INTRAVITREAL BEVACIZUMAB (AVASTIN) AND RANIBIZUMAB (LUCENTIS) FOR CHOROIDAL NEOVASCULARIZATION OVERLYING CHOROIDAL OSTEOMA Carol L. Shields, MD,* Pedro F. Salazar, MD,* Hakan Demirci, MD,* William E. Benson, MD,† Jerry A. Shields, MD*
Purpose: To report the effect of anti-vascular endothelial growth factor (VEGF) therapy for choroidal neovascularization overlying choroidal osteoma. Method: In an interventional case report, intravitreal anti-VEGF therapy was used for tumor-related choroidal neovascularization. Results: A 34-year-old woman with bilateral choroidal osteoma had a decrease in visual acuity in the right eye from 20/30 to 20/100. Ophthalmoscopy revealed partially decalcified circumpapillary, macular choroidal osteoma with overlying subretinal hemorrhage and choroidal neovascular membrane. Intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) resulted in membrane regression and visual acuity improvement to 20/50 at 6 weeks. Further therapy with intravitreal ranibizumab (Lucentis; Genentech, Inc.) resolved persistent subretinal fluid, and visual acuity improved to 20/30 at the 6-month follow-up. Conclusions: Therapy with intravitreal anti-VEGF medications might be an alternative for patients with choroidal neovascularization overlying choroidal osteoma. RETINAL CASES & BRIEF REPORTS 2:18 –20, 2008
31%, and poor vision of 20/200 or worse in 56%.2 Several therapies for CNVM have been attempted, including laser photocoagulation, photodynamic therapy, and subretinal surgery with membrane extraction. For subfoveal CNVM, each of these therapies can pose a risk for retinal damage and reduced vision. We describe our experience with intravitreal anti–vascular endothelial growth factor (VEGF) therapy for CNVM overlying choroidal osteoma. Approval was obtained from the Institutional Review Board at Wills Eye Institute (Thomas Jefferson University, Philadelphia, PA) for the publication of this report.
From the *Ocular Oncology Service and the †Retina Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania.
C
horoidal osteoma is a benign intraocular tumor, classically found in young women.1,2 Over the long term, choroidal osteoma can exhibit tumor growth in 51% of cases, tumor decalcification in 46%, development of choroidal neovascular membrane (CNVM) in Support provided by the Retina Research Foundation of the Retina Society, Cape Town, South Africa (C.L.S.); the Paul Kayser International Award of Merit in Retina Research, Houston, TX (J.A.S.); a donation from Michael, Bruce, and Ellen Ratner, New York, NY (J.A.S., C.L.S.); the LuEsther Mertz Retina Research Foundation, New York, NY (C.L.S.); the Fundacion Oftalmologica Nacional, Bogota´, Colombia (P.F.S.); and the Eye Tumor Research Foundation, Philadelphia, PA (C.L.S., J.A.S.). Reprint requests: Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107; e-mail: [email protected]
Case Report A 33-year-old woman was found at routine examination to have choroidal osteoma in each eye. Visual acuity was 20/30 in both eyes. Choroidal osteoma in the right eye measured 13 mm in
18
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ANTI-VEGF THERAPY FOR CNVM OVERLYING CHOROIDAL OSTEOMA
Fig. 2. After treatment with bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) and ranibizumab (Lucentis; Genentech, Inc.), choroidal neovascular membrane (CNVM) resolved, and visual acuity returned to 20/30 by 4 months. Choroidal osteoma remains stable, and the overlying CNVM appears fibrotic without overlying subretinal fluid or hemorrhage (top). Optical coherence tomography shows the flat retina overlying the regressed, flattened CNVM (bottom).
tumor was 70% decalcified, particularly in the submacular region. The left eye remained stable. Intravitreal bevacizumab ([1.25 mg] Avastin; Genentech, Inc., South San Francisco, CA) was injected, and CNVM and hemorrhage resolved in 6 weeks; visual acuity improved to 20/50 in the right eye with shallow persistent subretinal fluid. Subsequently, intravitreal ranibizumab ([0.5 mg] Lucentis; Genentech, Inc.) injection was administered monthly for three sessions, and the subretinal fluid resolved, with a final visual acuity of 20/30 in the right eye at the 6-month follow-up (Fig. 2).
Fig. 1. Choroidal osteoma in a 34-year-old woman with visual acuity loss from 20/30 to 20/100 due to choroidal neovascular membrane (CNVM). A, The partially decalcified choroidal osteoma shows overlying macular hemorrhage and gray subfoveal CNVM (top). Optical coherence tomography depicts the retina elevated over an ill defined subretinal optically dense plaque in the fovea (bottom). B, Fluorescein angiography displays hyperfluorescence of the osteoma with overlying hyperfluorescence of the CNVM.
diameter and 1.2 mm in thickness with 10% decalcification. Choroidal osteoma in the left eye measured 16 mm in diameter and 1.2 mm in thickness with 20% decalcification. Thirteen months later, visual acuity in the right eye had deteriorated to 20/100 from subfoveal CNVM producing subretinal fluid and hemorrhage (Fig. 1). The
Discussion VEGF plays an important role in neovascular agerelated macular degeneration. Inhibition of VEGF with intravitreal ranibizumab and bevacizumab has shown promising results. In an analysis of 716 patients in the MARINA study at the 24-month followup, the ranibizumab-treated patients did better on average than the sham-treated patients.3 In a study of 53 eyes with neovascular age-related macular degeneration treated with bevacizumab, mean visual acuity improved from 20/160 to 20/125.4 Anti-VEGF medications have also been used to treat diabetic macular
20
RETINAL CASES & BRIEF REPORTSℜ
edema, proliferative diabetic retinopathy, and consequences of retinal vascular obstruction. Anti-VEGF therapy also plays an important role in the management of some cancers. Cancer cells release proangiogenic factors that stimulate growth of capillaries for tumor nourishment. Systemic bevacizumab treatment has been used in the management of colorectal, renal, lung, breast, pancreatic, and ovarian cancers.5 Anti-VEGF therapy has not yet been investigated for the treatment of intraocular tumors, but its use for radiation retinopathy and papillopathy is being explored. In this case, the use of anti-VEGF therapy was not for tumor regression but for resolution of CNVM. In an analysis of 74 consecutive eyes with choroidal osteoma, CNVM developed in 46% by the 20-year follow-up.2 Given the median age of 25 years at presentation, nearly 50% of patients would be expected to manifest CNVM by 45 years old. The visual consequences of CNVM in this relatively young age group and the possibility of bilateral involvement could be devastating. The results of this case with
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resolution of CNVM and visual acuity recovery after anti-VEGF therapy are promising. Key words: eye, choroid, osteoma, choroidal neovascular membrane, bevacizumab (Avastin), ranibizumab (Lucentis). References 1. 2.
3.
4.
5.
Shields CL, Shields JA, Augsburger JJ. Review of choroidal osteomas. Surv Ophthalmol 1988;33:17–27. Shields CL, Sun H, Demirci H, Shields JA. Factors predictive of tumor growth, tumor decalcification, choroidal neovascularization and visual outcome in 74 eyes with choroidal osteoma. Arch Ophthalmol 2005;123:658–666. Boyer DS, Antoszyk AN, Awh CC, et al. MARINA Study Group. Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology 2007;114:246–252. Rich RM, Rosenfeld PJ, Puliafito CA, et al. Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Retina 2006;26:495– 511. Shih T, Lindley C. Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies. Clin Ther 2006;28:1779– 1802.
Purpose: To report the effect of anti-vascular endothelial growth factor (VEGF) therapy for choroidal neovascularization overlying choroidal osteoma. Method: In an interventional case report, intravitreal anti-VEGF therapy was used for tumor-related choroidal neovascularization. Results: A 34-year-old woman with bilateral choroidal osteoma had a decrease in visual acuity in the right eye from 20/30 to 20/100. Ophthalmoscopy revealed partially decalcified circumpapillary, macular choroidal osteoma with overlying subretinal hemorrhage and choroidal neovascular membrane. Intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) resulted in membrane regression and visual acuity improvement to 20/50 at 6 weeks. Further therapy with intravitreal ranibizumab (Lucentis; Genentech, Inc.) resolved persistent subretinal fluid, and visual acuity improved to 20/30 at the 6-month follow-up. Conclusions: Therapy with intravitreal anti-VEGF medications might be an alternative for patients with choroidal neovascularization overlying choroidal osteoma. RETINAL CASES & BRIEF REPORTS 2:18 –20, 2008
31%, and poor vision of 20/200 or worse in 56%.2 Several therapies for CNVM have been attempted, including laser photocoagulation, photodynamic therapy, and subretinal surgery with membrane extraction. For subfoveal CNVM, each of these therapies can pose a risk for retinal damage and reduced vision. We describe our experience with intravitreal anti–vascular endothelial growth factor (VEGF) therapy for CNVM overlying choroidal osteoma. Approval was obtained from the Institutional Review Board at Wills Eye Institute (Thomas Jefferson University, Philadelphia, PA) for the publication of this report.
From the *Ocular Oncology Service and the †Retina Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania.
C
horoidal osteoma is a benign intraocular tumor, classically found in young women.1,2 Over the long term, choroidal osteoma can exhibit tumor growth in 51% of cases, tumor decalcification in 46%, development of choroidal neovascular membrane (CNVM) in Support provided by the Retina Research Foundation of the Retina Society, Cape Town, South Africa (C.L.S.); the Paul Kayser International Award of Merit in Retina Research, Houston, TX (J.A.S.); a donation from Michael, Bruce, and Ellen Ratner, New York, NY (J.A.S., C.L.S.); the LuEsther Mertz Retina Research Foundation, New York, NY (C.L.S.); the Fundacion Oftalmologica Nacional, Bogota´, Colombia (P.F.S.); and the Eye Tumor Research Foundation, Philadelphia, PA (C.L.S., J.A.S.). Reprint requests: Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107; e-mail: [email protected]
Case Report A 33-year-old woman was found at routine examination to have choroidal osteoma in each eye. Visual acuity was 20/30 in both eyes. Choroidal osteoma in the right eye measured 13 mm in
18
19
ANTI-VEGF THERAPY FOR CNVM OVERLYING CHOROIDAL OSTEOMA
Fig. 2. After treatment with bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) and ranibizumab (Lucentis; Genentech, Inc.), choroidal neovascular membrane (CNVM) resolved, and visual acuity returned to 20/30 by 4 months. Choroidal osteoma remains stable, and the overlying CNVM appears fibrotic without overlying subretinal fluid or hemorrhage (top). Optical coherence tomography shows the flat retina overlying the regressed, flattened CNVM (bottom).
tumor was 70% decalcified, particularly in the submacular region. The left eye remained stable. Intravitreal bevacizumab ([1.25 mg] Avastin; Genentech, Inc., South San Francisco, CA) was injected, and CNVM and hemorrhage resolved in 6 weeks; visual acuity improved to 20/50 in the right eye with shallow persistent subretinal fluid. Subsequently, intravitreal ranibizumab ([0.5 mg] Lucentis; Genentech, Inc.) injection was administered monthly for three sessions, and the subretinal fluid resolved, with a final visual acuity of 20/30 in the right eye at the 6-month follow-up (Fig. 2).
Fig. 1. Choroidal osteoma in a 34-year-old woman with visual acuity loss from 20/30 to 20/100 due to choroidal neovascular membrane (CNVM). A, The partially decalcified choroidal osteoma shows overlying macular hemorrhage and gray subfoveal CNVM (top). Optical coherence tomography depicts the retina elevated over an ill defined subretinal optically dense plaque in the fovea (bottom). B, Fluorescein angiography displays hyperfluorescence of the osteoma with overlying hyperfluorescence of the CNVM.
diameter and 1.2 mm in thickness with 10% decalcification. Choroidal osteoma in the left eye measured 16 mm in diameter and 1.2 mm in thickness with 20% decalcification. Thirteen months later, visual acuity in the right eye had deteriorated to 20/100 from subfoveal CNVM producing subretinal fluid and hemorrhage (Fig. 1). The
Discussion VEGF plays an important role in neovascular agerelated macular degeneration. Inhibition of VEGF with intravitreal ranibizumab and bevacizumab has shown promising results. In an analysis of 716 patients in the MARINA study at the 24-month followup, the ranibizumab-treated patients did better on average than the sham-treated patients.3 In a study of 53 eyes with neovascular age-related macular degeneration treated with bevacizumab, mean visual acuity improved from 20/160 to 20/125.4 Anti-VEGF medications have also been used to treat diabetic macular
20
RETINAL CASES & BRIEF REPORTSℜ
edema, proliferative diabetic retinopathy, and consequences of retinal vascular obstruction. Anti-VEGF therapy also plays an important role in the management of some cancers. Cancer cells release proangiogenic factors that stimulate growth of capillaries for tumor nourishment. Systemic bevacizumab treatment has been used in the management of colorectal, renal, lung, breast, pancreatic, and ovarian cancers.5 Anti-VEGF therapy has not yet been investigated for the treatment of intraocular tumors, but its use for radiation retinopathy and papillopathy is being explored. In this case, the use of anti-VEGF therapy was not for tumor regression but for resolution of CNVM. In an analysis of 74 consecutive eyes with choroidal osteoma, CNVM developed in 46% by the 20-year follow-up.2 Given the median age of 25 years at presentation, nearly 50% of patients would be expected to manifest CNVM by 45 years old. The visual consequences of CNVM in this relatively young age group and the possibility of bilateral involvement could be devastating. The results of this case with
●
2008
●
VOLUME 2
●
NUMBER 1
resolution of CNVM and visual acuity recovery after anti-VEGF therapy are promising. Key words: eye, choroid, osteoma, choroidal neovascular membrane, bevacizumab (Avastin), ranibizumab (Lucentis). References 1. 2.
3.
4.
5.
Shields CL, Shields JA, Augsburger JJ. Review of choroidal osteomas. Surv Ophthalmol 1988;33:17–27. Shields CL, Sun H, Demirci H, Shields JA. Factors predictive of tumor growth, tumor decalcification, choroidal neovascularization and visual outcome in 74 eyes with choroidal osteoma. Arch Ophthalmol 2005;123:658–666. Boyer DS, Antoszyk AN, Awh CC, et al. MARINA Study Group. Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology 2007;114:246–252. Rich RM, Rosenfeld PJ, Puliafito CA, et al. Short-term safety and efficacy of intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Retina 2006;26:495– 511. Shih T, Lindley C. Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies. Clin Ther 2006;28:1779– 1802.
