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Intravitreal bevacizumab and triamcinolone treatment for choroidal neovascularization in Best disease
Intravitreal bevacizumab and triamcinolone treatment for choroidal neovascularization in Best disease Mehmet Çakır, MD, Osman Çekiç, MD, PhD, and Ö. Faruk Yılmaz, MD
An 11-year-old girl with active subfoveal choroidal neovascularization associated with Best disease responded well to a single intravitreal injection of combined bevacizumab and triamcinolone acetonide. Choroidal neovascularization regressed, subretinal serous fluid resorbed, and visual acuity improved from 20/400 to 20/100. The patient remained stable for 6 months after injection.
B
est disease is an autosomal-dominant macular dystrophy representing itself with a range of fundus manifestations. The classic ophthalmoscopic appearance of Best disease is symmetrical, bilateral, yellow– orange macular vitelliform lesions.1 The fovea can progress from normal fovea to previtelliform stage, vitelliform stage, scrambled-egg stage, cyst stage, pseudohypopyon stage, and round chorioretinal atrophy stage.2 Even in the presence of a large vitelliform lesion, patients typically maintain relatively good visual acuity. However, visual acuity may diminish considerably in many cases, notably in the presence of choroidal neovascularization (CNV).1,2 To date, no available proven treatment modality exists for CNV in eyes with Best disease. We report a case of CNV complicating Best disease in a child treated by an intravitreal injection of combined bevacizumab and triamcinolone.
Case Reports An 11-year-old girl referred to our clinic for recently reduced visual acuity in her left eye. Best-corrected visual acuity was 20/50 in the right eye and 20/400 in the left eye. Past medical history was remarkable for meningitis at 2 years of age. Intraocular pressures were 15 mm Hg bilaterally. Dilated funduscopic examination revealed a bilateral macular vitelliform lesion, minimally active CNV with a small amount of old retinal blood adjacent to it, and chorioretinal atrophy in the right eye, and scrambled-egg-stage vitelliform macular
Author affiliations: Beyog˘lu Eye Training and Research Hospital, Istanbul, Turkey Submitted February 10, 2008. Revision accepted June 25, 2008. Published online December 22, 2008. Reprint requests: Mehmet Çakır, MD, Beyog˘lu Eye Training and Research Hospital, I˙stanbul, Turkey (email: [email protected]). J AAPOS 2009;13:94-96. Copyright © 2009 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2009/$36.00 ⫹ 0 doi:10.1016/j.jaapos.2008.06.014
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dystrophy as well as subfoveal CNV and surrounding subretinal hemorrhage in the left eye (Figure 1A and 1D). Fluorescein angiography showed dye leakage consistent with an active subfoveal CNV and a localized hypofluorescence caused by subretinal hemorrhage inferior to the hyperfluorescent area in the left eye (Figure 1E). The right eye showed hyperfluorescence from a window defect at the retinal pigment epithelial level and mild leakage from a minimally active CNV scar in the macular region (Figure 1B). Optical coherence tomography (OCT) revealed subretinal reflection of classic subfoveal CNV, surrounding subretinal and intraretinal serous fluid, and cystoid macular edema above the lesion in the left eye (Figure 1F). CNV as well as minimal subretinal fluid also was demonstrated by OCT in the right eye (Figure 1C). With parental consent, 1.25 mg of bevacizumab and 2 mg of triamcinolone acetonide combination was uneventfully injected into the left eye under general anesthesia. A topical antibiotic drop was prescribed for 5 days after injection. One month after injection, visual acuity had improved to 20/100. Visual acuity in the right eye was 20/40. Intraocular pressure was 15 mm Hg in the right and 16 mm Hg in the left eye. Shrinkage and fibrosis of CNV as well as resorption of subretinal hemorrhage were detected by fluorescein angiography in the left eye (Figure 2A and B). OCT revealed decreased subretinal and intraretinal fluid in the left eye. An intraretinal macrocyst also appeared (Figure 2C). CNV in the right eye was completely inactive. Two months after injection, visual acuity was 20/100, and intraocular pressure was 17 mm Hg in the left eye. Decreased leakage from the CNV was detected by fluorescein angiography. OCT showed no more subretinal fluid but did show an intraretinal cyst in the left eye. The electrooculogram showed a light peak to dark ratio of 1.9 in the right eye and 2.1 in the left eye. Six months after injection, visual acuity had stabilized at 20/100 in the left eye. The macular appearance was stable without recurrence of the subretinal fluid (Figure 2D, 2E and 2F). Bilateral intraocular pressures were 15 mm Hg.
Discussion Best disease may sometimes associate with subretinal CNV, after the development of which visual acuity
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Volume 13 Number 1 / February 2009
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FIG 1. Color fundus pictures of the patient at presentation (A and D). Minimal dye leakage in the right eye caused by mostly fibrotic choroidal neovascularization (CNV ) (B), and hyperfluorescence and dye leakage from an active CNV as well as blocked fluorescence caused by subretinal hemorrhage inferior to CNV lesion (E). Optical coherence tomography demonstrates minimal subretinal fluid around CNV lesion in the right eye (C) and fusiform retinal elevation with large amount of sub- and intraretinal fluid accumulation consistent with an active CNV in the left eye (F).
rapidly deteriorates.2 Selected eyes of children with a definite subfoveal CNV complex and no membrane regression may benefit from submacular surgery.3 Photodynamic therapy with verteporfin alone4 or combined with intravitreal triamcinolone injection5 for subfoveal or juxtafoveal CNV in Best disease have also been successfully tried. Leu et al6 demonstrated that a single intravitreal injection of bevacizumab effectively induced morphologic and functional improvement in a juvenile suffering from subfoveal CNV secondary to Best disease. Bevacizumab is an antiangiogenic antibody that blocks the vascular endothelial growth factor to induce regression of CNV and resolution of macular edema.6 Its use in children is experimental; it has not been established as systemically safe for children even when injected intravitreally. Nor has the safety and efficacy of
Journal of AAPOS
triamcinolone and bevacizumab in the pediatric population been established. Because we think the addition of triamcinolone potentiates the antiangiogenic effect of bevacizumab and decreases the need for repeat injections in our clinical experience, we prefer to combine them.7 Triamcinolone also decreases vascular permeability and diminishes inflammatory process. We did not consider multiple antivascular endothelial growth factor injections for our case as suggested in the treatment of CNV associated with age-related macular degeneration in the elderly.8,9 Our patient responded well to a single intravitreal injection of bevacizumab and triamcinolone and developed significant subfoveal scar tissue as desired. No adverse effects attributable to these agents or procedure, such as significant elevation of intraocular pressure, were encountered in our case.
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FIG 2. One month after injection, contracture and fibrotic scar of the lesion with minimal subretinal hemorrhage located inferiorly (A). Fluorescein angiography revealed hyperfluorescence with regressed and demarcated borders of CNV (B). Optical coherence tomography showed decreased subretinal fluid and the presence of an intraretinal macrocyst (C). At 6 months, the lesion is stabilized without any activation (D). An inactive CNV is confirmed by fluorescein angiography (E). Optical coherence tomography shows further contracted CNV without any subretinal fluid. Intraretinal macrocyst persisted (F).
CNV regressed, subretinal fluid resolved, and visual acuity improved beginning one month after injection. References 1. Hartnett ME, Trese M, Capone A Jr., Keats BJB, Steidl SM. Pediatric retina. Philadelphia (PA): Lippincott Williams & Wilkins; 2005. p. 102-3. 2. Deutman AF, Hoyng CB, van Lith-Verhoeven JJC. Macular dystrophies/vitelliform dystrophy. In: Ryan SJ, Schachat AP, editors. Retina: Volume II–Medical Retina. St. Louis (MO): Elsevier Mosby; 2006. p. 1177-81. 3. Sears J, Capone A Jr., Aaberg T Sr., Lewis H, Grossniklaus H, Sternberg P Jr., De Juan E. Surgical management of subfoveal neovascularization in children. Ophthalmology 1999;106:920-24. 4. Andrade RE, Farah ME, Costa RA. Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in Best disease. Am J Ophthalmol 2003;136:1179-81.
5. Nobrega M, Bortolotto C, Farah M. Combined photodynamic therapy and intravitreal triamcinolone injection for choroidal neovascularization in Best disease. Can J Ophthalmol 2007;42:761-2. 6. Leu J, Schrage NF, Degenring RF. Choroidal neovascularization secondary to Best’s disease in a 13-year-old boy treated by intravitreal bevacizumab. Graefe’s Arch Clin Exp Ophthalmol 2007; 245:1723-5. 7. Çakır M, Çekiç O, Yılmaz ÖF. Combined intravitreal bevacizumab and triamcinolone injection in a child with Coats disease. J AAPOS 2008;12:309-11. 8. Kaiser PK, Blodi BA, Shapiro H, Acharya NR, MARINA Study Group. Angiographic and optical coherence tomographic results of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology 2007;114:1868-75. 9. Kaiser PK, Brown DM, Zhang K, Hudson HL, Holz FG, Shapiro H, Schneider S, Acharya NR. Ranibizumab for predominantly classic neovascular age-related macular degeneration subgroup analysis of first-year ANCHOR results. Am J Ophthalmol 2007;144:850-57.
Journal of AAPOS
An 11-year-old girl with active subfoveal choroidal neovascularization associated with Best disease responded well to a single intravitreal injection of combined bevacizumab and triamcinolone acetonide. Choroidal neovascularization regressed, subretinal serous fluid resorbed, and visual acuity improved from 20/400 to 20/100. The patient remained stable for 6 months after injection.
B
est disease is an autosomal-dominant macular dystrophy representing itself with a range of fundus manifestations. The classic ophthalmoscopic appearance of Best disease is symmetrical, bilateral, yellow– orange macular vitelliform lesions.1 The fovea can progress from normal fovea to previtelliform stage, vitelliform stage, scrambled-egg stage, cyst stage, pseudohypopyon stage, and round chorioretinal atrophy stage.2 Even in the presence of a large vitelliform lesion, patients typically maintain relatively good visual acuity. However, visual acuity may diminish considerably in many cases, notably in the presence of choroidal neovascularization (CNV).1,2 To date, no available proven treatment modality exists for CNV in eyes with Best disease. We report a case of CNV complicating Best disease in a child treated by an intravitreal injection of combined bevacizumab and triamcinolone.
Case Reports An 11-year-old girl referred to our clinic for recently reduced visual acuity in her left eye. Best-corrected visual acuity was 20/50 in the right eye and 20/400 in the left eye. Past medical history was remarkable for meningitis at 2 years of age. Intraocular pressures were 15 mm Hg bilaterally. Dilated funduscopic examination revealed a bilateral macular vitelliform lesion, minimally active CNV with a small amount of old retinal blood adjacent to it, and chorioretinal atrophy in the right eye, and scrambled-egg-stage vitelliform macular
Author affiliations: Beyog˘lu Eye Training and Research Hospital, Istanbul, Turkey Submitted February 10, 2008. Revision accepted June 25, 2008. Published online December 22, 2008. Reprint requests: Mehmet Çakır, MD, Beyog˘lu Eye Training and Research Hospital, I˙stanbul, Turkey (email: [email protected]). J AAPOS 2009;13:94-96. Copyright © 2009 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/2009/$36.00 ⫹ 0 doi:10.1016/j.jaapos.2008.06.014
94
dystrophy as well as subfoveal CNV and surrounding subretinal hemorrhage in the left eye (Figure 1A and 1D). Fluorescein angiography showed dye leakage consistent with an active subfoveal CNV and a localized hypofluorescence caused by subretinal hemorrhage inferior to the hyperfluorescent area in the left eye (Figure 1E). The right eye showed hyperfluorescence from a window defect at the retinal pigment epithelial level and mild leakage from a minimally active CNV scar in the macular region (Figure 1B). Optical coherence tomography (OCT) revealed subretinal reflection of classic subfoveal CNV, surrounding subretinal and intraretinal serous fluid, and cystoid macular edema above the lesion in the left eye (Figure 1F). CNV as well as minimal subretinal fluid also was demonstrated by OCT in the right eye (Figure 1C). With parental consent, 1.25 mg of bevacizumab and 2 mg of triamcinolone acetonide combination was uneventfully injected into the left eye under general anesthesia. A topical antibiotic drop was prescribed for 5 days after injection. One month after injection, visual acuity had improved to 20/100. Visual acuity in the right eye was 20/40. Intraocular pressure was 15 mm Hg in the right and 16 mm Hg in the left eye. Shrinkage and fibrosis of CNV as well as resorption of subretinal hemorrhage were detected by fluorescein angiography in the left eye (Figure 2A and B). OCT revealed decreased subretinal and intraretinal fluid in the left eye. An intraretinal macrocyst also appeared (Figure 2C). CNV in the right eye was completely inactive. Two months after injection, visual acuity was 20/100, and intraocular pressure was 17 mm Hg in the left eye. Decreased leakage from the CNV was detected by fluorescein angiography. OCT showed no more subretinal fluid but did show an intraretinal cyst in the left eye. The electrooculogram showed a light peak to dark ratio of 1.9 in the right eye and 2.1 in the left eye. Six months after injection, visual acuity had stabilized at 20/100 in the left eye. The macular appearance was stable without recurrence of the subretinal fluid (Figure 2D, 2E and 2F). Bilateral intraocular pressures were 15 mm Hg.
Discussion Best disease may sometimes associate with subretinal CNV, after the development of which visual acuity
Journal of AAPOS
Volume 13 Number 1 / February 2009
Çakır, Çekiç, and Yılmaz
95
FIG 1. Color fundus pictures of the patient at presentation (A and D). Minimal dye leakage in the right eye caused by mostly fibrotic choroidal neovascularization (CNV ) (B), and hyperfluorescence and dye leakage from an active CNV as well as blocked fluorescence caused by subretinal hemorrhage inferior to CNV lesion (E). Optical coherence tomography demonstrates minimal subretinal fluid around CNV lesion in the right eye (C) and fusiform retinal elevation with large amount of sub- and intraretinal fluid accumulation consistent with an active CNV in the left eye (F).
rapidly deteriorates.2 Selected eyes of children with a definite subfoveal CNV complex and no membrane regression may benefit from submacular surgery.3 Photodynamic therapy with verteporfin alone4 or combined with intravitreal triamcinolone injection5 for subfoveal or juxtafoveal CNV in Best disease have also been successfully tried. Leu et al6 demonstrated that a single intravitreal injection of bevacizumab effectively induced morphologic and functional improvement in a juvenile suffering from subfoveal CNV secondary to Best disease. Bevacizumab is an antiangiogenic antibody that blocks the vascular endothelial growth factor to induce regression of CNV and resolution of macular edema.6 Its use in children is experimental; it has not been established as systemically safe for children even when injected intravitreally. Nor has the safety and efficacy of
Journal of AAPOS
triamcinolone and bevacizumab in the pediatric population been established. Because we think the addition of triamcinolone potentiates the antiangiogenic effect of bevacizumab and decreases the need for repeat injections in our clinical experience, we prefer to combine them.7 Triamcinolone also decreases vascular permeability and diminishes inflammatory process. We did not consider multiple antivascular endothelial growth factor injections for our case as suggested in the treatment of CNV associated with age-related macular degeneration in the elderly.8,9 Our patient responded well to a single intravitreal injection of bevacizumab and triamcinolone and developed significant subfoveal scar tissue as desired. No adverse effects attributable to these agents or procedure, such as significant elevation of intraocular pressure, were encountered in our case.
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Volume 13 Number 1 / February 2009
FIG 2. One month after injection, contracture and fibrotic scar of the lesion with minimal subretinal hemorrhage located inferiorly (A). Fluorescein angiography revealed hyperfluorescence with regressed and demarcated borders of CNV (B). Optical coherence tomography showed decreased subretinal fluid and the presence of an intraretinal macrocyst (C). At 6 months, the lesion is stabilized without any activation (D). An inactive CNV is confirmed by fluorescein angiography (E). Optical coherence tomography shows further contracted CNV without any subretinal fluid. Intraretinal macrocyst persisted (F).
CNV regressed, subretinal fluid resolved, and visual acuity improved beginning one month after injection. References 1. Hartnett ME, Trese M, Capone A Jr., Keats BJB, Steidl SM. Pediatric retina. Philadelphia (PA): Lippincott Williams & Wilkins; 2005. p. 102-3. 2. Deutman AF, Hoyng CB, van Lith-Verhoeven JJC. Macular dystrophies/vitelliform dystrophy. In: Ryan SJ, Schachat AP, editors. Retina: Volume II–Medical Retina. St. Louis (MO): Elsevier Mosby; 2006. p. 1177-81. 3. Sears J, Capone A Jr., Aaberg T Sr., Lewis H, Grossniklaus H, Sternberg P Jr., De Juan E. Surgical management of subfoveal neovascularization in children. Ophthalmology 1999;106:920-24. 4. Andrade RE, Farah ME, Costa RA. Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in Best disease. Am J Ophthalmol 2003;136:1179-81.
5. Nobrega M, Bortolotto C, Farah M. Combined photodynamic therapy and intravitreal triamcinolone injection for choroidal neovascularization in Best disease. Can J Ophthalmol 2007;42:761-2. 6. Leu J, Schrage NF, Degenring RF. Choroidal neovascularization secondary to Best’s disease in a 13-year-old boy treated by intravitreal bevacizumab. Graefe’s Arch Clin Exp Ophthalmol 2007; 245:1723-5. 7. Çakır M, Çekiç O, Yılmaz ÖF. Combined intravitreal bevacizumab and triamcinolone injection in a child with Coats disease. J AAPOS 2008;12:309-11. 8. Kaiser PK, Blodi BA, Shapiro H, Acharya NR, MARINA Study Group. Angiographic and optical coherence tomographic results of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology 2007;114:1868-75. 9. Kaiser PK, Brown DM, Zhang K, Hudson HL, Holz FG, Shapiro H, Schneider S, Acharya NR. Ranibizumab for predominantly classic neovascular age-related macular degeneration subgroup analysis of first-year ANCHOR results. Am J Ophthalmol 2007;144:850-57.
Journal of AAPOS