Macular Telangiectasia
All content on Eyewiki is protected by copyright law and the Terms of Service. This content may not be reproduced, copied, or put into any artificial intelligence program, including large language and generative AI models, without permission from the Academy.
Disease Entity
Disease
Macular telangiectasia (Mac Tel) is a disease that causes abnormalities of capillaries of the fovea or perifoveal region that are associated with loss of outer nuclear layers and the ellipsoid zone, Eventually, these abnormalities can progress to cystic cavitation-like changes in all retinal layers, or to development of full-thickness macular hole or subretinal neovascularization in advanced stages. It was first described by Dr. Donald Gass in 1968 as a different entity from Coats disease.
Mac Tel is divided into 3 main types:
- Type 1: Congenital and unilateral. Thought to be similar to and/or possibly a variant of Coats disease. Uncommon
- Type 2: Acquired and bilateral. The most common of the 3 types; usually found in middle-aged or older patients. According to the Beaver Dam Eye Study which graded only color fundus images, the average patient age was 63 years. Although the sex differences seen in type 2 were not initially described by Gass, Dr. Lawrence Yannuzzi found a slight female preponderance of 58%. The term "Mac Tel" is often used to refer to just type 2; therefore, this article will largely focus on type 2, as it has the most clinical relevance
- Type 3: A rare, poorly understood primarily occlusive phenomenon
Etiology
The Mac Tel Project found that the 28% of patients with type 2 Mac Tel had concomitant diabetes mellitus (DM) and 52% had concomitant hypertension (HTN). The prevalence of HTN and DM, as well as the older age of disease onset, can point toward long-term vascular stress as the etiology for Mac Tel. These vascular changes are associated with disruption of the outer nuclear layer and ellipsoid zone and lead to pseudolamellar macular holes. Retinal pigment epithelium (RPE) hyperplasia and migration into the inner retinal layers is seen with disease progression.
General Pathology
Gass postulated that Müller cells and parafoveal neural cells may be the primary sites that are initially affected. Histopathology has shown disruption of pericytes and ectatic vessels, with dilated venules diving at a right angle into deeper retinal layers with evidence of RPE hyperplasia. As discussed above, vascular occlusion, inflammatory changes, and other neurodegenerative processes lead to loss of the outer nuclear layer and the ellipsoid zone, with later formation of cyst-like cavitations that can encompass all retinal layers.
Pathophysiology
Chronic neurodegenerative processes, vascular inflammation, occlusion, and ectatic capillary changes lead to loss of outer retinal layers and formation of pseudolamellar macular holes with cyst-like cavitations that can also be seen in the inner retinal layers. Patients can develop retinal neovascularization temporal, which can cause exudation, intraretinal and subretinal hemorrhaging, and disciform scaring.
Primary Prevention and Treatment
Most clinicians would recommend controlling HTN and DM if present, as these 2 diseases have been shown to be prevalent in patients with Mac Tel. Treatment modalities for the disease have traditionally limited to anti-VEGF agents in cases of neovascularization. 1–4 Neuroprotective therapies, including ciliary neurotrophic factor (CNTF) implants such as ENCELTO, present as a new treatment modality for MacTel type 2.[1]
ENCELTO
Mechanism of Action
ENCELTO is an encapsulated, cell-based gene therapy that consists of allogenic retinal pigment epithelial (RPE) cells that secrete recombinant human ciliary neurotrophic factor (rhCNTF). rhCNTF is a neurotrophic factor endogenously produced by neurons and glia that promotes photoreceptor survival by initiating a protective signaling cascade. Although the full mechanism of action of ENCELTO is not fully understood, the proposed mechanism involves slowing the progression of ellipsoid zone (EZ) loss, which is a marker of photoreceptor degeneration, and increases retinal integrity in MacTel type 2.[1]
Indication
ENCELTO is indicated for the treatment of adults with idiopathic macular telangiectasia type 2 (MacTel).
Clinical Trials
The efficacy and safety of ENCELTO were evaluated in two randomized, multi-center, double-masked, sham-controlled Phase 3 trials: NTMT-03-A (Study 1) and NTMT-03-B (Study 2). Both studies enrolled adult patients with non-neovascular MacTel Type 2 and an ellipsoid zone (EZ) loss area between 0.16 and 2.00 mm² on spectral-domain OCT. Subjects also had a best corrected visual acuity (BCVA) of 54 letters or better (20/80 or better) on the ETDRS chart. Patients were randomized 1:1 to receive either ENCELTO implantation or a sham procedure mimicking the surgical experience without actual implant placement.
In Study 1 (n=115), ENCELTO significantly reduced the progression of EZ loss over 24 months compared to sham (mean rate of EZ loss: 0.075 mm² vs. 0.166 mm²; difference: -0.091 mm²; p<0.0001). ENCELTO also demonstrated a statistically significant preservation of retinal function, with a smaller decline in aggregate retinal sensitivity within the EZ break area (mean change: 25.27 dB vs. 43.02 dB; difference: -17.75 dB; p=0.02).
In Study 2 (n=113), ENCELTO showed significant slowing of structural degeneration, with a reduced rate of EZ area loss over 24 months (0.111 mm² vs. 0.160 mm²; difference: -0.049 mm²; p=0.0186). However, the secondary endpoint of aggregate retinal sensitivity loss did not achieve statistical significance (40.02 dB vs. 41.97 dB; p=0.83).5
Between both trials, ENCELTO proved successful as the first therapeutic option with demonstrated efficacy in slowing the neurodegenerative progression of MacTel Type 2. Its ability to preserve photoreceptor structure, and in some patients, function, represents a significant advancement in the management of this previously untreatable condition.[1]
Contraindications & Adverse Events
ENCELTO is contraindicated in patients with ocular or periocular infections. ENCELTO is also contraindicated in patients with known hypersensitivity to Endo-SFM, the medium in which ENCELTO is suspended.
Safety data were derived from both studies (n=117 treated) and showed ENCELTO was generally well tolerated. Adverse events occurring more frequently than sham included conjunctival hemorrhage (31%), delayed dark adaptation (23.1%), suture-related complications (15.4%), and vitreous hemorrhage (8.5%). Serious events were uncommon and included suture-related issues (n=5) and implant extrusion (n=1). Adverse events reported in ≥2% of ENCELTO-treated patients and at a higher frequency than sham included the following.[1]
| Adverse Event | ENCELTO (n=117) | Sham (n=111) |
| Conjunctival hemorrhage | 31% | 26% |
| Delayed dark adaptation | 23.1% | 1% |
| Foreign body sensation in eyes | 15% | 13.5% |
| Eye pain | 15% | 9% |
| Suture-related complications* | 15.4% | 2.7% |
| Miosis | 15.4% | 0% |
| Conjunctival hyperemia | 11% | 8% |
| Eye pruritus | 9% | 3.6% |
| Ocular discomfort | 9% | 1% |
| Vitreous hemorrhage | 8.5% | 0% |
| Blurred vision | 7% | 4% |
| Headache | 7% | 1% |
| Dry eye | 6% | 2% |
| Eye irritation | 5.1% | 2% |
| Cataract formation or progression | 5% | 0% |
| Vitreous floaters | 5% | 0% |
| Severe vision loss (>15 letters)** | 3% | 0% |
| Eye discharge | 3.4% | 0.9% |
| Anterior chamber cell | 3.4% | 0% |
| Iridocyclitis | 2.6% | 0% |
Dosing and Administration
ENCELTO is a single-use intravitreal surgical implant sutured to sclera at pars plana containing 200,000 to 440,000 allogeneic retinal pigment epithelial (RPE) cells that secrete recombinant human ciliary neurotrophic factor (rhCNTF). The implant is encapsulated within a semi-permeable polymer and includes a titanium fixation loop to allow surgical anchoring. The recommended dose includes one implant per affected eye that is administered via surgical intravitreal implantation under aseptic conditions. Please see package insert for preparation, surgical steps, and post operative management. ENCELTO should be surgically removed if infectious endophthalmitis develops or a vitrectomy with complete gas or silicone oil fill is necessary.[1]
Diagnosis
The diagnosis of Mac Tel is made by assessing patient history and conducting ophthalmic clinical exams. Ophthalmic imaging is also used.
History
Patients with Mac Tel type 2 often complain of metamorphopsia or scotoma. With disease progression, an increased scotoma can be perceived with decreased visual acuity (VA), as the scotoma affects the fovea and perifoveal area. However, VA rarely reaches legal blindness; the Mac Tel Project found that 50% of patients maintained a VA of 20/32 or better. However, VA can decrease if a macular hole develops. Vision can be severely diminished in Mac Tel types 1 and 3.
Physical Examination
In Mac Tel type 2, fundoscopic exam is initially significant for a decrease of foveal pit, with subsequent foveal or perifoveal ectatic vessels with possible presence of venules diving at a right angle into deeper retinal layers. Grayish discoloration of temporal perifoveal area is the earliest sign present. Ectatic vessels with evidence of venules diving at a right angle into deeper retinal layers. Of note, these findings may be subtle on routine retinal exam. Subretinal neovascularization temporal to fovea may be seen in this disease and can be associated with exudates or hemorrhage. RPE hyperplasia can also be seen at the fovea or temporal perifovea. Also, in later stages, pseudolamellar holes can develop into full-thickness macular holes.
Imaging
Fundus autofluorescence (FAF) is very useful, as it can detect functional changes before perceivable anatomic changes. For example, FAF shows increased foveal hyperautofluorescence secondary to loss of foveal luteopigment (xanthophyll is probably primarily stored in Müller cells, and this could be a surrogate measure of the health and concentration of Müller cells in affected areas). In more advanced stages with increased pigmentation, areas of RPE hyperplasia will appear as hypoautofluorescent spots.
Optical coherence tomography (OCT) shows temporal foveal pit enlargement secondary to loss of the outer nuclear layer and ellipsoid zone that can progress into large cysts (often called "cavitation") that can encompass all retinal layers. The cavitations are thought to be due to degenerative changes possibly caused by Müller cell depletion within the affected retina, creating structural void spaces rather than fluid-filled cystic cavities. When the degenerative changes are pronounced and include the inner retinal layers, only the internal limiting membrane (ILM) can be visualized, leaving a characteristic "ILM drape" over the affected area. The latter sign could be diagnostic. Additionally, hyperreflective areas on OCT correlate to areas of RPE hyperplasia and migration. OCT angiography (OCTA) has contributed to further understanding of the retinal vascular change by highlighting the telangiectatic changes and the dragging and crowding of vessels in areas of degenerative changes.
Fluorescein angiography (FA) shows the temporal foveal telangiectatic vessels in Mac Tel type 2 that leak in later frames. Evidence of venules diving at a right angle into deeper retinal layers can also be seen. Subretinal neovascularization, when present, is thought to be primarily retinal in origin, as FA shows a feeding arteriole and a draining venule.
Proposed Staging
Five distinct stages have been proposed to layout the progressive nature of Mac Tel:
- Stage 1: Normal fundus, with very subtle changes on FAF
- Stage 2: Loss of retinal transparency manifesting as graying of the affected area and hyperautofluorescence, as well as the appearance of mild telangiectatic change without exudation. Crystalline deposits at the level of the vitreoretinal interface (sub-ILM) could also be present
- Stage 3: Moderate telangiectatic changes, right-angle venules, and capillary remodeling in the outer retinal layers, without exudation
- Stage 4: Presence of pigmentary changes due to intraretinal RPE migration and hyperplasia that are thought to be secondary to the underlying degenerative changes
- Stage 5: Presence of retinochoroidal anastomosis leading to exudation and hemorrhage
Differential Diagnosis
Differential diagnoses of retinal capillary telangiectasia include branch retinal vein occlusion, diabetic retinopathy, and radiation retinopathy. In cases of neovascularization, age-related macular degeneration should also be ruled out.
Management
There have been no randomized clinical studies in Mac Tel. In non-neovascular cases, laser therapy, intravitreal anti–vascular endothelial growth factor (VEGF) injections, and corticosteroids have all been shown to not be effective in controlling the disease. For neovascular cases, intravitreal anti-VEGF injections are the mainstay of treatment, although transpupillary therapy and photodynamic therapy have been used in the past.
Neuroprotective agents are currently under investigation for the treatment of Mac Tel type 2. A phase 2 trial found decreased ellipsoid zone loss, increased macular thickness, and stable reading speed with intraocular delivery of ciliary neurotrophic factor (CNTF). The phase 3 multicenter Renexus (NT-501) trial compared the safety and efficacy of an intravitreal ocular implant designed to deliver therapeutic doses of CNTF vs sham treatment.
Associated full-thickness macular holes may be treated with pars plana vitrectomy surgery, membrane peeling, and gas tamponade, but these procedures may have lower-than-average closure rates and corresponding postoperative VA.
Prognosis
According to the Mac Tel Project, 60% of type 2 patients have a VA of 20/50 or better, with a mean VA of 20/40. Mac Tel can rarely lead to 20/200 or worse vision, especially when associated with full-thickness macular hole or retinal neovascularization associated with disciform scaring. However, about 79% of eyes with neovascularization and about 78% of eyes with macular hole have VA better than 20/200. Interestingly, eyes with VA 20/200 or worse (consider to be advanced disease) were reported to have pigmentary plaques, which are thought to be surrogate markers for photoreceptor degeneration.
Additional Resources
- Porter D. Blood pressure. American Academy of Ophthalmology. https://www.aao.org/eye-health/anatomy/blood-pressure-list. Published February 27, 2018. Accessed April 21, 2025.
- Turbert D. What is macular telangiectasia? American Academy of Ophthalmology. https://www.aao.org/eye-health/diseases/macular-telangiectasia-list. Published September 23, 2024. Accessed April 21, 2025.
References
1. Clemons TE, Gillies MC, Chew EY, et al; for the Macular Telangiectasia Project Research Group. Medical characteristics of patients with macular telangiectasia type 2 (MacTel type 2): MacTel Project Report No. 3. Ophthalmic Epidemiol. 2013;20(2):109-113.
2. Wu L, Evans T, Arevalo JF. Idiopathic macular telangiectasia type 2 (idiopathic juxtafoveolar retinal telangiectasis type 2A, Mac Tel 2). Surv Ophthalmol. 2013;58(6):536-559.
3. Charbel Issa P, Gillies MC, Chew EY, et al. Macular telangiectasia type 2. Prog Retin Eye Res. 2013;34:49-77.
4. Kedarisetti KC, Narayanan R, Stewart MW, et al. Macular telangiectasia type 2: a comprehensive review. Clin Ophthalmol. 2022;16:3297-3309.
5. Heeren TFC, Chew EY, Clemons T, et al; MacTel Study Group. Macular telangiectasia type 2: visual acuity, disease end stage, and the MacTel Area: MacTel Project Report Number 8. Ophthalmology. 2020;127(11):1539-1548.
