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`
`Intravitreal bevacizumab for myopic choroidal neovascularization: short-
`term and 1-year results
`
`Article  in  Bulletin de la Société belge d'ophtalmologie · January 2009
`
`Source: PubMed
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`INTRAVITREAL BEVACIZUMAB FOR MYOPIC
`CHOROIDAL NEOVASCULARIZATION: SHORT-TERM AND
`1-YEAR RESULTS
`
`SPIELBERG L., MD*, LEYS A., MD, PHD*
`
`ABSTRACT
`Purpose: To report three-month and one-year safety
`and efficacy results of intravitreal bevacizumab in-
`jection (IVB) for active choroidal neovascularization
`associated with pathological myopia (mCNV).
`
`Methods
`This retrospective interventional case series of 23 pa-
`tients (23 eyes) was conducted at the medical reti-
`na center in the Leuven University Hospital Depart-
`ment of Ophthalmology, a referral center for macu-
`lar diseases in Belgium. Charts were reviewed of all
`patients who received 1.25 mg IVB for active mCNV.
`If patients had two treated eyes, the eye with the
`longest follow-up was selected as the study eye. In-
`jections were repeated as needed based on a de-
`crease in visual acuity, an increase in central macu-
`lar thickness (CMT) of s100µ mm on optical cohe-
`rence tomography (OCT), the recurrence of macular
`edema on OCT and/or leakage on fluorescein angio-
`graphy (FA). For statistical analysis, patients were
`divided into two groups based on length of follow up:
`patients in Group 1 had a follow-up of >12 months,
`while those in Group 2 had <12 months of follow-
`up. Changes in visual acuity (VA), as measured by
`the Early Treatment of Diabetic Retinopathy Study
`(ETDRS) protocol, and CMT were analyzed, as were
`safety considerations such as intraocular inflamma-
`tion and endophthalmitis.
`Results: Twenty-three eyes of 23 patients with ages
`ranging from 20 to 84 years (mean 57.7 years) were
`included. Mean best-corrected visual acuity (BCVA)
`at baseline for all patients (n=23) was 45 letters
`(Snellen equivalent: 20/120; 8 lines). At 3 months
`
`zzzzzz
`
`* Medical Retina Department, Department of
`Ophthalmology, University Hospitals Leuven, Belgium
`
`Submitted: 14-05-09
`Accepted: 18-07-09
`
`after initial treatment, the mean BCVA improved sig-
`nificantly (P < 0.05) to 58 letters (20/602-; 10.5
`lines). Eight patients had >12 months of follow-up
`(Group 1); 15 patients had >3 months of follow-up
`(Group 2). The mean BCVA for Group 1 improved
`significantly (P < 0.05) from 45 letters (20/120; 8
`lines) to 60 letters (20/60; 11 lines), having recei-
`ved an average of 2.75 injections (range: 1-5) du-
`ring this period and an average of one injection the-
`reafter (mean follow-up after 12 months: 8 months).
`The mean BCVA for Group 2 improved significantly
`(P < 0.05) from 47 letters (20/1202+; 8 lines) to
`61 letters (20/601+; 11 lines), having received an
`average of 1.3 injections. CMT for all patients de-
`creased from a mean of 266 mm at baseline to 201
`mm at 1 month, 181 µmm at 3 months and 192 at
`12 months (Group 1). Greater patient age was cor-
`related with the need for more frequent injections.
`The oldest half of Group 1 (mean age 68.5 years)
`required an average of 3.75 injections, while the
`youngest half (mean age 39.5 years) required only
`1.75. In Group 2, an inverse correlation between age
`and time between injections was observed. A total
`of 42 injections were administered. No peri- or post-
`injection ocular or systemic side effects were noted
`in either group.
`Conclusion: Short-term and twelve-month results in-
`dicate that IVB is a safe and effective method to im-
`prove visual, reduce CMT and inhibit progression of
`mCNV.
`
`KEYWORDS
`
`anti-VEGF: Avastin: bevacizumab; choroidal
`neovascularization; myopia
`
`Bull. Soc. belge Ophtalmol., 312, 17-27, 2009.
`
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`INTRODUCTION
`Pathological myopia, defined as myopia with
`complications in the posterior segment, is a
`leading cause of legal blindness in many de-
`veloped countries (1), affecting approximately
`2% of the general population (2). Myopic cho-
`roidal neovascularization (mCNV) is a sight-
`threatening complication of pathological myo-
`pia and the second-leading cause of second-
`ary neovascular maculopathy, after age-relat-
`ed macular degeneration (AMD). Myopic CNV
`develops in approximately 5% to 10% of high-
`ly myopic eyes (3), making this the most com-
`mon vision-threatening complication of high
`myopia. Because of the subsequent atrophic
`changes, the disease has a poor prognosis, and
`mCNV thus leads to significant vision loss in
`patients who are often young and otherwise
`healthy. (4,5,6)
`
`Different therapeutic approaches, including ther-
`mal
`laser photocoagulation (7), radiothera-
`py (8), surgery (9,10) and verteporfin photo-
`dynamic therapy (PDT), (11) with or without
`triamcinolone acetonide, have been reported,
`without significant success. This has prompt-
`ed the search for more effective treatment mo-
`dalities for mCNV. The current study used
`bevacizumab to treat mCNV. The goal of the
`study was to determine whether 1.25 mg IVB
`on an as-needed basis would be efficacious and
`safe in the treatment of myopic CNV. The pri-
`mary endpoints were BCVA at 1, 3, 6, 9 and
`12 months. Secondary endpoints were CMT at
`the same time points, and safety during the en-
`tire follow-up period.
`
`METHODS
`A retrospective chart review was performed of
`23 eyes of 23 consecutive patients treated with
`1.25 mg IVB for mCNV. Only eyes with con-
`firmed presence of CNV on FA and pathologic
`myopia, defined as a refractive error (spherical
`equivalent) of -6.00 diopters (D) or more, and
`treated with 1.25 mg IVB, were included. Ex-
`clusion criteria were laser photocoagulation in
`the study eye; a history of triamcinolone ace-
`tonide sub-Tenon injection during the previous
`six months before the initial IVB; cataract sur-
`gery during follow-up; the presence of a seri-
`
`18
`
`ous posterior segment complication, such as
`retinal detachment or foveoschisis; and the pres-
`ence of severe cataract in the study eye. Of the
`23 eyes included in the review, 8 eyes had been
`followed up for 12 months or longer after the
`first injection (designated as Group 1) and 15
`eyes with at least 3 months of follow-up (Group
`2). Patients had been informed about the bene-
`fits, risks, off-label nature, and alternatives to
`treatment before treatment was initiated, as is
`standard in our department.
`
`Examinations
`Each patient underwent complete ocular ex-
`amination, including BCVA (Early Treatment of
`Diabetic Retinopathy protocol, ETDRS), OCT
`(Cirrus HD-OCT, Carl Zeiss Meditec, Jena, Ger-
`many) and FA at baseline. Each follow-up
`examination consisted of a complete dilated oc-
`ular examination, BCVA and OCT. The same
`examiner performed the BCVA and OCT exam-
`inations at each patient visit. Color fundus pho-
`tographs were obtained and FA was performed
`using a conventional digitalized fundus camera
`(Topcon TRC-50DX Fundus Camera, Topcon,
`Itabashi, Tokyo, Japan) before the initial IVB
`and later based on a decrease in visual acuity,
`an increase in CMT of s100 µmm on OCT, the
`recurrence of macular edema on OCT and/or
`leakage on FA.
`
`Intravitreal bevacizumab
`Patients received 1.25 mg / 0.05 ml intravit-
`real bevacizumab injections (Avastint, Roche,
`Basel, Switzerland) using the standard proto-
`col of the medical retina department of the De-
`partment of Ophthalmology at Leuven Univer-
`sity Hospital, following the instillation of topi-
`cal anesthetic drops under sterile conditions.
`Povidone-iodine 10% solution (Braunolt, B.
`Braun Medical, Diegem, Belgium) was applied
`to the periocular area; povidone-iodine 5% (Iso-
`Betadine Ophtat, Meda Pharma, Solna, Swe-
`den) solution was applied topically. Bevacizum-
`ab was injected into the vitreous cavity using a
`30-gauge needle inserted through the infero-
`temporal pars plana 3.0 mm (pseudophakic)
`or 3.5 mm (phakic) posterior to the limbus. Pa-
`tients were instructed to instill one drop of of-
`loxacine eye drops (Trafloxalt, Dr. Mann Phar-
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`ma, Berlin, Germany) into the in-
`jected eye three times daily for
`three days after the intravitreal in-
`jection.
`
`Fig. 1: Correlation between patient age and injection frequency in patients
`with 12-month follow-up (Group 1). X = data from Wu et al. (mean pa-
`tient age = 41.5 years; mean injection frequency = 1.4); Y = data from
`Rhéaume et al. (mean patient age = 53.5 years; mean injection frequency
`= 3.1)
`
`All patients had undergone FA be-
`fore the first IVB treatment. An
`’’evaluate-and-extend’’ regimen was
`followed, in which patients were
`initially followed up at 4-week in-
`tervals after the first injection. This
`interval was gradually extended to
`a maximum of three months be-
`tween visits. Retreatment was
`based on a decrease in visual acu-
`ity, an increase in CMT of s100
`µmm on OCT, the recurrence of
`macular edema on OCT and/or
`leakage on FA. Further, patients
`were advised to return to the clin-
`ic in between scheduled appointments for eval-
`uation if they experienced a loss of vision or in-
`creased metamorphopsia.
`
`For the purpose of analysis, ETDRS visual acu-
`ity data were converted into equivalent loga-
`rithms of the minimum angle of resolution (log
`MAR) values. Data were analyzed using the
`paired two-sample t-test for means. A p-value
`of less than 0.05 was considered to be statis-
`tically significant.
`
`RESULTS
`Fifteen women (65%) and eight men (35%)
`with a mean age of 57.7 years (range 20-84)
`were included in this study. Prior ocular treat-
`ment included photodynamic therapy in 10 pa-
`tients (5 in Group 1 and 5 in Group 2) and in-
`travitreal triamcinolone in 1 patient (Group 2).
`All treatments were performed at least 6 months
`prior to IVB. Three patients were pseudophak-
`ic. One patient had suffered a retinal detach-
`
`Table 1: Mean visual acuity measurements at baseline each of the main time points after initial intravitreal bevaci-
`zumab treatment for myopic choroidal neovascularization
`
`Patient group
`Group 1 (n = 8)
`Group 2 (n = 15)
`All patients (n = 23)
`
`Baseline
`20 / 120
`20 / 120++
`20 / 120+
`
`1m
`20 / 80-
`20 / 80+
`20 / 80
`
`3m
`20 / 80+
`20 / 60=
`20 / 80++
`
`6m
`20 / 80
`/
`/
`
`9m
`20 / 60+
`/
`/
`
`12m
`20 / 60
`/
`/
`
`BCVA
`
`BCVA = best-corrected visual acuity; VA = visual acuity
`
`Table 2: Central macular thickness at baseline, 1 and 3 months (all patients) and at 6, 9 and 12 months (Group 1).
`
`Group
`Group 1 (n=8)
`Group 2 (n=15)
`All patients (n=23)
`
`Baseline
`361
`367
`365
`
`µm = micrometers; m = months
`
`Central Macular Thickness (mm)
`3m
`6m
`276
`261
`284
`/
`281
`/
`
`1m
`307
`318
`314
`
`9m
`270
`/
`/
`
`12m
`262
`/
`/
`
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`11 lines) at 9 and 0.50 (20/60;
`11 lines) at 12 months (Table 1).
`In Group 2 (n=15), the mean
`BCVA was log MAR 0.75 (20/
`1202+; 8 lines) at baseline, 0.59
`(20/802-; 9.5 lines) at 1 month
`and 0.54 (20/80+; 10 lines) at 3
`months (Table 1). The mean dif-
`ferences in log MAR VA between
`baseline and each of the follow-
`up points for all patients and for
`both groups were statistically sig-
`nificant (P < 0.05).
`
`Increased patient age was associ-
`ated with the need for more fre-
`quent injections (Figures 1 and 2).
`Of the 8 patients with 12-month
`follow-up (Group 1), the oldest half
`(mean age: 68.5 years) required
`an average of 3.75 injections, while
`the youngest half (mean age: 39.5
`years) required 1.75 (Table 3). In those pa-
`tients with shorter follow up (Group 2), there
`was an inverse relationship between age and
`time between injections; older patients required
`more frequent injections (Figure 2). However,
`the mean visual acuity improvement was al-
`most identical between older and younger pa-
`tients, improving a mean of 3 lines in both the
`older and younger patients (Table 3). The mean
`CMT for all patients was 365 mm at baseline,
`314 mm at 1 month and 281 mm at 3 months
`(Table 2; Figure 3). For Group 1, the mean CMT
`was 261 mm at 6 months; 270 mm at 9 months
`and 262 at 12 months (Table 2). The mean dif-
`ferences in CMT between baseline and each of
`the follow-up points were statistically signifi-
`cant (P < 0.05).
`
`Fig. 2: Correlation between injection frequency (months between injec-
`tions) and patient age for all patients (n=23).
`
`ment in the study eye, which was treated with
`a scleral buckle 7 years prior to the first beva-
`cizumab injection. All patients in Group 1 had
`at least 12 months of follow-up. An OCT scan
`was performed at each patient visit to the clin-
`ic. No ocular or systemic side effects were not-
`ed.
`
`The mean log MAR BCVA for all patients (n=23)
`was 0.77 (Snellen equivalent: 20/120+; 8 ET-
`DRS lines) at baseline, 0.60 (20/80; 10 lines)
`at 1 month and 0.55 (20/602-; 10.5 lines) at
`three months. In Group 1 (n=8), the mean
`BCVA was log MAR 0.80 (20/120; 8 lines) at
`baseline, 0.63 (20/802-; 9.5 lines) at 1 month,
`0.58 (20/80+; 10 lines) at 3 months, 0.61
`(20/80; 10 lines) at 6 months, 0.48 (20/60+;
`
`Table 3: Age, visual acuity and injection frequency in patients with 12-month follow-up (Group 1)
`
`BCVA
`
`Older patients
`(n=4)
`Younger patients
`(n=4)
`All patients in current study
`(n=8)
`
`Mean Age
`(years)
`68.5
`
`Baseline
`VA
`20 160+
`
`Final VA
`
`20 / 80+
`
`ETDRS
`lines gained
`3
`
`39.5
`
`54.0
`
`20 / 100−
`
`20 / 50-
`
`20 / 120
`
`20 / 60
`
`3
`
`3
`
`Injections
`
`3.75
`
`1.75
`
`2.75
`
`BCVA = best corrected visual acuity; VA = visual acuity; * pro-rated from 2.6 injections over 10 months
`
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`present with these favorable fac-
`tors. Most are of middle or ad-
`vanced age (in Hayashi’s study:
`mean 49 years), have a VA worse
`than 20/40 (81%), have large CNV
`lesions (mean = 0.85 disc areas)
`and have subfoveal lesions (81%)
`at presentation. (16) Yoshida et
`al. reported that the angiographic
`features of the CNV in patients over
`the age of 40 had more profuse
`angiographic leakage and that pa-
`tients <40 years of age had signif-
`icantly better visual outcome. (5)
`Kojima et al found that the BCVA
`at 5 years after onset was signifi-
`cantly associated with patient age
`(P < 0.05, Spearman correla-
`tion). (17) The correlation between
`age and greater VA loss was sup-
`ported by Axer-Siegel et al., who
`found that 50% of the older age
`group and 20% of the younger age group had
`visual loss of 15 letters or more. Further, even
`young age does not protect against disease pro-
`gression. Axer-Siegel reported that 8% of the
`younger patients lost >15 letters despite treat-
`ment with PDT. (18)
`With regards to lesion location, although jux-
`tafoveal lesions have a better prognosis, most
`non-subfoveal lesions rapidly progress to the
`subfoveal area. Secretan et al. recorded the
`progression of patients with extra- and jux-
`tafoveal lesions and found that all juxtafoveal
`lesions in Secretan’s study became subfoveal
`within five years, with a mean final visual acu-
`ity of 20/160. (6) During this time patients
`were either treated with laser photocoagula-
`tion or left untreated.
`The only multicenter, randomized, controlled
`trial of PDT for mCNV conducted to date re-
`ported that treatment with PDT improves the
`visual outcome of myopic CNV (19). However,
`the effect of PDT was not sustained by the end
`of the second year. Indeed, some authors have
`reported that treatment of highly myopic eyes
`with PDT accelerates thrombosis of choroidal
`vessels and induces lacquer crack forma-
`tion. (20,21) Thus, PDT might have a nega-
`tive effect on the chorioretinal atrophy in mCNV,
`which is a key factor in the long-term progno-
`sis of the disease. (22) In fact, treatment with
`
`21
`
`Fig. 3: Central macular thickness (CMT) in micrometers (µm) for all
`patients (n= 23) at baseline, 1 and 3 months.
`
`DISCUSSION
`
`The results of this study suggest that intravit-
`real bevacizumab is a safe and effective treat-
`ment modality for choroidal neovasculariza-
`tion caused by pathological myopia. This sup-
`ports the conclusions of previously published
`studies in other populations. To our knowledge,
`this is the first study of this kind to be conduct-
`ed within the Belgian population.
`
`The visual outcome of myopic choroidal neovas-
`cularization is extremely poor if left untreated.
`Studies of the long-term outcome of untreated
`choroidal neovascularization due to patholog-
`ical myopia have shown that between 60 and
`73% of patients with subfoveal or juxtafoveal
`lesions end up with a final VA of < 20/
`200T(4,13,14). This visual loss is largely due
`to the development of chorioretinal atrophy
`around the regressed CNV. (15) Only a small
`percentage of patients retain good vision over
`the long term without treatment.
`
`Factors associated with a better prognosis (de-
`fined in these studies as a final VA better than
`20/40) have been shown by Hayashi et al. to
`be younger age, better initial VA, smaller CNV
`lesion and juxtafoveal lesion location. (16) How-
`ever, the vast majority of patients does not
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`Fig. 4: Female (78 yrs; -12 D) with metamorphopsia for 1 week prior to presentation. VA = 20/50. A,B,C: Fundus
`exam, OCT and FA (at 45 sec) show a bleeding subretinal membrane. CMT was 437 µm. Avastin was administered the
`same day. D,E,F: Three months after injection, the metamorphopsia has disappeared and the VA has improved to 20/
`32. Fundus exam, OCT and FA (at 36 sec) show a subretinal neovascular membrane without leakage. CMT = 295 µm.
`
`PDT results in only a slightly better visual out-
`come than would have been expected from the
`natural history of the disease. A large, retro-
`spective study by Costagliola et al reported a
`slight decrease in BCVA with standard PDT treat-
`ment over a 12-month follow-up period. (23)
`Ruiz-Moreno et al reported a slightly better out-
`come in a prospective study, with a small BCVA
`improvement at 12 months (1.4 lines) and 48
`months (0.6 lines). (24) However, PDT has not
`achieved truly satisfactory results, which has
`lead to the investigation of other treatment mo-
`dalities.
`The recent discovery of the complex pathogen-
`ic mechanisms responsible for choroidal neovas-
`cularization has lead to the development of treat-
`ment focused on interrupting this process. This
`pathogenesis consists of a cascade of retinal
`changes in which hypoxia or ischemia leads to
`atrophy of the choroidal vasculature and the up-
`regulation of angiogenic factors such as
`VEGF. (25-27) This leads to inflammation, an-
`giogenesis and subsequently neovasculariza-
`tion. (28) Higher intraocular concentrations of
`VEGF have been shown to be significantly re-
`lated to disease activity in neovascular
`
`AMD. (29) The discovery of the role of VEGF
`in the pathogenesis of neovascularization led
`to the development of a new class of pharma-
`cological agents that could block its action.
`These anti-VEGF antibodies, or anti-angiogen-
`ics, include pegaptanib, bevacizumab and ranibi-
`zumab, and have been used to treat CNV of oth-
`er etiologies, primarily AMD, (30,31) but also
`idiopathic CNV and myopic CNV.
`
`Because of the successful antiangiogenic treat-
`ment of CNV due to other etiologies, anti-VEGF
`treatment of mCNV has gained speed. The re-
`sults have been encouraging and similar to those
`obtained in the treatment of neovascular
`AMD. (32) However, very few trials have fol-
`low-up periods longer than 6 months, and none
`are large-scale, randomized studies. Thus, the
`optimal dosage and time intervals of re-injec-
`tion for long-term efficacy are largely unknown,
`as are the medium- and long-term effects of the
`treatment.
`
`A review of the available literature (up to Octo-
`ber, 2007), conducted by the American Acad-
`emy of Ophthalmology, suggests that anti-VEGF
`
`22
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`Fig. 5: Female (64y; -10 D) severely reduced vision for 2 weeks. VA = 20/126 OS. A,B,C: Fundus photo, FA (Heidel-
`berg, 3m14s) and OCT show myopic degeneration, retinal and peripapillar atrophy and an active, 100% classic subre-
`tinal membrane with a small hemorrhage on the inferior border of fixation. CMT = 298 µm. Avastin was administered
`the same day. D,E,F: Four months later. VA = 20/40. Minimally active lesion without macular edema. CMT = 265 µm.
`G,H,I: 13 months after first injection, 9 months after the second, VA = 20/25. Atrophic retinal lesions and peripapillar
`atrophy with an inactive lesion. CMT stable at 262 µm.
`
`pharmacotherapy, delivered by intravitreal in-
`jection, is a safe and effective treatment for
`neovascular AMD for up to 2 years. (33) Level
`I evidence exists to support this conclusion for
`the antiangiogenics pegaptanib and ranibizum-
`ab, but none for bevacizumab at this time. To
`our knowledge, no comparable study has been
`conducted for the treatment of myopic CNV.
`However, there have been several reports of the
`safety and efficacy of off-label bevacizumab for
`mCNV. (34-37)
`In these studies, visual acuity improved by 2
`or more lines in >75% of cases after a mean
`follow up of 5.0 and 4.4 months, respectively.
`Yamamoto et al reported a mean improvement
`of 2 or more lines in 91% of patients after a
`
`mean follow-up of 5.0 months. (35) Sakagu-
`chi et al reported an improvement of 2 or more
`lines in 75% of patients, after a mean follow-
`up of 4.4 months. (34) Wu et al followed 8 pa-
`tients up for 12 months and reported an im-
`provement of at least 3 ETDRS lines in all
`eyes, (36) while Rhéaume et al reported a 10-
`month follow-up of 10 eyes in which vision im-
`proved by a mean of 3.9 lines on the Snellen
`VA chart. There were no associated side ef-
`fects or complications reported in any of these
`4 studies. Studies by Konstantinidis) et
`al (38) and Silva et al (39) have shown simi-
`lar results with ranibizumab, also without com-
`plications or drug-related side effects during the
`follow-up period.
`
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`Fig. 6: Male (53 years; -10 D), with a history of an inferotemporal, peripheral, self-sealed retinal detachment and 4
`previous PDT sessions. VA = 20/80. A,B,C: Fundus exam, OCT and FA (28 sec) show an active membrane with recent
`hemorrhage and macular edema. CMT = 312 µm. Avastin was administered the following week. D,E,F: 5 months later:
`VA = 20/64-. Fundus exam, OCT and FA (at 26 sec) show an inactive membrane and an absence of hemorrhage, lipoid
`exudates and macular edema. CMT = 265 µm. No further Avastin was required during the 12-month follow-up.
`
`Our “evaluate-and-extend” regimen is a modi-
`fied “treat-and-extend” strategy. In the “treat-
`and-extend” approach, originally developed for
`neovascular age-related macular degeneration,
`treatment is administered at each patient vis-
`it, even in the absence of macular edema. If the
`macula remains free of edema, and the vision
`is stable, the interval between visits is extend-
`ed to a maximum of 10-11 weeks. The goal of
`“treat-and-extend” is to safely maintain the ben-
`efits of therapy while minimizing the number
`of visits and injections needed. Our modified
`’’evaluate-and-extend’’ approach utilized the
`same evaluation strategy, allowing for frequent
`evaluation of the fundus, but only treated as-
`needed, in case of recurrence. Extension of the
`time between visits was based on the degree
`of stability between the previous visit and the
`current one, up to a maximum of three months.
`This allowed for a lower reinjection rate.
`
`In our series of 8 patients followed up for at
`least 12 months, the mean time between in-
`jections was 4.4 months (based on a mean of
`2.75 injections in 12 months). This is similar
`to the reinjection frequency reported by Rhéaume
`
`et al (2.6 in 10 months, mean age 53), (37)
`but substantially more than the mean reported
`by Wu (1.4 in 12 months, mean age 41.5). (36)
`However, when analyzed in relation to patient
`age, the injection frequency of our study close-
`ly mirrors those of Rhéaume and Wu (Figure
`1).
`
`Taken together, these three studies suggest that
`the reinjection frequency is highly correlated
`with patient age. Of the 8 patients with 12-
`months of follow-up, the youngest four (mean
`39.5 years) required an average of 1.75 injec-
`tions, while the oldest four (mean 68.5 years)
`required 3.75. This suggests that younger pa-
`tients respond more efficiently to the effects of
`bevacizumab than those of more advanced age.
`Regarding VA, what we observed is that both
`baseline (20/160+ vs. 20/100-) and final (20/
`80+ vs. 20/50-) BCVA are better in younger pa-
`tients, but that overall improvement (3 lines)
`is similar between the two groups (Table 3).
`That younger age is correlated with superior VA
`at presentation, as well as a less damaging nat-
`ural progression, is well known. However, what
`has not yet been described is a correlation be-
`
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`A
`
`D
`
`B
`
`E
`
`C
`
`F
`
`Fig. 7: Female (63 years, -8.5 D) Presented at the emergency department with sudden onset of metamorphopsia OD,
`despite VA = 20/20. History of 7 previous PDT treatments OS. A,B,C: Fundus exam, OCT (Stratus) and FA (at 42 sec)
`showed 2 recent hemorrhages and 2 active subretinal neovascular membranes (superior and nasal of fovea). Avastin
`was administered the same day. CMT = 297 µm. D,E,F: Four months later, the patient reported stable vision. VA =
`20/20. Fundus exam, OCT (Cirrus) and FA (at 45 sec) show an inactive neovascular membrane. CMT = 193 µm.
`
`tween age and reinjection frequency. This is
`likely because few studies have exceeded 6
`months follow-up, and have treated on an in-
`dividualized, as-needed basis. Other studies
`conducted to date have had much shorter fol-
`low-up times and pre-determined injection
`schedules, making comparison difficult.
`
`The administration of multiple injections in an
`individualized regimen suggests that one-time
`treatment is not sufficient, and that frequent pa-
`tient visits and complete ophthalmic examina-
`tions are necessary to determine when injec-
`tions are needed. This is in line with the use of
`anti-angiogenics in the treatment of neovascu-
`lar AMD, in which individualized, OCT-guided
`treatment regimens, as outlined in the PrON-
`TO study, (40) are becoming more common
`now that the efficacy of the drugs has been es-
`tablished when given on a monthly basis.
`
`In the absence of evidence derived from ran-
`domized controlled trials supporting the use of
`bevacizumab for myopic CNV, many clinicians
`may feel obliged to use PDT as the first-line
`treatment. However, we do not feel that this is
`supported by the results of the studies conduct-
`
`ed. Despite the short follow-up times of the
`studies to date, and despite the fact that it is
`not yet known whether anti-VEGF treatment will
`favorably alter the long-term natural history of
`the disease, it is clear that there is significant
`improvement in the short- to medium-term, and
`that without treatment, there is an inevitable
`and irreparable decline in visual function.
`
`In conclusion, this short-term study shows that
`IVB effectively improves visual acuity and de-
`creases central CMT in patients with mCNV
`secondary to pathological myopia. A majority
`of eyes will require multiple injections for per-
`sistent or recurrent macular edema. Adverse
`events did not occur in our study and are likely
`to be rare.
`
`Advantages of this study are its 12-month fol-
`low-up time and the individualized, as-needed
`treatment regimen, which made it possible to
`differentiate injection frequency between dif-
`ferent age groups. However, this is a retrospec-
`tive study without controls, which makes it dif-
`ficult to evaluate the efficacy of IVB for mCNV.
`However, we observed a statistically signifi-
`cant mean improvement compared with the
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`natural history of the disease, which almost in-
`variably leads to a clinically significant loss of
`VA. In addition, the use of IVB is still off-label
`in many countries. A future multi-center, ran-
`domized, controlled clinical trial with even long-
`er follow-up may more clearly reveal the effi-
`cacy and safety of IVB for mCNV.
`
`Acknowledgements
`Carol Heughebaert provided excellent scienti-
`fic writing and editorial assistance. The au-
`thors would also like to thank Adrian Loehwing
`for her help with the statistical analysis.
`
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