MacTel and neovascular conversion: Jay Chhablani, MD, weighs in

Macular telangiectasia type 2 (MacTel) is generally described as a slowly progressive neurodegenerative disease, but a subset of patients develop neovascular complications that can accelerate vision loss and demand a different management approach, one that has grown more layered since revakinagene taroretcel-lwey (Encelto; Neurotech Pharmaceuticals) became the first FDA-approved treatment for the disease's non-neovascular, atrophic component.

Modern Retina spoke with Jay Chhablani, MD, professor of ophthalmology and vice chair of clinical trials and director of clinical research at the UPMC Vision Institute in Pittsburgh, Pennsylvania, whose published research includes imaging-based characterization of neovascular conversion in MacTel. In the following Q&A, Chhablani discusses how neovascular MacTel differs biologically from neovascular age-related macular degeneration (AMD), the clinical and imaging red flags that warrant urgent referral, how a thin evidence base shapes anti-VEGF treatment decisions, and where the biggest gaps remain in understanding disease conversion.

This Q&A has been edited for length and clarity.

Modern Retina: MacTel is typically described as a slowly progressive disease, but neovascular complications change that trajectory. How do you explain to patients and to referring clinicians what's happening when a MacTel eye develops a neovascular membrane?

Jay Chhablani, MD: MacTel is a slowly progressive neurodegenerative disease at its core, but when neovascularization develops, a second process is essentially added on top of it. I explain it as a switch in biology, from a degenerative, atrophic process to one that now has an exudative, vascular component.

To patients, I simplify it: your condition has been slowly affecting the support cells of the retina, but now abnormal blood vessels have grown, and those can leak or bleed, which is why vision can change more quickly.

For referring clinicians, I emphasize that this is not classic AMD-type choroidal neovascularization (CNV). It's typically driven by deep retinal capillary remodeling, so the behavior, imaging, and response to treatment can differ.

MR: Sudden vision change is the classic red flag for neovascular conversion in MacTel. What should clinicians look for at that visit, how urgently does the patient need a retina referral, and since these vessels typically arise from the deep retinal circulation rather than the choroid, as in AMD, how does that change what you look for on OCT and angiography, and how you counsel patients on prognosis?

Chhablani: The key symptom is a sudden change, such as new distortion, central blur, or a drop in reading vision. Patients often describe it as a smudge or as lines bending. On exam and imaging, look for new intraretinal or subretinal fluid on optical coherence tomography (OCT), hyperreflective material in the outer retina, and subtle hemorrhage that's often more minimal than what you'd see in AMD. The threshold for referral should be low and fast, ideally within days rather than weeks. Unlike non-neovascular MacTel, where one can monitor, this is a situation where early anti-VEGF can stabilize vision.

In MacTel, the neovascular complex often originates from the deep retinal circulation, sometimes forming a retinal-retinal or retinal-subretinal anastomosis rather than classic choroidal neovascularization. On OCT, one may see primarily intraretinal changes, hyperreflective lesions, cystic spaces, or outer retinal disruption, sometimes with less subretinal fluid than expected in AMD. OCT angiography is very helpful, showing abnormal vessels extending from the deep capillary plexus extending outward, while fluorescein and indocyanine green angiography tend to show less dramatic leakage than in AMD.

For counseling, I tell patients that the disease behaves differently than AMD and that vision outcomes can be variable, sometimes limited more by the underlying neurodegeneration than by the neovascular component itself. Even when the vessels are treated, the baseline disease still matters.

MR: With Encelto now approved for MacTel, retina specialists have, for the first time, a treatment aimed at the non-neovascular, atrophic side of the disease. Does that approval change how aggressively you screen for or think about the neovascular subtype, and could a patient ever need both approaches?

Chhablani: The approval of Encelto is important because it addresses, for the first time, the non-neovascular, neurodegenerative side of MacTel. It absolutely makes me more attentive overall to these patients, but it doesn't reduce vigilance for neovascular conversion. If anything, it reinforces the need to phenotype carefully.

A patient could need both approaches: one therapy targeting the atrophic or neurodegenerative component, and anti-VEGF targeting the neovascular complication. This is becoming more of a dual-pathway disease, and management may need to reflect that.

MR: The evidence base for anti-VEGF in neovascular MacTel is far thinner than in AMD, small case series rather than large randomized trials. How does that evidence gap affect your day-to-day decision-making, and where do you lean on judgment versus data?

Chhablani: The evidence base is limited, mostly small series and real-world experience. In practice, I rely on biological plausibility, since VEGF is still a driver of leakage, along with the consistent clinical observation that many of these lesions respond to anti-VEGF therapy, at least anatomically.

Judgment comes in when deciding whether to initiate treatment early or observe borderline cases, and in determining treatment interval, since these lesions often don't follow classic AMD protocols. It's a balance: use the available data, but individualize heavily based on imaging and response.

MR: How do you counsel a patient who presents late, and how do you decide when treatment is still worth attempting versus when you're managing expectations instead?

Chhablani: Late presenters are challenging because vision loss may be due to both the neovascular process and underlying retinal atrophy. I treat if there's active fluid or recent decline. But if there's dense atrophy or longstanding structural damage, the focus shifts more toward realistic expectations and visual rehabilitation, rather than aggressive treatment.

MR: MacTel and AMD are both age-related, both can produce macular neovascularization, and there are documented cases of the two coexisting in the same patient, sometimes the same eye. How do you avoid anchoring on one diagnosis and missing that you're either looking at the other disease, or both at once?

Chhablani: This is a real diagnostic pitfall. The overlap between MacTel and AMD can be subtle, especially in older patients. To avoid anchoring, look carefully at MacTel hallmarks, including temporal parafoveal changes, inner and outer retinal cavitations, and right-angle venules, while also assessing for drusen and retinal pigment epithelium (RPE) changes suggestive of AMD. OCT angiography helps clarify the origin of the neovascularization.

MR: Outside of what's already been studied and published, what's the biggest knowledge gap in the MacTel space right now?

Chhablani: The biggest gap, in my view, is understanding the transition point, what drives a MacTel eye from purely neurodegenerative to neovascular. We still don't fully know the molecular triggers, the role of Müller cell dysfunction versus vascular remodeling, or the predictive biomarkers for conversion. If we could identify patients before they convert, that would fundamentally change management, especially now that there are therapies targeting the non-neovascular side.