Idiopathic macular telangiectasia type 2 (MacTel) is a bilateral, progressive, and irreversible macular disease. Although initially considered a vascular disease because of its characteristic effect on blood vessels, which makes them appear telangiectatic, we now suspect that MacTel is neurodegenerative in origin.1,2
In MacTel, the Müller glial cells surrounding and supporting retinal neurons become dysfunctional, leading to structural changes such as progressive neuronal atrophy and outer retinal disorganization.2 MacTel can also lead to severe deteriorations in the visual function of patients in ways that hinder their ability to perform tasks necessary for everyday life, such as reading or driving.3
The emergence of the first US Food and Drug Administration (FDA)-approved therapy for MacTel type 2 makes it an ideal time for us as eyecare professionals to familiarize ourselves with this condition so that we can be knowledgeable to support our patients who may be losing their functional vision due to MacTel.
MacTel: Clinical practice vs clinical trials
Although MacTel is considered a rare disease, I suppose that many patients with MacTel—perhaps the majority—are either undiagnosed or misdiagnosed as having a different, more common macular disease or degeneration. Why might this happen?
One reason is that the symptoms of MacTel are relatively nonspecific and overlap with those of other ocular disorders, such as diabetic retinopathy and retinal vein occlusion.4,5 Routine monocular vision testing in the clinic may misrepresent the impact of a patient’s disease, as the visual acuity can often remain 20/25 or better until much of the central macula is overtaken by disease.3
Clinically, the signs of MacTel can mimic those seen in other diseases. Changes in the retinal pigment epithelium (RPE) may resemble those seen in age-related macular degeneration (AMD);6 for example, cystoid cavitations and draping of the internal limiting membrane seen on optical coherence tomography (OCT) may resemble cystoid macular edema and an epiretinal membrane, respectively.
Figure 1: OCT of MacTel patient showing cystoid degenerative changes with loss of photoreceptors temporal to the fovea.
Figure 1: Courtesy of Roger A Goldberg, MD, MBA.
Difficulties in diagnosing MacTel
Due to these factors, diagnosing MacTel in routine clinical practice may be somewhat challenging. It is important to assess the totality of a patient’s complaints to fully recognize the factors that may indicate a MacTel diagnosis.
For example, patients with MacTel may present with problems seeing in low light or have difficulty reading,7,8 so a patient with good best-corrected visual acuity who complains of these problems may prompt suspicion of MacTel.
Methods that measure functional outcomes, such as low luminance testing and reading speed, may help assess and monitor the progression of MacTel, but these tests are not routinely conducted in eyecare settings.
Using multimodal imaging to detect MacTel
The tools and techniques available in a clinical trial setting can facilitate more accurate diagnosis and monitoring than in day-to-day practice. OCT and OCT angiography (OCT-A) are invaluable due to their ability to detect the structural and vascular changes in MacTel, such as vessel density, differential involvement of retinal plexuses, and retinal neovascularization.
Characteristic structural changes in MacTel that can be observed with OCT include hyporeflective cavities in the retina and disruption of the external limiting membrane and photoreceptor inner segment-outer segment border and interdigitation zone. Characteristic structural changes seen on OCT-A include vessel ectasia, particularly in the deep plexus, and vessel rarefaction with increasing intervascular spaces.8
Fluorescein angiography (FA) can also be helpful in detecting structural changes, particularly in determining the presence of choroidal neovascularization, a potential complication of MacTel that can result in significant vision loss from subretinal hemorrhage, disciform scarring, and cystoid macular edema.1
In addition, from a functional perspective, microperimetry, in particular, is well-suited for monitoring of MacTel due to its ability to test visual function outside of the central fovea and identify loss of macular sensitivity,10 though this type of testing has heretofore mostly been limited to the clinical trial setting.
Figure 2: Fluorescein angiography of a MacTel patient showing characteristic juxtafoveal leakage.
Figure 2: Courtesy of Roger A Goldberg, MD, MBA.
Emergence of a novel therapeutic approach: ENCELTO
While anti-vascular endothelial growth factor (anti-VEGF) therapy is effective for treating choroidal neovascularization associated with MacTel,11 the FDA has just recently approved ENCELTO (revakinagene taroretcel-lwey) on March 6th, 2025, indicated for the treatment of adults with MacTel type 2.12
ENCELTO is an encapsulated cell therapy (ECT) consisting of a small capsule implanted and anchored to the sclera. The capsule is made of a semi-permeable membrane containing genetically modified RPE cells engineered to produce ciliary neurotrophic factor (CNTF). In prior research, CNTF has been shown to have a neuroprotective effect by promoting photoreceptor survival.13
In two phase 3 trials, ENCELTO demonstrated that it slows the progression of retinal degeneration, as measured by the structural outcome of ellipsoid zone (EZ) loss, a proxy measure for loss of photoreceptors.14 ENCELTO was also generally well-tolerated, with most treatment-related emergent ocular adverse events being related to surgery.
Because implantation has been associated with severe vision loss, infectious endophthalmitis, retinal tear and detachment, vitreous hemorrhage, implant extrusion, cataract formation, suture-related complications, and delayed dark adaptation, any signs or symptoms of these adverse events should be reported as soon as possible.14
ENCELTO is contraindicated in patients with active or suspected ocular or periocular infections or known hypersensitivity to Endothelial Serum Free Media.14 Important safety information can be found here. Regarding functional outcomes, treatment with ENCELTO was shown to slow the retinal sensitivity loss on microperimetry and the rate of reading speed loss compared to sham therapy.15
Looking toward the future
The approval of an effective therapy for MacTel highlights the progress we have made and the areas where we can still improve as a field, particularly in diagnosing this challenging condition. If you have a patient who you think may have MacTel, I encourage you to refer them to a retina specialist as early as possible, even if they are currently relatively asymptomatic.
Consistent with the importance of early management, post-hoc analyses demonstrated that lower EZ area loss, younger age, and no foveal involvement at baseline were associated with higher odds of achieving a response with ENCELTO.16
This new therapy has created an excellent opportunity for optometrists and retinal specialists to collaborate on caring for patients with MacTel. Optometrists often have long-standing relationships with their patients, have significant experience assessing and helping patients maximize their visual function, and have experience performing advanced visual testing.
This could be used to help monitor the status and progression of disease by periodically testing reading speed or central visual fields. It is exciting to know we now have an available therapy for a blinding disease that was once considered untreatable.
Dr. Goldberg is a paid consultant and investigator for Neurotech Pharmaceuticals. He received no compensation for authoring this article.
