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Keywords:

  • anti-VEGF;
  • bevacizumab;
  • choroidal neovascularisation;
  • pathological myopia;
  • ranibizumab

Abstract

  1. Top of page
  2. A
  3. Introduction
  4. Methods
  5. Conclusion
  6. Reference

Myopic choroidal neovascularization (CNV) is a vision-threatening complication in the eyes with pathological myopia, which is particularly prevalent among young and middle-aged Asians globally. To date, the verteporfin in photodynamic therapy study is the only randomized-controlled study in treatment of subfoveal myopic CNV. However, its long-term benefit is controversial. Recently, intravitreal injections of anti-vascular endothelial growth factors have shown promising results. In the absence of randomized-controlled trial comparing the efficacy of anti-vascular endothelial growth factors with photodynamic therapy and placebo, the purpose of this article is to review the current studies on functional and anatomical outcomes in both subfoveal and juxtafoveal myopic CNV. Furthermore, the influences of various doses and frequencies, as well as age and previous photodynamic therapy treatment on its effect are described.


Introduction

  1. Top of page
  2. A
  3. Introduction
  4. Methods
  5. Conclusion
  6. Reference

Asians are well known for having the highest rate of myopia in the world.1 The incidence of pathological myopia, defined as myopia with complications at the posterior segment, is among the most frequent causes of visual impairment in Asian populations.2 The Beijing Eye Study found that myopic retinopathy was present in 3.1% of population above 40 years.3 The Taiwanese Shihpai Eye Study and the Tajimi Study in Japan showed that myopic retinopathy is one of the most frequent causes of visual impairment and blindness.4,5 In Hong Kong, a pilot study of 355 adult Chinese aged 40 years or older showed that pathological myopia accounted for 31% of those with low vision.6 Although myopia was found to be less prevalent in Western countries than in Asia,7–10 myopia has also been reported to be a major cause of low vision.11–14 It is one of the main causes of visual impairment in the Italian Priverno Eye Study,11 and in the Danish Copenhagen City Eye Study, myopia-related retinal disorders were the major contributors to poor vision among subjects aged 20–64 years.12

Choroidal neovascularization (CNV) is a vision-threatening complication in the eyes with pathological myopia, which develops in 4–11% of affected eyes.15,16 It is also the most common cause of CNV in young individuals, accounting for 62% of CNV in patients younger than 50 years in one series.17 Most of these patients are part of the workforce so that their visual rehabilitation is of particular importance from a socioeconomic standpoint. Furthermore, natural history studies have reported poor visual outcome in these patients without treatment. Before the safety and efficacy of anti-vascular endothelial growth factor (anti-VEGF) was proved, treatment options were limited to laser photocoagulation for extra- and juxtafoveal CNV, and verteporfin photodynamic therapy (PDT) for subfoveal CNV. Because of the promising short-term efficacy and safety of anti-VEGF therapy from pilot studies, anti-VEGF was proposed to be the first-line treatment of subfoveal and juxtafoveal myopic CNV.18

Methods

  1. Top of page
  2. A
  3. Introduction
  4. Methods
  5. Conclusion
  6. Reference

A systematic review of literature up to February 2011 was performed searching for keywords ‘pathological myopia’, ‘choroidal neovascularization’, ‘myopic choroidal neovascularization’, ‘degenerative myopia’, ‘anti-vascular endothelial growth factor’, ‘bevacizumab’, ‘ranibizumab’ and ‘intravitreal injection’. The databases Medline, The Cochrane Library, Embase.com, Web of Knowledge and Google Scholar were used. The search was limited to studies in human subjects, in English and non-English languages.

Clinical features of myopic CNV

Patients who develop myopic CNV may experience metamorphopsia, a distortion of vision such that straight lines appear wavy, or present with scotoma, that is, seeing a dark spot in the central vision, or decrease in central vision. Myopic CNV typically appears as a small (less than 1 disc diameter in size), flat, greyish, subretinal membrane situated between the neurosensory retina and retinal pigment epithelium.19,20 The most common locations are subfoveal, followed by juxtafoveal, and rarely extrafoveal CNV. There is minimal subretinal fluid, exudate or haemorrhage. Over 80% have a classic pattern of leakage on fluorescein angiography, with transit phase hyperfluorescence followed by minor leakage in late phases.21 Optical coherence tomography (OCT) produces high resolution cross sectional images of the retina useful in the diagnosis of CNV in pathological myopia, excluding the presence of foveoschisis, vitreomacular tractions and small macular holes.22 Furthermore, OCT measures the macular thickness, which provides an indirect index of leakage as a result of perfusion of the CNV.22

Natural history

Unlike CNV in age-related macular degeneration (AMD), more than 50% of affected patients present at age 50 years or younger.21 A predominance of myopic CNV in female (67%) may reflect oestrogen receptor expression in the CNV as well as external influence of oestrogen.21,23 Natural history studies revealed that the long-term visual prognosis of myopic subfoveal CNV was generally poor,19,20,24–28 only a few studies reported that some patients retained relatively good vision over the long term without any treatment.16,28

Yoshida et al. studied the natural history of patients with minimum follow-up of 10 years; 70.4% of eyes had a baseline visual acuity better than 6/60, while 55.5% of eyes still retained visual acuity of better than 6/60 after 3 years. However, 96.3% of eyes had visual acuity of 6/60 or worse within 5–10 years after the onset of myopic CNV.29 The CNV in pathological myopia tends to progressively enlarge with fibrotic evolution, and chorioretinal atrophy subsequently develops around the myopic CNV, which results in poor long-term visual outcome.27,29

Several studies had identified prognostic factors in patients with myopic CNV.27,28,30 Patients older than 40 years at onset, larger CNV size and poor presenting visual acuity had poorer prognosis.

Limited data is available regarding the natural history of juxtafoveal myopic CNV.24,26 Secretan et al. studied 50 untreated eyes with non-subfoveal myopic CNV, and reported all lesions were subfoveal within 5 years and the mean visual acuity was 6/48.24 Bottoni and Tilanus reported the median visual acuity of nine patients after 4 years of follow-up was 6/12.26 These variable results may be due to several factors, including different angiographic definition of the location of CNV among studies, and discrepancies in the duration of myopic CNV onset and baseline visual acuity, which may be related to the size and extent of chorioretinal atrophy at the time when patients were presented in the studies.

Knowledge on the natural history of myopic CNV is important for clinicians in deciding for active treatment that may improve the prognosis of patients.

Direct thermal laser photocoagulation

Thermal laser photocoagulation was proposed for the treatment of juxtafoveal and extrafoveal myopic CNV. The most convincing study was a randomized, controlled trial by Soubrane et al.31 After a mean follow-up of over 2 years, 54% of treated eyes maintained visual acuity >6/30 compared with 11% of untreated eyes. However, at 5 years, the significant difference in visual outcome was not maintained because of the extension of photocoagulation scars (atrophic creep), which was reported in 92–100% of the treated eyes.24,32–34

PDT with verteporfin

PDT with verteporfin became the standard treatment for subfoveal myopic CNV. The verteporfin in photodynamic therapy (VIP) study is still the only randomized, double-masked, placebo-controlled study for treating subfoveal myopic CNV.21 At 1 year, visual loss of eight or more Early Treatment Diabetic Retinopathy Study (ETDRS) chart letters occurred in 28% of treated eyes versus 56% of untreated eyes. However, at 2 years, the difference between these groups was no longer significant, as 29 (36%) of the verteporfin-treated eyes and 20 (51%) of eyes in the placebo group lost at least eight letters.35 Additional studies also found that visual outcome after PDT could not be maintained at 2 years and beyond.36–40 The visual prognosis after PDT was found to be associated with age; older patients were less likely to benefit from treatment.41 Other investigators have attempted to improve or extend the efficacy of PDT by enhancing the fluence42 or combining PDT with intravitreal triamcinolone acetonide injection.43,44 However, these studies may be limited by small size, and the results were inconclusive.

The VIP study did not evaluate the efficacy of PDT in non-subfoveal myopic CNV. Several studies had reported more satisfactory long-term outcomes in treating patients with juxtafoveal and extrafoveal myopic CNV.45–49 Virgili et al. evaluated 100 eyes with a mean follow-up of 16.5 months and found the probability of losing three or more lines of vision was 10–15% during the second year.45 Pece et al. found that visual acuity was stabilized in a prospective study of 49 eyes with juxtafoveal CNV.46 Some authors still considered PDT is an effective treatment for non-subfoveal myopic CNV.

Intravitreal bevacizumab

Clinical studies found that patchy chorioretinal atrophy and lacquer cracks in pathological myopia correlated with myopic CNV.50 In pathological myopia, elongation of the axial length of the eye induces mechanical tissue strain that leads to choroidal ischemia, followed by atrophy of retinal pigment epithelium (RPE) and subsequent vascular endothelial growth factor (VEGF) release.15 Bevacizumab (Avastin; Genetech, San Francisco, California, USA) is a full-length monoclonal antibody that binds and inhibits all isoforms of VEGF A.51 It was approved by the United States Food and Drug Administration (FDA) for treating patients with metastatic colorectal cancer in February 2004.52 The use of intravitreal bevacizumab in myopic CNV is a natural extension of the previous work in treating neovascular AMD.53 The first report was a series of nine patients with AMD treated by systemic bevacizumab.54 In 2005, Nguyen et al. reported the use of systemic bevacizumab in eyes with subfoveal myopic CNV.55 Following the promising results of the systemic use of bevacizumab in treating CNV, a smaller dose of bevacizumab was injected intravitreally and resulted in anatomical improvements without significant toxicity.56–58 Lynch and Cheng reviewed 7113 intravitreal bevacizumab injections in treating various ocular conditions, and the complication rate was <0.21%.59

Visual outcome with less than 1 year follow-up

Laud et al., Yamamoto et al. and Sakaguchi et al. reported the off-label use of intravitreal bevacizumab in eyes with subfoveal myopic CNV, and demonstrated promising short-term results with no ocular or systemic side effects in small case series.60–62 Subsequent case series with a follow-up duration of less than 1 year60–69 also showed similar results with significant improvement in visual acuity, usually more than three lines on the ETDRS charts, after only a few injections. The final visual acuity was found to be >0.4 in more than half the reported series (Table 1). The ocular side effects of anti-VEFG injections reported in myopic eyes were rare. One case of marginal crack line formation after treatment-related contraction of the myopic CNV, one case of contralateral vitritis and a case of retinal detachment following intravitreal injection have been reported.70–72 No significant incidence of systemic complications and ocular complications, such as increased intraocular pressure, cataract and endophthalmitis, were observed.

Table 1.  Summary of studies on myopic CNV patients after intravitreal bevacizumab with follow-up of less than 1 year
AuthorDrugYear publishedStudy designFollow-up (months)Number of eyesDosageTreatment protocolNumber of juxtafoveal CNV (%)Number of previous PDT (%)Baseline BCVAFinal BCVA
  • Visual acuities were given in Snellen decimals if not specified. BCVA, best-corrected visual acuity; CNV, choroidal neovascularization; PDT, photodynamic therapy; PRN, pro re nata.

Laud et al.62Bevacizumab2006Retrospective741.251 + PRN2 (50)3 (75)0.420.57
Hernandez-Rojas et al.64Bevacizumab2007Prospective3142.501 + PRN1 (7.1)N/A0.100.33
Sakaguchi et al.61Bevacizumab2007Prospective481.001 + PRN2 (25)N/A0.260.51
Yamamoto et al.60Bevacizumab2007Retrospective5111.251 + PRN05 (45.5)0.180.46
Chan et al.63Bevacizumab2007Prospective6221.253 + PRN2 (9.1)11 (50)0.250.44
Rensch et al.66Bevacizumab2008Retrospective6131.503 + PRN0N/A0.230.30
Arias et al. 68Bevacizumab2008Prospective6171.251 + PRN09 (52.9)0.130.20
Rheaume and Sebag69Bevacizumab2008Retrospective10102.501 + PRN4 (40)3 (30)0.250.57
Dithmar et al.65Bevacizumab2009Prospective4231.251 + PRNN/AN/A0.250.44
Yodoi et al.89Bevacizumab2009Prospective6221.251 + PRN12 (54.5)4 (18.2)0.210.46
Gharbiya et al.112Bevacizumab2010RCT6161.251 + PRNN/A029.50 letters45.37 letters

Visual outcome at 1 year

Since 2009, both prospective and retrospective studies have been published on the outcomes of intravitreal bevacizumab with at least 1 year of follow-up (Table 2).73–78 All of the investigators reported the statistically significant visual improvement of two lines or more was sustained at 12 months. Chan et al. studied 29 eyes prospectively, and the mean best-corrected visual acuity (BCVA) improved from baseline 0.24 to 0.42 at 12 months, with 72.4% of eyes improved two lines or more.76 One series reported a case of foveoschisis on OCT and another case of peripheral retinal tear during follow-up, which may or may not have been related to intravitreal injections.76 Otherwise, no significant ocular and systemic adverse events after intravitreal anti-VEGF were reported.

Table 2.  Summary of studies on myopic CNV patients treated with intravitreal bevacizumab with follow-up of 1 year
AuthorDrugYear publishedStudy designFollow-up (months)Number of eyesDosageTreatment protocolNumber of juxtafoveal CNV (%)Number of previous PDT (%)Baseline BCVAFinal BCVAPrognostic factors
  • Visual acuities were given in Snellen decimals if not specified. BCVA, best-corrected visual acuity; CNV, choroidal neovascularization; PDT, photodynamic therapy; PRN, pro re nata.

Wu and Chen78Bevacizumab2009Prospective14.982.501 + PRNN/AN/A0.240.80 
Chan et al.76Bevacizumab2009Prospective12291.253 + PRN4 (13.8)13 (44.8)0.240.42 
Gharbiya et al.77Bevacizumab2009Prospective12201.253 + PRNN/A2 (10)0.250.57 
Ikuno et al.74Bevacizumab2009Retrospective12631.001 + PRN31 (49.2)00.270.47Number of injections, chorioretinal atrophy
Ruiz-Moreno et al.87Bevacizumab2009Prospective12291.251 + PRN013 (44.8)0.280.42 
Hayashi et al.99Bevacizumab2009Prospective15161.251 + PRN016 (100)0.170.26 
Yoon et al.113Bevacizumab2010Retrospective12631.251 + PRN25 (39.7) + 8 (12.7, extrafoveal)N/A0.270.47 
Scupola et al.90Bevacizumab2010Prospective12151.251 + PRN0N/A0.310.52 
Ruiz-Moreno et al.73Bevacizumab2010Retrospective121071.251 + PRN10 (9.4)32 (29.9)0.190.30Age, degree of myopia
Wakabayashi et al.93Bevacizumab2011Retrospective12121.003 + PRN15 (48.4) + 7 (22.6, extrafoveal)00.340.60Baseline VA, symptom duration, axial length
Wakabayashi et al.93Bevacizumab2011Retrospective12191.001 + PRN00.380.71

Visual outcome at 2 years

Because the VIP study showed that PDT could not maintain statistically significant visual improvement in patients with subfoveal myopic CNV at 2 years21,35, and in the absence of randomized controlled clinical trials comparing the results with PDT, the visual outcome of intravitreal bevacizumab at 2 years is of particular interest. To date, only few studies had reported the efficacy of intravitreal bevacizumab at 2 years (Table 3).79–84 Ikuno et al. studied 31 patients in which 11 patients were treated with intravitreal bevacizumab compared with 20 patients with PDT.82 BCVA improvement from baseline was significant at 3–12 months in the intravitreal bevacizumab group, although the significance was lost at 18 and 24 months. Voykov et al. prospectively studied a heterogeneous group of 21 patients who received either intravitreal bevacizumab alone or in combination with PDT.80 The overall gain in BCVA at 24 months was not statistically significant, and combination therapy did not show additional benefit. These investigators speculated that the secondary expanding chorioretinal atrophy in myopic eyes may have overwhelmed the effect of treatment based on previous long-term study on functional outcome and fluorescein angiographic findings of patients after PDT.85 Ruiz-Moreno et al. followed 19 eyes with three initial monthly injections prospectively, including both treatment naïve and previously PDT-treated eyes, and found that the gain in BCVA at 1 year did not remain statistically significant at 2 years.79 The suboptimal outcome in this series may be because of the inclusion of cases with previous PDT treatment. On the other hand, two studies that included only treatment naïve eyes had reported the significant improvement of BCVA was maintained at 2 years after intravitreal bevacizumab. Baba et al. reported that 12 eyes had significant improvement from 0.75 logMAR unit at baseline to 0.50 logMAR unit at 24 months.83 Nakanishi et al. studied 23 eyes, and the mean pre-treatment BCVA was 0.74 logMAR unit, which improved significantly to 0.46 logMAR unit at 24 months.81 One case from this series developed severe inflammation and underwent pars plana vitrectomy.86 At present, there is no conclusion regarding the long-term efficacy of intravitreal bevacizumab in altering the natural history of myopic CNV owing to the small number of cases and without comparison with control group.

Table 3.  Summary of studies on myopic CNV patients treated with intravitreal bevacizumab with follow-up of 2 years
AuthorDrugYear publishedStudy designFollow-up (months)Number of eyesDosageTreatment protocolNumber of juxtafoveal CNV (%)Number of previous PDT (%)Baseline BCVAFinal BCVAPrognostic factors
  • Visual acuities were given in Snellen decimals if not specified. BCVA, best-corrected visual acuity; CNV, choroidal neovascularization; PDT, photodynamic therapy; PRN, pro re nata.

Baba et al.83Bevacizumab2010Retrospective24121.251 + PRN4 (33.3)00.180.32 
Gharbiya et al.84Bevacizumab2010Retrospective24201.253 + PRNN/AN/A24.8 letters44 letters 
Ikuno et al.82Bevacizumab2010Retrospective24111.001 + PRN3 (27.3)00.210.28CNV size, myopic atrophy
Voykov et al.80Bevacizumab2010Retrospective24211.251 + PRN (11 eyes) or combined with PDT (10 eyes)N/A5 (20.8)0.230.28 
Ruiz-Moreno and Montero79Bevacizumab2010Prospective24191.253 + PRNN/A8 (42.1)0.290.34 
Nakanishi et al.81Bevacizumab2011Retrospective24231.251 + PRN9 (39.1)00.180.37CNV size, baseline VA

Anatomical outcomes

All the studies have described reduction in fluorescein leakage or CNV size reduction on angiography in 80% or above of patients at the final follow-up. However, a statistically significant reduction of mean central foveal thickness was not registered in some of the studies.77,87,88 The OCT feature seemed to be a characteristic finding of myopic CNV, which generally showed a mild degree of exudation.15,22 Yodoi et al. and Scupola et al. showed the improvement in retinal sensitivity after intravitreal bevacizumab by performing microperimetry studies with follow-up of 6 and 12 months.89,90

Dose and frequency

On the basis of the results of the PrONTO study,91 three monthly injections were proposed as the initial treatment of eyes with exudative AMD, followed by pro re nata (PRN) retreatment for persistent or recurrent cases. However, myopic CNV differs from AMD CNV due to the role of RPE and the release of different VEGF-related factors.92 Furthermore, myopic CNV patients are often younger, and a smaller dose of anti-VEGF may be effective because of the healthier RPE. Some authors performed a single initial injection followed by PRN retreatment in pilot studies (Tables 1–3). No obvious differences in functional and anatomical outcome, as well as the number of ocular or systemic adversities, were noticed between these studies. Wakabayashi et al. retrospectively compared 19 eyes that received single initial injection + PRN with 12 eyes that received three monthly injections + PRN. The single injection + PRN group received significantly fewer total number of injections with no significant differences in BCVA gained from baseline to 12 months, recurrence rate and the number of re-injections compared with the three injections + PRN group.93 Some authors believed that high dose of bevacizumab may oversuppress VEGF, which is important in many physiological conditions, causing disturbance of retinal and choroidal circulation or induce retinal toxicity over the long-term.94 To date, no published study had shown that a single injection followed by PRN retreatment is suboptimal to three monthly treatment + PRN in treating myopic CNV. Doses of 1, 1.25, 1.5 and 2.5 mg have been tested in pilot studies and obtained similar results (Tables 1–3). A single, low-dose (1 or 1.25 mg) injection may constitute a better option in an off-label therapy and avoid unnecessary risks and expenses from extra intravitreal injections.

The influence of age on visual outcome

Studies that followed the natural course of myopic CNV patients for 5–10 years concluded that younger patients had better visual prognosis.27–30 Previous studies had shown that gain in visual acuity after PDT was not maintained after 2 years, and it was even less effective in older patients.36,95,96 To date, studies had reported contradicting results on the influence of age on the prognosis after intravitreal bevacizumab treatment. In a prospective study of 17 patients, Arias et al. found that patients aged ≤50 years improved by a mean of 8.7 letters and similarly in older patients (8.3 letters) without statistically significant difference.68 Contrary to this finding, two subsequent studies with 1 year follow-up found that younger patients had significantly better visual outcome. Gharbiya et al. followed 20 patients prospectively, and the change in mean BCVA in patients younger than 50 years was 23.62 letters, while in older patients was 14.58 letters at 12 months. Moreover, the need for additional injection was also significantly more frequent in the older group.77 Ruiz-Moreno et al. studied 107 eyes retrospectively and reported the average BCVA was higher among patients younger than 50 years with lower number of retreatment, although the improvement in BCVA at month 12 was statistically significant in both the older and younger age groups.73 However, it was not clear how the age of 50 was chosen as a cut-off point in these studies. Dividing age into two groups for analysis has certain weakness; it implies a jump process, which is biologically implausible as the vision of patients is not stable over time until a certain age, where it deteriorates rapidly to be stable again afterwards. A multivariate analysis would better reflect the association of age with visual outcome, which should be a slow but continuously ongoing biological process.96 Nonetheless, limiting the indications for intravitreal bevacizumab to patients by age may be considered by many ophthalmologists as the loss of a chance to improve visual acuity.97

Visual outcome in patients with previous PDT

Five studies had documented the 1 year visual outcome of eyes with previous PDT.73,76,77,87,98,99 Three out of the five studies found that these patients had a more limited visual outcome.76,77,87 In a prospective study, Chan et al. reported that the group of patients with previous PDT at least 6 months prior to intravitreal bevacizumab had a mean visual improvement of two lines, whereas treatment naïve patients had a mean improvement of three lines. Ruiz-Moreno et al. compared 13 eyes that had previous PDT 3 months prior to treatment matched with 16 treatment naïve eyes. The group with previous PDT did not gain mean BCVA from baseline to 1 year. The poorer outcome in patients after PDT may be caused by a longer evolution of the CNV in PDT-treated eyes. Furthermore, repeated PDT sessions may cause RPE and choriocapillary atrophy, which have been related to poorer visual outcome.100

On the contrary, few studies found that previous PDT treatment had no influence on the efficacy of intravitreal bevacizumab at 12 months. Ruiz-Moreno et al. found that previous PDT treatment did not have significant difference in visual outcome compared with treatment naïve eyes after bevacizumab in a series of 107 eyes.73 In a non-comparative series of 16 myopic CNV patients who were refractory to or had recurred after PDT, Hayashi et al. reported significant improvement from 0.77 logMAR unit at baseline to 0.58 logMAR unit at final visit (mean follow-up 15 months) after intravitreal bevacizumab.99

Visual outcome in juxtafoveal CNV

Only one study reported the efficacy of intravitreal bevacizumab at 12 months in patients with only subfoveal CNV.87 Majority of studies included both subfoveal and juxtafoveal myopic CNV patients; some studies did not provide separate results for each subtype of myopic CNV and some had very few cases of juxtafoveal CNV.61,73,74,76,77 It is important to note that the natural history of juxtafoveal CNV is not well known, and a substantial proportion of myopic CNV, about one-fourth to one-half of eyes, had non-subfoveal location at presentation.20,31 One study compared the results of laser photocoagulation, PDT and intravitreal bevacizumab for patients with juxtafoveal CNV and suggested that bevacizumab offered the best functional results at 2 years of follow-up.101 However, the study lacked a control group. To date, no particular treatment has precise indication for non-subfoveal CNV as it is still not known whether treatment can alter its natural course.

Intravitreal ranibizumab

Ranibizumab (Lucentis; Genetech, San Francisco, California, USA) is a fragment of a recombinant monoclonal antibody that binds to and inhibits all the biologically active forms of VEGF-A. In 2006, the FDA approved intravitreal injection of ranibizumab for treatment of neovascular AMD. It has several theoretical advantages over bevacizumab. The primary difference between these two drugs is their molecular weight: ranibizumab is a 48-kDa Fab fragment, whereas bevacizumab is a full-length 149-kDa antibody. Ranibizumab may have higher and faster retinal penetration ability, attributable to its smaller molecular size. In addition, ranibizumab is affinity-matured and may provide better VEGF inhibition compared with bevacizumab through stronger molecular binding. However, it may have a shorter half-life than the larger bevacizumab molecule. Therefore, it has been proposed that the clinical efficacy of the two drugs maybe different.102

Fewer papers had reported clinical experience with ranibizumab possibly because it is a more expensive drug (Table 4).103–110 Silva et al. retrospectively evaluated 26 eyes with myopic CNV for 3–6 months,104 while Konstantinidis et al. prospectively evaluated 14 eyes with an average of 8 months of follow-up.105 These short-term studies showed a positive trend in visual recovery. At 12 months, Mones et al. prospectively treated 23 patients with a single injection followed by PRN retreatments, and almost 70% of patients gained at least one line of vision and the average number of injections was 1.5.106 Similarly, Silva et al.,103 Lalloum et al.,108 Vadala et al.110 and Calvo-Gonzalez et al.109 examined eyes prospectively with a non-loading dose, and BCVA improved from baseline significantly at 12 months. Lai et al. also obtained comparable visual outcome at 1 year using a loading dose of three monthly injections in their protocol, and 75% of the 16 patients gained vision with only one patient needed retreatment.107 In addition to significant closure of CNV and reduction of central foveal thickness in OCT, Varano et al. performed microperimetry studies and showed the improvement in retinal sensitivity at 36 weeks after ranibizumab.111

Table 4.  Summary of studies on myopic CNV patients treated with intravitreal ranibizumab
AuthorDrugYear publishedStudy designFollow-up (months)Number of eyesDosageTreatment protocolNumber of juxtafoveal CNV (%)Number of previous PDT (%)Baseline BCVAFinal BCVAPrognostic factors
  • Visual acuities were given in Snellen decimals if not specified. BCVA, best-corrected visual acuity; CNV, choroidal neovascularization; PDT, photodynamic therapy; PRN, pro re nata.

Konstantinidis et al.105Ranibizumab2009Prospective8.4140.501 + PRN3 (21)7 (50)0.190.48 
Lai et al.107Ranibizumab2009Retrospective12160.503 + PRN2 (12.5%)00.260.52 
Mones et al.106Ranibizumab2009Prospective12230.501 + PRNN/A9 (39.1)53 letters62.6 letters 
Silva et al.103Ranibizumab2010Prospective12340.501 + PRNN/A13 (38.2)51.8 letters59.6 letters 
Lalloum et al.108Ranibizumab2010Prospective17320.501 + PRN4 (12.5)13 (40.6)0.200.40 
Vadala et al.110Ranibizumab2010Prospective13.3400.501 + PRN11 (27.5)15 (37.5)0.210.54 
Gharbiya et al.112Ranibizumab2010RCT6160.501 + PRNN/A026.44 letters43.75 letters 
Calvo-Gonzalez et al.109Ranibizumab2011Prospective15.9670.501 + PRN37 (51.3)42 (62.7)53.4 letters65.4 lettersBaseline VA, CNV location

One randomized control study compared the outcome of intravitreal ranibizumab with bevacizumab in treating myopic CNV. Gharbiya et al.112 enrolled 32 patients and reported the improvement of BCVA, as well as reduction in central foveal thickness measured by OCT, and the resolution of fluorescein leakage on angiography had no statistically significant difference at 6 months between the two drugs.

Comparison of anti-VEGF with PDT

Four studies have compared the efficacy of anti-VEGF with PDT in treatment of myopic CNV patients and found that anti-VEGF had better visual outcome.82,83,88,113 Baba et al. retrospectively studied 24 eyes and found that the BCVA did not change after PDT but significantly improved after intravitreal bevacizumab.83 Hayashi et al. studied 42 eyes treated with PDT, 43 eyes with intravitreal bevacizumab and 74 control eyes. Intravitreal bevacizumab-treated patients had significantly better BCVA than PDT-treated and control eyes at 1 year.88 The CNV size continued to decrease during the 12-month follow-up in eyes successfully treated by intravitreal bevacizumab, and the size did not decrease, or even increased, in 65% of the successfully treated PDT eyes. Ikuno et al. did not find significant improvement of BCVA in both PDT- and intravitreal bevacizumab-treated women age 50 years or older at 24 months.82 However, the intravitreal bevacizumab group had significant better BCVA at 12 months and 24 months than the PDT group. Yoon et al. compared 63 eyes treated with anti-VEFG, 51 eyes with PDT and 28 eyes with combination of both treatments.113 The anti-VEGF group had significant improvement in visual acuity at 12 months compared with PDT and combination therapy groups. Nevertheless, the optimal treatment for myopic CNV is unclear to date because of a lack of randomized clinical trials.

Intravitreal pegaptanib

Only one case report114 was found in Medline search using intravitreal pegaptanib (Macugen; Eyetech Pharmaceuticals; Pfizer Inc, New York, USA) to treat a 35-year-old female with myopic CNV refractory to laser photocoagulation, PDT and intravitreal triamcinolone acetonide. Visual acuity improved from counting fingers to 6/12 after five, 6-weekly injections.

Future investigations

Studies have reported encouraging short-term treatment outcomes in myopic CNV patients after intravitreal bevacizumab and ranibizumab up to 1 year, and case control studies suggested that intravitreal anti-VEGF may achieve better short-term results than PDT. In the absence of randomized controlled clinical trials comparing the results with PDT, the visual outcome of intravitreal anti-VEGF at 2 years is of particular interest, as the VIP study had shown that the long-term results of PDT was suboptimal.21,35

Several reports underline that age, previous PDT treatment, lesion dimension, duration of symptoms, pre-treatment visual acuity and axial length may influence treatment prognosis. These prognostic factors deserve more investigation to guide ophthalmologists in deciding for the best individualized treatment for patients with myopic CNV.

To date, very limited amount of published data and only the short-term effects of intravitreal anti-VEGF in juxtafoveal myopic CNV are available. Many of the published studies on intravitreal anti-VEGF had included both subfoveal and juxtafoveal myopic CNV patients. These two disease subtypes may have separate clinical characteristics at presentation and different natural history course. Because many studies have mixed the two groups together in the analysis of functional and anatomical outcomes, the true efficacy of anti-VEFG on juxtafoveal myopic CNV is not clear. Furthermore, clinicians should not neglect the long-term studies of PDT in the treatment of non-subfoveal myopic CNV patients that showed significant efficacy and safety.45,46,48

No consensus on follow-up protocol and indications of retreatment had been determined. OCT alone may have poor sensitivity in diagnosing recurrence, as myopic CNV can often have minimal leakage and choroid is usually thin. OCT may not be easy to perform in myopic eyes, the macular thickness may be irrelevant and the presence of fluid very scarce.22 The extent of perfusion of the CNV in pathological myopia may be difficult to evaluate without fluorescein angiography. The differences in follow-up protocol, indication for retreatment as well as pre-treatment characteristics may explain the differences in visual outcomes reported by various studies.

Conclusion

  1. Top of page
  2. A
  3. Introduction
  4. Methods
  5. Conclusion
  6. Reference

To date, only case series (level IV evidence) had studied the efficacy of intravitreal bevacizumab and ranibizumab on subfoveal and juxtafoveal myopic CNV, which achieved better short-term visual outcomes than PDT (level I evidence for treatment of subfoveal myopic CNV). Nonetheless, intravitreal anti-VEGF has been proposed to be the first-line treatment of myopic CNV in patients of all ages since 2009.18 Although ranibizumab and bevacizumab seemed to have similar benefit, as proven in a small sample size RCT study, the choice of drug depends on the availability and costs. A single, low-dose (1.25 mg bevacizumab or 0.5 mg ranibizumab) injection followed by monthly evaluation and PRN retreatment may help patients achieve good short-term visual outcome as there is no evidence that higher dosage or three monthly loading doses provided superior outcome.

Reference

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  2. A
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  4. Methods
  5. Conclusion
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