Retina Conference Janelle Fassbender, MD, PhD University of Louisville Department of Ophthalmology and Visual Sciences 01/23/2014

Subjective CC/HPI: 52 year old HF c/o the right half of faces looking abnormal. POH: None PMH: Hypertension, hyperlipidemia, type 2 DM Meds: Metformin, 3 anti-hypertensive agents, omeprazole, prevastatin FOH: Mother with macular hole

Objective OD OS OD OS Va(sc): 20/ /50-2 Pupils: 3 No RAPD 3 IOP: EOM: Full Full

Anterior and Posterior Segments Anterior segment: WNL OU ON: c/d 0.2 pink/sharp c/d 0.2 pink/sharp Macula: Cystic foveal lesion Cystic foveal lesion Vessels: WNL WNL Periphery: WNL WNL OD OS

OCT OD

OCT OD Parafoveal intra-retinal cavity extending to and involving the outer retina; irregularity of the ELM, focal discontinuity of the photoreceptor ellipsoid line and cone outer segment sheaths

OCT OS Intra-retinal cystic foveal lesion extending to RPE with interruption of the photoreceptor outer segments.

Fluorescein angiogram OD: Mid A-V phase with leakage temporal to fovea.

Fluorescein angiogram OS: Temporal leakage and focal hyperfluorescence.

Differential Diagnosis Parafoveal telangiectasia Parafoveal telangiectasia Non-Proliferative Diabetic Retinopathy Non-Proliferative Diabetic Retinopathy Stage 1 macular hole Stage 1 macular hole Hypertensive retinopathy Hypertensive retinopathy Branch retinal vein occlusion Branch retinal vein occlusion

Diagnosis Parafoveal telangiectasia Parafoveal telangiectasia

Plan Follow up in 4-5 months. Follow up in 4-5 months.

Parafoveal telangiectasia Also known as idiopathic juxtafoveolar retinal telangiectasis or idiopathic macular telangiectasia Also known as idiopathic juxtafoveolar retinal telangiectasis or idiopathic macular telangiectasia First described by Gass in 1968 First described by Gass in 1968 Initial classification in 1982 by Gass and Oyakawa Initial classification in 1982 by Gass and Oyakawa Heterogeneous group of disorders classified into 3 types with independent etiologies. Heterogeneous group of disorders classified into 3 types with independent etiologies. Prevalence of 0.1% per Beaver Dam Eye Study (2010) Prevalence of 0.1% per Beaver Dam Eye Study (2010)

Pathophysiology No actual telangiectasis – vessel wall thickening with eventual capillary dilatation (Green et al, 1980; Gass et al, 1982). No actual telangiectasis – vessel wall thickening with eventual capillary dilatation (Green et al, 1980; Gass et al, 1982). Metabolic alteration, endothelial permeability, nutritional deficiency  degeneration of the middle and outer retina. Metabolic alteration, endothelial permeability, nutritional deficiency  degeneration of the middle and outer retina. Neural, Muller or endothelial cell etiology (Cohen etal,2007) ? Neural, Muller or endothelial cell etiology (Cohen etal,2007) ? Crystalline deposit – degenerated Muller footplates Crystalline deposit – degenerated Muller footplates Fluorescein leakage – loss of Muller-mediated barrier Fluorescein leakage – loss of Muller-mediated barrier Outer retinal atrophy – loss of Muller cell nutritional and mechanical support Outer retinal atrophy – loss of Muller cell nutritional and mechanical support Cystoid spaces of type 1 compared to 2, retinal vein occlusion, and diabetic macular edema (Oh et al, ePub ahead). Cystoid spaces of type 1 compared to 2, retinal vein occlusion, and diabetic macular edema (Oh et al, ePub ahead).

MacTel Project (2005) International consortium to study cause, natural history, progression and epidemiology International consortium to study cause, natural history, progression and epidemiology Resulted in multiple publications describing clinical findings, diagnostic methods, and epidemiology. Resulted in multiple publications describing clinical findings, diagnostic methods, and epidemiology. 27 candidate genes – None associated to MacTel (Parmalee et al, 2010). 27 candidate genes – None associated to MacTel (Parmalee et al, 2010). Genome-wide linkage study (Parmalee et al, 2012) : Genome-wide linkage study (Parmalee et al, 2012) : Probable AD transmission with reduced penetrance and expressivity. Probable AD transmission with reduced penetrance and expressivity. Linked to 1q41-42 (LOD 3.45) Linked to 1q41-42 (LOD 3.45)

Pathophysiology ATM was characterized in 1988 as the causal gene for ataxia telangiectasia (AT) ATM was characterized in 1988 as the causal gene for ataxia telangiectasia (AT) Chronic oxidative stress resulting in DNA damage activates ATM and leads to increased apoptotic activity. Chronic oxidative stress resulting in DNA damage activates ATM and leads to increased apoptotic activity. Loss of ATM function leads to genome instability Loss of ATM function leads to genome instability Allelic variants noted in 13/30 macular telangiectasia, especially of European ancestry (Barbezetto, 2008). Allelic variants noted in 13/30 macular telangiectasia, especially of European ancestry (Barbezetto, 2008). 11/16 with polypoidal choroidal vasculopathy or macular telangiectasia (Mauget-Faysee, 2003) 11/16 with polypoidal choroidal vasculopathy or macular telangiectasia (Mauget-Faysee, 2003)

Bevacizumab therapy for idiopathic macular telangiectasia type II Kovach and Rosenfeld, Retina Jan;29(1):27-32 Purpose: To determine if inhibition of VEGF-A affects visual acuity, fluorescein angiographic (FA), and optical coherence tomography (OCT) outcomes in patients with perifoveal telangiectasia (PT) type 2A. Purpose: To determine if inhibition of VEGF-A affects visual acuity, fluorescein angiographic (FA), and optical coherence tomography (OCT) outcomes in patients with perifoveal telangiectasia (PT) type 2A. Results: 9 eyes of 8 patients. After treatment, follow-up ranged from 4 to 27 months. Results: 9 eyes of 8 patients. After treatment, follow-up ranged from 4 to 27 months. Non-proliferative - Mean BCVA remained stable (n = 4). Non-proliferative - Mean BCVA remained stable (n = 4). Proliferative - BCVA was unchanged or improved after treatment (n = 5). Proliferative - BCVA was unchanged or improved after treatment (n = 5). All eyes demonstrated decreased intraretinal leakage on FA after an injection of bevacizumab, and eyes with proliferative PT showed decreased growth and leakage of the subretinal neovascularization. All eyes demonstrated decreased intraretinal leakage on FA after an injection of bevacizumab, and eyes with proliferative PT showed decreased growth and leakage of the subretinal neovascularization. The mean decrease in OCT central retinal thickness – 6 um non-proliferative; 26 um proliferative. The mean decrease in OCT central retinal thickness – 6 um non-proliferative; 26 um proliferative.

Conclusions: Intravitreal Avastin Non-proliferative PT: Non-proliferative PT: Decreases fluorescein angiographic leakage in PT but has no short-term effect on visual acuity or OCT appearance. Decreases fluorescein angiographic leakage in PT but has no short-term effect on visual acuity or OCT appearance. Proliferative PT: Proliferative PT: Arrests the leakage and growth of subretinal neovascularization with the possibility of visual acuity improvement. Arrests the leakage and growth of subretinal neovascularization with the possibility of visual acuity improvement.

References Oh, JH, et al Characteristics of cystoid spaces in type 2 idiopathic macular telangiectasia on spectral domain OCT. Retina. [Epub ahead of print] Oh, JH, et al Characteristics of cystoid spaces in type 2 idiopathic macular telangiectasia on spectral domain OCT. Retina. [Epub ahead of print] Wu, Evans, Arevalo Idiopathic macular telangiectasia type 2. Surv Ophthalmol, 58(6): Wu, Evans, Arevalo Idiopathic macular telangiectasia type 2. Surv Ophthalmol, 58(6): Mauget-Faysse, et al Idiopathic and radiation-induced ocular telangiectasia: the involvement of the ATM gene. Invest Ophthalmol Vis Sci. 44(8): Barbazetto IA, et al ATM gene variants in patients with idiopathic perifoveal telangiectasia. Invest Ophthalmol Vis Sci, 49(9): Kovach and Rosenfeld Bevacizumab therapy for idiopathic macular telangiectasia type II. Retina. Jan;29(1):27-3. Kovach and Rosenfeld Bevacizumab therapy for idiopathic macular telangiectasia type II. Retina. Jan;29(1):27-3. Sawsan, et al Idiopathic juxtafoveolar telangiectasia: A current review. Middle East Afr J Ophthalmol, 17(3). Sawsan, et al Idiopathic juxtafoveolar telangiectasia: A current review. Middle East Afr J Ophthalmol, 17(3). Yannuzzi et al Idiopathic macular telangiectasia. JAMA Ophthalmol, 124(4): Yannuzzi et al Idiopathic macular telangiectasia. JAMA Ophthalmol, 124(4): Parmalee, et al Analysis of candidate genes for macular telangiectasia type 2. Molecular Vision, 16: Parmalee, et al Analysis of candidate genes for macular telangiectasia type 2. Molecular Vision, 16: Parmalee, et al Identification of a potential susceptibility locus for macular telangiectasia type 2. PLOS One, 7(8). Parmalee, et al Identification of a potential susceptibility locus for macular telangiectasia type 2. PLOS One, 7(8). Cohen et al Optical coherence tomography findings in nonproliferative group 2a juxtafoveal retinal telangiectasis. Retina, 27(1): Cohen et al Optical coherence tomography findings in nonproliferative group 2a juxtafoveal retinal telangiectasis. Retina, 27(1):59-66.