After years of firing blanks at MacTel, researchers may have finally hit their target…by aiming at the neurons instead of the vessels. Could CNTF therapy be the game changer the field’s been waiting for?
Macular telangiectasia type 2 (MacTel) has long been the unsolved puzzle on the retina specialist’s board. As Prof. Frank Holz (Germany) quipped during his talk at EURETINA 2025,1 “There have been several attempts to tackle this particular disease…whenever we see a leakage, then there seems to be a golden bullet to shut.” Sadly, that “golden bullet” usually ricocheted.
Over the years, nearly every therapy imaginable was fired at MacTel: laser photocoagulation, microthermal laser, photodynamic therapy, steroids, indocyanine green (ICG), even photothrombosis. “You name it,” said Prof. Holz, “The list is really long, but we must say that this was not changing the outcomes in patients in many respects.”
When it comes to nutrition, the story wasn’t much rosier. Macular pigment carotenoids such as lutein and zeaxanthin—mainstays in age-related macular degeneration (AMD)—have been considered for MacTel due to their antioxidant and blue-light filtering properties. But the evidence remains underwhelming.2
While a diet rich in carotenoids is generally sound advice for retinal health, there’s little to suggest it halts MacTel progression. For now carotenoids remains supportive, not transformative.2
The introduction of anti-vascular endothelial growth factor (anti-VEGF) agents sparked hope. Referencing work by Peter Issa and colleagues,3 Prof. Holz noted that early imaging showed “a significant amount of hypofluorescence that either largely resolved or improved after several months of treatment with ranibizumab.” Yet the improvement proved fleeting.
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“When the therapy was terminated after 12 months, there was a massive rebound,” he recalled. “It looked the same as before, so there was no long-lasting effect and no functional benefit.”
Worse still, there was evidence of harm. “There was no functional benefit for anti-vascular endothelial growth factor treatment whatsoever,” Prof. Holz stated. Optical coherence tomography (OCT) revealed retinal thinning, not a good sign in this context. “Treated eyes…had faster loss of photoreceptors. They had worse visual acuity,” he added.
His takeaway was firm. “The key message is: don’t use anti-VEGF therapy in the non-proliferative stage of MacTel. Unless there is rapid proliferation involving intraretinal or subretinal neovascularization, in which case, anti-VEGF treatment may be worthwhile,” he emphasized.
Rethinking the battle plan
The game changer in MacTel research was the shift from thinking vascular to thinking neural.
What was once considered a vascular oddity is now recognized as primarily a neurodegenerative disease. As Prof. Holz explained, neuronal damage occurs first, and the vascular changes follow as secondary effects.
This insight refocused attention on neuroprotection—specifically, the ciliary neurotrophic factor (CNTF), a protein that supports photoreceptor survival. “Preclinical models have shown that photoreceptors could be rescued by injecting into the eye the CNTF factor,” said Prof. Holz. These findings paved the way for clinical application.
Enter Neurotech Pharmaceuticals’ (Rhode Island, USA) NT-501 (Encelto), an encapsulated cell therapy implant that delivers CNTF directly into the eye. Acting as a self-sustaining reservoir, it continuously produces CNTF over time, offering sustained neuroprotective effects. Impressively, explanted human devices have shown CNTF production lasting up to 14 years, according to Prof. Holz.
The surgical procedure is straightforward. The tiny device is implanted in the vitreous and sutured to the sclera, maintaining steady intraocular CNTF levels without the need for repeated injections.
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From promise to performance
To secure regulatory approval, strong evidence was essential. Prof. Holz shared data from two parallel Phase III trials (NTMT03A and NTMT03B) conducted across 47 international sites. Participants received either the Encelto implant or underwent sham surgery, with investigators masked to the assignments.4
Eligible patients were aged 21 to 80, each with an ellipsoid zone (EZ) break of moderate size—“not too small” to risk spontaneous regression and “not too large” to remain treatable.4
The primary endpoint was the change in EZ area loss from baseline to month 24, a structural marker accepted by regulators.4 “The primary endpoint was chosen at two years, and not 12 months, due to the slow progression of the disease,” said Prof. Holz.
Secondary endpoints included changes in retinal sensitivity within the EZ break and monocular reading speed, a functional marker of vision.4
The top-line results were impressive. At 24 months, the primary endpoint was met in both trials, with a 54% and 36% reduction in EZ area loss, respectively.4 “Both studies showed a similar effect on function and structured outcome,” said Prof. Holz.
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Retinal sensitivity preservation was mixed—significant in NTMT03A, not in NTMT03B—but functional vision outcomes were more consistent.4 “Patients treated could read faster in the end compared to baseline and compared to the sham-treated eye,” he noted.
Safety outcomes were reassuring, with no significant differences in visual acuity loss or treatment-emergent serious adverse events between the NT-501 and sham groups.4
In summary, these trials mark the first real success in changing the natural course of MacTel. “Treatment with NT-501 versus sham preserved more photoreceptors through two years in both Phase III clinical trials. Overall, the results do demonstrate that the therapy works. Encapsulated cell therapy is effective and found to be generally safe and well tolerated,” Prof. Holz concluded.
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Hope with a capital H
For years, MacTel has left clinicians with little more than crossed fingers and cautious monitoring. Now, with advances in imaging, a deeper understanding of its neurodegenerative roots, and the dawn of CNTF-based therapy, a new era is beginning.
If the momentum continues, the field may soon move from “managing decline” to “preserving function”—and perhaps, one day, to “restoring vision.” That’s not just progress. For MacTel patients and retina specialists alike, it’s a long-overdue glimmer of hope.
Editor’s Note: Prof. Frank G. Holz’s insights in this article are based on his Day 3 presentation at an EURETINA 2025 Paris session on MacTel Type 2, titled “Current and Upcoming Therapies”. This content is intended exclusively for healthcare professionals. It is not intended for the general public. Products or therapies discussed may not be registered or approved in all jurisdictions, including Singapore. A version of this article was first published in PIE Issue 37.
References
- Holz F. MacTel Type 2: Bridging Diagnosis and Emerging Therapies. Lecture at EURETINA 2025. Paris, France. September 6, 2025.
- Richer S, Stoumbos VD, Bowling N, et al. The emerging roles of the macular pigment carotenoids lutein and zeaxanthin. Prog Retin Eye Res. 2021;81:100897.
- Pauleikhoff L, Heeren TFC, Issa PC, et al. Fundus autofluorescence imaging in macular telangiectasia type 2: MacTel Study report number 9. Am J Ophthalmol. 2021;228:27-34.
- Chew EY, Gillies M, Jaffe GJ, et al. Cell-based ciliary neurotrophic factor therapy for macular telangiectasia type 2. NEJM Evidence. 2025;4(8):EVIDoa2400481.
