-1 and MMP-9
i n  p r i m a r y  p t e r y g i u m .  T h e y  a l s o  f o u n d
overexpression of TGF-b1, which may lead to
hyperplasia of collagen fibers and accumulation
o f  m e t a m o r p h i c  f i b e r s . ( 2 1 ) I n  c o n t r a s t ,  t h e
Brazilian study on MMP-9 expression in 42
primary and 19 recurrent pterygia found no
significant difference in MMP-9 expression
between the pterygia and normal conjunctiva.(16)

Pterygia do not erode through the full
thickness cornea and thus are distinct from
malignant tumors. In their view, the pterygium
is a mixed soft tissue tumor that is strongly
associated with non-ionizing UV radiation.(13) As
the investigators note, in this respect the
pterygium is highly unusual, because UV-
induced tumors in humans are generally of
epithelial origin, while UV radiation effects on
keloids, if any, are commonly inhibitory. The
pterygium is also unusual because researchers
have been unable to discover an analogous tumor
in animals or reconstitute the disease in organ
cultures. The implication is that pterygium
involves species-specific mechanisms mediated
by in vivo cell-cell or cell-matrix interactions.
The molecules involved in this disease may have
therefore arisen from divergent evolution in the
h u m a n  o c u l a r  s u r f a c e .  T h e  o r i g i n  o f  t h e
epithelium overlying pterygial lesions to be still
unclear, although suspected to be conjunctival.
This view is at variance.(12) who maintain that in
the pterygium the migrating limbus is followed
by conjunctival epithelium, implying that the
epithelium covering the body of the pterygium
is of conjunctival origin.(12,13)

The global gene expression study used the
U133A microarray, and the microarray data were
subsequently validated by relative quantitative
real time polymerase chain reaction (qPCR) and
immunohistochemistry. The study revealed that
several genes were upregulated, while apostosis
genes were downregulated in pterygium. The
upregulated genes included fibronectin (FN1),

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Tradjutrisno                                                                                                                                                                             Pterygium

carcinoembryonic antigen (CEACAM5 or CEA),
CD24, SPARC, microseminoprotein (MSMB)
and TFF1. The downregulated genes coding for
apoptosis were TGM2, IGFBP3 and DUSP1.
This down-regulation of apoptosis in pterygium
reinforced the over-proliferative tendency of the
lesion.(13)

A  s i m i l a r  s t u d y  h a d  b e e n  c o n d u c t e d
previously by John-Aryankayalil et al.(22) In this
study, over expression was found of novel and
previously identified extracellular-matrix-related,
proinflammatory, angiogenic, fibrogenic, and
oncogenic genes in human pterygium. There was
one notable difference, in that the CLIC2 gene
was down regulated in a study,(22) but significantly
upregulated in other study.(13)

The winglike shape of a pterygium and the
mechanisms supporting its centripetal growth
have also been investigated. The concomitant
breakdown of the limbal barrier and subsequent
conjunctivalization of the cornea may explain the
shape and formation of a primary pterygium.
Because the growth pattern of pterygia mirrors
the radial arrangement of corneal nerves,
advanced the hypothesis that directional growth
of pterygia may be facilitated by neuropeptides.(23)

In support of their hypothesis, the researchers
f o u n d  t h a t  s u b s t a n c e  P  a t  n a n o m o l a r
c o n c e n t r a t i o n s  i n d u c e d  c e l l  m i g r a t i o n  i n
pterygium fibroblasts and vascular endothelium
in a dose-dependent fashion, which was inhibited
by an NK1 receptor antagonist. On the other hand,
pterygium epithelial cells were not migratory in
these experiments. They therefore concluded that
NK1 receptors are present in pterygia and that
substance P is a potent chemoattractant for
pterygium fibroblasts and vascular endothelial
cells. Thus substance P may contribute to the
shape of pterygia through its profibrogenic and
angiogenic action.(23)

UV irradiation of biological tissues may
induce a direct phototoxic effect or an indirect
effect through formation of radical oxygen species

(ROS). ROS damage cellular proteins, lipids, and
DNA in a process known as oxidative stress. In
addition, ROS can induce cyclooxygenase 2
(COX 2) formation via activation of the NF-kB
signaling pathway. Both ROS and COX 2 were
found to play the most important role in UV-
related cutaneous carcinogenesis. Because
pterygium is currently considered to be a UV-
related tumor, a study in Taiwan demonstrated
cyclooxygenase-2 expression in the epithelium of
90 pterygia.(24) UV radiation-induced DNA lesions
caused by ROS have been associated with
initiation and progression in a multistage model
of carcinogenesis. A most typical oxidative lesion
product is 8-OHdG, since guanine is the most
easily oxidized naturally occurring base. 8-OHdG
frequently mispairs with adenine during DNA
replication, leading to G-C to T-A transversion,
and thus gives rise to mutations. It has also been
established that it is a sensitive marker of
oxidative DNA damage. G-C to T-A transversions,
induced by the presence of 8-OHdG during DNA
replication, have also been observed in the ras
oncogene and p53 in human skin cancers of sun-
exposed areas and in UV-induced mouse skin
cancers. In their study of 31 Ecuadorian pterygia,
Perra et al. (19) found 8-OHdG in 21 (68%)
specimens, and p53 expression in 11 (35%). A
study had previously reported the ocurrence of a
G-C to T-A transversion in exon 6, codon 213 of
p53, which is typical of oxidative lesions, and also
the presence of 8-OHdG in 23% of 52 pterygia
samples.(25)

The in vivo confocal microscopy study of
Gheck et al.(6) substantially confirmed previous
observations on the features of pterygia. In their
view, ultraviolet radiation causes micro traumas
that are responsible for the inflammatory lesions.
Certain UV-sensitive tumor supressor genes
(p53) may play a role in the pathogenesis of
pterygia, whilst other factors, such as dust, wind,
heat and dryness, are of secondary importance.
Their theory is based on localized areas of



185

dryness of the conjunctiva (dellen) due to
destruction of the lipid layer of the tear film,
leading to an increased evaporation. These dellen
i n d u c e  a  c i c a t r i z i n g  r e s p o n s e  w i t h  t h e
proliferation and growth of inflammatory
conjunctival tissues. It is notable that the mucus
produced by the pterygium differs from normal
conjunctival mucus. The cellular proliferation,
inflammation, modification of conjunctival
tissue and angiogenesis are dependent on the
presence of growth factors such as fibroblast
growth factor (FGF), platelet-derived growth
factor (PDGF), transforming growth factor
(TGF) and tumor necrosis factor-α (TNF-α),
some of which are produced by the fibroblasts.(6)

A study found increased telomerase activity
in pterygia compared with normal conjunctival
tissues.(26) They studied 27 tissue samples from
pterygia, in which 14 epithelial tissues from
pterygia (51.9%) were positive for telomerase
activity, whereas telomerase activity was positive
in only three of 9 normal conjunctival tissues
(33.3%), although there was no significant
statistical difference between pterygium-covered
conjunctival epithelia and normal conjunctival
epithelial tissues. Telomerase functions by
maintaining a constant telomere length, thus
ensuring the retention of chromosomal stability
attributed to functional telomeres and alters the
cell’s biological clock, effectively preventing a
cell from aging. Telomerase activity is usually
found in immortal cells such as germline cells,
stem cells, malignant cells, cells from some types
of benign and premalignant skin tumors, and also
in cutaneous tissues chronically exposed to UV
radiation. Because pterygia are believed to be
also caused by chronic UV radiation, Park et
al.(26) searched for telomerase activity in pterygia,
w i t h  t h e  a b o v e m e n t i o n e d  r e s u l t s .  T h e
researchers suggest that the difference in
telomerase activity between normal conjunctival
epithelium and that of pterygium may be caused
by an activation of telomerase or a clonal

expansion of telomerase positive cells due to
chronic sun exposure.

To elucidate the role of angiogenesis in the
pathogenesis of pterygia, Aspiotis et al. (27)

investigated the microvessel density and the
expression of vascular endothelial growth factor
(VEGF) and thrombospondin-1 (TSP-1) in tissue
sections of 52 pterygia and 7 normal conjunctiva.
The researchers found a higher microvessel
density and an increased level of VEGF in
pterygia as compared to normal conjunctiva, and
a statistically significant positive correlation
b e t w e e n  m i c r o v e s s e l  d e n s i t y  v a l u e s  a n d
pterygial VEGF expression. On the other hand,
there was a low level of TSP-1 expression in
approximately half of the pterygia.

The contribution of cellular immunity to
pterygium pathogenesis was studied in Turkey
by Tekelioglu et al.(28) who found higher rates of
intercellular adhesion molecule-1 (ICAM-1)-
positive cells, vascular cell adhesion molecule-
1 (VCAM-1)-positive cells, human leucocyte
antigen (HLA)-DR-positive cells and CD4 and
CD8 lymphocytes in pterygium tissue samples.

F i n a l l y,  i n  a  m o r e  r e c e n t  r e v i e w  o f
p t e r y g i u m  p a t h o g e n e s i s ,  a p a r t  f r o m  t h e
previously mentioned factors, such as UV
radiation, limbal stem cells, oxidative stress,
growth factors and cytokines, the possible
pathogenetic roles of altered phospholipase D,
human papilloma virus (HPV) involvement and
Ki-ras proto-oncogene mutations are discussed.(9)

Pterygium: benign neoplasm?
P t e r y g i u m  a n d  p a p i l l o m a  a r e  b e n i g n

conjunctival tumors that can be treated by
surgical excision. However, recurrences are
frequently observed, and recurrent lesions tend
to grow more rapidly than primary lesions.
A l t h o u g h  t h e  e t i o l o g y  o f  p t e r y g i u m  a n d
papilloma has not been established, human
papillomavirus (HPV) is thought to be one of
the causative factors.(29) Another study found

Tradjutrisno                                                                                                                                                                             Pterygium



186

Tradjutrisno                                                                                                                                                                             Pterygium

unifying theory capable of explaining all of the
c h a r a c t e r i s t i c s  o f  t h e  p t e r y g i u m .  A s  b o t h
exuberant growth and benign neoplasm are
essentially cellular proliferations, whether
normal or aberrant, we have to a wait further
studies for a solution to this interesting scientific
puzzle.

REFERENCES

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2. Gazzard G, Saw SM, Farook M, Koh D, Widjaja
D, Chia SE, et al. Pterygium in Indonesia:
prevalence, severity and risk factors. Br J
Ophthalmol 2002;86:1341–6.

3. Wong TY, Foster PJ, Johnson GJ, Seah SK, Tan
DT. The prevalence and risk factors for pterygium
in an adult Chinese population in Singapore: the
Tanjong Pagar survey. Am J Ophthalmol 2001;131:
76–83.

4. Kanski JJ. Clinical ophthalmology: a systematic
approach. 5th ed. Butterworth-Heinemann:
Edinburgh;2003.

5. Fuchs E. Uber das pterygium. Albert von Graefes
Arch Klin Exp Ophthalmol 1892;38:1. Cited by
Gheck L, Dupas B, Denion E, Amar N, Baudouin
C. Apport de la microscopie confocale in vivo à
l’étude des ptérygions. [Advantages of the in vivo
confocal microscope for investigation of the
pterygium]. J Fr Ophtalmol 2007;30:3-10.

6. Gheck L, Dupas B, Denion E, Amar N, Baudouin
C. Apport de la microscopie confocale in vivo à
l’étude des ptérygions. [Advantages of the in vivo
confocal microscope for investigation of the
pterygium]. J Fr Ophtalmol 2007;30:3-10.

7. Vogt J, Harrison BJ, Spearman H, Cossins J,
Vermeer S, Cate LN, et al. Mutation analysis of
CHRNA1, CHRNB1, CHRND, and RAPSN genes
in multiple pterygium syndrome/fetal akinesia
atients. Am J Hum Genet 2008;82:222–7.

8. Buratto L, Phillips RL, Carito G. Clinical anatomy.
In: Pterygium surgery. Buratto L, Phillips RL, Carito
GC, editors. Thorofare:Slack;2000.p.17-20.

9. Detorakis ET, Spandidos DA. Pathogenetic
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HPV in 50% of 10 pterygia with the same types
as in conjunctival papillomas. They suggested
that persistent conjunctival HPV may possibly
play a part in the recurrence of pterygia post
excision.(30) In addition, Rodrigues et al.(20) HPV
DNA in 21 of 36 pterygia in Brazil, along with
a b n o r m a l  5 3  e x p r e s s i o n  i n  1 4  o f  t h e  3 6
s p e c i m e n s ,  a n d  c o n c l u d e d  t h a t  a b n o r m a l
expression of p53 and HPV DNA are required
co-factors for the development of pterygium.

The different and sometimes contradictory
results of various studies and the fact that some
features, eg. p53 mutations, were only found in
a  p r o p o r t i o n  o f  p t e r y g i a ,  m a y  b e  d u e  t o
d i ff e r e n c e s  i n  m e t h o d o l o g y  a n d  s t u d y
populations. However, it may also be indicative
of multiple causative factors, implying that the
pterygium may not be a distinct disease entity
but should rather be viewed as a final common
outcome of various etiological factors, such as
geography and ethnicity, with UV radiation-
induced damage as the main factor. In connection
with ethnicity, the variable findings of p53
protein expression in pterygia by several study
groups might be explained by the observation
that the frequency of p53 mutations in cancer
can vary among different races. Ueda et al.(31)

d e m o n s t r a t e d  t h a t  t h e  i n c i d e n c e  o f
i m m u n o r e a c t i v i t y  f o r  p 5 3  i s  r e l a t e d  t o
differences in development of pterygium with
race as well as environmental factors.

CONCLUSIONS

From the abovementioned observations and
theories it may be concluded that the pterygium
remains an enigma, having the features of an
exuberant growth but also those of a benign
neoplasm. The previously held opinion that the
pterygium is a degenerative condition should in
all probability be revised, but not (yet) discarded.
At present there is a plethora of data, but no



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Univ Med                                                                                                             Vol.28 No.3