Management of macular telangiectasia type 2 may be near

Macular telangiectasia type 2 is a progressive and relatively rare neurodegenerative disease of the macula that typically affects patients who are older than 40 years of age, more predominantly women.

Initially, macular telangiectasia (MacTel) type 2 was considered a retinal vascular disease; however, over the past decade, studies have revealed that it is in fact a neurodegenerative condition (Kedarisetti and colleagues).

In MacTel type 2, Müller cells, which are important for maintaining the blood-retinal barrier and surround and provide nutrients to retinal neurons, become dysfunctional, leading to atrophy and disorganization of the outer retina (Kedarisetti and colleagues).

Diagnosis

Patients with MacTel type 2 often initially present with symptoms in their fifth decade of life, and as the disease advances, they will notice impairment of their central vision (Kedarisetti and colleagues). This impairment can significantly affect daily life, leading to challenges with reading, driving and working and an increased risk for falls and injuries. It may also take a toll on mental health.

Due to the relative rarity and low awareness surrounding MacTel type 2, diagnosis is often delayed, and the disease may be misdiagnosed, for example, as age-related macular degeneration (Charbel Issa and colleagues). The hallmark sign of MacTel type 2 is the presence of black hyporeflective spaces on OCT imaging; diagnosis is usually established on a combination of examination, OCT imaging, fluorescein angiography and possibly fundus autofluorescence (Kim and colleagues).

Clinicians may misinterpret the black spaces identified on OCT as edema, which can contribute to misdiagnosis. If patients with MacTel type 2 are misdiagnosed, they may undergo unnecessary treatment aimed at addressing swelling in the retina, which will ultimately prove fruitless, as neurodegeneration is the true culprit behind their vision loss.

Current management strategies

There is currently no approved treatment for MacTel type 2. Once diagnosed, patients should be followed and monitored for development of subretinal neovascularization, known as proliferative MacTel. Subretinal neovascularization can result in significant loss of vision due to subretinal hemorrhage, cystoid macular edema, hard exudates and disciform scarring (Kedarisetti and colleagues).

If subretinal neovascularization does occur, treatment with anti-VEGF therapies has been found to improve visual acuity and involute neovascularization (Roller and colleagues; Toygar and colleagues). However, anti-VEGF therapies do not seem to show efficacy in nonproliferative MacTel (Roller and colleagues).

Hope on the horizon

While there are currently no approved therapies for MacTel, over the past decade, there have been ongoing investigations for a promising novel therapeutic approach. NT-501 (Neurotech Pharmaceuticals) is a surgically implanted encapsulated cell therapy that delivers ciliary neurotrophic factor (CNTF) intravitreally. CNTF has demonstrated the ability to slow photoreceptor degeneration in several preclinical models. Its mechanism involves activation of the gp130 receptor in Müller cells, which suggests its potential as a neuroprotective treatment for diseases associated with Müller cell loss (Duncan).

The investigational product, NT-501, has already completed pivotal phase 3 clinical trials, which demonstrated that eyes that received the implant had significantly reduced ellipsoid zone area loss, representing a 56.4% reduction in retinal degeneration at 24 months vs. eyes that received sham therapy. NT-501 has been generally well tolerated; ocular treatment-emergent adverse events likely related to CNTF have included delayed dark adaptation and miosis (Wykoff; Chew and colleagues).

The NT-501 implant is currently under review by the FDA (Maharjan) and, if approved, would be the first therapy for MacTel type 2 and a meaningful advance in cell therapy for the eye. By addressing the underlying neurodegenerative pathogenesis of MacTel, NT-501 may provide neuroprotective effects in slowing the progression of retinal deterioration and preserving patients’ remaining vision.

Conclusion

Although MacTel type 2 may be a relatively rare condition, it is important to accurately diagnose and follow patients with this disease, especially now that we may be on the cusp of having an effective therapy for the first time. If we can help affected individuals and slow the progression of their disease, we can positively affect our patients’ lives and offer them hope for dealing with a condition that has long been considered untreatable.

• References:
• Charbel Issa P, et al. Prog Retin Eye Res. 2013;doi:10.1016/j.preteyeres.2012.11.002.
• Chew EY, et al. Ophthalmology. 2019;doi:10.1016/j.ophtha.2018.09.041.
• Duncan JL. Ophthalmology. 2019;doi:10.1016/j.ophtha.2018.12.023.
• Kedarisetti KC, et al. Clin Ophthalmol. 2022;doi:10.2147/OPTH.S373538.
• Kim YH, et al. Ophthalmic Epidemiol. 2021;doi:10.1080/09286586.2021.1872088.
• Kim YH, et al. Sci Rep. 2020;doi:10.1038/s41598-020-73803-9.
• Maharjan EK. FDA grants priority review to novel treatment for macular telangiectasia type 2. Optometry Times. Published June 20, 2024. Accessed Sept. 25, 2024.
• Roller AB, et al. Retina. 2011;doi:10.1097/IAE.0b013e31820d3feb.
• Toygar O, et al. Retina. 2016;doi:10.1097/IAE.0000000000001035.
• Wykoff CC. Trial updates in GA, MacTel type 2 and DME. Retina Specialist. Published Oct. 3, 2023. Accessed Sept. 25, 2024.

• For more information:
• Diana V. Do, MD, a professor of ophthalmology and vice chair for clinical affairs at Byers Eye Institute at Stanford University and clinic chief of ophthalmology at Stanford Health Care, can be reached at dianado@stanford.edu.

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Disclosures:
Do reports consulting for and receiving research funding from Neurotech Pharmaceuticals.

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