“Peer Perspectives,” a new series from Retinal Physician, affords readers the opportunity to go behind the scenes and learn from one-on-one conversations between expert retina specialists. In this inaugural conversation in the series, Sophie J. Bakri, MD, and Roger A. Goldberg, MD, present advances in the care of patients with macular telangiectasia type 2 (MacTel). Their three-part conversation provides an introduction to the disease and covers topics including diagnosis, treatment, patient management, and more. In this first conversation, Dr. Bakri and Dr. Goldberg introduce the disease and then discuss steps to an accurate diagnosis and the impact of MacTel on the patient.
What Is MacTel?
Sophie J. Bakri, MD: It’s a pleasure to discuss MacTel today with you, Roger. Why don’t we start with some basics? What is MacTel and how does it progress?
Roger A. Goldberg, MD: Great questions, Sophie. MacTel is short for idiopathic macular telangiectasis type 2. Type 1 MacTel is actually a different disease. It's unilateral and more akin to Coats disease.
Type 2 is generally what people are talking about when they use the shorthand “MacTel,” which is the slowly progressing bilateral disease that we often think about. The name is actually a misnomer, because although the disease is called macular telangiectasia, the telangiectatic changes in the blood vessels are secondary to what's truly a neurodegenerative disease.
MacTel is a disease that affects the Müller glial cells and causes them to first become dysfunctional and then actually degenerate. Those Müller glial cells help provide structural support to the retina, neuroprotective support, and regulatory support to the retinal neurons and the retinal vasculature. They also help protect the photoreceptors from cell death through various neurotrophic factors, such as ciliary neurotrophic factor (CNTF).
MacTel causes apoptosis and loss of these Müller glial cells, which causes secondary loss of the photoreceptors. Then you also get all the morphologic changes we’re used to seeing in MacTel, including those telangiectatic vessels, which is how the disease got its name from the original Donald Gass classification scheme.
Dr. Bakri: Yes, and it’s a disease we’ve come to learn much more about in recent years.
Dr. Goldberg: I agree. We've learned a tremendous amount about MacTel in the last 2 decades. Just as our imaging technologies have gotten so much better, so too has our understanding of the disease.
Making a Diagnosis
Dr. Goldberg: Sophie, with regards to the diagnosis, I’ll ask two questions: First, are patients referred for MacTel, or are they typically referred for something else? And second, what imaging tests do you like to do to confirm the diagnosis?
Dr. Bakri: Those are excellent questions. Awareness of MacTel is growing, and I now receive many referrals in which the referring clinician has already made or suspects the diagnosis. However, in many cases, the referral is prompted by the detection of intraretinal cavities on optical coherence tomography (OCT), and the referring ophthalmologist or optometrist is uncertain whether they are dealing with age-related macular degeneration (AMD), diabetic macular edema, central serous chorioretinopathy, or another entity. So regardless of whether MacTel is suspected, our goal is to confirm the correct diagnosis.
Most referred patients have already undergone OCT imaging, but we routinely obtain high-resolution OCT with multiple line scans. This allows us to visualize hallmark features of MacTel, such as intraretinal cavities and disruption of the ellipsoid zone, particularly in the parafoveal region. The integrity of the ellipsoid zone is especially important as it correlates with visual function and photoreceptor health—an aspect that will become increasingly relevant as treatment strategies evolve.
OCT angiography (OCTA) is another valuable, non-invasive tool that can reveal parafoveal capillary telangiectasias and aid in diagnosis. In addition, I often order a fluorescein angiogram (FA), which typically demonstrates late-phase leakage temporal to the fovea and early-phase visualization of telangiectatic vessels. Fundus autofluorescence is also obtained per our protocol and may show increased autofluorescence in the affected areas.
Overall, while the diagnostic process is often initiated with OCT, I rely on a combination of high-quality OCT and FA to confirm the diagnosis of MacTel.
Dr. Goldberg: Patients with MacTel get referred to me most commonly for macular degeneration because they have changes in the retinal pigment epithelium (RPE) parafoveally. Sometimes on the OCT you can actually see the RPE migration, which appears as a dense hyperreflective cluster that's migrated up into the retina from the RPE layer.
I think the second most common diagnosis that gets referred to me is for cystoid macular edema (CME) because of the cystic cavities that you mentioned. Or sometimes, since many MacTel patients are also diabetic, they are referred for diabetic macular edema.
Finally, a significant number often get referred for epiretinal membrane (ERM) because a lot of our referring doctors have OCTs and see the internal limiting membrane (ILM) spanning an area of tissue loss, which we often call the “ILM drape sign.” Essentially, there is hollowing out and loss of the tissue but preservation of the internal limiting membrane, and it looks like there's an ERM spanning the surface of the retina.
And of course, patients get referred for MacTel also. I agree that awareness is growing.
Recognizing the Signs
Dr. Bakri: One of the ongoing challenges is making a diagnosis in the very early stages of MacTel. In most cases, the clinical features are sufficiently evident to make the diagnosis with confidence. However, when only subtle early changes are present, it can be difficult to counsel patients definitively. That said, with time and serial imaging, the characteristic findings often evolve, allowing the diagnosis to become more apparent.
Dr. Goldberg: So much of what we do is pattern recognition. I find that for the early changes, when you see on the OCT—again, just temporal to the fovea—almost like an asymmetric thinning of the retina, even if there aren't those kind of classic hallmark signs that we just mentioned, you get this thinning from loss of tissue. When I see that, I'll order either the OCTA or the fluorescein angiogram, and then you can see much more characteristic temporal leakage on the FA.
On the OCTA, it can be difficult to interpret very subtle changes on the superficial plexus. It's really in the deeper plexus where you see these telangiectasias with a greater distance between the vessels than you see, for example, on the nasal side.
Also, the diagnosis can be difficult in cases that have choroidal neovascularization (CNV) as a complication. I think OCTA, and maybe to a lesser extent FA, can be helpful in determining if a secondary CNV is present. All the cases have temporal leakage, but that doesn't mean they all have CNV present.
Early on, I will ask if the patient has a history of tamoxifen use, or, at least, a history of cancer. Tamoxifen retinopathy can closely resemble some of the early features and findings of MacTel.
Dr. Bakri: That’s an important point. Our goal is to diagnose MacTel as early as possible—while still maintaining diagnostic certainty—given the increasing relevance of early intervention. With ongoing clinical trials and now an FDA-approved treatment (revakinagene taroretcel-lwey [Encelto; Neurotech Pharmaceuticals]), timely diagnosis is more important than ever.
Equally important is helping patients understand their prognosis. Many patients seek clarity and closure, and a confirmed diagnosis can provide both. Moreover, although visual acuity may remain relatively preserved in the early stages, the functional burden of MacTel can still be significant. Fortunately, there are now several support groups available to help patients navigate the emotional and practical challenges associated with the disease.
Managing Symptoms and Challenges
Dr. Goldberg: Yes, this is a disease where visual acuity does not correspond to visual function. MacTel patients will report difficulties with activities such as reading and doing computer or near work. It can be caused by a mismatch between the eyes, which is usually just temporal or juxtafoveal. But on the temporal aspect, they may have a visual confusion of the 2 eyes competing against each other, so they’ll often occlude one eye.
The other things I hear are challenges with depth perception, contrast sensitivity, or night vision. Sometimes it's not so much night vision but that the patient takes a long time to accommodate or adjust to being in a dark environment.
Sophie, what are some of the symptoms or complaints from your patients with MacTel?
Dr. Bakri: Blurry vision is often a complaint, but then when you press the patient more on it, it’s that they're reading a line and then the letters disappear. That will correspond to the cavities that we see on the OCT or the loss of the ellipsoid zone. Vision generally tends to be in the 20/30 to 20/60 visual acuity range.
Dr. Goldberg: MacTel is not nearly as common as macular degeneration, but studies have shown that it can have a profound reduction in quality-adjusted life years and adversely affect a wide range of activities. If you sit and talk to these patients, you find they are often significantly affected.
Dr. Bakri: It’s also important for the patient to connect with an ophthalmologist who's an expert in MacTel so they can be offered the best treatment for their condition. Now that there is a treatment, we need to decide who the best candidates are and when they would most benefit from it.
In the next installment, Dr. Bakri and Dr. Goldberg will discuss advances in the treatment of MacTel.
