Seminars in Ophthalmology
ISSN: 0882-0538 (Print) 1744-5205 (Online) Journal homepage: http://www.tandfonline.com/loi/isio20
Pro Re Nata Intravitreal Bevacizumab for the Treatment of Idiopathic Choroidal Neovascular Membrane Kumar Saurabh, Rupak Roy, Pradeep Kumar Panigrahi, Aneesha Lobo & Anindya Kishore Majumdar To cite this article: Kumar Saurabh, Rupak Roy, Pradeep Kumar Panigrahi, Aneesha Lobo & Anindya Kishore Majumdar (2014): Pro Re Nata Intravitreal Bevacizumab for the Treatment of Idiopathic Choroidal Neovascular Membrane, Seminars in Ophthalmology, DOI: 10.3109/08820538.2014.962172 To link to this article: http://dx.doi.org/10.3109/08820538.2014.962172
Published online: 13 Nov 2014.
Submit your article to this journal
Article views: 29
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=isio20 Download by: [University of Wisconsin Oshkosh]
Date: 11 November 2015, At: 01:32
Seminars in Ophthalmology, Early Online, 1–4, 2014 ! Informa Healthcare USA, Inc. ISSN: 0882-0538 print / 1744-5205 online DOI: 10.3109/08820538.2014.962172
ORIGINAL ARTICLE
Pro Re Nata Intravitreal Bevacizumab for the Treatment of Idiopathic Choroidal Neovascular Membrane
Downloaded by [University of Wisconsin Oshkosh] at 01:32 11 November 2015
Kumar Saurabh, Rupak Roy, Pradeep Kumar Panigrahi, Aneesha Lobo, and Anindya Kishore Majumdar Aditya Birla Sankara Nethralaya, Kolkata, India
ABSTRACT Purpose: To study the efficacy of intravitreal bevacizumab on a pro re nata basis for treatment of idiopathic choroidal neovascular membrane. Material and methods: Thirty-seven eyes of 37 patients presenting with idiopathic choroidal neovascular membrane were included in the study. Intravitreal bevacizumab (1.25 mg/0.05 ml) was given on a pro re nata basis from the base line. Results: Twenty-one (58.3%) patients were male and 15 (41.7%) were female aged 13–49 years. Idiopathic choroidal neovascular membrane showed a classic leak on fluorescein angiogram in all the eyes. Subfoveal location (25; 67.6%) was the commonest site of involvement. Mean number of intravitreal bevacizumab injections required to achieve resolution was 2.81 ± 1.4. At final follow-up, 31 (83.8%) eyes had maintained or improved vision (Group A) and six (16.2%) eyes had worsening of vision (Group B). There was no significant difference in mean age, gender, and mean number of injections between groups A and B. Conclusion: Intravitreal bevacizumab on a pro re nata basis is effective in the treatment of idiopathic choroidal neovascular membrane. A larger controlled study would be required to formulate an accurate injection protocol. Keywords: Efficacy, idiopathic choroidal neovascular membrane, injection protocol
INTRODUCTION
angiography (FA), leading to a prominent role of photodynamic therapy (PDT) for treatment.5,6 However, the visual outcome after PDT has been known to be variable and there have been concerns about damage to the retinal pigment epithelium.5–7 Intravitreal anti-VEGF has also been shown to have promising results in the treatment of idiopathic CNVM, though optimum injection protocol and long-term safety profile are yet to be elucidated.8,9 The limited information, lack of definite etiology, multiple available treatment options, and varied presentation make the management of idiopathic CNVM an evolving process which requires more data from different populations.2,9 We aim to study the profile of idiopathic CNVM and its visual outcome with intravitreal bevacizumab from eastern India.
Choroidal neovascular membrane (CNVM) in patients below 50 years of age without any secondary pathology is considered to be idiopathic CNVM.1 It is essentially a diagnosis of exclusion.2 Secondary pathologies like pathological myopia, angioid streaks, trauma, heredomacular degenerations, and choroiditis need to be excluded to reach a diagnosis of idiopathic CNVM.2 In comparison to CNVM due to age-related macular degeneration (ARMD), idiopathic CNVM carries better visual prognosis.3,4 Moreover, idiopathic CNVM can have an unpredictable course due to its varied presentations in different patients.5 The majority of eyes with idiopathic CNVM present as classic membrane on fluorescein
Received 10 June 2014; accepted 31 August 2014; published online 12 November 2014 Correspondence: Kumar Saurabh, Sankara Nethralaya, 147, Mukundpur, E. M. Bypass, Kolkata 700099, India. E-mail: [email protected]
1
2
K. Saurabh et al.
Downloaded by [University of Wisconsin Oshkosh] at 01:32 11 November 2015
MATERIAL AND METHODS We carried out a retrospective case series of consecutive patients with active idiopathic CNVM treated with intravitreal Anti-VEGF. The study was approved by the institutional review board of first author. Patients below 50 years of age with active CNVM as noted on a fluorescein angiogram (FA) were included in the study. Exclusion criteria were secondary pathologies like choroiditis, myopia more than –6 Diopter or higher, angioid streaks, trauma, heredomacular degenerations, visually significant cataract or corneal pathology, previous retinal surgery, previous treatment with anti-VEGF agents, and follow-up of less than three months. Age, gender, and laterality were noted from the medical records. Best-corrected visual acuity (BCVA) was noted with Snellen’s chart and was converted to logMAR scale. Anterior segment examination with slit lamp, fundus examination with indirect ophthalmoscope, and slit lamp biomicroscopy were performed at all visits. All patients underwent FA using a Carl Zeiss FF 450 Plus (Carl Zeiss Medictec, Dublin, CA) at first visit for confirmation of diagnosis and assessment of the activity. Optical coherence tomography was performed using a Topcon 3D 2000 (Topcon Medical Systems, Oakland, NJ) at each visit to assess the activity and response to treatment. All patients underwent intravitreal bevacizumab 1.25 mg (Avastin; Genentech, CA) on a pro re nata (PRN) basis. Retreatment criteria were persistent or recurrent intraretinal oedema, subretinal fluid, and and subretinal hemorrhge on clinical examination and OCT.
RESULTS Thirty-seven eyes of 37 consecutive patients with idiopathic CNVM presenting between January 2008 and May 2013 were included in the study. There were 21 (58.3%) male and 15 (41.7%) female patients aged 13–49 years (mean 36.1 ± 10 years). Out of 37 eyes with idiopathic CNVM, 19 (51.3%) had BCVA of 20/60 or better. Twelve (32.4%) eyes had BCVA less than 20/60 to 20/200, one (2.7%) had less than 20/200 to 20/400, and five (13.5%) eyes had BCVA of less than 20/400. CNVM was unilateral in all of the eyes. Subfoveal location was the commonest site of CNVM, as seen in 25 (67.6%) eyes. Juxtafoveal CNVM was seen in 11 (29.7%) eyes and in one remaining (2.7%) eye CNVM was extrafoveal. On FA, 36 (97.3%) eyes had classic CNVM and one (2.7%) had occult CNVM. A total of 104 (mean 2.81 ± 1.4; range 1–7) intravitreal injections were given in our study patients. Two intravitreal bevacizumab injections were required in 15 (40.5%) eyes and three were required in nine (24.3%) eyes (Table 1). Mean follow-up was 14.7 ± 12.4
TABLE 1. Requirement of intravitreal bevacizumab injection. Number of intravitreal injections
Number of eyes (n = 37)
One Two Three Four Five Six Seven
4 15 9 2 5 1 1
(10.8%) (40.5%) (24.3%) (5.4%) (13.5%) (2.70%) (2.70%)
TABLE 2. Characteristics of eyes with maintained or improved vision (Group A) and eyes with worsened vision (Group B). Group A (n = 31) Mean age in years Number of females in percentage Number of males in percentage Mean number of injections
Group B (n = 6)
p Value
35.9 + 9.8 41.9
37.2 + 12 50
0.88 0.09
58.1
50
0.10
4+2
0.12
2.6 + 1.2
months (range 3 to 42 months). None of the eyes had a recurrence of CNVM at the end of follow-up. No systemic adverse effect was noted in the patients during the follow-up period. At final follow-up, 21 (56.7%) eyes had BCVA of 20/60 or better. Ten (27%) eyes had BCVA less than 20/60 to 20/200, two (5.4%) eyes had less than 20/200 to 20/400, and four (10.8%) eyes had BCVA less than 20/400. A total of 31 (83.8%) eyes had maintained or improved vision (Group A), while six (16.2%) eyes (Group B) had worsening of existing vision at final follow-up (Table 2). There was no significant difference in mean age, gender, and mean number of injections between groups A and B (Table 2).
DISCUSSION Idiopathic CNVM can adversely affect the quality of life and productivity in patients of working age.10 It is a rare disease with significant variation in its presentation.5,10 It has been reported in patients as young as 21 months in whom it was removed surgically.11 At the other end of the spectrum, idiopathic CNVM has been reported as an inaugural sign of multiple evanescent white dot syndrome.12 Patients with idiopathic intracranial hypertension have also been reported to develop idiopathic peripapillary CNVM.13–15 Added to the varied presentation, the absence of randomized clinical trials on treatment of idiopathic CNVM makes the management of this disease an evolving process.2,9 Photodynamic therapy (PDT) has been used for treatment, with the understanding that it provides a favorable outcome in Seminars in Ophthalmology
Downloaded by [University of Wisconsin Oshkosh] at 01:32 11 November 2015
Bevacizumab for Idiopathic Choroidal Neovascular Membrane classic CNVM; however, the results have been variable.2,5,6,16,17 Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is increasingly being used for the treatment of idiopathic CNVM, though the injection protocol remains uncertain.8,9,18,19 Understanding this disease and its management is an evolving process and would benefit from increased reporting from different populations. Most of our patients were male, similar to another Indian study by Mandal et al., but unlike Chinese and Western studies in which about half of the patients were female.5,18–20 All of our patients had unilateral CNVM, similar to other studies, where the majority of eyes had unilateral disease.5,6,18–20 Bevacizumab has been found to achieve a favorable outcome when used at baseline and then PRN in most of the studies on idiopathic CNVM.2,9,10,18,19 Heier et al. compared the efficacy of monthly ranibizumab with three monthly ranibizumab followed by PRN injections for nonARMD CNVM and had found comparable efficacy with both treatment protocols.21 They also mentioned that patients on PRN protocol received 38% fewer injections than those on monthly injection protocols to achieve a similar outcome.21 Though there is no similar study comparing different injection protocols for bevacizumab, multiple studies show the efficacy of PRN bevacizumab in idiopathic CNVM.2,9,10,18 Our study, in which the majority of patients had maintained or improved vision at final follow-up, adds to the evidence that bevacizumab on a PRN basis achieves the desired outcome in eyes with idiopathic CNVM. In the study by Mandal et al., they had reported resolution of CNVM with a single injection in 47% (15 out of 32 eyes).18 Zhang et al. reported the resolution of idiopathic CNVM with a single injection in 40% (16 out of 40 eyes).10 Another report from Japan by Inoue et al. notes the single injection resolution rate to be zero where all seven of their patients required re-injections.9 Our single injection resolution rate was 10.8% (four out of 37 eyes), which is different from the other reports. This may mean that data from different populations may throw up different patterns of response to intravitreal bevacizumab. The mean number of injections required in our study was 2.81, which is similar to a study by Inoue et al (2.71).9 Mandal et al. and Zhang et al. report a mean number of required injections at 1.7 and 2, respectively.10,18 Common among these studies is the fact that each of them used less than three intravitreal bevacizumab injections on average to achieve resolution of CNVM. This may mean that the requirement of intravitreal injections and protocol for injections in idiopathic CNVM may be different from those in ARMD-related CNVM. However, further comparative study considering different treatment protocols shall be required to buttress this assumption about idiopathic CNVM. !
2014 Informa Healthcare USA, Inc.
3
We have found that, though not statistically significant, the average number of injections required by patients with maintained or improved vision was less than those with worsening of vision at final follow-up. A significant difference would have proved that the higher number of injections in idiopathic CNVM may not mean better visual outcome. However, our study stops short of making that assumption. A larger controlled study would throw light on this aspect of management of idiopathic CNVM. Our study is retrospective and uncontrolled with limited sample size and short follow-up, which can be cited as drawbacks. A controlled study with longer follow-up, comparing different injection protocols, would be ideal to study the management of idiopathic CNVM. However, our study does provide first data on idiopathic CNVM from the eastern part of India. It also stresses the fact that intravitreal bevacizumab in a PRN regimen was effective in the treatment of idiopathic CNVM.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. Lindblom B, Andersson T. The prognosis of idiopathic choroidal neovascularization in persons younger than 50 years of age. Ophthalmology 1998;105:1816–1820. 2. Kang HM, Koh HJ. Intravitreal anti-vascular endothelial growth factor therapy versus photodynamic therapy for idiopathic choroidal neovascularization. Am J Ophthalmol 2013;155:713–719. 3. Macular Photocoagulation Study Group. Krypton laser photocoagulation for idiopathic neovascular lesions: Results of a randomized clinical trial. Arch Ophthalmol 1990;108:832–837. 4. Macular Photocoagulation Study Group. Argon laser photocoagulation for idiopathic neovascularization: Results of a randomized clinical trial. Arch Ophthalmol 1983;101:1358–1361. 5. Chan WM, Lam DS, Wong TH, et al. Photodynamic therapy with verteporfin for subfoveal idiopathic choroidal neovascularization: One-year results from a prospective case series. Ophthalmology 2003;110:2395–2402. 6. Spaide RF, Martin ML, Slakter J, et al. Treatment of idiopathic subfoveal choroidal neovascular lesions using photodynamic therapy with verteporfin. Am J Ophthalmol 2002;134:62–68. 7. Postelmans L, Pasteels B, Coquelet P, et al. Severe pigment epithelial alterations in the treatment area following photodynamic therapy for classic choroidal neovascularization in young females. Am J Ophthalmol 2004;138:803–808. 8. Chan WM, Lai TY, Liu DT, Lam DS. Intravitreal bevacizumab (Avastin) for choroidal neovascularization secondary to central serous chorioretinopathy, secondary to punctateinner choroidopathy, or of idiopathic origin. Am J Ophthalmol 2007;143:977–983.
Downloaded by [University of Wisconsin Oshkosh] at 01:32 11 November 2015
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9. Inoue M, Kadonosono K, Watanabe Y, et al. Intravitreal bevacizumab for subfoveal idiopathic choroidal neovascularization. Retina 2010;30:733–738. 10. Zhang H, Liu ZL, Sun P, Gu F. Intravitreal bevacizumab for treatment of subfoveal idiopathic choroidal neovascularization: Results of a 1-year prospective trial. Am J Ophthalmol 2012;153:300–306. 11. Daniels AB, Jakobiec FA, Westerfeld CB, et al. Idiopathic subfoveal choroidal neovascular membrane in a 21-monthold child: Ultrastructural features and implication for membranogenesis. J AAPOS 2010;14:244–250. 12. Papadia M, Herbort CP. Idiopathic choroidal neovascularisation as the inaugural sign of multiple evanescent white dot syndrome. Middle East Afr J Ophthalmol 2010; 17:270–274. 13. Lee IJ, Maccheron LJ, Kwan AS. Intravitreal bevacizumab in the treatment of peripapillary choroidal neovascular membrane secondary to idiopathic intracranial hypertension. J Neuroophthalmol 2013;33:155–157. 14. Sathornsumetee B, Webb A, Hill DL, et al. Subretinal hemorrhage from a peripapillary choroidal neovascular membrane in papilledema caused by idiopathic intracranial hypertension. J Neuroophthalmol 2006;26: 197–199.
15. Morse PH, Leveille AS, Antel JP, Burch JV. Bilateral juxtapapillary subretinal neovascularization associated with pseudotumor cerebri. Am J Ophthalmol 1981;91: 312–317. 16. Giovannini A, Neri P, Mercanti L, Brue` C. Photodynamic treatment versus photodynamic treatment associated with systemic steroids for idiopathic choroidal neovascularisation. Br J Ophthalmol 2007;91:620–623. 17. Lam A, Lee HC, Ho AC, et al. Photodynamic therapy in young patients. Ophthalmic Surg Lasers Imaging 2006;37: 182–189. 18. Mandal S, Garg S, Venkatesh P, et al. Intravitreal bevacizumab for subfoveal idiopathic choroidal neovascularization. Arch Ophthalmol 2007;125:1487–1492. 19. Qi HJ, Li XX, Tao Y. Outcome of intravitreal bevacizumab for idiopathic choroidal neovascularization in the Chinese population. Can J Ophthalmol 2010;45:381–385. 20. Ho AC, Yannuzzi LA, Pisicano K, DeRosa J. The natural history of idiopathic subfoveal choroidal neovascularization. Ophthalmology 1995;102:782–789. 21. Heier JS, Brown D, Ciulla T, et al. Ranibizumab for choroidal neovascularization secondary to causes other than age-related macular degeneration: A phase I clinical trial. Ophthalmology 2011;118:111–118.
Seminars in Ophthalmology
ISSN: 0882-0538 (Print) 1744-5205 (Online) Journal homepage: http://www.tandfonline.com/loi/isio20
Pro Re Nata Intravitreal Bevacizumab for the Treatment of Idiopathic Choroidal Neovascular Membrane Kumar Saurabh, Rupak Roy, Pradeep Kumar Panigrahi, Aneesha Lobo & Anindya Kishore Majumdar To cite this article: Kumar Saurabh, Rupak Roy, Pradeep Kumar Panigrahi, Aneesha Lobo & Anindya Kishore Majumdar (2014): Pro Re Nata Intravitreal Bevacizumab for the Treatment of Idiopathic Choroidal Neovascular Membrane, Seminars in Ophthalmology, DOI: 10.3109/08820538.2014.962172 To link to this article: http://dx.doi.org/10.3109/08820538.2014.962172
Published online: 13 Nov 2014.
Submit your article to this journal
Article views: 29
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=isio20 Download by: [University of Wisconsin Oshkosh]
Date: 11 November 2015, At: 01:32
Seminars in Ophthalmology, Early Online, 1–4, 2014 ! Informa Healthcare USA, Inc. ISSN: 0882-0538 print / 1744-5205 online DOI: 10.3109/08820538.2014.962172
ORIGINAL ARTICLE
Pro Re Nata Intravitreal Bevacizumab for the Treatment of Idiopathic Choroidal Neovascular Membrane
Downloaded by [University of Wisconsin Oshkosh] at 01:32 11 November 2015
Kumar Saurabh, Rupak Roy, Pradeep Kumar Panigrahi, Aneesha Lobo, and Anindya Kishore Majumdar Aditya Birla Sankara Nethralaya, Kolkata, India
ABSTRACT Purpose: To study the efficacy of intravitreal bevacizumab on a pro re nata basis for treatment of idiopathic choroidal neovascular membrane. Material and methods: Thirty-seven eyes of 37 patients presenting with idiopathic choroidal neovascular membrane were included in the study. Intravitreal bevacizumab (1.25 mg/0.05 ml) was given on a pro re nata basis from the base line. Results: Twenty-one (58.3%) patients were male and 15 (41.7%) were female aged 13–49 years. Idiopathic choroidal neovascular membrane showed a classic leak on fluorescein angiogram in all the eyes. Subfoveal location (25; 67.6%) was the commonest site of involvement. Mean number of intravitreal bevacizumab injections required to achieve resolution was 2.81 ± 1.4. At final follow-up, 31 (83.8%) eyes had maintained or improved vision (Group A) and six (16.2%) eyes had worsening of vision (Group B). There was no significant difference in mean age, gender, and mean number of injections between groups A and B. Conclusion: Intravitreal bevacizumab on a pro re nata basis is effective in the treatment of idiopathic choroidal neovascular membrane. A larger controlled study would be required to formulate an accurate injection protocol. Keywords: Efficacy, idiopathic choroidal neovascular membrane, injection protocol
INTRODUCTION
angiography (FA), leading to a prominent role of photodynamic therapy (PDT) for treatment.5,6 However, the visual outcome after PDT has been known to be variable and there have been concerns about damage to the retinal pigment epithelium.5–7 Intravitreal anti-VEGF has also been shown to have promising results in the treatment of idiopathic CNVM, though optimum injection protocol and long-term safety profile are yet to be elucidated.8,9 The limited information, lack of definite etiology, multiple available treatment options, and varied presentation make the management of idiopathic CNVM an evolving process which requires more data from different populations.2,9 We aim to study the profile of idiopathic CNVM and its visual outcome with intravitreal bevacizumab from eastern India.
Choroidal neovascular membrane (CNVM) in patients below 50 years of age without any secondary pathology is considered to be idiopathic CNVM.1 It is essentially a diagnosis of exclusion.2 Secondary pathologies like pathological myopia, angioid streaks, trauma, heredomacular degenerations, and choroiditis need to be excluded to reach a diagnosis of idiopathic CNVM.2 In comparison to CNVM due to age-related macular degeneration (ARMD), idiopathic CNVM carries better visual prognosis.3,4 Moreover, idiopathic CNVM can have an unpredictable course due to its varied presentations in different patients.5 The majority of eyes with idiopathic CNVM present as classic membrane on fluorescein
Received 10 June 2014; accepted 31 August 2014; published online 12 November 2014 Correspondence: Kumar Saurabh, Sankara Nethralaya, 147, Mukundpur, E. M. Bypass, Kolkata 700099, India. E-mail: [email protected]
1
2
K. Saurabh et al.
Downloaded by [University of Wisconsin Oshkosh] at 01:32 11 November 2015
MATERIAL AND METHODS We carried out a retrospective case series of consecutive patients with active idiopathic CNVM treated with intravitreal Anti-VEGF. The study was approved by the institutional review board of first author. Patients below 50 years of age with active CNVM as noted on a fluorescein angiogram (FA) were included in the study. Exclusion criteria were secondary pathologies like choroiditis, myopia more than –6 Diopter or higher, angioid streaks, trauma, heredomacular degenerations, visually significant cataract or corneal pathology, previous retinal surgery, previous treatment with anti-VEGF agents, and follow-up of less than three months. Age, gender, and laterality were noted from the medical records. Best-corrected visual acuity (BCVA) was noted with Snellen’s chart and was converted to logMAR scale. Anterior segment examination with slit lamp, fundus examination with indirect ophthalmoscope, and slit lamp biomicroscopy were performed at all visits. All patients underwent FA using a Carl Zeiss FF 450 Plus (Carl Zeiss Medictec, Dublin, CA) at first visit for confirmation of diagnosis and assessment of the activity. Optical coherence tomography was performed using a Topcon 3D 2000 (Topcon Medical Systems, Oakland, NJ) at each visit to assess the activity and response to treatment. All patients underwent intravitreal bevacizumab 1.25 mg (Avastin; Genentech, CA) on a pro re nata (PRN) basis. Retreatment criteria were persistent or recurrent intraretinal oedema, subretinal fluid, and and subretinal hemorrhge on clinical examination and OCT.
RESULTS Thirty-seven eyes of 37 consecutive patients with idiopathic CNVM presenting between January 2008 and May 2013 were included in the study. There were 21 (58.3%) male and 15 (41.7%) female patients aged 13–49 years (mean 36.1 ± 10 years). Out of 37 eyes with idiopathic CNVM, 19 (51.3%) had BCVA of 20/60 or better. Twelve (32.4%) eyes had BCVA less than 20/60 to 20/200, one (2.7%) had less than 20/200 to 20/400, and five (13.5%) eyes had BCVA of less than 20/400. CNVM was unilateral in all of the eyes. Subfoveal location was the commonest site of CNVM, as seen in 25 (67.6%) eyes. Juxtafoveal CNVM was seen in 11 (29.7%) eyes and in one remaining (2.7%) eye CNVM was extrafoveal. On FA, 36 (97.3%) eyes had classic CNVM and one (2.7%) had occult CNVM. A total of 104 (mean 2.81 ± 1.4; range 1–7) intravitreal injections were given in our study patients. Two intravitreal bevacizumab injections were required in 15 (40.5%) eyes and three were required in nine (24.3%) eyes (Table 1). Mean follow-up was 14.7 ± 12.4
TABLE 1. Requirement of intravitreal bevacizumab injection. Number of intravitreal injections
Number of eyes (n = 37)
One Two Three Four Five Six Seven
4 15 9 2 5 1 1
(10.8%) (40.5%) (24.3%) (5.4%) (13.5%) (2.70%) (2.70%)
TABLE 2. Characteristics of eyes with maintained or improved vision (Group A) and eyes with worsened vision (Group B). Group A (n = 31) Mean age in years Number of females in percentage Number of males in percentage Mean number of injections
Group B (n = 6)
p Value
35.9 + 9.8 41.9
37.2 + 12 50
0.88 0.09
58.1
50
0.10
4+2
0.12
2.6 + 1.2
months (range 3 to 42 months). None of the eyes had a recurrence of CNVM at the end of follow-up. No systemic adverse effect was noted in the patients during the follow-up period. At final follow-up, 21 (56.7%) eyes had BCVA of 20/60 or better. Ten (27%) eyes had BCVA less than 20/60 to 20/200, two (5.4%) eyes had less than 20/200 to 20/400, and four (10.8%) eyes had BCVA less than 20/400. A total of 31 (83.8%) eyes had maintained or improved vision (Group A), while six (16.2%) eyes (Group B) had worsening of existing vision at final follow-up (Table 2). There was no significant difference in mean age, gender, and mean number of injections between groups A and B (Table 2).
DISCUSSION Idiopathic CNVM can adversely affect the quality of life and productivity in patients of working age.10 It is a rare disease with significant variation in its presentation.5,10 It has been reported in patients as young as 21 months in whom it was removed surgically.11 At the other end of the spectrum, idiopathic CNVM has been reported as an inaugural sign of multiple evanescent white dot syndrome.12 Patients with idiopathic intracranial hypertension have also been reported to develop idiopathic peripapillary CNVM.13–15 Added to the varied presentation, the absence of randomized clinical trials on treatment of idiopathic CNVM makes the management of this disease an evolving process.2,9 Photodynamic therapy (PDT) has been used for treatment, with the understanding that it provides a favorable outcome in Seminars in Ophthalmology
Downloaded by [University of Wisconsin Oshkosh] at 01:32 11 November 2015
Bevacizumab for Idiopathic Choroidal Neovascular Membrane classic CNVM; however, the results have been variable.2,5,6,16,17 Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is increasingly being used for the treatment of idiopathic CNVM, though the injection protocol remains uncertain.8,9,18,19 Understanding this disease and its management is an evolving process and would benefit from increased reporting from different populations. Most of our patients were male, similar to another Indian study by Mandal et al., but unlike Chinese and Western studies in which about half of the patients were female.5,18–20 All of our patients had unilateral CNVM, similar to other studies, where the majority of eyes had unilateral disease.5,6,18–20 Bevacizumab has been found to achieve a favorable outcome when used at baseline and then PRN in most of the studies on idiopathic CNVM.2,9,10,18,19 Heier et al. compared the efficacy of monthly ranibizumab with three monthly ranibizumab followed by PRN injections for nonARMD CNVM and had found comparable efficacy with both treatment protocols.21 They also mentioned that patients on PRN protocol received 38% fewer injections than those on monthly injection protocols to achieve a similar outcome.21 Though there is no similar study comparing different injection protocols for bevacizumab, multiple studies show the efficacy of PRN bevacizumab in idiopathic CNVM.2,9,10,18 Our study, in which the majority of patients had maintained or improved vision at final follow-up, adds to the evidence that bevacizumab on a PRN basis achieves the desired outcome in eyes with idiopathic CNVM. In the study by Mandal et al., they had reported resolution of CNVM with a single injection in 47% (15 out of 32 eyes).18 Zhang et al. reported the resolution of idiopathic CNVM with a single injection in 40% (16 out of 40 eyes).10 Another report from Japan by Inoue et al. notes the single injection resolution rate to be zero where all seven of their patients required re-injections.9 Our single injection resolution rate was 10.8% (four out of 37 eyes), which is different from the other reports. This may mean that data from different populations may throw up different patterns of response to intravitreal bevacizumab. The mean number of injections required in our study was 2.81, which is similar to a study by Inoue et al (2.71).9 Mandal et al. and Zhang et al. report a mean number of required injections at 1.7 and 2, respectively.10,18 Common among these studies is the fact that each of them used less than three intravitreal bevacizumab injections on average to achieve resolution of CNVM. This may mean that the requirement of intravitreal injections and protocol for injections in idiopathic CNVM may be different from those in ARMD-related CNVM. However, further comparative study considering different treatment protocols shall be required to buttress this assumption about idiopathic CNVM. !
2014 Informa Healthcare USA, Inc.
3
We have found that, though not statistically significant, the average number of injections required by patients with maintained or improved vision was less than those with worsening of vision at final follow-up. A significant difference would have proved that the higher number of injections in idiopathic CNVM may not mean better visual outcome. However, our study stops short of making that assumption. A larger controlled study would throw light on this aspect of management of idiopathic CNVM. Our study is retrospective and uncontrolled with limited sample size and short follow-up, which can be cited as drawbacks. A controlled study with longer follow-up, comparing different injection protocols, would be ideal to study the management of idiopathic CNVM. However, our study does provide first data on idiopathic CNVM from the eastern part of India. It also stresses the fact that intravitreal bevacizumab in a PRN regimen was effective in the treatment of idiopathic CNVM.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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