A, Color fundus photographs taken in 2009. B, Fundus fluorescein angiograms in the late phase recorded in 2009. A and B, Arrowheads indicate the ectatic retinal venule noted to change its angle by 90° on the surface of the retina. C, Blue-wavelength autofluorescence images taken in 2009. D, Optical coherence tomographic images taken in 2009. E, Optical coherence tomographic images taken in 2014.
The characteristic multimodal fundus images included are from different patients diagnosed as having macular telangiectasia type 2.
eFigure 1. Right eye color fundus photograph 2014
eFigure 2. Left eye color fundus photograph 2014
eFigure 3. Right eye fundus fluorescein angiography late phase image 2014
eFigure 4. Left eye Fundus fluorescein angiography late phase image 2014
Gillies MC, Mehta H, Bird AC. Macular Telangiectasia Type 2 Without Clinically Detectable Vasculopathy. JAMA Ophthalmol. 2015;133(8):951-954. doi:10.1001/jamaophthalmol.2015.1796
Macular telangiectasia type 2 is a bilateral disease with characteristic alterations of the macular capillary network and neural atrophy. Vascular and neurodegenerative hypotheses have been proposed to explain these clinical findings, but many questions regarding the pathogenesis remain.
We report the case of a 69-year-old woman with macular telangiectasia type 2 in whom multimodal fundus imaging identified neuronal features without clinically detectable vasculopathy.
Conclusions and Relevance
We hypothesize that parallel neuronal and vascular pathogenic pathways secondary to Müller cell dysfunction, the cause of which remains obscure, explain the clinical features of this case of macular telangiectasia type 2.
Macular telangiectasia type 2 (MacTel) is a bilateral disease with characteristic alterations of the macular capillary network and neural atrophy.1 Its prevalence has been shown to be as high as 0.1% in persons aged 43 to 86 years in the Beaver Dam Eye Study based on grading from stereoscopic fundus photographs.2 Vascular and neurodegenerative hypotheses have been proposed to explain the clinical findings.1,3- 5 We report a case in which the neuronal features occurred without clinically detectable vasculopathy and discuss how these observations affect our understanding of the disease process.
Macular telangiectasia type 2 is a bilateral disease usually characterized by retinal vasculopathy and neural atrophy.
Vascular and neurodegenerative hypotheses have been proposed to explain these clinical findings, but many questions regarding the pathogenesis remain.
A case of macular telangiectasia type 2 is described in which multimodal imaging showed that the neuronal features occurred without clinically detectable vasculopathy.
We hypothesize that parallel neuronal and vascular pathogenic pathways secondary to Müller cell dysfunction, the cause of which remains obscure, explain the clinical features of macular telangiectasia type 2.
A 69-year-old woman had central metamorphopsia for more than 20 years. Her medical history was significant for β-thalassemia trait and hypertension. She was hypermetropic with no history of ocular trauma or surgery. Her family history was unremarkable. In 2009, her best-corrected visual acuity was 20/60 OD and 20/40 OS. Color fundus photography (Figure 1A) showed bilateral loss of normal foveal transparency but no visible telangiectatic changes. In the right eye, an ectatic retinal venule was noted to change its angle by 90° on the surface of the retina, but stereoscopic information indicates there were no typical “dilated and blunted retinal venules that extend at right angles into the depth of the parafoveolar retina”3 as described by Gass and Blodi. Fundus fluorescein angiography (FFA) confirmed absence of classic temporal juxtafoveal leakage (Figure 1B). Blue-wavelength autofluorescence showed bilateral loss of luteal pigment inferotemporal to the fovea characteristic of MacTel (Figure 1C). Cirrus high-definition optical coherence tomographic imaging (Carl Zeiss Meditec) in 2009 showed bilateral inner retinal cavitation with no disruption of the outer retinal layers (Figure 1D). Five years later, her BCVA was 20/80 OD and 20/60 OS. Optical coherence tomography showed development of outer retinal cavitation with bilateral subfoveal disruption of the ellipsoid layer and external limiting membrane (Figure 1E). There was still no visible telangiectasia or temporal juxtafoveal dye leakage on FFA (eFigures 1-4 in the Supplement).
While cases with telangiectatic changes in the absence of neuronal features have been previously described in the MacTel Natural History Study,6 this is the first reported case, to our knowledge, of the neurodegenerative features of MacTel occurring without fluorescein leakage or any visible telangiectatic component. Although no telangiectasis was visible on FFA in this case, we cannot completely exclude the possibility that some degree of vasculopathy was present but not detectable with clinical examination, including FFA.
We suggest that the distinct neuronal and vascular features of MacTel can be reconciled as the sequelae of Müller cell dysfunction. Müller cells provide nutritional and regulatory support to both retinal neurons and vascular cells.1 Loss of central Müller cell markers has been shown to occur in several postmortem samples of eyes with MacTel, but it is unknown whether this is the primary cause of MacTel or secondary to some other insult.7,8
Loss of normal macular transparency has been described as a feature of MacTel.1 Franze et al9 used confocal microscopy to show evidence that Müller cells may be living optical fibers in healthy vertebrate retina, transferring light with low scatter from the retinal surface to the photoreceptor cell layer. If this is correct, their disruption would predictably decrease transmission and reflectance through the retina, potentially reducing normal macular transparency.
There is limited evidence that loss of macular pigment may be a sign of Müller cell dysfunction in MacTel. Selective disruption of photoreceptors with preservation of Müller cells and the retinal vasculature did not lead to luteal pigment depletion in primate studies.10 However, the identification of lutein binding proteins principally in photoreceptors could suggest a primary photoreceptor disease.11 Further studies are warranted to determine what role, if any, Müller cells play in the accumulation and/or storage of macular pigment.1
Independence of vasculopathy and photoreceptor degeneration secondary to induced Müller cell dysfunction has been demonstrated in a transgenic mouse model.12 Treatment with ciliary neurotrophic factor attenuated the photoreceptor degeneration but had no effect on the vasculopathy, while a neutralizing murine vascular endothelial growth factor antibody effectively blocked the vascular leak but neither attenuated nor exacerbated the photoreceptor degeneration.12
Müller cell dysfunction, possibly characterized clinically by loss of luteal pigment and loss of normal macular transparency, has a central role in the disease process (Figure 2). In early stages of neuronal degeneration in MacTel, there is increased reflectivity of the outer nuclear layer followed by disruption or decreased reflectivity of the ellipsoid layer. Later, there can be inner or outer retinal cavitation and retinal thinning. The vasculopathy of MacTel is characterized by temporal juxtafoveal angiographic leakage. Vascular remodeling and deep intraretinal neovascularization with right-angle vessels subsequently develop. Hyperpigmentation and/or subretinal neovascularization may accompany the outer retinal neovascularization. The vascular and neuronal features of MacTel usually occur together.
We hypothesize that parallel neuronal and vascular pathogenic pathways secondary to Müller cell dysfunction, the cause of which remains obscure, explain the clinical features of this case.
Corresponding Author: Mark C. Gillies, PhD, FRANZCO, Macular Research Group, Save Sight Institute, 8 Macquarie St, Sydney, New South Wales 2000, Australia (firstname.lastname@example.org).
Submitted for Publication: November 5, 2014; final revision received April 21, 2015; accepted April 26, 2015.
Published Online: June 11, 2015. doi:10.1001/jamaophthalmol.2015.1796.
Author Contributions: Drs Gillies and Mehta had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Gillies, Mehta.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Mehta.
Critical revision of the manuscript for important intellectual content: Gillies, Bird.
Obtained funding: Gillies.
Administrative, technical, or material support: Gillies, Mehta.
Study supervision: Gillies, Bird.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Gillies reported serving as a consultant for Pfizer, Novartis, and Bayer; receiving unrestricted educational grants from Bayer, Novartis, and Allergan; and receiving payment for lectures, including service on speakers bureaus, from Pfizer and Novartis. No other disclosures were reported.