SHORT-TERM EFFECTS OF INTRAVITREAL BEVACIZUMAB IN TYPE II IDIOPATHIC MACULAR TELANGIECTASIA Peter Charbel Issa, MD, Hendrik P. N. Scholl, MD, MA, Frank G. Holz, MD
Purpose: To report the effect of intravitreal bevacizumab in type 2 idiopathic macular telangiectasia (type 2 IMT). Design: Interventional case report. Methods: A 51 year-old female patient with type 2 IMT presented with gradual visual deterioration and reading difficulties. In one affected eye, two intravitreal bevacizumab injections were performed with a four weeks interval. Examinations included ETDRS visual acuity, slit-lamp biomicroscopy, digital fluorescein angiography, optical coherence tomography (OCT) and microperimetry at baseline and during a 12-week review period. Results: Following treatment the patient noted a visual improvement particularly during reading. On angiography a reduction in size and intensity of the hyperfluorescent area was recorded and the retinal sensitivity improved on microperimetry. Conclusions: In absence of other efficacious therapeutic modalities, the observations indicate a beneficial therapeutic effect of intravitreal bevacizumab in type2-IMT, and implicate a pathophysiological role of VEGF in this disease entity. RETINAL CASES & BRIEF REPORTS 1:189 –191, 2007
From the Department of Ophthalmology, University of Bonn, Germany.
Both atrophy and secondary neovascularization may occur with disease progression. We describe the shortterm outcome for a patient with Type 2 IMT in absence of neovascularization who was treated with intravitreal injection of bevacizumab.
T
ype 2 idiopathic macular telangiectasia (Type 2 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 Group 1, the latter being primarily exudative and unilateral with a male predilection. Group 3 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
Case Report A 51-year-old woman with nonproliferative type2 IMT presented with visual loss and reading difficulties. Best-corrected visual acuity at initial presentation was 54 Early Treatment Diabetic Retinopathy Study (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, intraretinal crystalline deposits, and right-angled venules. Digital fluorescein angiography (Heidelberg Retina Angiograph 2, Heidelberg Engineering, Heidelberg, Germany) revealed dilated parafoveal capillaries in the early phase and a diffuse parafoveal hyperfluorescence in the late phase (Figure 1, A and B). Optical coherence tomography (Stratus OCT; Carl Zeiss Meditec, Oberkochen, Germany) showed a typical foveolar hyporeflective space while intraretinal retinal thickness was within normal limits.2 Microperimetry (MP1; Nidek Technologies, Italy) demonstrated reduction of retinal sensitivity temporal to the fovea (Figure 2A). After obtaining informed consent, intra-
No author has proprietary interest. Supported by the Lowy Medical Research Institute (The Macular Telangiectasia Project, www.mactelresearch.org), DFG Heisenberg fellowship SCHO 734/2-1; EU FP6, Integrated Project “EVIGENORET” (LSHG-CT-2005-512036). Reprint requests: Frank G. Holz, MD, Department of Ophthalmology, University of Bonn, Ernst-Abbe-Str. 2, D-53127 Bonn, Germany; e-mail: [email protected]
189
190
RETINAL CASES & BRIEF REPORTSℜ
●
2007
●
VOLUME 1
●
NUMBER 4
Fig. 1. A, 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, 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 at 8 weeks after the initial injection (C) while it remained unchanged in the left eye (D).
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.
vitreal injection of 1.5 mg (0.06 mL) bevacizumab (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 (Figure 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 (Figure 2B).
191
INTRAVITREAL BEVACIZUMAB FOR TYPE 2-IMT
Discussion To our knowledge, there has been no therapy with proven benefit for nonproliferative Type 2 IMT. Vascular endothelial growth factor (VEGF) has potent neovascular properties and destabilizes the blood–retina barrier.3 It has been hypothesized that intravitreal delivery of drugs inhibiting VEGF, such as bevacizumab (antiVEGF antibody), may be beneficial but has not been reported.4 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 reported 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 latephase parafoveal hyperfluorescence without fluid accumulation on optical coherence tomography images.
The effect of an anti-VEGF 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. References 1.
2.
3. 4. 5.
Gass JD, Blodi BA. Idiopathic juxtafoveolar retinal telangiectasis. Update of classification and follow-up study. Ophthalmology 1993;100:1536–1546. 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 SJ, ed. Retina. Elsevier Mosby; 2006:1409–1415. Gass JDM. Macular dysfunction caused by retinal vascular diseases. Stereoscopic Atlas of Macular Diseases. St. Louis: Mosby; 1997:504–513.
Purpose: To report the effect of intravitreal bevacizumab in type 2 idiopathic macular telangiectasia (type 2 IMT). Design: Interventional case report. Methods: A 51 year-old female patient with type 2 IMT presented with gradual visual deterioration and reading difficulties. In one affected eye, two intravitreal bevacizumab injections were performed with a four weeks interval. Examinations included ETDRS visual acuity, slit-lamp biomicroscopy, digital fluorescein angiography, optical coherence tomography (OCT) and microperimetry at baseline and during a 12-week review period. Results: Following treatment the patient noted a visual improvement particularly during reading. On angiography a reduction in size and intensity of the hyperfluorescent area was recorded and the retinal sensitivity improved on microperimetry. Conclusions: In absence of other efficacious therapeutic modalities, the observations indicate a beneficial therapeutic effect of intravitreal bevacizumab in type2-IMT, and implicate a pathophysiological role of VEGF in this disease entity. RETINAL CASES & BRIEF REPORTS 1:189 –191, 2007
From the Department of Ophthalmology, University of Bonn, Germany.
Both atrophy and secondary neovascularization may occur with disease progression. We describe the shortterm outcome for a patient with Type 2 IMT in absence of neovascularization who was treated with intravitreal injection of bevacizumab.
T
ype 2 idiopathic macular telangiectasia (Type 2 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 Group 1, the latter being primarily exudative and unilateral with a male predilection. Group 3 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
Case Report A 51-year-old woman with nonproliferative type2 IMT presented with visual loss and reading difficulties. Best-corrected visual acuity at initial presentation was 54 Early Treatment Diabetic Retinopathy Study (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, intraretinal crystalline deposits, and right-angled venules. Digital fluorescein angiography (Heidelberg Retina Angiograph 2, Heidelberg Engineering, Heidelberg, Germany) revealed dilated parafoveal capillaries in the early phase and a diffuse parafoveal hyperfluorescence in the late phase (Figure 1, A and B). Optical coherence tomography (Stratus OCT; Carl Zeiss Meditec, Oberkochen, Germany) showed a typical foveolar hyporeflective space while intraretinal retinal thickness was within normal limits.2 Microperimetry (MP1; Nidek Technologies, Italy) demonstrated reduction of retinal sensitivity temporal to the fovea (Figure 2A). After obtaining informed consent, intra-
No author has proprietary interest. Supported by the Lowy Medical Research Institute (The Macular Telangiectasia Project, www.mactelresearch.org), DFG Heisenberg fellowship SCHO 734/2-1; EU FP6, Integrated Project “EVIGENORET” (LSHG-CT-2005-512036). Reprint requests: Frank G. Holz, MD, Department of Ophthalmology, University of Bonn, Ernst-Abbe-Str. 2, D-53127 Bonn, Germany; e-mail: [email protected]
189
190
RETINAL CASES & BRIEF REPORTSℜ
●
2007
●
VOLUME 1
●
NUMBER 4
Fig. 1. A, 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, 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 at 8 weeks after the initial injection (C) while it remained unchanged in the left eye (D).
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.
vitreal injection of 1.5 mg (0.06 mL) bevacizumab (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 (Figure 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 (Figure 2B).
191
INTRAVITREAL BEVACIZUMAB FOR TYPE 2-IMT
Discussion To our knowledge, there has been no therapy with proven benefit for nonproliferative Type 2 IMT. Vascular endothelial growth factor (VEGF) has potent neovascular properties and destabilizes the blood–retina barrier.3 It has been hypothesized that intravitreal delivery of drugs inhibiting VEGF, such as bevacizumab (antiVEGF antibody), may be beneficial but has not been reported.4 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 reported 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 latephase parafoveal hyperfluorescence without fluid accumulation on optical coherence tomography images.
The effect of an anti-VEGF 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. References 1.
2.
3. 4. 5.
Gass JD, Blodi BA. Idiopathic juxtafoveolar retinal telangiectasis. Update of classification and follow-up study. Ophthalmology 1993;100:1536–1546. 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 SJ, ed. Retina. Elsevier Mosby; 2006:1409–1415. Gass JDM. Macular dysfunction caused by retinal vascular diseases. Stereoscopic Atlas of Macular Diseases. St. Louis: Mosby; 1997:504–513.
