RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN FUNDUS FLAVIMACULATUS Amparo Navea Tejerina, MD, PHD, Maria Garcı´a-Pous, MD, Elena Palacios Pozos, MD, M. Carmen Desco Esteban, MD, PHD, Jorge Mataix Boronat, MD, PHD
Purpose: To report the features of a case with late-onset fundus flavimaculatus (FFM) complicated by choroidal neovascularization (CNV) and treated with ranibizumab. Methods: Retrospective interventional case report. Patient: A 51-year-old woman presented with right eye decreased vision. Fundus flavimaculatus with CNV was diagnosed by electroretinography and fluorescein angiography. Results: Two intravitreal injections of ranibizumab were needed for the treatment. At the end of follow-up (9 months) no leakage was observed and visual acuity improved. Conclusion: Choroidal neovascularization is a rare complication of FFM. Ranibizumab, an anti-VEFG drug, stopped neovascularization and improved final visual acuity in this case, so it must be considered in the treatment of CNV in late onset FFM. RETINAL CASES & BRIEF REPORTS 2:250 –252, 2008
From Fundacio´n Oftalmolo´gica del Mediterra´eno, Valencia, Spain.
tifocal electroretinography (mfERG), with good response to ranibizumab treatment.
F
undus flavimaculatus (FFM) is a hereditary retinal dystrophy characterized by the presence of yellowish flecks with onset between the third or fourth decade of life and a slow course.1 Pathologic studies show an accumulation of lipofuscin-like pigment throughout the retinal pigment epithelium (RPE). Macular atrophy is a common finding in FFM, leading to a progressive loss of vision. However, choroidal neovascularization (CNV) is a rare complication of FFM and it is associated with a rapid progression and poor prognosis.2 Ranibizumab, a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A, has been effective in the treatment of CNV in agerelated macular degeneration (AMD).3,4 We report a case of FFM associated with juxtafoveolar CNV, which is well documented by fluorescein angiography (FA), optical coherence tomography (OCT), and mul-
Case Report A 51-year-old woman had a 4-week history of decrease in visual acuity (VA) and metamorphopsia in her right eye. Her personal and family history was unremarkable. Her best-corrected VA (BCVA) in the right eye was 20/60 with great metamorphopsia and 20/20 in the left eye with Early Treatment Diabetic Retinopathy Study charts. The fundus examination showed yellowish spots in both eyes all through the macula and extending out to the midperiphery. In the right eye a yellowish juxtafoveal lesion with edema and hemorrhage was observed. FFM with CNV associated was suspected. FA showed the typical phenomenon known as the dark or silent choroid with hyperfluorescence of the flecks in late phase of the FA in both eyes, and in the right eye a predominantly classic juxtafoveal CNV with late leakage of the dye. Optical coherence tomography was performed and a reflective yellow-red band just anterior to the RPE/choriocapillaris layer with cystoid spaces within the retina confirmed the CNV presence (Figure 1). Electroretinography showed scotopic and photopic responses below normal, compatible with the diagnosis of FFM. mfERG demonstrated severe reduction in amplitudes, responses and delays in implicit times in central retina from the right eye, and in the left eye a reduction in mfERG response amplitudes in the pericentral retina but not in the fovea. Hitherto, photodynamic therapy and sodium pegaptanib were the only treatments approved for CNV, but nowadays, ranibizumab has been approved for this condition and its
The authors report no conflicts of interest. Reprint requests: Dr. Maria Garcı´a-Pous, C/Purı´ssima 32, 46780 Oliva, Valencia, Spain; e-mail: [email protected]
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RANIBIZUMAB FOR CNV IN FF
Fig. 1. A, Classic choroidal neovascularization with hemorrhage and fundus flavimaculatus image. B, Fluorescein angiography at presentation with leakage of the dye in the late phase and multiple hyperfluorescent dots in posterior pole and middle periphery. C, Optical coherence tomography at presentation with neovascular degeneration and intraretinal cysts.
Fig. 2. A, Nine months after ranibizumab intraocular injection, a scar with no hemorrhage is present. B, Fluorescein angiography in late phase shows hyperfluorescence with no more leakage. C, The intraretinal cysts have disappeared in the optical coherence tomography and a scar is present.
251
RETINAL CASES & BRIEF REPORTSℜ
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effectiveness for CNV in AMD is proved.3,4 Ranibizumab 0.5 mg was administered by intravitreal injection through an area 3.5 to 4.0 mm posterior to the limbus in an operating room in sterile conditions. Topical antibiotics before and after the injection were administered. Four weeks after the treatment, BCVA in the right eye improved to 20/31 without metamorphopsia, FA showed no leakage, and in the OCT there were no cystoid spaces in the lesion. At a 3-month follow-up, visual acuity decreased to 20/40 in the right eye and a recurrence was diagnosed by fundus examination and OCT. Another injection of ranibizumab was performed. At a 9-month follow-up, BCVA was 20/25 and ophthalmologic findings remained stable and showed no evidence of CNV recurrence (Figure 2).
2008
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sults (stopping the progression and improving VA) than photodynamic therapy in the treatment of CNV in AMD.3,4 This is the first case report about ranibizumab and CNV in late onset FFM and it demonstrates that ranibizumab may be used successfully for CNV in conditions other than CNV in AMD. References 1.
2.
Discussion In this case, ranibizumab has stopped the leakage and the progression of the CNV, and BCVA has improved during the follow-up. Previous reports about CNV in FFM were treated with photodynamic therapy with stabilization of the CNV and improvement of VA.1,2 Nowadays, ranibizumab has shown better re-
●
3.
4.
Souied EH, Pawlak D, Algan M, Sayag D, Coscas G, Soubrane G. Photodynamic therapy for choroidal neovascularization on late-onset fundus flavimaculatus. Am J Ophthalmol 2005;140: 312–314. Valmaggia C, Niederberger H, Helbig H. Photodynamic therapy for choroidal neovascularization in fundus flavimaculatus. Retina 2002;22:111–113. Ferrara N, Damico L, Shams N, Lowman H, Kim R. Development of ranibizumab, an anti–vascular endothelial growth factor antigen binding fragment, as therapy for Neovascular age-related macular degeneration. Retina 2006;26:859–870. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355:1419–1431.
Purpose: To report the features of a case with late-onset fundus flavimaculatus (FFM) complicated by choroidal neovascularization (CNV) and treated with ranibizumab. Methods: Retrospective interventional case report. Patient: A 51-year-old woman presented with right eye decreased vision. Fundus flavimaculatus with CNV was diagnosed by electroretinography and fluorescein angiography. Results: Two intravitreal injections of ranibizumab were needed for the treatment. At the end of follow-up (9 months) no leakage was observed and visual acuity improved. Conclusion: Choroidal neovascularization is a rare complication of FFM. Ranibizumab, an anti-VEFG drug, stopped neovascularization and improved final visual acuity in this case, so it must be considered in the treatment of CNV in late onset FFM. RETINAL CASES & BRIEF REPORTS 2:250 –252, 2008
From Fundacio´n Oftalmolo´gica del Mediterra´eno, Valencia, Spain.
tifocal electroretinography (mfERG), with good response to ranibizumab treatment.
F
undus flavimaculatus (FFM) is a hereditary retinal dystrophy characterized by the presence of yellowish flecks with onset between the third or fourth decade of life and a slow course.1 Pathologic studies show an accumulation of lipofuscin-like pigment throughout the retinal pigment epithelium (RPE). Macular atrophy is a common finding in FFM, leading to a progressive loss of vision. However, choroidal neovascularization (CNV) is a rare complication of FFM and it is associated with a rapid progression and poor prognosis.2 Ranibizumab, a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A, has been effective in the treatment of CNV in agerelated macular degeneration (AMD).3,4 We report a case of FFM associated with juxtafoveolar CNV, which is well documented by fluorescein angiography (FA), optical coherence tomography (OCT), and mul-
Case Report A 51-year-old woman had a 4-week history of decrease in visual acuity (VA) and metamorphopsia in her right eye. Her personal and family history was unremarkable. Her best-corrected VA (BCVA) in the right eye was 20/60 with great metamorphopsia and 20/20 in the left eye with Early Treatment Diabetic Retinopathy Study charts. The fundus examination showed yellowish spots in both eyes all through the macula and extending out to the midperiphery. In the right eye a yellowish juxtafoveal lesion with edema and hemorrhage was observed. FFM with CNV associated was suspected. FA showed the typical phenomenon known as the dark or silent choroid with hyperfluorescence of the flecks in late phase of the FA in both eyes, and in the right eye a predominantly classic juxtafoveal CNV with late leakage of the dye. Optical coherence tomography was performed and a reflective yellow-red band just anterior to the RPE/choriocapillaris layer with cystoid spaces within the retina confirmed the CNV presence (Figure 1). Electroretinography showed scotopic and photopic responses below normal, compatible with the diagnosis of FFM. mfERG demonstrated severe reduction in amplitudes, responses and delays in implicit times in central retina from the right eye, and in the left eye a reduction in mfERG response amplitudes in the pericentral retina but not in the fovea. Hitherto, photodynamic therapy and sodium pegaptanib were the only treatments approved for CNV, but nowadays, ranibizumab has been approved for this condition and its
The authors report no conflicts of interest. Reprint requests: Dr. Maria Garcı´a-Pous, C/Purı´ssima 32, 46780 Oliva, Valencia, Spain; e-mail: [email protected]
250
RANIBIZUMAB FOR CNV IN FF
Fig. 1. A, Classic choroidal neovascularization with hemorrhage and fundus flavimaculatus image. B, Fluorescein angiography at presentation with leakage of the dye in the late phase and multiple hyperfluorescent dots in posterior pole and middle periphery. C, Optical coherence tomography at presentation with neovascular degeneration and intraretinal cysts.
Fig. 2. A, Nine months after ranibizumab intraocular injection, a scar with no hemorrhage is present. B, Fluorescein angiography in late phase shows hyperfluorescence with no more leakage. C, The intraretinal cysts have disappeared in the optical coherence tomography and a scar is present.
251
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252
effectiveness for CNV in AMD is proved.3,4 Ranibizumab 0.5 mg was administered by intravitreal injection through an area 3.5 to 4.0 mm posterior to the limbus in an operating room in sterile conditions. Topical antibiotics before and after the injection were administered. Four weeks after the treatment, BCVA in the right eye improved to 20/31 without metamorphopsia, FA showed no leakage, and in the OCT there were no cystoid spaces in the lesion. At a 3-month follow-up, visual acuity decreased to 20/40 in the right eye and a recurrence was diagnosed by fundus examination and OCT. Another injection of ranibizumab was performed. At a 9-month follow-up, BCVA was 20/25 and ophthalmologic findings remained stable and showed no evidence of CNV recurrence (Figure 2).
2008
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VOLUME 2
●
NUMBER 3
sults (stopping the progression and improving VA) than photodynamic therapy in the treatment of CNV in AMD.3,4 This is the first case report about ranibizumab and CNV in late onset FFM and it demonstrates that ranibizumab may be used successfully for CNV in conditions other than CNV in AMD. References 1.
2.
Discussion In this case, ranibizumab has stopped the leakage and the progression of the CNV, and BCVA has improved during the follow-up. Previous reports about CNV in FFM were treated with photodynamic therapy with stabilization of the CNV and improvement of VA.1,2 Nowadays, ranibizumab has shown better re-
●
3.
4.
Souied EH, Pawlak D, Algan M, Sayag D, Coscas G, Soubrane G. Photodynamic therapy for choroidal neovascularization on late-onset fundus flavimaculatus. Am J Ophthalmol 2005;140: 312–314. Valmaggia C, Niederberger H, Helbig H. Photodynamic therapy for choroidal neovascularization in fundus flavimaculatus. Retina 2002;22:111–113. Ferrara N, Damico L, Shams N, Lowman H, Kim R. Development of ranibizumab, an anti–vascular endothelial growth factor antigen binding fragment, as therapy for Neovascular age-related macular degeneration. Retina 2006;26:859–870. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355:1419–1431.
