INTRAVITREAL RANIBIZUMAB FOR NAIVE EXTRAFOVEAL CHOROIDAL NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION MAURIZIO B. PARODI, MD,* PIERLUIGI IACONO, MD,† CARLO LA SPINA, MD,* LORENZO IULIANO, MD,* GIUSEPPE LO GIUDICE, MD,‡ UGO INTROINI, MD,* FRANCESCO BANDELLO, MD, FEBO* Purpose: To investigate the effect of intravitreal ranibizumab on extrafoveal choroidal neovascularization secondary to age-related macular degeneration. Methods: Eighteen eyes affected by extrafoveal choroidal neovascularization secondary to age-related macular degeneration were prospectively enrolled in this study. After an initial intravitreal ranibizumab, all patients were reevaluated monthly over 12 months of follow-up. Further retreatments were performed on a pro re nata basis, depending on detection of any type of fluid on optical coherence tomography and/or the presence of leakage on fluorescein angiography. Primary outcome measures were mean changes in best-corrected visual acuity and the proportion of eyes gaining at least 15 letters (3 Early Treatment Diabetic Retinopathy Study [ETDRS] lines) at the end of the follow-up. Secondary outcome measures were central macular thickness variations and changes in choroidal neovascularization size. Results: Mean best-corrected visual acuity presented a significant improvement during the follow-up period, being 0.3 ± 0.2 logMAR at baseline and 0.2 ± 0.2 logMAR at the 12month examination (P , 0.001). An improvement of at least 3 EDTRS lines was achieved by 6 eyes (33.3%), whereas 6 patients (33.3%) gained 1 to 2 lines. The mean central macular thickness at baseline was 314 ± 87 mm, changing to 268 ± 65 mm at the 12-month examination (P = 0.003). The mean lesion size was 1.4 ± 1.4 mm2 and remained stable throughout the follow-up, being 1.8 ± 2.9 mm2 at 12 months (P = 0.64). Conclusion: Intravitreal ranibizumab administered after a pro re nata regimen with monthly evaluation is a beneficial approach for the management of extrafoveal choroidal neovascularization secondary to age-related macular degeneration over 12 months of follow-up. Further studies are warranted to confirm our preliminary results. RETINA 34:2167–2170, 2014
A
as the gold standard therapy for subfoveal CNV,2 many different treatment options have been proposed for nonsubfoveal CNV.5–12 More specifically, laser photocoagulation is known to be effective, but is burdened by a high risk of recurrence.13 Interesting results have also been obtained by combining photodynamic therapy with intravitreal triamcinolone.9 Regarding the intravitreal anti-VEGF approach, the data available on its use in the management of nonsubfoveal CNV related to AMD are currently too limited to enable firm conclusions to be drawn.11,12
ge-related macular degeneration (AMD) is a leading cause of blindness and visual disability in patients above age 50 in the developed world.1 Choroidal neovascularization (CNV) is a major visually threatening complication of an exudative variant of AMD.1,2 A CNV is most frequently located in the subfoveal area, but juxtafoveal lesions have been reported in up to 20% of cases. An extrafoveally located CNV is relatively infrequent, amounting from 5% to 7% of cases.3,4 Although, to date, there is a solid literature supporting antivascular endothelial growth factor (anti-VEGF) 2167
2168 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
The aim of this study is to record a 1-year follow-up of naive extrafoveal CNV secondary to AMD treated with intravitreal ranibizumab (IVR). Methods All patients affected by extrafoveal classic CNV secondary to AMD referred to the Department of Ophthalmology of San Raffaele Scientific Institute in Milan from May 2009 to June 2010 were considered for this prospective study. The research was approved by the local institutional review board and adhered to the tenets of the Declaration of Helsinki. Each patient was carefully informed about the purpose of research, and provided signed consent to all procedures. Eligibility criteria were diagnosis of AMD, evidence of naive CNV with extrafoveal location (defined as .199 mm from the fovea), best-corrected visual acuity (BCVA) of at least 1.2 logMAR (approximately corresponding to 20/320 Snellen equivalent), and exudative manifestations (fluid and/or hemorrhage) involving the fovea. Exclusion criteria were any other ocular disease that could compromise vision in the study eye, pregnancy; previous corticosteroid therapy (either local injection or oral administration), previous anti-VEGF treatment, uncontrolled systemic hypertension, peripheral vascular disease, and history of thromboembolism or stroke. Each patient underwent an ophthalmologic examination, including measurement of BCVA using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, slit-lamp biomicroscopy, fundus color photography, fluorescein angiography, and optical coherence tomography (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany). The CNV area on fluorescein angiography was measured on the angiogram taken just before the arteriovenous phase by means of image analysis software (Retina Angiography Area Measurement Program; Heidelberg Engineering). After the first injection of IVR (0.5 mg/0.05 mL) (Lucentis; Novartis, Basel, Switzerland), all patients were reevaluated monthly by means of From the *Department of Ophthalmology, University VitaSalute, Scientific Institute San Raffaele, Milan, Italy; †G. B. Bietti Foundation for Study and Research in Ophthalmology, IRCCS, Rome, Italy; and ‡San Paolo Ophthalmic Center, Sant’ Antonio Hospital, Padua, Italy. F. Bandello is an advisory board member of Allergan, Novartis Pharmaceuticals Corporation, Farmila-Thea, Bayer Schering Pharma, Pfizer, Alcon, Bausch and Lomb, Genentech, Alimera Sciences, Sanofi Aventis, Thrombogenics. The other authors have no conflicting interest to disclose. Reprint requests: Pierluigi Iacono, MD, G. B. Bietti Foundation for Study and Research in Ophthalmology, IRCCS, Via Livenza 3, Rome, Italy 00198; e-mail: [email protected]
2014 VOLUME 34 NUMBER 11
a complete ophthalmic examination, including fluorescein angiography and optical coherence tomography, over 12 months of the planned follow-up. Further retreatments were performed on a pro re nata basis, depending on detection of any type of fluid on optical coherence tomography and/or the presence of leakage on fluorescein angiography. Primary outcome measures were mean changes in BCVA and the proportion of eyes gaining at least 15 letters (3 ETDRS lines) at the end of the follow-up. Secondary outcomes included central macular thickness variations, changes in the CNV size, and extension to the fovea over the follow-up. Statistical analysis was performed using the Friedman nonparametric test for significance of the difference between the distributions of nonindependent samples involving repeated measures. Dunn multiple comparison test was used for the posttest analysis. A two-tailed P , 0.05 was taken as statistically significant. All calculations were performed with GraphPad Prism version 5.00 (GraphPad Software, San Diego, CA).
Results Of 316 patients with newly diagnosed neovascular AMD who were receiving ranibizumab treatment at our center during the period of our study, 19 patients were prospectively recruited for the study. A single patient moved abroad just 1 month after the enrollment and was excluded from data analysis. The current data collection allowed us to estimate prevalence of extrafoveal CNV to be roughly 6%. Overall 18 patients (18 eyes) fulfilling the inclusion and exclusion criteria were considered for this study. The mean age of the patients was 71.5 ± 10 years. Ten patients (55.5%) were men. Choroidal neovascularization was a classic type in all cases (Figure 1). The mean distance of CNV from the fovea was 436.6 ± 93.3 mm. Impairment in BCVA was related to the presence of subfoveal fluid in all 18 cases, and associated with subretinal hemorrhage in 4 cases. Mean BCVA presented a significant improvement during the follow-up period (Figure 2), being 0.3 ± 0.2 logMAR (approximately corresponding to 20/40 Snellen equivalent; 95% confidence interval, 0.23– 0.41) at baseline, and 0.2 ± 0.2 logMAR (approximately corresponding to 20/30 Snellen equivalent; 95% confidence interval, 0.09–0.30) at the 12-month examination (P , 0.001). Dunn multiple comparison post hoc analysis revealed that this result was driven by a significant difference between the mean BCVA at baseline and that at 3, 6, 9, and 12 months during the follow-up. In detail (Table 1), a functional improvement of at least 3
2169
RANIBIZUMAB FOR EXTRAFOVEAL CNV SECONDARY TO AMD PARODI ET AL
Fig. 1. Fluorescein angiograms of a representative case with extrafoveal CNV, at baseline and at the end of follow-up.
EDTRS lines was achieved by 6 eyes (33.3%), whereas 6 patients (33.3%) gained 1 or 2 lines. Three patients (16.6%) remained stable, and 2 eyes (11.1%) lost between 1 and 3 lines. A single case (5.5%) experienced visual loss of over 3 lines because of subfoveal invasion. This patient showed a foveal extension of the CNV at the third month and had received eight IVR injections overall by the end of the follow-up. The mean central macular thickness at baseline was 314 ± 87 mm (95% confidence interval, 271–357), changing to 268 ± 65 mm (95% confidence interval, 235–301) at the 12-month examination (P = 0.003). Dunn multiple comparison post hoc analysis revealed that this result was driven by a significant difference between the mean central macular thickness at baseline and that at 3 months and 9 months during the followup. The mean lesion size was 1.4 ± 1.4 mm2 and remained stable throughout the follow-up, being 1.8 ± 2.9 mm2 at 12 months (P = 0.64). The mean number of IVR injections was 5 ± 2 (range, 3–9) by the end of 12 months. At the end of the follow-up, all the patients displayed a stabilized CNV with no fluorescein leakage or fluid on optical coherence tomography.
No systemic or ocular side effects were registered over the whole 12-month follow-up. Discussion Extrafoveally located AMD-related CNV is relatively infrequent, accounting for 5% to 7% of cases.3,4 At present, there is no general consensus regarding the most appropriate means of managing extrafoveal CNV secondary to AMD. Macular Photocoagulation Study reported beneficial outcomes of laser photocoagulation in reducing the severe long-term visual loss, but the results were burdened by high recurrence rates and progressive enlargement of the laser scar.13 Photodynamic therapy alone, or in combination with intravitreal triamcinolone, has been shown to produce limited functional improvement.7–9 With the advent of the anti-VEGF approach to AMD-related CNV, some authors have extended this approach to the treatment of CNV with a nonsubfoveal location. For example, Mones et al11 recorded improved visual acuity in a single case treated with bevacizumab. Arias et al12 also described the results of 4 extrafoveal CNV from a broader case series, which had been treated with IVR, showing BCVA improvement in 2 eyes. To try to cast light on this topic, we designed an open-label, interventional prospective study to assess the effect of a therapy with IVR on extrafoveal CNV related to AMD. Table 1. Frequency Distribution of Changes in Visual Acuity From Baseline to a 12-Month Follow-up Change in Visual Acuity
Fig. 2. Best-corrected visual acuity (logMAR) changes significantly over 12 months of follow-up. Dunn multiple comparison post hoc analysis revealed that such a result was driven by a significant difference among mean BCVA at baseline and at 3, 6, 9, and 12 months of follow-up.
$3-line increase $1-line to ,3-line increase No change $1-line to ,3-line decrease $3-line decrease
18 Eyes, n (%) 6 6 3 2 1
(33.3) (33.3) (16.6) (11.1) (5.5)
2170 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
Overall, the results we achieved were encouraging. We registered a statistically significant improvement in BCVA at the end of the scheduled 12-month followup, with 2 of 3 patients gaining at least 1 ETDRS line. Examination of the anatomical features also gave positive results, with a statistically significant decrease in central macular thickness, along with a stabilized CNV size over the follow-up. Only one patient experienced a subfoveal extension of the CNV with consequent BCVA deterioration. Although a specific comparison is not appropriate, it is still worth noting that fewer injections were required to arrest the activity than those recorded for subfoveal CNV in the CATT study (5 ± 2 vs. 6.9 ± 3.0), which had a similar study design.14 It is likely that just as with extrafoveal CNV related to pathologic myopia,15 extrafoveal CNV might be less aggressive than subfoveal CNV secondary to AMD and require fewer retreatments. We acknowledge that this study has several limitations, especially regarding the absence of a control group and the limited number of patients. Nevertheless, bearing in mind that the natural history of AMD-related CNV is poor, and that the previously proposed treatments for extrafoveal CNV associated with AMD are unable to guarantee significant improvement in visual acuity, we do not believe it is ethically correct to eschew the treatment that has been proven to be effective for AMD-related CNV with subfoveal location. Moreover, because extrafoveal CNV associated with AMD is quite infrequent, it may be very difficult to plan a randomized clinical trial comparing different treatment options. But bearing in mind that our study is indisputably underpowered, we cannot directly compare its results with those achievable with conventional laser photocoagulation and claim that the anti-VEGF approach is better. In conclusion, even taking into account the abovementioned shortcomings, the present pilot study provides a contribution to the management of AMDrelated CNV with extrafoveal location, showing that an improvement in visual acuity of at least three EDTRS lines can be achieved in about one third of patients. Further studies are warranted to confirm these preliminary results in a longer-term follow-up. Key words: ranibizumab, age-related macular degeneration, extrafoveal choroidal neovascularization.
2014 VOLUME 34 NUMBER 11
References 1. Bressler NM, Bressler SB, Congdon NG, et al. Age-Related Eye Disease Study (AREDS) Research Group. Potential public health impact of Age-Related Eye Disease Study Results: AREDS report no. 11. Arch Ophthalmol 2003;121:1621–1624. 2. Lim LS, Mitchell P, Seddon JM, et al. Age-related macular degeneration. Lancet 2012;379:1728–1738. 3. Beaumont PE, Kang HK. Lesion morphology in age-related macular degeneration and its therapeutic significance. Arch Ophthalmol 2006;124:807–812. 4. Olsen TW, Feng X, Kasper TJ, et al. Fluorescein angiographic lesion type frequency in neovascular age-related macular degeneration. Ophthalmology 2004;111:250–255. 5. Chakravarthy U, Soubrane G, Bandello F, et al. Evolving European guidance on the medical management of neovascular age-related macular degeneration. Br J Ophthalmol 2006;90: 1188–1196. 6. Tranos P, Peter NM, Nath R, et al. Visual function following transpupillary thermotherapy with adjusted laser parameters for the treatment of exudative age-related macular degeneration: a pilot study. Clin Experiment Ophthalmol 2006;34:226–232. 7. Voelker M, Gelisken F, Ziemssen F, et al. Verteporfin photodynamic therapy for extrafoveal choroidal neovascularization secondary to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2005;243:1241–1246. 8. Etter J, Fekrat S. Photodynamic therapy and intravitreal triamcinolone for extrafoveal choroidal neovascularization in neovascular age-related macular degeneration. Ann Ophthalmol (Skokie) 2006;38:239–241. 9. Spaide RF, Sorenson J, Maranan L. Combined photodynamic therapy and intravitreal triamcinolone for nonsubfoveal choroidal neovascularization. Retina 2005;25:685–690. 10. Mikuni E, Shimada H, Mori R, et al. Surgical removal of juxtafoveal and extrafoveal choroidal neovascularization in age-related macular degeneration [in Japanese]. Nihon Ganka Gakkai Zasshi 2003;107:695–701. 11. Mones JM, Lopez MA, Prieto JA, Rodriguez JP. Extrafoveal choroidal neovascularization secondary to wet age-related macular degeneration treated with intravitreal bevacizumab. Ophthalmic Surg Lasers Imaging 2007;38:226–228. 12. Arias L, Ruiz-Moreno JM, Gomez-Ulla F, et al. A 1-year retrospective review of ranibizumab for naive nonsubfoveal choroidal neovascularization secondary to age-related macular degeneration. Retina 2009;29:1444–1449. 13. Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy. Three-year results from randomized clinical trials. Arch Ophthalmol 1986;104: 694–701. 14. CATT Research Group, Martin DF, Maguire MG, et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 2011;364:1897–1908. 15. Parodi MB, Iacono P, Papayannis A, et al. Intravitreal bevacizumab for extrafoveal choroidal neovascularization secondary to pathologic myopia. Retina 2013;33:593–597.
A
as the gold standard therapy for subfoveal CNV,2 many different treatment options have been proposed for nonsubfoveal CNV.5–12 More specifically, laser photocoagulation is known to be effective, but is burdened by a high risk of recurrence.13 Interesting results have also been obtained by combining photodynamic therapy with intravitreal triamcinolone.9 Regarding the intravitreal anti-VEGF approach, the data available on its use in the management of nonsubfoveal CNV related to AMD are currently too limited to enable firm conclusions to be drawn.11,12
ge-related macular degeneration (AMD) is a leading cause of blindness and visual disability in patients above age 50 in the developed world.1 Choroidal neovascularization (CNV) is a major visually threatening complication of an exudative variant of AMD.1,2 A CNV is most frequently located in the subfoveal area, but juxtafoveal lesions have been reported in up to 20% of cases. An extrafoveally located CNV is relatively infrequent, amounting from 5% to 7% of cases.3,4 Although, to date, there is a solid literature supporting antivascular endothelial growth factor (anti-VEGF) 2167
2168 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
The aim of this study is to record a 1-year follow-up of naive extrafoveal CNV secondary to AMD treated with intravitreal ranibizumab (IVR). Methods All patients affected by extrafoveal classic CNV secondary to AMD referred to the Department of Ophthalmology of San Raffaele Scientific Institute in Milan from May 2009 to June 2010 were considered for this prospective study. The research was approved by the local institutional review board and adhered to the tenets of the Declaration of Helsinki. Each patient was carefully informed about the purpose of research, and provided signed consent to all procedures. Eligibility criteria were diagnosis of AMD, evidence of naive CNV with extrafoveal location (defined as .199 mm from the fovea), best-corrected visual acuity (BCVA) of at least 1.2 logMAR (approximately corresponding to 20/320 Snellen equivalent), and exudative manifestations (fluid and/or hemorrhage) involving the fovea. Exclusion criteria were any other ocular disease that could compromise vision in the study eye, pregnancy; previous corticosteroid therapy (either local injection or oral administration), previous anti-VEGF treatment, uncontrolled systemic hypertension, peripheral vascular disease, and history of thromboembolism or stroke. Each patient underwent an ophthalmologic examination, including measurement of BCVA using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, slit-lamp biomicroscopy, fundus color photography, fluorescein angiography, and optical coherence tomography (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany). The CNV area on fluorescein angiography was measured on the angiogram taken just before the arteriovenous phase by means of image analysis software (Retina Angiography Area Measurement Program; Heidelberg Engineering). After the first injection of IVR (0.5 mg/0.05 mL) (Lucentis; Novartis, Basel, Switzerland), all patients were reevaluated monthly by means of From the *Department of Ophthalmology, University VitaSalute, Scientific Institute San Raffaele, Milan, Italy; †G. B. Bietti Foundation for Study and Research in Ophthalmology, IRCCS, Rome, Italy; and ‡San Paolo Ophthalmic Center, Sant’ Antonio Hospital, Padua, Italy. F. Bandello is an advisory board member of Allergan, Novartis Pharmaceuticals Corporation, Farmila-Thea, Bayer Schering Pharma, Pfizer, Alcon, Bausch and Lomb, Genentech, Alimera Sciences, Sanofi Aventis, Thrombogenics. The other authors have no conflicting interest to disclose. Reprint requests: Pierluigi Iacono, MD, G. B. Bietti Foundation for Study and Research in Ophthalmology, IRCCS, Via Livenza 3, Rome, Italy 00198; e-mail: [email protected]
2014 VOLUME 34 NUMBER 11
a complete ophthalmic examination, including fluorescein angiography and optical coherence tomography, over 12 months of the planned follow-up. Further retreatments were performed on a pro re nata basis, depending on detection of any type of fluid on optical coherence tomography and/or the presence of leakage on fluorescein angiography. Primary outcome measures were mean changes in BCVA and the proportion of eyes gaining at least 15 letters (3 ETDRS lines) at the end of the follow-up. Secondary outcomes included central macular thickness variations, changes in the CNV size, and extension to the fovea over the follow-up. Statistical analysis was performed using the Friedman nonparametric test for significance of the difference between the distributions of nonindependent samples involving repeated measures. Dunn multiple comparison test was used for the posttest analysis. A two-tailed P , 0.05 was taken as statistically significant. All calculations were performed with GraphPad Prism version 5.00 (GraphPad Software, San Diego, CA).
Results Of 316 patients with newly diagnosed neovascular AMD who were receiving ranibizumab treatment at our center during the period of our study, 19 patients were prospectively recruited for the study. A single patient moved abroad just 1 month after the enrollment and was excluded from data analysis. The current data collection allowed us to estimate prevalence of extrafoveal CNV to be roughly 6%. Overall 18 patients (18 eyes) fulfilling the inclusion and exclusion criteria were considered for this study. The mean age of the patients was 71.5 ± 10 years. Ten patients (55.5%) were men. Choroidal neovascularization was a classic type in all cases (Figure 1). The mean distance of CNV from the fovea was 436.6 ± 93.3 mm. Impairment in BCVA was related to the presence of subfoveal fluid in all 18 cases, and associated with subretinal hemorrhage in 4 cases. Mean BCVA presented a significant improvement during the follow-up period (Figure 2), being 0.3 ± 0.2 logMAR (approximately corresponding to 20/40 Snellen equivalent; 95% confidence interval, 0.23– 0.41) at baseline, and 0.2 ± 0.2 logMAR (approximately corresponding to 20/30 Snellen equivalent; 95% confidence interval, 0.09–0.30) at the 12-month examination (P , 0.001). Dunn multiple comparison post hoc analysis revealed that this result was driven by a significant difference between the mean BCVA at baseline and that at 3, 6, 9, and 12 months during the follow-up. In detail (Table 1), a functional improvement of at least 3
2169
RANIBIZUMAB FOR EXTRAFOVEAL CNV SECONDARY TO AMD PARODI ET AL
Fig. 1. Fluorescein angiograms of a representative case with extrafoveal CNV, at baseline and at the end of follow-up.
EDTRS lines was achieved by 6 eyes (33.3%), whereas 6 patients (33.3%) gained 1 or 2 lines. Three patients (16.6%) remained stable, and 2 eyes (11.1%) lost between 1 and 3 lines. A single case (5.5%) experienced visual loss of over 3 lines because of subfoveal invasion. This patient showed a foveal extension of the CNV at the third month and had received eight IVR injections overall by the end of the follow-up. The mean central macular thickness at baseline was 314 ± 87 mm (95% confidence interval, 271–357), changing to 268 ± 65 mm (95% confidence interval, 235–301) at the 12-month examination (P = 0.003). Dunn multiple comparison post hoc analysis revealed that this result was driven by a significant difference between the mean central macular thickness at baseline and that at 3 months and 9 months during the followup. The mean lesion size was 1.4 ± 1.4 mm2 and remained stable throughout the follow-up, being 1.8 ± 2.9 mm2 at 12 months (P = 0.64). The mean number of IVR injections was 5 ± 2 (range, 3–9) by the end of 12 months. At the end of the follow-up, all the patients displayed a stabilized CNV with no fluorescein leakage or fluid on optical coherence tomography.
No systemic or ocular side effects were registered over the whole 12-month follow-up. Discussion Extrafoveally located AMD-related CNV is relatively infrequent, accounting for 5% to 7% of cases.3,4 At present, there is no general consensus regarding the most appropriate means of managing extrafoveal CNV secondary to AMD. Macular Photocoagulation Study reported beneficial outcomes of laser photocoagulation in reducing the severe long-term visual loss, but the results were burdened by high recurrence rates and progressive enlargement of the laser scar.13 Photodynamic therapy alone, or in combination with intravitreal triamcinolone, has been shown to produce limited functional improvement.7–9 With the advent of the anti-VEGF approach to AMD-related CNV, some authors have extended this approach to the treatment of CNV with a nonsubfoveal location. For example, Mones et al11 recorded improved visual acuity in a single case treated with bevacizumab. Arias et al12 also described the results of 4 extrafoveal CNV from a broader case series, which had been treated with IVR, showing BCVA improvement in 2 eyes. To try to cast light on this topic, we designed an open-label, interventional prospective study to assess the effect of a therapy with IVR on extrafoveal CNV related to AMD. Table 1. Frequency Distribution of Changes in Visual Acuity From Baseline to a 12-Month Follow-up Change in Visual Acuity
Fig. 2. Best-corrected visual acuity (logMAR) changes significantly over 12 months of follow-up. Dunn multiple comparison post hoc analysis revealed that such a result was driven by a significant difference among mean BCVA at baseline and at 3, 6, 9, and 12 months of follow-up.
$3-line increase $1-line to ,3-line increase No change $1-line to ,3-line decrease $3-line decrease
18 Eyes, n (%) 6 6 3 2 1
(33.3) (33.3) (16.6) (11.1) (5.5)
2170 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
Overall, the results we achieved were encouraging. We registered a statistically significant improvement in BCVA at the end of the scheduled 12-month followup, with 2 of 3 patients gaining at least 1 ETDRS line. Examination of the anatomical features also gave positive results, with a statistically significant decrease in central macular thickness, along with a stabilized CNV size over the follow-up. Only one patient experienced a subfoveal extension of the CNV with consequent BCVA deterioration. Although a specific comparison is not appropriate, it is still worth noting that fewer injections were required to arrest the activity than those recorded for subfoveal CNV in the CATT study (5 ± 2 vs. 6.9 ± 3.0), which had a similar study design.14 It is likely that just as with extrafoveal CNV related to pathologic myopia,15 extrafoveal CNV might be less aggressive than subfoveal CNV secondary to AMD and require fewer retreatments. We acknowledge that this study has several limitations, especially regarding the absence of a control group and the limited number of patients. Nevertheless, bearing in mind that the natural history of AMD-related CNV is poor, and that the previously proposed treatments for extrafoveal CNV associated with AMD are unable to guarantee significant improvement in visual acuity, we do not believe it is ethically correct to eschew the treatment that has been proven to be effective for AMD-related CNV with subfoveal location. Moreover, because extrafoveal CNV associated with AMD is quite infrequent, it may be very difficult to plan a randomized clinical trial comparing different treatment options. But bearing in mind that our study is indisputably underpowered, we cannot directly compare its results with those achievable with conventional laser photocoagulation and claim that the anti-VEGF approach is better. In conclusion, even taking into account the abovementioned shortcomings, the present pilot study provides a contribution to the management of AMDrelated CNV with extrafoveal location, showing that an improvement in visual acuity of at least three EDTRS lines can be achieved in about one third of patients. Further studies are warranted to confirm these preliminary results in a longer-term follow-up. Key words: ranibizumab, age-related macular degeneration, extrafoveal choroidal neovascularization.
2014 VOLUME 34 NUMBER 11
References 1. Bressler NM, Bressler SB, Congdon NG, et al. Age-Related Eye Disease Study (AREDS) Research Group. Potential public health impact of Age-Related Eye Disease Study Results: AREDS report no. 11. Arch Ophthalmol 2003;121:1621–1624. 2. Lim LS, Mitchell P, Seddon JM, et al. Age-related macular degeneration. Lancet 2012;379:1728–1738. 3. Beaumont PE, Kang HK. Lesion morphology in age-related macular degeneration and its therapeutic significance. Arch Ophthalmol 2006;124:807–812. 4. Olsen TW, Feng X, Kasper TJ, et al. Fluorescein angiographic lesion type frequency in neovascular age-related macular degeneration. Ophthalmology 2004;111:250–255. 5. Chakravarthy U, Soubrane G, Bandello F, et al. Evolving European guidance on the medical management of neovascular age-related macular degeneration. Br J Ophthalmol 2006;90: 1188–1196. 6. Tranos P, Peter NM, Nath R, et al. Visual function following transpupillary thermotherapy with adjusted laser parameters for the treatment of exudative age-related macular degeneration: a pilot study. Clin Experiment Ophthalmol 2006;34:226–232. 7. Voelker M, Gelisken F, Ziemssen F, et al. Verteporfin photodynamic therapy for extrafoveal choroidal neovascularization secondary to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2005;243:1241–1246. 8. Etter J, Fekrat S. Photodynamic therapy and intravitreal triamcinolone for extrafoveal choroidal neovascularization in neovascular age-related macular degeneration. Ann Ophthalmol (Skokie) 2006;38:239–241. 9. Spaide RF, Sorenson J, Maranan L. Combined photodynamic therapy and intravitreal triamcinolone for nonsubfoveal choroidal neovascularization. Retina 2005;25:685–690. 10. Mikuni E, Shimada H, Mori R, et al. Surgical removal of juxtafoveal and extrafoveal choroidal neovascularization in age-related macular degeneration [in Japanese]. Nihon Ganka Gakkai Zasshi 2003;107:695–701. 11. Mones JM, Lopez MA, Prieto JA, Rodriguez JP. Extrafoveal choroidal neovascularization secondary to wet age-related macular degeneration treated with intravitreal bevacizumab. Ophthalmic Surg Lasers Imaging 2007;38:226–228. 12. Arias L, Ruiz-Moreno JM, Gomez-Ulla F, et al. A 1-year retrospective review of ranibizumab for naive nonsubfoveal choroidal neovascularization secondary to age-related macular degeneration. Retina 2009;29:1444–1449. 13. Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy. Three-year results from randomized clinical trials. Arch Ophthalmol 1986;104: 694–701. 14. CATT Research Group, Martin DF, Maguire MG, et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 2011;364:1897–1908. 15. Parodi MB, Iacono P, Papayannis A, et al. Intravitreal bevacizumab for extrafoveal choroidal neovascularization secondary to pathologic myopia. Retina 2013;33:593–597.
