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ORIGINAL ARTICLE
Year : 2011  |  Volume : 18  |  Issue : 3  |  Page : 220-223  

Intravitreal bevacizumab as a primary treatment for idiopathic choroidal neovascularization


1 Department of Vitreo-retinal service, Dhahran Eye Specialist Hospital, Dhahran, KSA
2 Department of Vitreo-retinal service, University Hospital of Wales, Cardiff, UK

Date of Web Publication20-Aug-2011

Correspondence Address:
Rizwan A Cheema
5 Clos Padrig, Cardiff, CF3 2AF, UK

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-9233.84051

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   Abstract 

Purpose : To report long-term outcomes of the use of intravitreal bevacizumab in subjects with idiopathic choroidal neovascularization (ICNV).
Materials and Methods : Six consecutive subjects with ICNV were included in this prospective study. All subjects received 1.25 mg intravitreal bevacizumab at diagnosis. A decrease in best corrected visual acuity (BCVA), presence of increased retinal edema or hemorrhage, increased retinal thickness on optical coherence tomography (OCT) or increased leakage documented by fluorescein angiography prompted further injections of bevacizumab.
Results : The study cohort was comprised of 3 males and 3 females with a mean age of 31.17 years. Mean follow-up was 13.8 months (range, 8 months to 20 months). Following intravitreal bevacizumab injection, vision improved in 3 subjects, remained stable in 3 subjects and no patient lost visual acuity. The mean BCVA improved to logMAR 0.20 at final follow-up from baseline at 0.950 logMAR (P=0.031). The mean central macular thickness and central foveal thickness at the last postoperative visits were reduced from pre-treatment levels of 374.33 ± 146.52 and 347.16 ± 213.97 to 251.20±35.36 and 215.33 ± 43.94 μm, respectively. (P = 0.99 and P = 0.16, respectively). Four subjects required repeat treatments. The total number of repeat treatments was 4. Two subjects required no repeat injections, 3 subjects had 1 retreatment and one subject required 2 additional treatments. The injections were well tolerated by all the subjects, with no ocular or systemic adverse events.
Conclusion : Intravitreal injection of 1.25 mg bevacizumab in patients with ICNV is effective in improving and stabilizing vision. Additional studies, particularly determination of optimal protocol for timing of re-injection are required to assess long-term effects.

Keywords: Anti Vascular Endothelial Growth Factor Therapy, Avastin, Choroidal Neovascularization, Idiopathic choroidal Neovascularization, Intravitreal Bevacizumab


How to cite this article:
Cheema RA, Mushtaq J, Cheema MA. Intravitreal bevacizumab as a primary treatment for idiopathic choroidal neovascularization. Middle East Afr J Ophthalmol 2011;18:220-3

How to cite this URL:
Cheema RA, Mushtaq J, Cheema MA. Intravitreal bevacizumab as a primary treatment for idiopathic choroidal neovascularization. Middle East Afr J Ophthalmol [serial online] 2011 [cited 2019 Sep 15];18:220-3. Available from: http://www.meajo.org/text.asp?2011/18/3/220/84051


   Introduction Top


Choroidal neovascularization (CNV) is an important cause of poor central vision and visual loss. CNV causes exudation, hemorrhage and fibrosis at the macula resulting in extensive damage to photoreceptors. Most cases of CNV are caused by wet age related macular degeneration (ARMD), myopia, trauma and inflammatory disorders. However, a small minority of patients may develop CNV without apparent cause and are grouped as a distinct entity called idiopathic CNV (ICNV).

Recently, encouraging results have been reported for managing CNV associated with ARMD with intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Anti-VEGF agents, such as pegaptanib, [1] ranibizumab [2] and bevacizumab, [3] have also been used in the management of CNV associated with other disorders such as myopia, [4] inflammation [5] and trauma [6],[7] with good outcomes. To our knowledge no studies have been published reporting long-term (1 year or longer) results of anti-VEGF therapy for ICNV. The aim of this prospective study is to report long-term results of the use of intravitreal bevacizumab in patients with ICNV in Eastern province of Saudi Arabia.


   Materials and Methods Top


Subject selection

Six consecutive subjects with ICNV were included in this prospective study. The study was approved by the institutional review board of the hospital and informed consent was obtained. The subjects were recruited from the retina clinic at Dhahran Eye Specialist Hospital, a tertiary referral ophthalmic hospital in the Eastern province of Saudi Arabia. The diagnosis of ICNV was established in each subject by clinical examination, optical coherence tomography (OCT) and fluorescein angiography. Individuals with features of ARMD, myopia, history of trauma, choroiditis, presumed ocular histoplasmosis syndrome (POHS), hereditary eye disease, and any other cause of secondary CNV were excluded from the study.

Prior to treatment, all patients underwent a full ophthalmic assessment, including best corrected visual acuity (BCVA), slit lamp biomicroscopy, intraocular pressure, digital color fundus photographs and fluorescein angiography (Kowa VX10i-Kowa Co. Ltd., Tokyo, Japan). Evaluation of the macula with OCT was performed with commercially available equipment (OCT/SLO- OPKO Health Inc., Miami, FL., USA) to image intraretinal edema, subretinal fluid or pigment epithelial detachment. Retinal thickness was measured in a circle of 3.5 mm in diameter corresponding to five zones (central, nasal, temporal, superior and inferior) centered on the fixation point. Mean thickness on the 1 mm circle centered on the fovea (CC) was measured and thickness of all five zones was used to calculate average macular thickness (CMT).

Intravitreal bevacizumab injection and follow-up

All subjects received intravitreal injection of anti-VEGF agent bevacizumab (Avastin® , Genentech Inc., San Francisco, CA, USA). The lids and conjunctiva were cleansed with 10% and 5% povidone and iodine, respectively, followed by an injection of 2% lidocaine to anesthetise the conjunctiva. Bevacizumab (1.25 mg) was injected with a 30 g needle through the pars plana (3.5 mm from limbus) into the vitreous. An eye pad was placed and 0.3% gatifloxacin topical drops were prescribed to be instilled four times daily for four days. One patient required general anesthetic for intravitreal injection due to his young age of 13 years.

At each follow-up visit, a full ophthalmic assessment including evaluation of retinal morphology with OCT was performed. Fluorescein angiography to document leakage from ICNV was performed at a follow-up visit if the activity of the lesion could not be determined by clinical evaluation and OCT assessment. BCVA, macular appearance, and OCT findings were used to decide whether the subject should have a repeat injection of intravitreal bevacizumab. A decrease in BCVA, presence of increased retinal edema or hemorrhage, increased retinal thickness on OCT or increased leakage documented on fluorescein angiography prompted additional treatment with bevacizumab.

Outcome measures

The primary outcome measure was number of eyes that had improvement of vision (gain of ≥0.2 logMAR), were stable (within 0.2 log MAR) or had moderate vision loss (loss of ≥0.2 logMAR) at the last follow-up visit. Secondary outcome measures were change in mean BCVA (Snellen converted to logMAR), macular thickness (CC and CMT), number of retreatments (additional injections of bevacizumab) and adverse affects. Statistical analysis, Wilcoxon signed ranked test for non-parametric and t-test for parametric data, was performed with SPSS statistical software (version 13.0.1, IBM Corp., Somers, NY, USA). P>0.05 was considered statistically significant.


   Results Top


Six consecutive subjects with ICNV were included in the study between September 2008 and July 2010. The mean follow-up duration was 13.8 months (range, 8 months to 20 months). There were 3 males and 3 females with a mean age of 31.17 years (range, 13 years to 51 years). The location of ICNV was subfoveal in one subject, juxtafoveal in 4 subjects and extrafoveal in 1 subject. No subject had a macular lesion in the fellow eye. The mean BCVA before treatment was 0.950±1.03 logMAR (median 0.6; range: 0.3 logMAR to 3.0 logMAR). The mean CMT and CC before treatment were 374.33±146.52 μm and 347.16±213.97 μm, respectively. A total 11 intravitreal bevacizumab injections performed for the study cohort (mean, 2 injections; median 2 injections; range 1 injection to 3 injections). Two patients underwent one injection, three patients 2 injections and one patient received 3 injections.

Following intravitreal bevacizumab treatment, vision improved in 3 subjects (gain of ≥0.2 logMAR), vision remained stable in 3 subjects (within 0.2 logMAR) and no subjects lost visual acuity. The mean BCVA improved to logMAR 0.20 at final follow-up from a baseline of 0.950 logMAR (P=0.031) [Figure 1]. The mean CMT decreased from 374.33±146.52 μm before treatment to 251.20±35.36 μm at last visit (P = 0.99). The mean CC decreased from 347.16±213.97 μm before treatment to 215.33±43.94 μm at last visit (P = 0.16). The injections were well tolerated by all the patients with no ocular or systemic ill effects.
Figure 1: Change in average best-corrected logMAR visual acuity over time following initial treatment with bevacizumab

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   Case Report Top


A 13-year-old male attended with sudden onset of metamorphopsia in his right eye in January 2009. There was no history of trauma. BCVA was recorded at 20/160 (0.9 logMAR) There were no signs of ocular inflammation in the anterior or posterior segment of the eye. Fundus examination of the right eye showed a greyish elevated lesion with surrounding subretinal fluid in the superior juxtafoveal aspect of the macula. Fluorescein angiography and OCT confirmed CNV. The CMT thickness and CC were 324.0 μm and 253.0 μm, respectively [Figure 2].The patient was diagnosed with ICNV. The patient had an intravitreal injection of 1.25 mg bevacizumab. After treatment, the lesion was quiescent with resolution of retinal edema. No further activity in the lesion was detected during 18 months of follow-up, and no further treatments were performed. At last visit the visual acuity was 20/20 (logMAR 0.0) and CMT and CC were 238.0 μm and 143.0 μm, respectively [Figure 3].
Figure 2: Color fundus photograph, fl uorescence angiogram and optical coherence tomography analysis in a 13-year-old male patient at presentation. (a) Color fundus photograph showing juxtafoveal idiopathic choroidal neovascularization. (b and c) Flourescene angiogram in early and late phase. (d and e) optical coherence tomography showing idiopathic choroidal neovascularization with retinal thickening in 5 zones at macula

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Figure 3: Color fundus photograph and optical coherence tomography analysis in a 13-year-old male patient at 18 months follow-up following intravitreal injection of bevacizumab given at fi rst visit. (a) Color fundus photograph showing regression of idiopathic choroidal neovascularization. (b and c) optical coherence tomography documenting reduction in size of lesion and improvement of retinal thickness

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   Discussion Top


Idiopathic choroidal neovascularization (ICNV) is a distinct clinical entity and may account for 17% of cases [8] with CNV in patients less than 50 years old. The natural history of idiopathic CNV, as compared to CNV due to wet ARMD, [9] is not necessarily associated with a profound loss of vision. [10] Various treatments such as, intravitreal and subtenons steroids, transpupillary thermotherapy, surgical removal and photodynamic therapy with verteporfin, [11],[12] have been attempted with varying success in preventing visual loss in patients with ICNV. Recently, intravitreal anti-VEGF treatment has proved very effective and beneficial in patients with CNV of varying etiology and ICNV. [13]

Several studies have reported encouraging results following intravitreal injection of bevacizumab for ICNV. Mandal et al.,[14] evaluated short-term visual and anatomical outcomes following intravitreal bevacizumab in 32 patients with subfoveal ICNV. During a mean follow-up period of 4.2 months, most patients showed marked improvement in visual acuity and a decrease in central macular thickness. [10] Inoue et al.,[15] reported one-year follow-up of intravitreal bevacizumab in 7 subjects with ICNV, and found that treatment is effective in stabilizing or improving vision. Qi et al.,[16] also reported encouraging efficacy and safety of intravitreal bevacizumab for ICNV in Chinese patients. The results of our study confirm these previous studies and show that bevacizumab is effective for longer than one year for ICNV cases. In our study with a mean follow-up of 13.8 months, all subjects experienced either an improvement or stabilization of vision. There was no loss of visual acuity in the cohort after treatment. There was statistically significant increase in mean BCVA of 12 lines (P =0.031). There was a concomitant reduction of mean CC and CMT during follow-up; however, these changes were not statistically significant (P>0.05, both cases). Clinically we believe the reduction of CC and CMT does explain the increase in BCVA seen in our cohort.

Various studies have evaluated the optimal dosing frequency of anti-VEGF therapy in patients with wet ARMD, while optimal frequency of reinjection in patients with ICNV remains undetermined. A meta-analysis conducted by Jyothi et al.,[17] found that the initial gain in vision appears greater in patients given a regimen including 6-week loading dose of intravitreal bevacizumab, though not sustained at 12 months, followed by a PRN dose administered at the physician's discretion. On the contrary, Ghazi et al.,[18] found that injections as frequent as one month in wet ARMD did not appear to be necessary since treatment effect of each injection lasts for at least eight weeks. We opted to use bevacizumab therapy in our patients' PRN, based on the changes in visual acuity, clinical examination, and the presence or absence of fluid as observed by OCT. The majority of improvement in average visual acuity occurred in the first 8 weeks following treatment with stabilization afterwards. The mean number of intravitreal bevacizumab injections received by patients in our study was 2. Two patients had one injection, three patients 2 injections and one patient received 3 injections to control activity of ICNV during follow-up. Based on our limited experience, we feel that an aggressive regimen of monthly loading injections followed by maintenance therapy is not necessary in patients with ICNV.

In conclusion, intravitreal injection of bevacizumab in patients with ICNV is effective in improving and stabilizing vision and an approach of PRN therapy is effective in controlling activity of disease in the longer term. However, additional studies with a larger sample size are required. Additionally, research efforts should focus on determining the optimal protocol for timing of re-injection and the long-term effect of therapy in patients with ICNV.

 
   References Top

1.Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinsod M, Guyer DR; VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 2004;351:2805-16.  Back to cited text no. 1
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2.Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355:1419-31.  Back to cited text no. 2
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3.Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology 2006;113:363-372.e5.  Back to cited text no. 3
    
4.Gharbiya M, Giustolisi R, Allievi F, Fantozzi N, Mazzeo L, Scavella V, et al. Choroidal neovascularization in pathologic myopia: Intravitreal ranibizumab versus bevacizumab--a randomized controlled trial. Am J Ophthalmol 2010;149:458-64.e1.  Back to cited text no. 4
    
5.Fine HF, Zhitomirsky I, Freund KB, Barile GR, Shirkey BL, Samson CM, Yannuzzi LA, et al. Bevacizumab (avastin) and ranibizumab (lucentis) for choroidal neovascularization in multifocal choroiditis. Retina 2009;29:8-12.  Back to cited text no. 5
    
6.Artunay O, Rasier R, Yuzbasioglu E, Sengül A, Bahcecioglu H. Intravitreal bevacizumab injection in patients with choroidal neovascularization due to choroid rupture after blunt-head trauma. Int Ophthalmol 2009;29:289-91.  Back to cited text no. 6
    
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8.Cohen SY, Laroche A, Leguen Y, Soubrane G, Coscas GJ. Etiology of choroidal neovascularization in young patients. Ophthalmology 1996;103:1241-4.  Back to cited text no. 8
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9.Grossniklaus HE, Green WR. Choroidal neovascularization. Am J Ophthalmol 2004;137:496-503.  Back to cited text no. 9
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10.Ho AC, Yannuzzi LA, Pisicano K, DeRosa J. The natural history of idiopathic subfoveal choroidal neovascularization. Ophthalmology 1995;102:782-9.  Back to cited text no. 10
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11.Ehrlich R, Kramer M, Rosenblatt I, Weinberger D, Mimouni K, Priel E, et al. Photodynamic therapy for choroidal neovascularization in young adult patients. Int Ophthalmol 2010;30:345-51.  Back to cited text no. 11
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12.Sickenberg M, Schmidt-Erfurth U, Miller JW, Pournaras CJ, Zografos L, Piguet B, et al. A preliminary study of photodynamic therapy using verteporfin for choroidal neovascularization in pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. Arch Ophthalmol 2000;118:327-36.  Back to cited text no. 12
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13.Gomi F, Nishida K, Oshima Y, Sakaguchi H, Sawa M, Tsujikawa M, et al. Intravitreal bevacizumab for idiopathic choroidal neovascularization after previous injection with posterior subtenon triamcinolone. Am J Ophthalmol 2007;143:507-10.   Back to cited text no. 13
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14.Mandal S, Garg S, Venkatesh P, Mithal C, Vohra R, Mehrotra A. Intravitreal bevacizumab for subfoveal idiopathic choroidal neovascularization. Arch Ophthalmol 2007;125:1487-92.  Back to cited text no. 14
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15.Inoue M, Kadonosono K, Watanabe Y, Sato S, Kobayashi S, Yamane S, et al. Results of 1-year follow-up examinations after intravitreal bevacizumab administration for idiopathic choroidal neovascularization. Retina 2010;30:733-8.  Back to cited text no. 15
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16.Qi HJ, Li XX, Tao Y. Outcome of intravitreal bevacizumab for idiopathic choroidal neovascularization in the Chinese population. Can J Ophthalmol 2010;45:381-5.  Back to cited text no. 16
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17.Jyothi S, Chowdhury H, Elagouz M, Sivaprasad S. Intravitreal bevacizumab (Avastin) for age-related macular degeneration: A critical analysis of literature. Eye (Lond) 2010;24:816-24.  Back to cited text no. 17
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18.Ghazi NG, Kirk TQ, Knape RM, Tiedeman JS, Conway BP. Is monthly retreatment with intravitreal bevacizumab (Avastin) necessary in neovascular age-related macular degeneration? Clin Ophthalmol 2010;4:307-14.  Back to cited text no. 18
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    Figures

  [Figure 1], [Figure 2], [Figure 3]


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