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Subconjunctival Bevacizumab Injection in Treatment of

Recurrent Pterygium
Hussein Alhammami1, Qassim Farhood2* and Hassanein Shuber3
1.
2.

3.

FICMS, Ophthalmology Department, Medical College Kufa University, Iraq


FICMS-OPH, Ophthalmology Department, Medical College, University of
Babylon, Iraq
FICMS, Ophthalmology Department, Medical College, Al Mustanseriah
University, Iraq

Abstract
Objective : To determine the clinical effect of subconjunctival injection of
bevacizumab in regression or halting growth in patients with recurrent pterygium.
Method and materials: The study was an off-label; 2-dosing,
interventional case series

involving 20 patients with recurrent pterygium. They

received subconjunctival bevacizumab (0.2 ml/2.5 mg). Vascularity and thickness


of Pterygium was graded. Size of the pterygium (measured by surface area in cm 2)
was recorded from baseline to 6 months, after injection. Treatment-related
complications and adverse events were reported. The main outcome of
measurements was the change in grading, size, vascularity, thickness and color
intensity.
Results: 9 males (45%), 11 females (55%) of 20 patients were conducted
in study with a mean age of 50.46 years 18.30 (rang 38-70). There was a
significant reduction in grading with significant difference in the mean surface
area of pterygium at different intervals (P<0.05) and the size of pterygium was
reduced. The reduction of color intensity was significant (P=0.031). No significant
topical or systemic adverse reactions were recorded.

J. Clin. Exp Opthalmol Volume 4, 2013


ISSN:2155-9750 JCEO. An open access journal

Conclusions: Subconjunctival bevacizumab injection is useful in


management of patients with recurrent pterygium without significant local or
systemic adverse effects.
Keywords:

Subconjunctival

injection;

Bevacizumab;

Recurrence;

Pterygium
I.

Introduction
Pterygium is a triangular sheet of fibro vascular tissue that invades the
cornea [1,2]. It occurs in the interpalpebral fissure, more common on the nasal
side of the eye and often bilateral [1-3]. Physicians have known pterygia for
thousands of years [2,4-6] but the pathogenesis of pterygia is not fully understood
[7-10].
Various studies have implicated environmental factors, such as ultraviolet
light, chronic irritation, and inflammation. Recent studies have also provided
evidence implicating genetic components, antiapoptotic mechanisms, cytokines,
growth factors, extracellular matrix remodeling, immunological mechanisms, and
viral infections in the pathogenesis of the disease [7-11].
Vascular growth factors such as vascular endothelial growth factor
(VEGF) have been detected in pterygium [12-15].There is marked elevation of
VEGF in pterygia in comparison to normal conjunctival samples [12-15].
Although the pathogenesis of pterygia is still poorly understood, their formation
and progression are known to depend on neovascularization. It has been
postulated that the development of pterygia depends on a changed angiogenic
stimulator-to-inhibitor ratio. Jin et al. showed that pterygia contain drastically

J. Clin. Exp Opthalmol Volume 4, 2013


ISSN:2155-9750 JCEO. An open access journal

decreased levels of pigment epithelium-derived factor, angiogenic inhibitor, and


elevated VEGF levels [15].
The treatment of pterygium is still controversial, with various treatments
being advocated in the scientific literature [16]. As pterygia is composed of
proliferating fibrovascular tissue and its formation and progression require
neovascularization [17,18], many molecules that positively regulate angiogenesis
have been identified, suggesting that growth factors may be involved directly or
indirectly in the pathogenesis of pterygia.
Bevacizumab

(Avastin)

is

full-length, humanized,

monoclonal

antibody against all types of VEGF. It binds to and neutralizes the biologic
activity of all types of human VEGF, so it prevents interaction with its receptors
on the surface of endothelial cells [17]. Bevacizumab has been used to treat
choroidal neovascularization due to age-related macular degeneration (ARMD),
and more recently diabetic macular edema. Various clinical trials have shown that
when administered intravitreally, it is well tolerated and associated with
improvement in visual acuity, decreased central retinal thickness, and reduction in
angiographic leakage [18-20]. This study determined the clinical effect and safety
of subconjunctival injection of bevacizumab for recurrent pterygium.
Once validated, this technique may obviate the need for surgery as well as
provide an alternative form of therapy for recurrent pterygia that is simpler, faster,
and easier to perform compared to existing methods of pterygium removal.
II.

Patients and Methods


This off-label, 2-dosing, interventional case series was conducted in

patients with recurrent pterygium from March 2010 to July 2011. 20 patients, 9

J. Clin. Exp Opthalmol Volume 4, 2013


ISSN:2155-9750 JCEO. An open access journal

males (45%) and 11 females (55%) are involved with a mean age of (50.46
18.30 years), range (38-70) (Table 1).
Each pterygium was measured and graded according to Tan and
coworkers grading scheme proposed in 1997 [21]. Grading was based on the
visibility of the underlying episcleral blood vessels. This has been previously
described and validated as a marker of severity. The pterygia were classified into
grades 1, 2 and 3 based on slit lamp evaluation.
Grade 1 (atrophic) had clearly visible episcleral vessels under the body of the
pterygium.
Grade 2 (intermediate) had partially visible episcleral vessels under the body
of the pterygium.
Grade 3 (fleshy) had totally obscured episcleral vessels underlying the body of
the pterygium.
On baseline examination, at least Grade 2 patients with pterygium were
included in the study.
III.

Exclusion criteria
Exclusion criteria included previous ocular surgeries except pterygium

removal, conditions in which Bevacizumab is contraindicated including (allergy


to bevacizumab, hypertension, proteinuria, bleeding tendencies, previous
myocardial infarction or stroke, pregnant and lactating women), evidence of other
ocular diseases except refractive errors, history of ocular trauma, pterygium
invading more than 3 mm of the cornea and inability to follow up patient for the
duration of the study. Full detailed history and full informed written consent was
obtained from all patients included in the study.

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ISSN:2155-9750 JCEO. An open access journal

A complete eye evaluation was performed for each patient. This included
visual-acuity measurement, applanation tonometry, slit lamp examination, and
anterior segment photography. The dimensions of the pterygium were determined
by measuring its length in centimeters from base (using the caruncle as landmark)
to apex, and width in centimeters at the base and apical areas. All injections were
performed in operating room. Topical anesthesia using 0.5% proparacaine
hydrochloride eye drops (Alcaine, Alcon), subconjunctival injection of 0.2 ml (5
mg) of Bevacizumab (100 mg/4 ml Roche) following the injection of 0.2 ml
lidocain 2% in subconjunctival area of pterygium body using a 1-ml syringe with
29-gauge needle, the patient was asked to direct the eye in extreme horizontal
gaze to have adequate exposure of the pterygium and injection repeated on week
2, the patient contacted with predetermined follow-up schedule. Patients were
followed up after a week, one month, three months and six months from the last
injection. In each visit, complete ophthalmologic evaluation was performed; any
complications and adverse events were noted. Anterior segment photography
using Topcon fundus camera with lens adapter for anterior segment imaging was
done.
Post injection complications such as subconjunctival hemorrhage,
persistent epithelial defect, infection and uveitis were noted. Any adverse events
were noted, these may include systemic effects such as hypertension or any
thromboembolic incidents, or any allergic reactions to the medications and
products used in the study.
The drug was considered having a biological effect when any regression in
the size or decrease in vascularity and thickness of pterygium grading occurred.

J. Clin. Exp Opthalmol Volume 4, 2013


ISSN:2155-9750 JCEO. An open access journal

IV.

Statistical analysis
Both descriptive and analytic approaches were used in the data analysis.

Statistical analysis was carried out using the Statistical Package for the Social
Sciences (SPSS version 10). Chi-square was used to determine the association
between grades and time intervals. A p value less than or equal to 0.05 was
considered statistically significant.
V.

Results
This study showed that is no statistically significant difference between

males and females in the mean pterygium size (>0.05) during the follow up
period. On comparing the pterygium gradings at different time intervals:
statistically significant difference was noted (p<0.01).
This study showed that the average of pterygium size reduction and the
reduction of color intensity after 6 months follow up period were statistically
significant (P=0.01), (P=0.031) subsequently. At baseline, there were 11(55%)
patients with grade 2 pterygium and 9 (45%) patients with grade 3. On 6 months
follow up 9 patients (45%) fall in the grade 1, 9 (45%) patients in grade 2 and
only 2 patients remained in grade 3 (10%) (Table 2 and Figure 1).
Regarding the visual acuity changes, comparison of the Snellens visual
acuity at different time intervals showed no statistically significant difference
(p>0.05).
Systolic and diastolic blood pressure at different time intervals showed no
significant difference (p>0.05) (Table 3).

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Apart from subconjunctival hemorrhage which occurred in 4 patients


(20%) and resolved within 2 weeks, no ocular surface toxicity, persistent epithelial
defects, corneal abrasion, infections, or uveitis were reported during the study.
Age(years)
Mean
Range

50.46
38-70

Male
Female

9
11

Grade 2
Grade 3

11
9

Gender

Grade of pterygium

IOP (mm Hg)


Mean
range
Systolic Blood pressure(mm Hg)
Mean
Range
Diastolic blood pressure(mm Hg)
Mean
Range

12.46 2.42
12-19
122 7.7
100-140
79.33 5.94
60-100

Table 1: Demography of the patients.


Time
interval

Grading
Total
Grade 1
Grade II
Grade III
0
11
9
20
Baseline
0%
55,0%
45,0%
100,0%
4
11
5
20
1 Months
20,0%
55,0%
25,0%
100,0%
8
9
3
20
3 Months
40,0%
45,0%
15,0%
100,0%
9
9
2
20
6 Months
45,0%
45,0%
10,0%
100,0%
There is a significant relationship between grades and time interval, P<0.01
Table 2: Distribution of patients according to grading related to time interval.

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Figure 1: Regression of blood vessels and size of pyterigium after 6 months of


injection of Avastin.
Systolic blood Pressure
Diastolic blood Pressure
(mmHg)
(mmHg)
Mean
P
Mean
P
Baseline
122 + 7.74
79.33 + 5.94
One month
120.67
+ > 0.05
76.66 + 8.16 > 0.05
10.32
3 months
121.33
+ 0.64
81.33 + 8.34
10.6
6 months
119.3
+
78.67
+
10.99
8.34
Table 3: Distribution of patients regarding the levels of blood pressure (means) at
different time intervals.
Time Interval

VI.

Discussion
Surgery has been considered as a main treatment for primary pterygium

[5,6]; however, complications such as recurrence and even worsening of


pterygium following the surgery may occur [7]. The recurrence rate was estimated
to be between 15% to 75% in simple excision and about 6% in the free flap
operations. Some substances such as mitomycin C and 5-FU are recommended to
decrease the chance of recurrence; however, their usage is associated with other
undesirable complications such as infection and scleral necrosis [6-8]. On the
other hand, many patients ask for conservative treatment at least to suppress
further progression of corneal neovascularization and abolish the symptoms,
especially the congestion. Medical therapies have failed to give acceptable
benefits in this relation [4,5]. It is noteworthy to indicate that the pathophysiology
of recurrent pterygium is different from that of primary pterygium, containing
more fibrous tissues and abnormal neovascularization rather than elastic
degeneration [4-6].

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ISSN:2155-9750 JCEO. An open access journal

VEGF level has been shown to be increased in pterygium and is suggested


to be either directly or indirectly involved in its pathogenesis [12-15,17].
Immunohistochemistry studies have shown that VEGF levels are more expressed
in pterygium than in normal conjunctiva [12,15,22]. Decreased anti-angiogenic
factors, together with increased stimulators, have been hypothesized in the
formation and progression of pterygia [15]. The findings of abundant expression
of VEGF in pterygium may lead to the anti-VEGF therapy development in order
to induce the regression of blood vessels and size of pterygium. Pterygium is a
chronic, degenerative disorder described histologically as elastotic degeneration of
conjunctival tissue. It has a stromal overgrowth of fibroblasts and blood vessels
accompanied by an inflammatory cell infiltrate and abnormal extracellular matrix
accumulation composed of elastin and collagen [7].
In a study done by Asergadoo [23], he concluded that if pterygium is going
to recur, it usually grows back or shows signs of recurrence during the first three
months. Recurrence is sometimes seen as late as nine months. In a recent study to
define the time interval necessary to follow patients after pterygium removal to
identify a recurrence, a one - year follow up time was likely acceptable [24]. The
minimum follow up in this study was 6 months.
In a study on a rat model of corneal alkali burns, Manzano et al. have
shown a 40% reduction of corneal neovascularization by topical application of
bevacizumab [25]. Over expression of VEGF in pterygium tissue [26,27] and
ocular inflammation [28] together with the abundance of new vessels supported
the role of angiogenesis in the formation of pterygia [26,27,29-31]. Vascular

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ISSN:2155-9750 JCEO. An open access journal

endothelial growth factor gene 460 polymorphism was associated with pterygium
formation in Chinese female patients [32].
Bahar et al. [31] reported the use of subconjunctival bevacizumab on
corneal vessel density in recurrent pterygia. Subconjunctival bevacizumab was
well tolerated but did not cause regression of corneal vessels in recurrent pterygia.
No side-effects of subconjunctival bevacizumab injections have been reported so
far [33- 36].
No local irritation, allergic reaction, or surface epitheliopathy was
observed. This is in contrast with a 60% rate of spontaneous loss of epithelial
integrity as recently reported by Kim et al. [37], where the investigators used
topical bevacizumab at a slightly higher concentration (1.25%) twice daily for a
much longer period (3 months), and adverse effects generally appeared during the
second month of treatment.
This suggests that the duration of treatment may well determine the safety
of topical bevacizumab. A study done by Dastjerdi shows a highly variable effect
across the cohort treated with topical bevacizumab in the treatment of corneal
neovascular vessels (NV). Generally, this study shows that topical bevacizumab
1% is effective in the treatment of clinically stable corneal NV as evidenced by a
nearly 50% reduction in 2 corneal NV size [38].
Felipe et al. in their study showed that subconjunctival injection of 1.25
mg bevacizumab given every 2 weeks for 10 weeks did not result in significant
change in the size of the pterygium. No serious ocular and systemic adverse
events were noted [39] but in this study, subconjunctival injection of 0.2 ml (5
mg) Bevacizumab significantly reduced the size of pterygium.

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ISSN:2155-9750 JCEO. An open access journal

VII.

Conclusion
This study showed that subconjunctival injection of bevacizumab is useful

in treatment of patients with recurrent pterygium without local or systemic


adverse effects. So simplicity of the procedure, cosmetic satisfaction and the lack
of major complications after treatment lead us to recommend this regimen as the
first choice for the treatment of recurrent pterygium.

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ISSN:2155-9750 JCEO. An open access journal

J. Clin. Exp Opthalmol Volume 4, 2013


ISSN:2155-9750 JCEO. An open access journal

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Injeksi Subkonjungtiva Bevacizumab untuk Terapi Pterigium


Berulang
Hussein Alhammami1, Qassim Farhood2* and Hassanein Shuber3
1.
2.

3.

FICMS, Ophthalmology Department, Medical College Kufa University, Iraq


FICMS-OPH, Ophthalmology Department, Medical College, University of
Babylon, Iraq
FICMS, Ophthalmology Department, Medical College, Al Mustanseriah
University, Iraq

Abstrak
Tujuan: Untuk mengetahui pengaruh klinis dari injeksi subkonjuntiva
bevacizumab dalam kemunduran atau menghentikan pertumbuhan pada pasien
dengan pterigium berulang.
Metode dan bahan: Penelitian ini merupakan off-label; 2-dosis, serangkaian
kasus yang melibatkan 20 pasien dengan pterigium berulang. Mereka menerima
bevacizumab subkonjunctiva (0,2 ml / 2,5 mg). Vaskularisasi dan ketebalan
Pterygium yang dinilai. Ukuran pterygium dicatat (diukur dengan luas permukaan
dalam cm2) dari awal sampai 6 bulan setelah injeksi. Komplikasi dari pengobatan
dan efek samping telah dilaporkan. Hasil utama pengukuran adalah perubahan
pada penilaian, ukuran, vaskularisasi, ketebalan dan intensitas warna.
Hasil: 9 pria (45%), 11 perempuan (55%) dari 20 pasien yang dilakukan dalam
penelitian dengan usia rata-rata 50,46 tahun 18.30 (rentang 38-70). Ada
penurunan yang signifikan dalam penilaian dengan perbedaan yang signifikan
pada daerah permukaan rata-rata pterygium pada interval yang berbeda (P <0,05)
dan pengurangan ukuran pterygium. Penurunan intensitas warna yang signifikan
(P = 0.031). Tidak ada catatan efek samping yang signifikan topikal atau sistemik.
Kesimpulan: injeksi bevacizumab Subkonjunctiva berguna dalam pengelolaan
pasien dengan pterigium berulang tanpa efek samping lokal atau sistemik yang
signifikan.

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ISSN:2155-9750 JCEO. An open access journal

Kata kunci: injeksi Subconjunctival; bevacizumab; kekambuhan; pterigium


I.

Pendahuluan
Pterygium adalah lembaran segitiga dari jaringan pembuluh darah fibro

yang menyerang kornea [1,2]. Hal ini terjadi di celah interpalpebral, lebih umum
di sisi hidung mata dan sering bilateral [1-3]. Para Dokter telah mengenal pterygia
selama ribuan tahun [2,4-6] tetapi patogenesis pterygia tidak sepenuhnya
dipahami [7-10].
Berbagai penelitian mengidentifikasi faktor-faktor yang berhubungan
dengan lingkungan seperti sinar ultraviolet, iritasi kronis, dan peradangan.
Penelitian terbaru juga telah membuktikan adanya pengaruh komponen genetik,
mekanisme antiapoptotik, sitokin, faktor pertumbuhan, matriks ekstraselular
renovasi, mekanisme imunologi, dan infeksi virus dalam patogenesis penyakit
Pterigium

[7-11].

Faktor

pertumbuhan

pembuluh

darah

seperti

faktor

pertumbuhan endotel vaskular (Vascular Endothelial Growth Factor/ VEGF) telah


terdeteksi di pterygium [12-15] . Ini ditandai dengan peningkatan VEGF di
pterygia dibandingkan dengan sampel konjungtiva yang normal [12-15].
Meskipun patogenesis pterygia masih kurang dipahami, pembentukan dan
perkembangan mereka diketahui tergantung pada neovaskularisasi. Telah
dipahami bahwa perkembangan pterygia tergantung pada perubahan angiogenik
rasio stimulator-to-inhibitor. Jin et al. menunjukkan bahwa pterygia terdapat
penurunan drastis kadar epitel pigmen faktor yang diturunkan, inhibitor
angiogenesis, dan peningkatan kadar VEGF [15].
Pengobatan pterygium masih kontroversial, dengan berbagai perawatan
yang dianjurkan dalam literatur ilmiah [16]. Pterygia terdiri dari proliferasi

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jaringan fibrovaskular serta pembentukan dan perkembangannya membutuhkan


neovaskularisasi [17,18], banyak molekul yang secara positif mengatur
angiogenesis

telah

diidentifikasi,

menunjukkan

bahwa

faktor

faktor

pertumbuhan mungkin terlibat langsung ataupun tidak langsung dalam


patogenesis pterygia.
Bevacizumab

(Avastin)

adalah

full-length,

humanized,

antibodi

monoklonal terhadap semua jenis VEGF. Ini mengikat dan menetralkan aktivitas
biologis semua jenis VEGF manusia, sehingga mencegah interaksi dengan
reseptor pada permukaan sel endotel [17]. Bevacizumab telah digunakan untuk
mengobati neovaskularisasi koroid karena berkaitan dengan usia degenerasi
makula (ARMD), dan baru-baru ini untuk edema makula diabetes. Berbagai uji
klinis telah menunjukkan bahwa ketika diberikan intravitreally, ini ditoleransi
dengan baik dan berhubungan dengan peningkatan ketajaman visual, penurunan
ketebalan retina sentral, dan pengurangan kebocoran angiografi [18-20].
Penelitian ini menentukan efek klinis dan keamanan injeksi subkonjunctiva
bevacizumab untuk pterygium berulang.
Setelah divalidasi, teknik ini dapat menghilangkan kebutuhan untuk
operasi serta memberikan bentuk terapi alternatif untuk pterygia berulang yang
lebih sederhana, lebih cepat, dan lebih mudah untuk dilakukan dibandingkan
dengan metode pemindahan pterigium yang sudah ada.
II.

Pasien dan Metode


Ini off-label, 2-dosis, kasus intervensi yang dilakukan pada pasien dengan

pterigium berulang dari Maret 2010 hingga Juli 2011. 20 pasien, 9 laki-laki (45%)

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dan 11 perempuan (55%) yang terlibat dengan usia rata-rata (50,46 18.30
tahun), rentang usia (38-70) (Tabel 1).
Setiap pterigium telah diukur dan dinilai menurut Tan dan rekan kerja
'skema penilaian yang diusulkan pada tahun 1997 [21]. Penilaian didasarkan pada
visibilitas pembuluh darah yang mendasari episkleral. Hal ini telah dijelaskan
sebelumnya dan divalidasi sebagai penanda keparahan. Pterygia diklasifikasikan
ke dalam kelas 1, 2 dan 3 berdasarkan evaluasi slit lamp.
Kelas 1 ("atrofi"), pembuluh episcleral terlihat jelas di bawah tubuh pterygium
tersebut.
Kelas 2 ("menengah"), pembuluh episcleral sebagian terlihat di bawah tubuh
pterygium tersebut.
Kelas 3 ("berdaging") episcleral telah benar-benar tertutup oleh tubuh pterygium
tersebut.
Pada pemeriksaan awal, setidaknya pasien dengan pterigium kelas 2
dilibatkan dalam penelitian ini.
III.

Kriteria eksklusi
Kriteria eksklusi meliputi operasi ocular sebelumnya kecuali pemindahan

pterigium, termasuk kondisi di mana Bevacizumab merupakan kontraindikasi


(alergi terhadap bevacizumab, hipertensi, proteinuria, kecenderungan perdarahan,
infark miokard sebelumnya atau stroke, ibu hamil dan menyusui), bukti penyakit
mata lain kecuali kesalahan bias, riwayat trauma okular, pterigium lebih dari 3
mm kornea dan ketidakmampuan untuk menindaklanjuti pasien selama penelitian.
Riwayat dan informed consent lengkap tertulis diperoleh dari semua pasien yang
dilibatkan dalam penelitian ini.

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Evaluasi mata lengkap dilakukan untuk setiap pasien. Ini termasuk


pengukuran visual ketajaman, applanation tonometry, pemeriksaan lampu celah,
dan segmen anterior fotografi. Dimensi pterygium yang ditentukan dengan
mengukur panjang dalam sentimeter dari dasar (menggunakan caruncle sebagai
landmark) ke puncak, dan lebar dasar dalam sentimeter dan daerah apikal. Semua
suntikan dilakukan di kamar operasi. Anestesi topikal menggunakan 0,5% mata
proparacaine hidroklorida tetes (Alcaine, Alcon), injeksi subkonjuntiva dari 0,2
ml (5 mg) dari Bevacizumab (100 mg / 4 ml Roche) setelah injeksi 0,2 ml
lidokain 2% di daerah subkonjuntiva yang terdapat pterigium menggunakan jarum
suntik 1 ml dengan jarum 29-gauge, pasien diminta untuk mengarahkan mata pada
pandangan horisontal ekstrim untuk mendapatkan area yang tepat dari pterigium
dan injeksi kembali pada minggu ke 2, kemudian pasien dihubungi dengan jadwal
yang telah ditentukan. Pasien ditindaklanjuti setelah seminggu, sebulan, tiga bulan
dan enam bulan dari suntikan terakhir. Dalam setiap kunjungan, evaluasi
ophthalmologic lengkap dilakukan; komplikasi dan efek samping dicatat. Segmen
fotografi anterior menggunakan kamera fundus Topcon dengan adapter lensa
untuk segmen anterior pencitraan dilakukan.
Komplikasi pasca injeksi seperti perdarahan subkonjunctiva, cacat epitel
persisten, infeksi dan uveitis dicatat. Setiap efek samping yang dicatat, ini
mungkin termasuk efek sistemik seperti hipertensi atau insiden tromboemboli,
atau reaksi alergi terhadap obat-obatan dan produk yang digunakan dalam
penelitian ini.

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Obat tersebut dianggap memiliki efek biologis ketika berbagai macam


kemunduran dalam ukuran atau penurunan vaskularisasi dan gradasi ketebalan
pterygium terjadi.

IV.

Analisis statistik
Pendekatan deskriptif dan analitik telah digunakan dalam analisis data.

Analisis statistik dilakukan dengan menggunakan Paket Statistik untuk Ilmu


Sosial (SPSS versi 10). Chi-square digunakan untuk menentukan hubungan antara
nilai dan interval waktu. Nilai p kurang dari atau sama dengan 0,05 dianggap
signifikan secara statistik.
V.

Hasil
Studi ini menunjukkan bahwa ada perbedaan yang signifikan secara

statistik antara pria dan wanita dalam rata-rata ukuran pterygium (> 0,05) selama
periode tindak lanjut. Ketika membandingkan gradasi pterigium pada interval
waktu yang berbeda: perbedaan yang signifikan secara statistik tercatat (p <0,01).
Studi ini menunjukkan bahwa rata-rata pengurangan ukuran pterigium dan
pengurangan intensitas warna setelah 6 bulan masa tindak lanjut yang signifikan
secara statistik (P = 0,01), (P = 0.031) selanjutnya. Pada awal, ada 11 (55%)
pasien dengan kelas 2 pterygium dan 9 (45%) pasien dengan kelas 3. Pada 6 bulan
tindak lanjut 9 pasien (45%) jatuh di kelas 1, 9 (45%) pasien dalam kelas 2 dan
hanya 2 pasien tetap di kelas 3 (10%) (Tabel 2 dan Gambar 1).
Mengenai perubahan ketajaman visual, perbandingan ketajaman visual
Snellen tersebut pada interval waktu yang berbeda menunjukkan tidak ada
perbedaan yang signifikan secara statistik (p> 0,05).

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Tekanan darah sistolik dan diastolik pada interval waktu yang berbeda
tidak menunjukkan perbedaan yang signifikan (p>0,05) (Tabel3).
Selain perdarahan subconjunctival yang terjadi pada 4 pasien (20%) dan
diselesaikan dalam waktu 2 minggu, tidak ada toksisitas permukaan mata, cacat
epitel persisten, abrasi kornea, infeksi, atau uveitis dilaporkan selama penelitian.
Age(years)
Mean
Range

50.46
38-70

Male
Female

9
11

Grade 2
Grade 3

11
9

Gender

Grade of pterygium

IOP (mm Hg)


Mean
range
Systolic Blood pressure(mm Hg)
Mean
Range
Diastolic blood pressure(mm Hg)
Mean
Range

12.46 2.42
12-19
122 7.7
100-140
79.33 5.94
60-100

Table 1: Demography of the patients.

Fi
gure 1: Regression of blood vessels and size of pyterigium after 6 months of
injection of Avastin.
Time
interval
Baseline
1 Months

Grade 1
0
0%
4
20,0%

Grading
Grade II
11
55,0%
11
55,0%

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Total
Grade III
9
45,0%
5
25,0%

20
100,0%
20
100,0%

8
9
3
20
40,0%
45,0%
15,0%
100,0%
9
9
2
20
6 Months
45,0%
45,0%
10,0%
100,0%
There is a significant relationship between grades and time interval, P<0.01
Table 2: Distribution of patients according to grading related to time interval.
VI.
Diskusi
3 Months

Bedah telah dianggap sebagai terapi utama untuk pterigium primer [5,6];
Namun, komplikasi seperti kekambuhan dan bahkan memburuknya pterigium
setelah operasi dapat terjadi [7]. Tingkat kekambuhan diperkirakan antara 15%
sampai 75% pada eksisi sederhana dan sekitar 6% dalam operasi free flap.
Beberapa zat seperti mitomycin C dan 5-FU dianjurkan untuk mengurangi
kemungkinan kekambuhan; Namun, penggunaannya dikaitkan dengan komplikasi
yang tidak diinginkan lainnya seperti infeksi dan nekrosis scleral [6-8]. Di sisi
lain, banyak pasien meminta pengobatan konservatif setidaknya untuk menekan
perkembangan lebih lanjut dari neovaskularisasi kornea dan menghilangkan
gejala, terutama kongesti/sumbatan. Terapi medis telah gagal untuk memberikan
manfaat yang dapat diterima dalam hubungan ini [4,5]. Hal ini penting untuk
menunjukkan bahwa patofisiologi pterigium berulang adalah berbeda dari
pterygium primer, mengandung lebih banyak jaringan berserat dan abnormal
neovaskularisasi daripada kemunduran kelenturan [4-6].
Tingkat VEGF telah terbukti ditingkatkan oleh pterigium dan diasumsikan
terlibat dalam pathogenesis secara langsung maupun tidak langsung [12-15,17].
Studi imunohistokimia menunjukkan bahwa kadar VEGF lebih banyak dalam
pterigium daripada di konjungtiva yang normal [12,15,22]. Penurunan faktor antiangiogenik, bersama-sama dengan peningkatan stimulator, telah dihipotesiskan
dalam pembentukan dan perkembangan pterygia [15]. Penemuan
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ekspresi

berlimpah VEGF di pterigium dapat mengarah pada pengembangan terapi antiVEGF untuk menginduksi regresi pembuluh darah dan ukuran pterygium.
Pterigium adalah kronis, gangguan degeneratif yang dijelaskan secara histologis
sebagai degenerasi elastotic jaringan konjungtiva. Memiliki pertumbuhan stroma
fibroblas dan pembuluh darah yang berlebihan disertai dengan infiltrasi sel radang
dan ekstraseluler akumulasi matriks abnormal terdiri dari elastin dan kolagen [7].
Dalam sebuah penelitian yang dilakukan oleh Asergadoo [23], ia
menyimpulkan bahwa jika pterygium akan berulang,biasanya tumbuh kembali
atau menunjukkan tanda-tanda kekambuhan selama tiga bulan pertama.
Kekambuhan kadang-kadang dilihat dalam 9 bulan terakhir. Dalam penelitian
terbaru untuk menentukan interval waktu yang diperlukan untuk mengikuti pasien
setelah

pengangkatan

pterygium

untuk

mengidentifikasi

kambuh

dan

menidaklanjuti, adalah satu - tahun [24]. Minimum tindak lanjut dalam penelitian
ini adalah 6 bulan.
Dalam sebuah penelitian pada tikus yang terkena luka bakar alkali kornea,
Manzano et al. telah menunjukkan penurunan 40% dari neovaskularisasi kornea
oleh aplikasi topikal bevacizumab [25]. Selama ekspresi VEGF pada pterigium
jaringan [26,27] dan inflamasi okular [28] bersama dengan kelimpahan pembuluh
darah mendukung peran angiogenesis dalam pembentukan pterygia [26,27,29-31].
Faktor pertumbuhan endotel vaskuler gen 460 polimorfisme dikaitkan dengan
pembentukan pterygium pada pasien wanita Cina [32].
Bahar et al. [31] melaporkan penggunaan bevacizumab subconjunctival
pada

kepadatan

pembuluh

kornea

di

pterygia

berulang.

Bevacizumab

subconjunctival ditolerasi dengan baik, tetapi tidak menyebabkan regresi

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pembuluh kornea di pterygia berulang. Sejauh ini tidak ada efek samping dari
suntikan bevacizumab subconjunctival sejauh yang dilaporkan [33- 36].
Tidak ada iritasi lokal, reaksi alergi, atau epitheliopathy permukaan yang
didapatkan dari pengamatan. Hal ini berbeda dengan tingkat 60% dari hilangnya
spontan integritas epitel baru-baru ini dilaporkan oleh Kim et al. [37], di mana
para peneliti menggunakan bevacizumab topikal pada konsentrasi yang sedikit
lebih tinggi (1,25%) dua kali sehari untuk jangka waktu lebih lama (3 bulan), dan
efek samping umumnya muncul selama bulan kedua pengobatan.
Hal ini menunjukkan bahwa lamanya pengobatan mungkin menentukan
keamanan bevacizumab topikal.
Sebuah studi yang dilakukan oleh Dastjerdi menunjukkan efek sangat
bervariasi di seluruh kelompok yang diobati dengan bevacizumab topikal untuk
pengobatan pembuluh neovascular kornea (NV). Secara umum penelitian ini
menunjukkan bahwa topikal bevacizumab 1% efektif dalam pengobatan klinis NV
kornea yang dibuktikan dengan penurunan hampir 50% dalam 2 ukuran kornea
NV [38].
Felipe et al. dalam penelitian mereka menunjukkan bahwa injeksi
subkonjunctiva dari 1,25 mg bevacizumab diberikan setiap 2 minggu selama 10
minggu tidak menghasilkan perubahan signifikan dalam ukuran pterigium
tersebut. Tidak ada efek samping yang serius pada mata dan sistemik dicatat [39],
tetapi dalam penelitian ini, injeksi subconjunctival dari 0,2 ml (5 mg)
Bevacizumab secara signifikan mengurangi ukuran pterygium.

VII.

Kesimpulan

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Penelitian ini menunjukkan bahwa suntikan subkonjunctiva bevacizumab


berguna dalam pengobatan pasien dengan pterigium berulang tanpa efek samping
lokal atau sistemik. Jadi kemudahan prosedur, kepuasan kosmetik dan kurangnya
komplikasi utama setelah pengobatan membawa kita untuk merekomendasikan
regimen ini sebagai pilihan pertama untuk pengobatan pterigium berulang.

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