SHORT-TERM EFFECTS OF INTRAVITREAL BEVACIZUMAB IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA Peter Charbel Issa, MD, Hendrik P. N. Scholl, MD, MA, Frank G. Holz, MD
In a patient with type 2 idiopathic macular telangiectasia without neovascularizations, intravitreal bevacizumab treatment reduced the size and intensity of the hyperfluorescent area in late phase fluorescein angiography. Microperimetic assessment revealed an improved retinal sensitivity compared to baseline. This case suggests that vascular endothelial growth factor plays a pathophysiological role in this disease entity.
From the Department of Ophthalmology, University of Bonn, Bonn, Germany.
intraretinal crystalline deposits, and right-angled venules. Digital fluorescein angiography (Heidelberg Retina Angiograph 2; Heidelberg Engineering, Heidelberg, Germany) revealed dilated parafoveal capillaries and diffuse oval-shaped parafoveal hyperfluorescence in the late phase (Fig. 1, A and B). Optical coherence tomography (Stratus OCT; Carl Zeiss Meditec, Dublin, CA) showed a typical foveolar hyporeflective space with an internal limiting membrane drape, while parafoveolar retinal thickness was within normal limits.2 Microperimetry (MP1; Nidek Technologies, Italy) demonstrated reduction of retinal sensitivity temporal to the fovea (Fig. 2A). After obtaining informed consent, intravitreal injection of 1.5 mg (0.06 mL) bevacizumab (Genentech, Roche, Switzerland) was performed in the right eye. The patient subsequently noted improvement within the following weeks, particularly of reading abilities. Four weeks after the initial injection, visual acuity remained unchanged at 53 and 55 ETDRS letters (20/100 and 20/80) in the right and left eyes, respectively. Fluorescein angiography revealed a marked reduction of the late-phase hyperfluorescence in the treated eye (Fig. 1C). A second injection of bevacizumab was performed in the right eye. Four weeks and 8 weeks later, angiographic findings remained unchanged. Visual acuity 8 weeks after the initial injection was 57 and 58 ETDRS letters (20/80) in the right and left eyes, respectively; it was 60 and 58 ETDRS letters (20/63 and 20/80) in the right and left eyes, respectively, 12 weeks after the initial injection. Fundus microperimetry showed improvement of the threshold of sensitivity temporal to the fovea (Fig. 2B).
T
ype 2 idiopathic macular telangiectasia (IMT) is characterized by bilateral telangiectatic and incompetent macular capillaries with minimal angiographically visible exudation and no sex predilection. Gass and Blodi1 distinguished type 2 IMT from type 1 IMT, the latter being primarily exudative and unilateral with a male predilection. Type 3 IMT is bilateral with progressive obliteration of the capillary network marked by capillary aneurysms. Type 2 IMT is characterized by a slow decrease in visual acuity, reading difficulties, and/or metamorphopsia starting in the fifth to seventh decade of life.1 Both atrophy and secondary neovascularization may occur with disease progression. We describe the short-term outcome for a patient with type 2 IMT in absence of neovascularizations who was treated with intravitreal injection of bevacizumab. Case Report A 51-year-old woman with nonproliferative type 2 IMT presented with visual loss and reading difficulties. Best-corrected visual acuity at initial presentation was 54 ETDRS letters in the right eye and 55 ETDRS letters in the left eye (Snellen equivalent, 20/80). Ophthalmoscopy disclosed several telangiectatic vessels temporal to the fovea, slight graying of the parafoveal retina,
Discussion So far, to our knowledge, there has been no therapy with proven benefit for type 2 IMT in absence of secondary neovascularizations. Vascular endothelial growth factor (VEGF) has potent neovascular properties and destabilizes the blood–retina barrier.3 It has been hypothesized that treatment with intravitreal delivery of drugs inhibiting VEGF, such as bevacizumab (anti-VEGF antibody), may be beneficial but has not been reported.4 It
Supported by the DFG Heisenberg Fellowship SCHO 734/2-1, EU FP6, and Integrated Project “EVI-GENORET” (LSHG-CT2005-512036). None of the authors have any proprietary interest in this report. Reprint requests: Frank G. Holz, MD, Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, D-53127 Bonn, Germany; e-mail: [email protected]
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Fig. 1. A and B, Late-phase (10-minute) fluorescein angiography of a patient with type 2 idiopathic macular telangiectasia at baseline in the right ([study] A) eye and the left ([control] B) eye. Diffuse parafoveolar hyperfluorescence is shown in both eyes. C and D, Late-phase fluorescein angiography after two applications of intravitreal bevacizumab in the right eye. The diffuse hyperfluorescence in the right eye was apparently reduced in size and intensity 8 weeks after the initial injection (C), while it remained unchanged in the left eye (D).
is interesting that a functional benefit was reported by our patient and recorded by microperimetry, and a marked reduction in hyperfluorescence was documented by angiography. The mismatch between unchanged central visual acuity and better reading performance may be explained by improvement of the scotoma temporal to the fovea. Both a staining effect and minimal leakage have been considered as possible explanations for late-phase parafoveal
hyperfluorescence without fluid accumulation on optical coherence tomography images. The effect of an antiVEGF agent would suggest exudation from parafoveal vessels rather than a staining phenomenon as the underlying mechanism.5 This observation would further imply a role of VEGF in the pathophysiology of type 2 IMT. Our findings warrant further evaluation of anti-VEGF therapy for patients with type 2 IMT.
Fig. 2. Microperimetry before (A) and 3 months after (B) the first intravitreal bevacizumab treatment. On the interpolated color map, each color is associated with a sensitivity value on the basis of a false color scale. The maximum increase of light increment sensitivity was 8 dB located temporal to the fovea.
SHORT-TERM EFFECTS OF INTRAVITREAL BEVACIZUMAB IN TYPE 2 IMT
Key words: anti–vascular endothelial growth factor antibody, bevacizumab, fluorescein angiography, type 2 idiopathic macular telangiectasia, microperimetry, optical coherence tomography, idiopathic juxtafoveolar telangiectasia. References 1.
Gass JD, Blodi BA. Idiopathic juxtafoveolar retinal telangiectasis. Update of classification and follow-up study. Ophthalmology 1993;100:1536 –1546.
2.
3. 4. 5.
81
Paunescu LA, Ko TH, Duker JS, et al. Idiopathic juxtafoveal retinal telangiectasis: new findings by ultrahigh-resolution optical coherence tomography. Ophthalmology 2006; 113:48–57. Ng YS, Krilleke D, Shima DT. VEGF function in vascular pathogenesis. Exp Cell Res 2006;312:527–537. Chew E. Parafoveal telangiectasis. In: Ryan ed. Retina. New York: Elsevier Mosby; 2006:1409–1415. Gass JDM. Macular dysfunction caused by retinal vascular diseases. In: Stereoscopic Atlas of Macular Diseases. St. Louis: Mosby; 1997:504–513.
In a patient with type 2 idiopathic macular telangiectasia without neovascularizations, intravitreal bevacizumab treatment reduced the size and intensity of the hyperfluorescent area in late phase fluorescein angiography. Microperimetic assessment revealed an improved retinal sensitivity compared to baseline. This case suggests that vascular endothelial growth factor plays a pathophysiological role in this disease entity.
From the Department of Ophthalmology, University of Bonn, Bonn, Germany.
intraretinal crystalline deposits, and right-angled venules. Digital fluorescein angiography (Heidelberg Retina Angiograph 2; Heidelberg Engineering, Heidelberg, Germany) revealed dilated parafoveal capillaries and diffuse oval-shaped parafoveal hyperfluorescence in the late phase (Fig. 1, A and B). Optical coherence tomography (Stratus OCT; Carl Zeiss Meditec, Dublin, CA) showed a typical foveolar hyporeflective space with an internal limiting membrane drape, while parafoveolar retinal thickness was within normal limits.2 Microperimetry (MP1; Nidek Technologies, Italy) demonstrated reduction of retinal sensitivity temporal to the fovea (Fig. 2A). After obtaining informed consent, intravitreal injection of 1.5 mg (0.06 mL) bevacizumab (Genentech, Roche, Switzerland) was performed in the right eye. The patient subsequently noted improvement within the following weeks, particularly of reading abilities. Four weeks after the initial injection, visual acuity remained unchanged at 53 and 55 ETDRS letters (20/100 and 20/80) in the right and left eyes, respectively. Fluorescein angiography revealed a marked reduction of the late-phase hyperfluorescence in the treated eye (Fig. 1C). A second injection of bevacizumab was performed in the right eye. Four weeks and 8 weeks later, angiographic findings remained unchanged. Visual acuity 8 weeks after the initial injection was 57 and 58 ETDRS letters (20/80) in the right and left eyes, respectively; it was 60 and 58 ETDRS letters (20/63 and 20/80) in the right and left eyes, respectively, 12 weeks after the initial injection. Fundus microperimetry showed improvement of the threshold of sensitivity temporal to the fovea (Fig. 2B).
T
ype 2 idiopathic macular telangiectasia (IMT) is characterized by bilateral telangiectatic and incompetent macular capillaries with minimal angiographically visible exudation and no sex predilection. Gass and Blodi1 distinguished type 2 IMT from type 1 IMT, the latter being primarily exudative and unilateral with a male predilection. Type 3 IMT is bilateral with progressive obliteration of the capillary network marked by capillary aneurysms. Type 2 IMT is characterized by a slow decrease in visual acuity, reading difficulties, and/or metamorphopsia starting in the fifth to seventh decade of life.1 Both atrophy and secondary neovascularization may occur with disease progression. We describe the short-term outcome for a patient with type 2 IMT in absence of neovascularizations who was treated with intravitreal injection of bevacizumab. Case Report A 51-year-old woman with nonproliferative type 2 IMT presented with visual loss and reading difficulties. Best-corrected visual acuity at initial presentation was 54 ETDRS letters in the right eye and 55 ETDRS letters in the left eye (Snellen equivalent, 20/80). Ophthalmoscopy disclosed several telangiectatic vessels temporal to the fovea, slight graying of the parafoveal retina,
Discussion So far, to our knowledge, there has been no therapy with proven benefit for type 2 IMT in absence of secondary neovascularizations. Vascular endothelial growth factor (VEGF) has potent neovascular properties and destabilizes the blood–retina barrier.3 It has been hypothesized that treatment with intravitreal delivery of drugs inhibiting VEGF, such as bevacizumab (anti-VEGF antibody), may be beneficial but has not been reported.4 It
Supported by the DFG Heisenberg Fellowship SCHO 734/2-1, EU FP6, and Integrated Project “EVI-GENORET” (LSHG-CT2005-512036). None of the authors have any proprietary interest in this report. Reprint requests: Frank G. Holz, MD, Department of Ophthalmology, University of Bonn, Ernst-Abbe-Strasse 2, D-53127 Bonn, Germany; e-mail: [email protected]
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RETINAL CASES & BRIEF REPORTSℜ
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2007
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VOLUME 1
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NUMBER 2
Fig. 1. A and B, Late-phase (10-minute) fluorescein angiography of a patient with type 2 idiopathic macular telangiectasia at baseline in the right ([study] A) eye and the left ([control] B) eye. Diffuse parafoveolar hyperfluorescence is shown in both eyes. C and D, Late-phase fluorescein angiography after two applications of intravitreal bevacizumab in the right eye. The diffuse hyperfluorescence in the right eye was apparently reduced in size and intensity 8 weeks after the initial injection (C), while it remained unchanged in the left eye (D).
is interesting that a functional benefit was reported by our patient and recorded by microperimetry, and a marked reduction in hyperfluorescence was documented by angiography. The mismatch between unchanged central visual acuity and better reading performance may be explained by improvement of the scotoma temporal to the fovea. Both a staining effect and minimal leakage have been considered as possible explanations for late-phase parafoveal
hyperfluorescence without fluid accumulation on optical coherence tomography images. The effect of an antiVEGF agent would suggest exudation from parafoveal vessels rather than a staining phenomenon as the underlying mechanism.5 This observation would further imply a role of VEGF in the pathophysiology of type 2 IMT. Our findings warrant further evaluation of anti-VEGF therapy for patients with type 2 IMT.
Fig. 2. Microperimetry before (A) and 3 months after (B) the first intravitreal bevacizumab treatment. On the interpolated color map, each color is associated with a sensitivity value on the basis of a false color scale. The maximum increase of light increment sensitivity was 8 dB located temporal to the fovea.
SHORT-TERM EFFECTS OF INTRAVITREAL BEVACIZUMAB IN TYPE 2 IMT
Key words: anti–vascular endothelial growth factor antibody, bevacizumab, fluorescein angiography, type 2 idiopathic macular telangiectasia, microperimetry, optical coherence tomography, idiopathic juxtafoveolar telangiectasia. References 1.
Gass JD, Blodi BA. Idiopathic juxtafoveolar retinal telangiectasis. Update of classification and follow-up study. Ophthalmology 1993;100:1536 –1546.
2.
3. 4. 5.
81
Paunescu LA, Ko TH, Duker JS, et al. Idiopathic juxtafoveal retinal telangiectasis: new findings by ultrahigh-resolution optical coherence tomography. Ophthalmology 2006; 113:48–57. Ng YS, Krilleke D, Shima DT. VEGF function in vascular pathogenesis. Exp Cell Res 2006;312:527–537. Chew E. Parafoveal telangiectasis. In: Ryan ed. Retina. New York: Elsevier Mosby; 2006:1409–1415. Gass JDM. Macular dysfunction caused by retinal vascular diseases. In: Stereoscopic Atlas of Macular Diseases. St. Louis: Mosby; 1997:504–513.
