ophthalmologist to consider all possible
muscle pathologies that might be play-
ing a part, and specifically request MRI
planes and gaze directions that would
be informative in narrowing the differ-
ential diagnosis and in guiding treat-
ment. Ophthalmologists cannot rely on
radiologists or MRI technicians to
understand the nuances of extraocular
muscle anatomy and function well
enough to direct the imaging strategy
in complex situations such as these.
Just as new imaging modalities such
as optical coherence tomography are
revolutionising our understanding and
management of retinal disease,
imaging modalities are revolutionising
our understanding of extraocular mus-
cle structure, function, and innervation.
Ophthalmologists, and particularly stra-
bismus and orbital surgeons, should
review the new findings from orbital
magnetic resonance imaging and corre-
late an immunohistochemistry, since
even the fundamental anatomy of the
orbit has changed considerably from
what most have learned as residents,
challenging concepts such as ‘‘oblique
muscle dysfunction.’’
We owe it to
our patients to appreciate the progress
in clinical anatomy, and to apply rele-
vant and appropriate imaging techni-
ques in our presurgical evaluations.
Br J Ophthalmol 2006;90:664665.
doi: 10.1136/bjo.2006.091892
Correspondence to: Joseph L Demer, Jules Stein
Eye Institute, 100 Stein Plaza, UCLA, Los
Angeles, CA 90095-7002, USA; jld@ucla.edu
Grant Support: US Public Health Service,
National Institutes of Health, National Eye
Institute EY08313, and Research to Prevent
Blindness. JLD is Leonard Apt Professor of
Competing interests: none.
1 Demer JL, Ortube MC, Engle EC, et al. High
resolution magnetic resonance imaging
demonstrates abnormalities of motor nerves and
extraocular muscles in neuropathic strabismus.
J AAPOS 2006;(in press).
2 Thacker NM, Velez FG, Demer JL, et al.
Strabismic complications following endoscopic
sinus surgery: diagnosis and surgical
management. J AAPOS 2004;8:48894.
3 Demer JL. Pivotal role of orbital connective tissues
in binocular alignment and strabismus. The
Friedenwald lecture. Invest Ophthalmol Vis Sci
4 Demer JL. A 12 year, prospective study of
extraocular muscle imaging in complex
strabismus. J AAPOS 2003;6:33747.
5 Demer JL, Clark RA, Engle EC. Magnetic
resonance imaging evidence for widespread
orbital dysinnervation in congenital fibrosis
of extraocular muscles due to mutations in
KIF21A. Invest Ophthalmol Vis Sci
6 Demer JL, Miller JM. Orbital imaging in
strabismus surgery. In: Rosenbaum AL,
Santiago AP, eds. Clinical strabismus
management: principles and techniques.
Philadelphia: WB Saunders, 1999:8498.
7 Yannuzzi LA, Ober MD, Slakter JS, et al.
Ophthalmic fundus imaging: today and beyond.
Am J Ophthalmol 2004;137:51124.
8 Demer JL. The orbital pulley system: a revolution
in concepts of orbital anatomy. Ann NY Acad Sci
9 Demer JL. Clarity of words and thoughts about
strabismus. Am J Ophthalmol 2001;132:75759.
10 Tan KP, Sargent MA, J PK, et al. Ocular
overelevation in adduction in craniosynostosis: is
it the result of excyclorotation of the extraocular
muscles? J AAPOS 2006;9:5507.
A S Solomon
Can we provide medical and not surgical cure?
terygium is a common frequently
occurring ocular surface lesion
characterised by inflammation,
angiogenesis, and cellular proliferation,
which result in tissue remodelling.
In this issue of BJO (p 769), Wong
and colleagues present the finding of a
new gene that was changed in primary
It is the gene for insulin-like growth
factor binding protein-3, (IGFBP3),
which modulates the effects of insulin-
like growth factor on cells. IGFB3 was
significantly decreased in pterygium
samples compared with normal con-
junctiva. Decreased levels of IGFB3
protein have been strongly correlated
with the presence of cancer.
It might be
that the low level of IGFP3 is related to
loss of control of the cell proliferation
process, which explains the continued
growth of pterygium. Solomon and
found in their work an
insulin-like growth factor binding pro-
tein-2 (IGFBP2) overexpression in pter-
ygium body fibroblasts. This is strong
evidence to support the transformed
phenotype of these cells and may
explain the continual process of growth
of fibrovascular tissue. The above find-
ings elucidate two of many factors that
are implied in the appearance and the
development of pterygium.
An overall view of the growth
process of pterygium reveals a
multiplicity of factors that are corre-
lated and interrelated
We have to remember that the
increased incidence of pterygium is in
people and populations that are exposed
to excessive solar radiation. It is the
ultraviolet light (UV) that plays the
critical part in the pathogenesis of this
disease. UV radiation starts a chain of
events at the intracellular and extra-
cellular level that involve DNA, RNA,
and extracellular matrix composition. Di
Girolamo and colleagues
showed in
their work that UVB radiation stimu-
lated the induction of matrix matallo-
proteinase (MMP)-1 expression in
human ocular surface epithelial cells,
which is mediated through the ERK1/2
MAPK dependent pathway.
Nolan and colleagues
found that
UVB radiation creates overexpression
of heparin binding epidermal growth
factor (HB-EGF) in pterygial tissue.
HB-EGF is a potent mitogen and may
be considered a major driving force in
the development of pterygium. Di
Giorolamo and colleagues
the two above findings in another study.
They found that epidermal growth
factor receptor signalling is partially
responsible for the increased MMP-1
expression in ocular cells after UVB
radiation. Tsai and colleagues
a very important aspect of the pathology
of pterygiumoxidative DNA damage.
UV radiation is noxious to the conjunc-
tiva tissue either by direct phototoxic
effect or indirectly by formation of
radical oxygen species (ROS). One of
the markers of oxidative stress is 8-
hydroxydeoxyguanosine (8-OHdG). It is
the result of UV damage to DNA. An
overexpression of 8-OhdG in pterygia
was found in this study, a fact that
correlates the UV with the oxidative
damage to the conjunctiva and the
creation of pterygium. The same evidence
was found by Kau and colleagues.
Pterygium involves in its development
a vascular proliferative process.
Marcovici and colleagues
found that
VEGF and von-Willebrand factor (vWF)
are overexpressed in pterygium tissue.
This is evidence of the angiogenesis that
is found during the development of
group.bmj.com on October 20, 2011 - Published by bjo.bmj.comDownloaded from
An interesting finding can be related
to the angiogenesis process. Ozdemir
and colleagues
found that nitric oxide
levels (NO) are lower in pterygium
tissue than in normal conjunctiva. This
fact might be the result of hyper-
irrigation of blood by the rich vascular
net of the pterygium. This is opposite to
the ischaemic conditions through which
NO levels rise.
Naib-Majani and colleagues, in an
immunohistochemical study,
results on the distribution of the extra-
cellular matrix in pterygium. It was found
that collagens III and IV were expressed,
while collagens I, II, and VII were miss-
ing. Heparan sulfate was strongly
expressed in blood vessel walls and
epithelial membranes. The study indicates
an active involvement of MMPs 8, 9, and
13 in the pathogenesis of pterygium.
An overall view of the growth process
of pterygium reveals a multiplicity of
factors that are correlated and interre-
lated. Di Girolamo and colleagues
show, in an overview of the pathogen-
esis of pterygium, that the cytokines,
growth factors, and MMPs are the main
groups involved in that process. Climatic
and geographical location are factors
inducing the appearance of ptery-
12 13
We can observe three main factors
that lead to the final product, the
pterygiummitogenity, construction of
a new vascular net, and remodelling of
the extracellular matrix. Altogether they
create a new vascular and fibrotic tissue,
which has an aggressive way of growing
to and over the cornea. Today, surgical
removal is the common way to treat
pterygium, but the recurrence rate is
reported to be high.
It might be that understanding the
biochemical process, which takes place
in the growth of pterygium, can lead to
the development of topical medications
that may prevent or stop the pterygium
in its early stage.
Br J Ophthalmol 2006;90:665666.
doi: 10.1136/bjo.2006.091413
Correspondence to: Arieh S Solomon, MD,
PhD, Goldschleger Eye Research Institute,
Faculty of Medicine, Tel-Aviv University, Sheba
Medical Center, Tel-Hashomer, 52621, Israel;
1 Yu H, RohanT. Role of the insulin-like growth
factor family in cancer development and
progression. J Natl Cancer Inst
2 Solomon A, Grueterich M, Li DQ, et al. Over
expression of Insulin-like growth factor-binding
protein-2 in pterygium body fibroblasts. Invest
Ophthalmol Vis Sci 2003;44:57380.
3 Di Girolamo N, Coroneo MT, Wakefield D. UVB-
elicited induction of MMP-1 expression in human
ocular surface epithelial cells is mediated through
the ERK1/MAPK-dependent pathway. Invest
Ophthalmol Vis Sci 2003;44:470514.
4 Nolan TM, Di Giorlamo N, Sachdev NH, et al.
The role of ultraviolet irradiation and heparin-
binding epidermal growth factor-like growth
factor in the pathogenesis of pterygium.
Am J Pathol 2003;162:56774.
5 Di Girolamo N, Coroneo M, Wakefield D.
Epidermal growth factor receptor signaling is
partially responsible for the increased matrix
metalloproteinase-1 expression in ocular
epithelial cells after UVB radiation. Am J Pathol
6 Tsai YY, Cheng YW, Lee H, et al. Oxidative DNA
damage in pterygium. Mol Vis 2005;11:715.
7 Kau HC, Tsai CC, Lee CF, et al. Increased
oxidative DNA damage, 8-hydroxydeoxy-
guanosine, in human pterygium. Eye 2005 Aug
19 [Epub ahead of print].
8 Marcovici AL, Morad Y, Sandbank J, et al.
Angiogenesis in pterygium: morphometric and
immunohistochemical study. Curr Eye Res
9 Ozdemir G, Inanc F, Kilinc M. Investigation of
nitric oxide in pterygium. Can J Ophthalmol
10 Naib-Majani W, Eltohami I, Wernert N, et al.
Distribution of extracellular matrix proteins in
pterygium: an immunohistochemical study.
Graefes Arch Clin Exp Ophthalmol
11 Di Girolamo N, Chui J, Coroneo MT, et al.
Pathogenesis of pterygia: role of cytokines,
growth factors, and matrix melalloproteinases.
Prog Retin Eye Res 2004;23:195228.
12 Solomon AS. Immunologic basis for the
pathogenesis of pterygium. Am J Ophthalmol
13 Tan CS, Lim TH, Koh WP, et al. Epidemiology of
pterygium on a tropical island in the Riau
Archipelago. Eye 2005 Sep 16 [Epub ahead of
14 Fernandes M, Sangwan VS, Bansal AK, et al.
Outcome of pterygium surgery: analysis over 14
years. Eye 2005;19:118290.
Endoscopic and transscleral
P A Bloom, S Dharmaraj
Current status
iode laser transscleral cyclophoto-
coagulation (TSCP, or cyclodiode
as it is commonly known in the
United Kingdom), has become a popular
minimally invasive treatment for glau-
coma. Initially this modality was used
only in eyes with advanced end stage
glaucoma and with little or no visual
potential, where most other surgical
treatments had been tried and failed.
This was because of traditional mistrust
of earlier cycloablation methods, such as
cyclocryotherapy, that were associated
with a higher incidence of serious
complications than TSCP. As confidence
and experience of TSCP grows it is now
being safely applied increasingly earlier
in the glaucoma treatment paradigm
and in eyes with greater visual poten-
; it has even been suggested that
TSCP be used as a one off primary
treatment for glaucoma in developing
nations with poor access to reliable
medical and surgical follow up.
There is still, however, considerable
local and regional variation in the use of
this treatment (anecdotal impressions
suggest that it is used more commonly
and earlier for glaucoma treatment in
the United Kingdom than in the United
States), perhaps in part because of the
relative paucity of high quality labora-
tory and clinical studies demonstrating
if, why, and how it is effective. There is
even less evidence concerning endo-
scopic cyclophotocoagulation (ECP),
the more refined but less widely avail-
able cousin of TSCP.
In the April issue of the BJO, Lin et al
published an important laboratory
based study that adds to our under-
standing of the clinical effects and
complications of cyclophotocoagulation
They have attempted to quantify
the evolution of vascular changes fol-
lowing CP; their results demonstrate
that both TSCP and ECP are associated
with an acute occlusive vasculopathy,
but that with the endoscopic modality
the chronic underperfusion is less than
with the transscleral route.
The effects of CP on aqueous secretion
are multifactorial. It is widely accepted
that a major mechanism of aqueous
suppression after CP is coagulative
necrosis damage to the secretory ciliary
epithelium consequent upon laser
energy uptake by the pigmented ciliary
Further effects are caused
by ischaemia; in both TSCP and ECP,
some vascular damage occurs as a result
of propagation of laser energy from the
ciliary epithelium to nearby vessels in
the ciliary processes or from tissue
disruptions (‘‘pops’’), although these
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doi: 10.1136/bjo.2006.091413
2006 90: 665-666Br J Ophthalmol
A S Solomon
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... Pterygium is defined as a fibrovascular formation of triangular morphology that extends from the conjunctiva to the cornea [1]. This neoformation is more frequent in the nasal sector [1], and it is characterized by inflammation and fibrosis, leading to tissue remodeling [2]. Histopathologically, it affects the conjunctival collagen, leading to elastotic degeneration; Bowman s membrane and corneal surface destruction are observed along with stem cell alterations [2]. ...
... This neoformation is more frequent in the nasal sector [1], and it is characterized by inflammation and fibrosis, leading to tissue remodeling [2]. Histopathologically, it affects the conjunctival collagen, leading to elastotic degeneration; Bowman s membrane and corneal surface destruction are observed along with stem cell alterations [2]. A higher prevalence has been found in regions located thirtyseven degrees above and below the equator, with a higher ultraviolet (UV) intensity [1]. ...
Full-text available
This prospective and comparative study aimed to compare the use of a conjunctival autograft (CAG), plasma rich in growth factors fibrin membrane (mPRGF) or amniotic membrane transplantation (AMT) in primary pterygium surgery. Patients were assigned for surgery with CAG (group A), mPRGF (group B), or AMT (group C). Pterygium recurrence, Best Corrected Visual Acuity (BCVA), graft size (measured with anterior segment optical coherence tomography (AS-OCT)), and ocular surface symptoms (visual analogue scale (VAS) and ocular surface disease index (OSDI)) were evaluated. Thirteen eyes in group A, 26 in group B, and 10 in group C were evaluated. No changes in BCVA (p > 0.05) were found. Recurrence cases for groups A, B, and C were none, two, and two, respectively, and three cases of pyogenic granulomas in group A. The horizontal/vertical graft size was lower in group B vs group A (p < 0.05) from months 1 to 12. The improvement in VAS frequency for groups A, B, and C was: 35.5%, 86.2%, and 39.1%, respectively. The OSDI scale reduction for groups A, B, and C was: 12.7%, 39.0%, and 84.1%. The use of the three surgical techniques as a graft for primary pterygium surgery was safe and effective, showing similar results. The mPRGF graft represents an autologous novel approach for pterygium surgery.
... UVB radiation induces damage to cellular DNA, RNA, and extracellular matrix components through activation of different pathways [5]. UVB radiation also stimulates the expression of cytokines and growth factors in pterygium cells, which are considered to play pivotal role in the establishment and development of pterygium. ...
Full-text available
Background Pterygium is a condition characterized by epithelial overgrowth of the cornea, inflammatory cell infiltration and an abnormal extracellular matrix accumulation. Chronic UV exposure is considered as a pathogenic factor of this disease. Proteasome is an intracellular multi-subunit protease complex that degrades intracellular proteins. Among proteasome subunits the β5 (PSMB5), bearing chymotrypsin-like activity. It is considered as the main proteasome subunit and its expression is mediated by Nrf2-ARE pathway in many cell types. This study investigates the expression of PSMB5 in pterygium and the effect of UVB irradiation on its expression and activity in pterygium fibroblasts. Methods Normal conjunctival and pterygium specimens were obtained from the bulbar conjunctiva of patients undergoing cataract surgery and from patients with pterygium undergoing surgical removal of primary tissue, respectively. Fibroblasts were isolated upon treatment of specimens with clostridium collagenase. The expression of PSMB5 and Nrf2 in tissues and cells was ascertained by RT-PCR analysis and western blotting. Cell survival was measured by the MTT method and the proteasome chymotrypsin-like activity was determined by fluorometry. Results RT-PCR analysis showed that the expression of PSMB5 was significantly lower in pterygium than in normal conjunctiva. The expression of PSMB5 was mediated by the Nrf2/ARE pathway as indicated by using the Nrf2 activator Oltipraz. The expression of PSMB5 and Nrf2 by pterygium fibroblasts was suppressed in a dose dependent manner following UVB radiation of 0–50 mJ/cm² doses. The expression of PSMB5, but not of Nrf2, remained at almost the control levels, when UVB exposure was performed after pre-incubation of cells with the src kinases inhibitor PP2. UVB irradiation had very low deleterious effect on fibroblasts survival, while it did not affect the proteasome chymotrypsin-like activity. Conclusion In pterygium fibroblasts, UVB exposure leads to down-regulation of Nrf2/ARE-mediated PSMB5 gene expression, in which src kinases may be implicated. This effect may be partially responsible for the lower expression of PSMB5 detected in pterygium as compared to normal conjunctiva.
... IHC scores were assigned and higher scores indicated higher expression of nestin. [14] Nestin mRNA expression detected by real-time polymerase chain reaction TRIzol (Invitrogen, Massachusetts, USA) was used to extract total RNA from the brain tissue in SVZ, and the concentration and purity of RNA were analyzed using the ultramicro ultraviolet spectrophotometer (ND2000C, Thermo, Massachusetts, USA). Then, 2 µg of total RNA was reverse transcribed according to the manufacturer's instruction (TOYOBO, Osaka, Japan). ...
Full-text available
Background: Snakebites are a neglected threat to global human health with a high morbidity rate. The present study explored the efficacy of antivenom with hyperbaric oxygen (HBO) intervention on snakebites, which could provide the experimental basis for clinical adjuvant therapy. Methods: Male Sprague-Dawley rats (n = 96) were randomized into four groups: the poison model was established by injecting Deinagkistrodon acutus (D. acutus) venom (0.8 LD50) via the caudal vein; the antivenom group was injected immediately with specific antivenom via the caudal vein after successful establishment of the envenomation model; and the antivenom + HBO group was exposed to HBO environment for 1 h once at predetermined periods of 0 h, 4 h, 12 h, and 23 h after antivenin administration. Each HBO time point had six rats; the control group was left untreated. The rats in the experimental group were euthanized at the corresponding time points after HBO therapy, and brain tissue and blood were harvested immediately. Hematoxylin and eosin (H&E) staining was used to investigate the pathological changes in the rat brain. Immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), and Western blotting were used to detect the expression of Nestin mRNA and protein in the subventricular zone (SVZ) of the brain. The levels of coagulation function (prothrombin time, activated partial thromboplastin time [APTT], and fibrinogen) and oxidation/antioxidation index (malondialdehyde [MDA] and superoxide dismutase [SOD]) were analyzed. Data were analyzed using one-way analysis of variance. Results: The brain tissue from rats in the poison model was observed for pathological changes using H&E staining. Tissues showed edema, decreased cell number, and disordered arrangement in the SVZ in the snake venom group. The antivenom - HBO intervention significantly alleviated these observations and was more prominent in the antivenom + HBO group. The serum levels of SOD and MDA in the snake venom group were increased and the antivenom - HBO intervention further increased the SOD levels but significantly decreased the MDA levels; however, this was enhanced within 1 h after HBO administration (MDA: F = 5.540, P = 0.008, SOD: F = 7.361, P = 0.000). Activated partial thromboplastin time (APTT) was significantly abnormal after venom administration but improved after antivenom and was even more significant in the antivenom + HBO group 5 h after envenomation (F = 25.430, P = 0.000). Only a few nestin-positive cells were observed in the envenomation model. The expression levels were significant in the antivenom and antivenom + HBO groups within 1 and 5 h after envenomation and were more significant in the antivenom + HBO group as determined by IHC, real-time PCR, and Western blotting (P < 0.05). D. acutus envenomation has neurotoxic effects in the brain of rats. Conclusions: Antivenin and HBO, respectively, induced a neuroprotective effect after D. acutus envenomation by attenuating brain edema, upregulating nestin expression in SVZ, and improving coagulopathy and oxidative stress. The intervention efficacy of antivenom with HBO was maximum within 5 h after envenomation and was more efficacious than antivenom alone.
... (3) For years it has been well established that there are different factors that are interrelated and involved in the growth of pterygia. (4) The strongest link seems to be between ultraviolet light-B (UV-B) from the sun and the development of pterygia. UV-B can induce expression of growth factors and cytokines in epithelial cells of pterygia. ...
Full-text available
Background and Objective: Following the discovery of an abnormal expression of the p53 gene in the epithelium in pterygium, some researchers felt that pterygium is a tumor rather than a degenerative disease. Ultraviolet (UV) radiation has been reported to be associated with pterygium formation; however the mechanism whereby UV induces uncontrolled proliferation in pterygium cells is unclear. UV irradiation has a key role in the formation of reactive oxygen species (ROS) that can induce cyclooxygenase -2 (COX-2) production. Increased expression of COX-2 was found in many cancers and premalignant lesions. This study was conducted to investigate COX-2 expression in primary and recurrent pterygium tissues and to evaluate its role in pterygium formation and recurrence. Material and methods: In this study, 23 primary pterygia and 11 recurrent pterygia from subjects undergoing pterygium surgery as well as 14 normal conjunctival tissue specimens as control were studied immunohistochemically for COX-2 expression. Results: COX-2 was expressed in both normal conjunctiva as well as pterygia specimens (primary and recurrent). However, highly statistical significant differences were detected between control and primary pterygium tissues regarding COX-2 expression in surface epithelium (P <0.001), stromal inflammatory cells (P=0.001) and stromal blood vessels (P=0.004). Moreover, a highly statistical significant difference was found between control tissues and recurrent pterygium tissues concerning COX-2 expression in surface epithelium, stromal fibroblasts, inflammatory cells and blood vessels (P<0.001 in all). There was also a statistical significant difference between primary and recurrent pterygium tissues as regards COX-2 expression in surface epithelium (P=0.046), stromal fibroblasts (P=0.005), stromal inflammatory cells (P=0.007) and blood vessels (P= 0.051). Conclusion: COX-2 was highly expressed in pterygium tissues especially recurrent pterygium. It may play a role in pterygium formation and recurrence.
Background Pterygium is an important public health problem. The prevalence rates of this disease varies widely from 1.2% to 23.4%. Aim To determine the prevalence rates and the associated risk factors of pterygium in the high-altitude area - Ta'if city, Saudi Arabia. Material and method A cross-sectional study was carried out from September 2018 till September 2019 at the ophthalmology outpatient clinics of King Abdul-Aziz Specialist Hospital, Ta'if area. Results Prevalence rate of pterygium in the high-altitude area, Ta'if city, Saudi Arabia was 2.4%. It is significantly higher in older patients belonging to the age group of more than 40 years. As for gender, it was significantly higher in male patients compared to females (2.6% vs. 1.9%). Pterygium prevalence was significantly higher among patients with outdoor occupations compared to indoor occupations (2.9% vs. 2.1%), and among patients with sunlight exposure during daily activities for more than 5 hours (2.6% vs. 2%) (p =< 0.05). Conclusion The overall incidence of pterygium in Al-Ta'if area, Saudi Arabia, was 2.4% but still lower than overall worldwide incidence (10.2%). There was an increased incidence of pterygium with age, high-altitude areas, rural areas, outdoor occupations, which is directly proportional to dose of sunlight exposure. Furthermore, smoking might be reported as a protective factor against pterygium.
Introduction: To compare and evaluate the safety and efficacy of two surgical techniques for the management of primary pterygium. Materials & Methods: The study included 176 eyes of 176 patients with primary pterygium. The mean age was 49 ± 12 years (range 24–74 years). Simple excision under local anesthesia was performed followed by closure of the bare sclera by suture less and glue free conjunctival autograft in 76 eyes of 76 patients (group 1), versus the conventional method of a sutured conjunctival autograft in 100 eyes of 100 patients (group 2). Results: The pterygium recurrence rate was 6% for group 1, 8% for group 2. Graft dehiscence occurred in 4 eyes out of 50 (8%) in group 1. Graft retraction occurred in 6 (12%) out of 50 eyes for group 1 versus 6 eyes (6%) in group 2. Pyogenic granuloma occurred in 3 (3%) eyes out of 100 in group 2. No other serious complications were noted. At the 3 week visit the overall patient satisfaction score was statistically significantly higher for group 1 (P < 0.002) compared to group 2. At 3 months postoperatively, the gain in uncorrected visual acuity (UCVA) ranged from 0.2 to 0.5 Log MAR in 10 eyes. Conclusion: Sutureless and glue free conjunctival autograft technique is easy, safe, effective, prevents potential adverse reactions encountered with the use of foreign materials. This technique has an acceptable pterygium recurrence rate that is comparable to conventional sutured conjunctival autograft for primary pterygium. Medicine Today 2018 Vol.31(1): 1-8
AIM: To investigate the method and observe effectiveness of autologous limbal stem cell transplantation combined with amniotic membrane transplantation in the treatment of recurrent pterygium. METHODS: Medical records of all patients with recurrent pterygium treated by autologous limbal stem cell transplantation combined with amniotic membrane transplantation from January 2010 through June 2011 were retrospectively analyzed, and the recurrent rate was observed. RESULTS: Totally 30 cases (32 eyes) were analyzed. The followed up time was 12 to 24 months, mean 16 months. In all eyes, 30 were transparent or only left a little corneal nebula, without new blood vessels, recurrence occurred in 2 eyes, and the recurrent rate was 6%. CONCLUSION: Autologous limbal stem cell transplantation combined with amniotic membrane transplantation is a safe and effective method for recurrent pterygium.
Objective: To investigate the implementation of pterygium surgery among medical institutions partly in Shandong Province, and to promote the norms of pterygium surgery well cooperating with Shandong health strong foundation project. Design Cross-sectional survey. Participants: 73 hospitals which attended the 2009 training courses about promoting clinical application of pterygium surgery. Method: Questionnaires survey were conducted among 73 hospitals which attended the training courses. Main Outcome Measures: Can carry out ophthalmic microsurgical or not, with or without separate departments or wards, amounts of pterygium surgery every year, surgical approachs performed, recurrence rate, best promoting strategy, best gains of training courses, etc. Result: 75 questionnaires were sent out at the scene and 73 questionnaires were responded, including 10 provincial hospitals (13.70%), 43 municipal hospitals (58.90%) and 20 district hospitals (27.40%). 73 hospitals could carry out ophthalmic microsurgical, 68 hospitals own separate departments or wards. Less than 50 cases were performed in 10 hospitals every year, 50-100 cases in 34 hospitals, over 100 cases in 29 hospitals. 45 hospitals carried out pterygium excision combined with autologous stem cell transplantation, 14 hospitals carried out simple pterygium excision, 7 hospitals carried out pterygium excision combined with amniotic membrane transplantation, 7 hospitals carried out pterygium excision combined with antimetabolites therapy. The proportion of each grade hospitals whose recurrence rate of pterygium excision combined with autologous stem cell transplantation was less than 10% was as follow, 88.89% of provincial hospitals, 58.06% of municipal hospitals, 20% of district hospitals. 32 hospitals (43.84%) regarded the training courses as a good promoting method, 51 hospitals regarded the training course as an excellent opportunity to acquire surgical technique. Conclusions: Pterygium excision combined with autologous stem cell transplantation is the main trend of surgical approach in Shandong Province Medical Institute partly, with lower recurrence rate. Training courses are beneficial to normalization of the pterygium surgery andimprovement on the level of operation. (Ophthalmol CHN, 2013, 22: 354-356).
Aim: To evaluate the therapeutic effect of limbal corneal epithelial stem cell autograft combined with amniotic membrane transplantation on patients with recurrent pterygium. Methods: Eighty-two cases (91 eyes) with recurrent pterygium were randomly divided into 3 groups: excision of pterygium with limbal corneal epithelial stem cell autograft combined with amniotic membrane transplantation was as combine group 1 (31 cases, 34 eyes), amniotic membrane transplantation as amniotic membrane group (26 cases, 30 eyes) and limbal corneal epithelial stem cell autograft as stem cell group (25 cases, 27 eyes). They were followed up at regular intervals. Results: Eighty-two cases (91 eyes) were followed up for 4 to 31 months (average 15.30 ± 8.31 months). In combine group (31 cases, 34 eyes), during postoperative terms of follow-up (average 15.43 ± 8.31 months), no recurrent cases were found. Cases treated with amniotic membrane (26 cases, 30 eyes), within follow-up period (average 14.80 ± 8.86 months), 4 (13%) eyes recurred. As for stem cell group (25 cases, 27 eyes), during postoperative terms of follow-up (average 15.58 ± 8.06 months), three (11%) recurrent cases were found. There was significant difference among 3 groups, but there was no difference between amniotic membrane group and stem cell group. In the term of follow-up, no infection, repulsion, diplopia or moving obstacle of eye-ball were found in all cases. Conclusion: Limbal corneal epithelial stem cell autograft combined with amniotic membrane transplantation is the most effective way on recurrent pterygium treatment.
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Pterygia are common, frequently recurring ocular surface lesions characterized by tissue remodeling, cellular proliferation, angiogenesis, and inflammation. The increased incidence of pterygia in persons exposed to excessive solar radiation suggests that ultraviolet (UV) light may play a critical role in the pathogenesis of this disease. These investigations were focused on the expression of collagenase-1 (matrix metalloproteinase [MMP]-1) in pterygia and cultured pterygium epithelial cells, to determine whether the expression of this protease could be modified after exposure to UVB. Pterygium, conjunctival, and limbal epithelial cells were subcultured and exposed to various amounts of UVB. The conditioned medium and RNA were harvested for analysis by gelatin zymography, Western blot analysis, ELISA, and RT-PCR. Furthermore, whole pterygium specimens were irradiated to determine secreted MMP-1 levels. Immunohistochemical analysis revealed enhanced MMP-1 expression in pterygia that corresponded precisely with p63-positive epithelial cells. In contrast, significantly less MMP-1 reactivity was found in normal conjunctiva, limbus, and cornea. A dose- and time-dependent increase in MMP-1 was observed when pterygium epithelial cells were exposed to UVB with no significant modulation of inhibitor activity. MMP-1 was not affected in irradiated normal conjunctival epithelial cells or in pterygium fibroblasts but was induced in limbal epithelial cells. Although the induction of MMP-1 after UVB was not mediated by an intermediate soluble factor, the extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein kinase (MAPK) intracellular pathway was involved. Collectively, these data support the hypothesis of the involvement of UV light and MMPs in the development of pterygia and may assist in devising new therapeutic approaches for the treatment and prevention of pterygia.
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The insulin-like growth factors (IGFs) are mitogens that play a pivotal role in regulating cell proliferation, differentiation, and apoptosis. The effects of IGFs are mediated through the IGF-I receptor, which is also involved in cell transformation induced by tumor virus proteins and oncogene products. Six IGF-binding proteins (IGFBPs) can inhibit or enhance the actions of IGFs. These opposing effects are determined by the structures of the binding proteins. The effects of IGFBPs on IGFs are regulated in part by IGFBP proteases. Laboratory studies have shown that IGFs exert strong mitogenic and antiapoptotic actions on various cancer cells. IGFs also act synergistically with other mitogenic growth factors and steroids and antagonize the effect of antiproliferative molecules on cancer growth. The role of IGFs in cancer is supported by epidemiologic studies, which have found that high levels of circulating IGF-I and low levels of IGFBP-3 are associated with increased risk of several common cancers, including those of the prostate, breast, colorectum, and lung. Evidence further suggests that certain lifestyles, such as one involving a high-energy diet, may increase IGF-I levels, a finding that is supported by animal experiments indicating that IGFs may abolish the inhibitory effect of energy restriction on cancer growth. Further investigation of the role of IGFs in linking high energy intake, increased cell proliferation, suppression of apoptosis, and increased cancer risk may provide new insights into the etiology of cancer and lead to new strategies for cancer prevention.
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To examine the expression pattern of insulin-like growth factor-binding protein (IGFBP)-2 in cultured primary pterygium fibroblasts and compare it with expression in normal conjunctival fibroblasts. Profile of gene expression by normal conjunctival and primary pterygium fibroblasts was performed by using a cDNA microarray. The overexpression of IGFBP-2 thus identified was further confirmed by RT-PCR and Western blot analysis of cultured cells and by immunohistochemistry on primary pterygium and normal conjunctival tissue sections. A dramatically increased expression of IGFBP-2 mRNA was demonstrated in cDNA microarray membranes from two different pterygium fibroblasts. This finding was confirmed by RT-PCR in four additional different pterygium fibroblasts and by Western blot analysis of their culture supernatants. Immunohistochemistry of frozen sections from primary pterygium demonstrated increased staining in extracellular matrix of the stroma, compared with that of the normal conjunctiva. IGFBP-2 was also found in goblet cells of both normal conjunctival and pterygium epithelia. The increased expression of IGFBP-2 mRNA and protein in pterygium fibroblasts is further strong evidence to support the transformed phenotype of these cells and helps explain why there is increased growth of fibrovascular tissue. This phenotype may be used as a marker to assess the malignant nature of pterygium growth and recurrence.
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To report the outcome of pterygium surgery performed at a tertiary eye care centre in South India. Retrospective analysis of medical records of 920 patients (989 eyes) with primary and recurrent pterygia operated between January 1988 and December 2001. The demographic variables, surgical technique (bare sclera, primary closure, amniotic membrane transplantation (AMT), conjunctival autograft (CAG), conjunctival-limbal autograft (CLAG), or surgical adjuvants), recurrences and postoperative complications were analysed. A total of 496 (53.9%) were male and 69 (7.5%) had bilateral pterygia. Bare sclera technique was performed in 267 (27.0%) eyes, primary conjunctival closure in 32 (3.2%), AMG in 123 (12.4%), CAG in 429 (43.4%), and CLAG in 70 (7.1%). Adjuvant mitomycin C was used in 44 (4.4%) cases. The mean duration of follow-up was 8.9+/-17.0 and 5.9+/-8.8 months for unilateral primary and recurrent pterygia, respectively. The overall recurrence rate was 178 (18.0%). Following primary and recurrent unilateral pterygium excision respectively, recurrences were noted in 46 (19.4%) and 1 (33.3%) eyes after bare sclera technique, five (16.7%) and 0 after primary closure, 28 (26.7%) and 0 with AMG, 42 (12.2%) and five (31.3%) with CAG, and nine (17.3%) and two (40%) with CLAG. Recurrences were significantly more in males with primary (23.3 vs 10.7%, P<0.0001) and recurrent (26.7 vs 0%, P=0.034) pterygia, and in those below 40 years (25.2 vs 14.8%, P=0.003). CAG appears to be an effective modality for primary and recurrent pterygia. Males and patients below 40 years face greater risk of recurrence. Bare sclera technique has an unacceptably high recurrence. Prospective studies comparing CAG, CLAG, and AMG for primary and recurrent pterygia are needed.
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Epidemiological evidence suggests that UV irradiation plays the most important role in pterygial formation. The noxious effects of UV irradiation are either directly by a UV phototoxic effect or indirectly by formation of radical oxygen species (ROS). ROS are very harmful to cells, because they injure cellular DNA, proteins, and lipids (called oxidative stress). Among numerous types of oxidative DNA damage, the formation of 8-hydroxydeoxyguanosine (8-OHdG) presents only a minor fraction of UV induced DNA damage, but it is a ubiquitous marker of oxidative stress. If pterygium is related to UV, we surmised oxidative stress exists in pterygium. To provide the molecular evidence of UV radiation, 8-OHdG was detected in pterygium. Moreover, human 8-oxoguanine glycosylase (hOGG1) is the key component responsible for the removal of 8-OHdG. To determine whether the hOGG1 was expressed in pterygium, this enzyme was also evaluated. Immunohistochemical staining using a monoclonal antibody to 8-OHdG and hOGG1 were performed on 52 pterygial specimens and 6 normal conjunctiva. There were 12 (23.1%) pterygial specimens positive for 8-OHdG staining, limited to the nuclei of the epithelial layer. No substantial staining was visible in the subepithelial fibrovascular layers. In pterygium with 8-OHdG staining, there were 4 (4/11, 36.4%) specimens with hOGG1 expression. However, in pterygium without 8-OHdG staining, there were only 3 (3/41, 7.3%) specimens with hOGG1 expression. hOGG1 expression was significantly associated with 8-OHdG positive staining. All normal controls were negative for 8-OHdG and hOGG1 staining. Our study demonstrated for the first time 8-OHdG in pterygium, which represented oxidative stress in pterygium. The increased level of 8-OHdG in pterygium is not due to decreased expression of hOGG1, while increased levels of 8-OHdG induced the expression of hOGG1.
To evaluate the role of angiogenesis in the pathogenesis of pterygium by comparing the expression of von-Willebrand factor (vWF) and vascular endothelial growth factor (VEGF) in pterygium, and in normal superior bulbar conjunctiva. 23 human samples from pterygium and the superior bulbar conjunctiva were stained using rabbit anti-vWF and anti-VEGF antibodies. The density of vWF and VEGF positive vessels, VEGF staining intensity and the number of VEGF positive stromal, epithelial and vascular endothelial cells were evaluated. Pterygium specimens had higher average vWF and VEGF positive microvascular counts per high power field (P = 0.0012), higher average VEGF staining intensity scores in epithelial, stromal and endothelial cells (p < 0.0001) and higher VEGF positive cell counts (P < 0.0001) than normal conjuctiva. Over-expression of VEGF in pterygium tissue, together with the abundance of vWF-stained new vessels, may support previous suggestions that angiogenesis may play a role in the formation of pterygium.
Ultraviolet (UV) light is one of the major factors implicated in the pathogenesis of pterygium. The mechanism by which UV light induces this disease remains elusive. The aim of this study was to evaluate the effects of UVB irradiation on the expression of growth factors in cultured pterygium epithelial cells and to demonstrate their distribution within pterygium. We cultured pterygial epithelial cells from pterygium explants and these cells were exposed to 20 mJ/cm(2) of UVB. Total RNA was extracted at 0, 6, and 12 hours after irradiation. (32)P-labeled cDNA was synthesized and analyzed using microarray technology to determine the differential expression of 268 growth factor and cytokine related genes. Semiquantitative reverse transcriptase-polymerase chain reaction was used to corroborate this data. Conditioned media derived from cells exposed to UVB irradiation was analyzed for protein expression by enzyme-linked immunosorbent assay. Immunohistochemistry was used to evaluate the distribution of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in pterygium tissue. Analysis of the hybridization signals revealed that the genes encoding HB-EGF, fibroblast growth factor 3, and cytotoxic trail ligand receptor were consistently elevated at 6 and 12 hours after UVB treatment. HB-EGF mRNA was elevated 6.8-fold at 6 hours after irradiation and was augmented in culture supernatants after the same treatment. Furthermore, HB-EGF reactivity was identified in the epithelium and vasculature of pterygium by immunohistochemistry. HB-EGF was present in normal limbal epithelium, although it was not induced in cultured limbal epithelial cells by UV irradiation. HB-EGF is a potent mitogen, localized in pterygium tissue, and significantly induced by UVB in pterygium-derived epithelial cells. We postulate that this growth factor is a major driving force in the development of pterygia and a means by which UV irradiation causes the pathogenesis of pterygium.
This study was carried out to monitor the expression of extracellular matrix proteins (ECMs) and metalloproteinases (MMPs) in pterygial tissue. Twenty primary nasal pterygia were studied by indirect routine immunohistochemistry using 13 different primary antibodies against 8 ECMs (five collagens, fibronectin, heparan sulfate, and laminin) fibroblast growth factor (bFGF), von Willebrand factor (vWF), and 3 MMPs (8, 9, and 13). Secondary antibodies were fluoresceinated. Intensity of reaction on individual sections was graded semi-quantitatively. No expression of collagens I, II, and VII was found. Antibodies against collagen III reacted strongly positively (+++) with the entire pterygial stroma. Collagen IV expression was strongly positive in the wall of pterygial blood vessels, moderately positive (++) in the epithelial basement membrane, and only weakly positive (+) all over the stroma. Antibodies against fibronectin reacted moderately positively with stroma, blood vessel walls and epithelial basement membrane. Heparan sulfate was strongly expressed in the blood vessel walls and epithelial basement membrane. Antibodies against bFGF reacted only with pterygial epithelium. Laminin was strongly expressed in blood vessel wall, moderately (++) in the epithelial basement membrane and weakly over the entire stroma. vWF was strongly positive (+++) with pterygial blood vessel walls. Antibody reactions for MMPs differed. It was strong with pterygial epithelium (MMPs 8, 9 and 13), strong to moderate with pterygial stroma (MMPs 8 and 13 versus 9), and absent to weak with pterygial vascular walls (MMPs 8 and 13 versus 9). This study documents the presence of several ECMs but excludes the expression of others in pterygial tissues. The results especially indicate an active involvement of MMPs 8, 9 and 13 in the pathogenesis of pterygia.
Pterygium is a common ocular surface disease apparently only observed in humans. Chronic UV exposure is a widely accepted aetiological factor in the pathogenesis of this disease and this concept is supported by epidemiological data, ray tracing models and histopathological changes that share common features with UV damaged skin. The mechanism(s) of pterygium formation is incompletely understood. Recent data have provided evidence implicating a genetic component, anti-apoptotic mechanisms, cytokines, growth factors, extracellular matrix remodelling (through the actions of matrix metalloproteinases), immunological mechanisms and viral infections in the pathogenesis of this disease. In this review, the current knowledge on pterygium pathogenesis is summarised, highlighting recent developments. In addition, we provide novel data further demonstrating the complexity of this intriguing disease.