There is still much we have to learn about macular telangiectasia (MacTel) type 2. Initially, it was believed to be primarily a vascular disease due to the telangiectatic changes and fluorescein leakage that were observed in the retinal vasculature of affected patients. We now know that MacTel is primarily a neurodegenerative and neurovascular condition, in which Müller cells—glial cells that support retinal neurons and the blood-retinal barrier—become dysfunctional, leading to atrophy of photoreceptors and visual loss.¹ The progressive, neurodegenerative nature of MacTel makes vision loss from this disease nonrecoverable.

MacTel is generally considered a rare disease, but there is good reason to think it may be more prevalent than previously believed.² One reason for this may be that, in its early stages, MacTel can be challenging to diagnose accurately. In fact, one retrospective analysis of 288 patients with confirmed diagnosis of MacTel found that roughly 36% of these patients had been initially misdiagnosed, meaningfully delaying access to appropriate care.³ As a vitreoretinal specialist working in a retina-only practice, I often see patients come to me with a referral for cystoid macular edema or retinal vein occlusion, only for the real culprit behind their visual complaints to be revealed as MacTel.

Accurately Diagnosing MacTel

Patients with MacTel are typically diagnosed during their 40s or 50s, usually as a bilateral condition that can be asymmetric in its presentation. The disease begins in the temporal parafoveal region, and the location of observed changes can be an important factor for differentiating MacTel from other retinal conditions.¹

One of the earliest changes in MacTel is retinal graying or loss of transparency of the temporal juxtafoveal region, which can be seen on fundus photography or red-free images.^1,4 Another early sign that can be observed on fundus photography is the development of fine crystals in the retina, which occurs in roughly half of patients with MacTel but does not correlate to disease severity.¹

Vascular changes in MacTel may be subtle and difficult to diagnose without the use of multimodal imaging that may include optical coherence tomography angiography (OCTA) and fluorescein angiography (FA). One classic finding is the dilated right-angled venules that appear to dive down into the deep capillary plexus. These can be seen on clinical examination and on color and FA imaging, but may not always be obvious early in the disease. On FA, patients with MacTel may show early-phase dilated leaking capillaries temporal to the fovea and late-phase diffuse areas of hyperfluorescence. However, it’s important to note that the leakage observed in MacTel is not associated with typical cystoid edema.¹ 

Although spectral domain-OCT (SD-OCT) is a particularly important imaging modality for diagnosing MacTel, multimodal imaging provides far more information. On OCT, the earliest sign of MacTel is a temporal widening of the foveal pit.¹ Other key OCT findings include the development of cavitations in the inner and outer retina and focal loss of the ellipsoid zone (EZ) that starts temporally with later extension into the foveal center. The cavitations are not cysts, in that they are not filled with exudated fluid, but represent cellular loss caused by Müller cell degeneration; this may not be seen in early stages of the disease. The pathologic finding of EZ loss correlates best with visual function; as it progresses from the perifoveal location into the foveal center, patients typically lose significant visual acuity.⁵

A draping of the internal limiting membrane (ILM) can also commonly be seen on OCT in patients with MacTel, where a thin membrane extends over a cavitation at the base of the fovea.⁶ These membranes can be confused with epiretinal membranes, and their removal does not improve vision. Chorioretinal neovascularization and a hyperplastic retinal pigment epithelium are also potential complications of late MacTel, which may appear as hyperreflective dots in the inner and outer nuclear layers on OCT. Neovascularization should be suspected if there is subretinal hemorrhage or new thickening of the retina. If these are observed, the presence of neovascularization can be confirmed with OCTA or FA.¹

Although the characteristic features listed above may be relatively easy to spot on imaging in later stages of the disease, in early stages, patients may have only developed a few of these features, which may also overlap with what is seen in other retinal conditions. As such, obtaining a diagnosis of MacTel requires taking the whole picture into consideration, looking for a group of features rather than focusing on one definitive sign.

Differentiating MacTel From Other Retinal Diseases

Many more commonly diagnosed retinal vascular conditions display similar features and symptoms to those of MacTel, making them a prime target for differential diagnosis. For example, the retinal capillary telangiectasia that occurs in MacTel can also be seen in small branch retinal vein occlusion,⁷ and the intraretinal cysts that can be observed in patients with diabetic retinopathy or retinal vein occlusion may appear to be similar to the hyporeflective cavitations in MacTel.⁸ In cases like this, checking for outer loss of the EZ and whether crystals are present can be very helpful in identifying MacTel, because there will likely not be EZ loss in a retinal vascular condition. The use of FA can also be invaluable for delineating between these vascular conditions and MacTel, and the presence of diffuse retinal hemorrhage and microaneurysms likely indicate diabetic involvement. However, it is possible for a patient to concomitantly have MacTel and diabetes, so this alone cannot rule out a diagnosis of MacTel.

Early stage (1 or 2) macular holes can also present with cavitations in the outer retinal layers that may resemble those seen in MacTel.⁹ In the retrospective analysis by Raming et al, macular hole was the most common incorrect diagnosis ascribed to patients with MacTel, although it should be noted patients can concomitantly have both macular hole and MacTel.³ Epiretinal membranes and vitreoretinal traction may also appear similar to the ILM drape that is seen in patients with MacTel. However, these typically manifest unilaterally, and patients with these conditions will not present with crystals or telangiectatic right-angled venules.

Age-related macular degeneration (AMD) is the most common cause of visual loss in adults aged over 50 years, and, like MacTel, can result in a loss of EZ and the presence of choroidal neovascularization.¹⁰ As such, AMD is another common misdiagnosis for patients with MacTel.³ If I saw a patient with drusen and EZ loss, I would suspect that they have geographic atrophy; however, if the patient does not have drusen but has crystals or telangiectatic and right-angled venules, I would begin to suspect MacTel. Similarly, if a patient presents with choroidal neovascularization in one eye and has these signs of MacTel in the other eye, that could be a clue that the neovascularization is secondary to MacTel instead of AMD.

Lastly, tamoxifen retinopathy can mimic many of the signs of early stage MacTel. Just like in MacTel, patients with tamoxifen retinopathy present with crystalline deposits, breaks in the EZ, and hyperreflective changes on OCT, and it has been hypothesized that these similarities occur because tamoxifen retinopathy also leads to the degeneration of Müller cells. To differentiate these conditions, location of these changes is key; in MacTel, these changes occur only in a region temporal to the foveal center (known as the “MacTel area”), whereas in tamoxifen retinopathy, these changes occur solely within the foveal center.¹¹

Conclusion

MacTel is an insidious disease, and even though patients with MacTel may not experience complete vision loss, it can have a significantly deleterious effect on visual function and quality of life.¹² I began practicing medicine before the popularization of OCT, and back in the days when we only had FA and color photographs to evaluate, we likely missed many early cases of MacTel. Now that we have access to sophisticated, multimodal retinal imaging, we can more confidently make this diagnosis, but only if we know what we are looking for. OM

Dante J. Pieramici, MD, FASRS, MD, is a retina specialist, surgeon, and partner at California Retina Consultants in Bakersfield. Dr Pieramici reports being an advisor to Neurotech.

References

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8. do Nascimento MVD, Iovino C, Yuan PHS, et al. Structural effects of intraretinal cysts on outer retinal layers in eyes with diabetic macular edema. Int J Retina Vitreous. 2024;10(1):85. doi:10.1186/s40942-024-00605-w

9. Premi E, Donati S, Azzi L, et al. Macular holes: main clinical presentations, diagnosis, and therapies. J Ophthalmol. 2022;2022:2270861. doi:10.1155/2022/2270861

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