Reframing the MacTel Zone

Macular telangiectasia type 2 (MacTel) is a chronic, progressive, neurodegenerative macular disease characterized by the loss of Müller glial cells, which support the functional and structural integrity of the retina (1). As the condition progresses, disturbances in central vision may range from blurring and difficulty reading to metamorphopsia and scotomas (2). Because MacTel affects the macula, patients may also report changes or difficulty in color perception (3). The disease may eventually result in varying degrees of vision loss resulting from less common sequelae, including subretinal neovascularization, fibrosis, atrophy of the foveal photoreceptor layer, and full-thickness macular holes (4).

Estimates for the prevalence of this condition vary – while approximately only 0.1 percent of the population was identified as being affected in a 2010 study (5), more recent diagnostic methods suggest it could be underdiagnosed (6).

Assessing structural changes and visual function

The region affected by MacTel is commonly described as the “MacTel area” or “MacTel zone.” This term refers to the primary region of disease involvement, a circumscribed, oval-shaped area centered over the fovea. When the foveal center begins to degenerate, more pronounced vision loss may occur (4).

Assessing visual acuity with a Snellen or early treatment diabetic retinopathy study (ETDRS) chart may not capture the full picture of visual loss in patients with MacTel, such as the degree of scotoma present, disruption in color vision, or altered contrast sensitivity. For example, affected individuals may be testing at 20/20 or 20/25 on an acuity chart, but complain about missing pieces of their overall visual field.

Advanced imaging techniques like spectral domain optical coherence tomography (SD-OCT) are useful for revealing structural changes. As the Müller cells degenerate, the ellipsoid zone is disrupted, which is considered a proxy for photoreceptor dysfunction and visual function loss (7). As the disease progresses, the inner retinal layers degenerate, eventually resulting in a draping of the internal limiting membrane over the affected area (8).

Multifocal electroretinographic (mfERG) imaging can also be helpful for reflecting inner retinal dysfunction in MacTel, and correlates with best corrected visual acuity (9). Additionally, microperimetry can complement the ability of mfERG in detecting changes to macular function (10).

Monitoring changes over time

In my clinical practice, patients with MacTel are monitored every 6 to 12 months, depending on the level of severity, longitudinal disease progression demonstrated, and contribution of other ocular comorbidities. Patients who are stable and asymptomatic with 20/25 or 20/30 vision, for instance, may opt to come in only annually, whereas those with more severe vision loss or asymmetric advanced findings may have greater anxiety about their condition and so prefer to be monitored more frequently.

Early signs of progression on dilated fundus examination include a blunted foveal reflex or macular graying (11). Intraretinal crystals at the level of the inner limiting membrane occur irrespective of disease stage in roughly half of MacTel patients (12). Bleeding or hemorrhage from subretinal neovascularization may be observed, as well as potential macular hole formation, which is a rare – but well-described – complication that can arise.

Fundus autofluorescence (FAF) is an optimal tool for identifying early – potentially subclinical – changes, preceding signs we can observe on examination or even OCT imaging. Macular pigment distribution changes over time with this condition, and it is thought that early loss of macular pigment density in the fovea alters the composition of fluorophores within the underlying retinal pigment epithelial layer, resulting in increased autofluorescence. Hyperautofluorescence in the temporal macula can therefore be an early indicator of the presence of MacTel (12).

Fluorescence lifetime imaging ophthalmoscopy (FLIO) has likewise been identified as a tool that may be able to detect pigmentary changes early in the disease process, before leakage is observed in fluorescein angiography (FA), though access to this imaging technique is currently not as widespread (11).

FA frequently reveals the presence of dilated, blunted, right-angle vessels that are characteristic of MacTel. Early-phase images show leakage of perifoveal telangiectatic vessels, and FA can also be useful for detecting some of the sequelae of more advanced disease, such as subretinal neovascularization and hemorrhage (13, 14).

Again, OCT is a critical diagnostic and monitoring tool, and can be especially useful to demonstrate changes in the disease over time. The stability of serial OCT images over a six- or 12-month period, or over the course of years, can be reassuring to patients. A library of reproducible OCT cuts can essentially become a long-term database for each patient, and, in my experience, some patients become so invested in this endeavor that they learn to read their own OCT scans.

Considering the whole patient

One of my late mentors, Joseph Maguire, was fond of reminding us retina fellows during training that “MD stands for medical doctor for a reason.” Throughout our daily encounters as eye care providers, we have numerous opportunities to potentially intervene and improve a patient’s quality of living beyond their ophthalmologic presentation.

With MacTel, I find it important to counsel patients regarding potential systemic risk factors that have been linked to the disease, such as underlying hypertension, diabetes, and obesity (15). If they haven’t recently, I encourage my patients to visit their primary care physician for routine wellness examinations and basic laboratory testing (i.e., hemoglobin A1c), for if we are vigilant at reinforcing whole-body health, we may help these individuals avoid potential ocular complications caused by such comorbidities.

Recently, the FDA approved the first therapy, ENCELTO (revakinagene taroretcel-lwey), to help slow progression of MacTel (16). The treatment is an encapsulated cell therapy that is surgically administered and designed to deliver ciliary neurotrophic factor continuously to the retina. While it is still early – and the product won’t be commercially available until mid-year 2025 – it does mean that we are finally able to impart a message of hope to MacTel patients, who may have spent years being told there was no treatment for their condition. The advent of therapy now places the onus on us as physicians to better familiarize ourselves with the condition, recognize it early, identify appropriate candidates for treatment, and have clear, effective conversations with patients about the potential benefits and risks of therapy.

Though it has historically been believed that MacTel progresses slowly and may not compromise visual acuity worse than 20/40-20/50 range, this may not hold true in every case, and further investigations are warranted to determine why the disease progresses at different rates in different individuals. Similarly, identifying better biomarkers that can be used to diagnose the disease at earlier stages, as well as portend a patient’s likelihood of progressing to more severe vision loss, is an important next step. Though the approval of the first therapy for MacTel is a tremendous victory for our field and patients, the work to improve outcomes in this disease is really just beginning.