Li, KKW

Wong, D

British Journal of Ophthalmology

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Title Avastin in myopic choroidal neovascularisation: Is age the limit?Author(s) Wong, D; Li, KKWCitation British Journal Of Ophthalmology, 2008, v. 92 n. 8, p. 1011-1012Issued Date 2008URL http://hdl.handle.net/10722/60143Rights British Journal of Ophthalmology. Copyright © B M J PublishingGroup.doi: 10.1136/bjo.2007.135681 2008 92: 1011-1012Br J Ophthalmol David Wong and Kenneth K W Li neovascularisation: is age the limit?Avastin in myopic choroidal http://bjo.bmj.com/content/92/8/1011.1.full.htmlUpdated information and services can be found at: These include:References http://bjo.bmj.com/content/92/8/1011.1.full.html#ref-list-1This article cites 19 articles, 6 of which can be accessed free at:serviceEmail alertingbox at the top right corner of the online article.Receive free email alerts when new articles cite this article. Sign up in theTopic collections (4999 articles)Epidemiology    (336 articles)Optics and refraction    (1082 articles)Retina    (494 articles)Optic nerve    (396 articles)Choroid    Articles on similar topics can be found in the following collectionsNotes http://group.bmj.com/group/rights-licensing/permissionsTo request permissions go to: http://journals.bmj.com/cgi/reprintformTo order reprints go to: http://journals.bmj.com/cgi/epTo subscribe to BMJ go to: group.bmj.com on October 18, 2010 - Published by bjo.bmj.comDownloaded from Avastin in myopic choroidalneovascularisation: is age thelimit?David Wong,1,2 Kenneth K W Li1There are a growing number of publica-tions supporting the use of Avastin(bevacizumab) for choroidal neovascular-isation (CNV) secondary to pathologicalmyopia (table 1).1–8 In this issue, Arias et al(see page 1035) reported a prospectivestudy of 17 patients;9 at the 6-monthfollow-up, the mean Early TreatmentDiabetic Retinopathy Study visual acuityimproved by 8.4 letters (p = 0.04), and themean optical coherence tomography(OCT) foveal thickness decreased by79.6 mm (p = 0.002). Is it time to changeour clinical practice? Is it time to abandonphotodynamic therapy (PDT) as the firstline treatment? The purist would say thatthe only evidence base from randomisedcontrolled trials is still that provided bythe Verteporfin in Photodynamic Therapy(VIP) Study.10 11 In this study, PDT wasshown to be effective in preventing visualloss fewer than eight letters in pathologi-cal myopia in the first year when com-pared with sham treatment.10 However,the effect of PDT was not sustained bythe end of the second year.11 Smaller caseseries have shown similar results.11 Otherinvestigators have attempted to improvethe efficacy of PDT by enhancing thefluence13 or combining PDT with intravi-treal triamcinolone acetonide injec-tion.14 15 These studies failed to persuade,either limited by the small number ofpatients or because the results wereinconsistent.But do all CNV secondary to patholo-gical myopia have a similar prognosis andresponse to treatment? The report on thenatural history of untreated CNV second-ary to pathological myopia by Kojima et alis now recognised as a landmark paper.16Using regression analysis, they investi-gated the prognostic factor in 54untreated eyes in 54 patients in Japan(prior to PDT being available) and foundthat the best corrected visual acuity(BCVA) at 5 years after onset was sig-nificantly associated with patient age,CNV size and initial BCVA (p,0.05,Spearman correlation). In a retrospectivestudy, Yoshida et al also examined theeffect of age on the natural history ofCNV secondary to pathological myopia.17They found that patients under the age of40 had significant better visual outcomethan patients over the age of 40. Theirresults need to be interpreted carefully, asthey included both juxtafoveal and sub-foveal cases. The authors nonethelessraised the important point that the visualprognosis of CNV secondary to patholo-gical myopia was not always consistent.The angiographic features of the CNV inpatients over the age of 40 had a moreprofuse angiographic leakage. Other inves-tigators have studied the effect of age onthe visual outcome of treatment of CNVsecondary to pathological myopia withPDT. Axer-Siegel et al, in a retrospectivestudy, found that 50% of the older agegroup and 20% of the younger age grouphad visual loss of 15 letters or more, andthe difference was significant; however,8% of the younger patients in the series ofAxer-Siegel et al continued to lose 15 ormore letters despite treatment withPDT.18In the VIP study, less than 25% improveone or more lines at 3 months.9 A treat-ment primarily aimed at preventing visualloss is likely to disappoint patients seekingto have their vision restored. In the wakeof several case series reporting visualimprovement with the use of Avastin,more and more physicians are persuadedto change from PDT to the off-label use ofanti-vascular endothelial growth factor(VEGF) agents for CNV in pathologicalmyopia.1–8 Until now, these interventionalstudies have relatively short follow-up of6 months. We do not yet know whethermultiple injections will eventually alterthe natural history favourably.In the absence of an evidence basederived from randomised controlled trialsupporting the use of Avastin for CNVsecondary to pathological myopia, inpatients with good vision at least, somemay feel obliged to use PDT as the first-line treatment. But in older patients, withlarger subfoveal CNV and more signifi-cant visual loss, our threshold for switch-ing to or even adding Avastin may belowered. It is noteworthy that Arias et alfound that patients aged (50 yearsimproved by a mean of 8.7 letters(p = 0.13), and patients older than50 years improved by a mean of 8.3 letters(p = 0.1). Avastin seemed to be effectivein older patients, whereas PDT might belimited by age.The use of anti-VEGF off-label for age-related macular degeneration is stillfraught with ethical difficulties and fund-ing problems within the National HealthService (NHS) in the UK.19 If we were touse an anti-VEGF, we of course have achoice of bevacizumab, ranibizumab andpegatanib, all of which are off-labeltreatments to CNV secondary to patho-logical myopia, and thus far, there are nopublications on the efficacy of latter twoagents. Rosenfeld pointed out thatGenentech or Roche should not beexpected to pay for an intravitrealAvastin clinical trial unless they plan toseek a labelled indication for Avastin inophthalmology, which seems unlikely.20Rather, the cost of such a trial is a societalresponsibility of those agencies and gov-ernments that stand to benefit frompreventing vision loss from neovascular-isation in pathological myopia. In the UK,the Inhibit VEGF in Age-related choroidalNeovascularisation (IVAN) trial is set upto study CNV secondary to age-relatedmacular degeneration and funded by theHealth Technology Assessment ClinicalTrials Programme of the UK NationalInstitute for Health Research.21 The IVANtrial compares: (a) an inexpensive drug,bevacizumab used ‘‘off-label’’ with anexpensive licensed drug, ranibizumab,and (b) continuous monthly treatmentwith reduced frequency of treatment. Thetrial has high research costs, but thisinvestment by the NHS represents goodvalue when set against potential savingsto the NHS should the less expensivedrug, or reduced treatment frequency, beshown to be as effective as the moreexpensive alternatives. The success of thistrial is reliant on a network of hospitalsand consultants working together. Thisnetwork covers all of the UK and isperfectly positioned to mount an intravi-treal Avastin trial on CNV in pathologicalmyopia. The VIP trial was probablyunderpowered, recruiting 120 patients,randomising 81 patients to PDT and 361 Eye Institute, Li Ka Shing Faculty of Medicine, TheUniversity of Hong Kong, Hong Kong SAR, China;2 St Paul’s Eye Unit, Royal Liverpool University Hospital,Liverpool, UKCorrespondence to: Professor D Wong, Royal LiverpoolUniversity Hospital, Prescot Street, LiverpoolL7 8XP, UK; shdwong@liv.ac.ukEditorialBr J Ophthalmol August 2008 Vol 92 No 8 1011 group.bmj.com on October 18, 2010 - Published by bjo.bmj.comDownloaded from to sham treatment. It will take theconcerted effort of all the consultants inUK to recruit sufficient patients to get ameaningful result. In the mean time, wecan only treat patients individually ontheir merit, as not all CNV secondary topathological myopia have the same prog-nosis or response.Competing interests: None.Accepted 20 January 2008Br J Ophthalmol 2008;92:1011–1012.doi:10.1136/bjo.2007.135681REFERENCES1. Laud K, Spaide RF, Freund KB, et al. Treatment ofchoroidal neovascularization in pathologic myopia withintravitreal bevacizumab. Retina 2006;26:960–3.2. Tewari A, Dhalla MS, Apte RS. Intravitrealbevacizumab for treatment of choroidalneovascularization in pathologic myopia. Retina2006;26:1093–4.3. Yamamoto I, Rogers AH, Reichel E, et al. Intravitrealbevacizumab (Avastin) as treatment for subfovealchoroidal neovascularisation secondary to pathologicalmyopia. Br J Ophthalmol 2007;91:157–60.4. Sakaguchi H, Ikuno Y, Gomi F, et al. Intravitrealinjection of bevacizumab for choroidalneovascularisation associated with pathologicalmyopia. Br J Ophthalmol 2007;91:161–5.5. Herna´ndez-Rojas ML, Quiroz-Mercado H, Dalma-Weiszhausz J, et al. Short-term effects of intravitrealbevacizumab for subfoveal choroidal neovascularizationin pathologic myopia. Retina 2007;27:707–12.6. Mandal S, Venkatesh P, Sampangi R, et al.Intravitreal bevacizumab (Avastin) as primarytreatment for myopic choroidal neovascularization.Eur J Ophthalmol 2007;17:620–6.7. Chan WM, Lai TY, Liu DT, et al. Intravitrealbevacizumab (Avastin) for myopic choroidalneovascularization: six-month results of a prospectivepilot study. Ophthalmology 2007;114:2190–6.8. Ruiz-Moreno JM, Gomez-Ulla F, Montero JA, et al.Intravitreous bevacizumab to treat subfoveal choroidalneovascularization in highly myopic eyes: short-termresults. Eye. Published Online First: 7 December 2007.doi:10.1038/sj.eye.6703052.9. Arias L, Planas N, Prades S, et al. Intravitrealbevacizumab (Avastin) for choroidalneovascularisation secondary to pathological myopia:6-month results. Br J Ophthalmol 2008;92:1035–9.10. Verteporfin in Photodynamic Therapy StudyGroup. Photodynamic therapy of subfoveal choroidalneovascularization in pathologic myopia withverteporfin. 1-year results of a randomized clinicaltrial—VIP report no. 1. Ophthalmology2001;108:841–52.11. Blinder KJ, Blumenkranz MS, Bressler NM, et al.Verteporfin therapy of subfoveal choroidalneovascularization in pathologic myopia: 2-yearresults of a randomized clinical trial—VIP report no. 3.Ophthalmology 2003;110:667–73.12. Pece A, Isola V, Vadala M, et al. Photodynamictherapy with verteporfin for subfoveal choroidalneovascularization secondary to pathologic myopia:long-term study. Retina 2006;26:746–51.13. Costa RA, Williams GA. Twofold illuminationphotodynamic therapy scheme for subfoveal choroidalneovascularization in pathologic myopia: results froma randomized pilot study. Retina 2006;26:757–64.14. Chan WM, Lai TY, Wong AL, et al. Combinedphotodynamic therapy and intravitreal triamcinoloneinjection for the treatment of choroidalneovascularisation secondary to pathological myopia:a pilot study. Br J Ophthalmol 2007;91:174–9.15. Marticorena J, Gomez-Ulla F, Fernandez M, et al.Combined photodynamic therapy and intravitrealtriamcinolone acetonide for the treatment of myopicsubfoveal choroidal neovascularization.Am J Ophthalmol 2006;142:335–7.16. Kojima A, Ohno-Matsui K, Teramukai S, et al.Estimation of visual outcome without treatment inpatients with subfoveal choroidal neovascularization inpathologic myopia. Graefes Arch Clin Exp Ophthalmol2006;244:1474–9.17. Yoshida T, Ohno-Matsui K, Ohtake Y, et al. Long-term visual prognosis of choroidal neovascularizationin high myopia: a comparison between age groups.Ophthalmology 2002;109:712–19.18. Axer-Siegel R, Ehrlich R, Weinberger D, et al.Photodynamic therapy of subfoveal choroidalneovascularization in high myopia in a clinical setting:visual outcome in relation to age at treatment.Am J Ophthalmol 2004;138:602–7.19. Wong D, Kyle G. Some ethical considerations for the‘‘off-label’’ use of drugs such as Avastin.Br J Ophthalmol 2006;90:1218–19.20. Rosenfeld PJ. Intravitreal Avastin for choroidalneovascularisation in pathological myopia: thecontroversy continues. Br J Ophthalmol2007;91:128–30.21. Health Technology Assessment Programme,National Institute for Health Research (NIHR),National Health Service, United Kingdom. Arandomised controlled trial (RCT) of alternativetreatments to Inhibit VEGF in patients withAge-related choroidal Neovascularisation(IVAN), ISRCTN reference no. 92166560. http://www.hta.ac.uk/project/1625.asp (accessed 25May 2008).Table 1 Summary of published studies on the use of Avastin (bevacizumab) in the treatment of choroidal neovascularisation secondary topathological myopiaYear Author Study No. of cases Dosage (mg)/no. of injections Follow-up period (months)2006 Laud et al1 Case report 4 1.25/2–3 7.32006 Tewari et al2 Case report 1 1.25/2 62007 Yamamoto et al3 Retrospective 11 1.25/1–2 5.52007 Sakaguchi et al4 Prospective 8 1/1–2 4.42007 Hernandez-Rojas et al5 Prospective 14 2.5/>1 32007 Mandal et al6 Prospective 12 1.25/1+ as necessary 62007 Chan et al7 Prospective 22 1.25/3 62007 Ruiz-Moreno et al8 Prospective 26 1.25/3 62008 Arias et al Prospective 17 1.25/1.1 6Editorial1012 Br J Ophthalmol August 2008 Vol 92 No 8 group.bmj.com on October 18, 2010 - Published by bjo.bmj.comDownloaded from 

Avastin in myopic choroidal neovascularisation: Is age the limit?

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Avastin in myopic choroidal neovascularisation: Is age the limit?

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