MacTel and radiation retinopathy

Macular Telangiectasia (MacTel): Type 1 vs. Type 2

Macular telangiectasia comprises two clinically, epidemiologically, and pathologically distinct entities:

MacTel Type 1 (Unilateral Aneurysmal Telangiectasia)

• Demographics: Unilateral in 98% of cases; striking predilection for males in the fourth to fifth decades of life (mean age ~40 years). Considered an abortive or localized macular variant of Coats disease.
• Pathophysiology: Primary vascular telangiectasia of the temporal macular capillary network. Dilated, ectatic capillaries, microaneurysms, and localized lipid exudation produce chronic macular oedema and exudative visual loss.
• Clinical Presentation: Metamorphopsia and moderate visual loss ($6/12$ to $6/36$). Slit-lamp biomicroscopy reveals prominent telangiectatic capillaries and aneurysms in the temporal half of the macula, surrounded by circinate rings of yellow lipid hard exudates and cystoid macular oedema.
• Therapeutic Response: Responds favourably to targeted focal argon laser photocoagulation directed at leaking aneurysms, as well as intravitreal anti-VEGF or dexamethasone implants.

MacTel Type 2 (Bilateral Idiopathic Perifoveal Telangiectasia)

• Demographics: Bilateral, symmetric, acquired disorder manifesting in the fifth to seventh decades (mean age 55–60 years). Equal gender distribution or slight female predominance. Highly associated with systemic metabolic syndrome, hypertension, and type 2 diabetes.
• The Paradigm Shift: A Neurodegenerative Disorder: Extensive clinicopathological research demonstrates that MacTel Type 2 is NOT a primary retinal vascular disease. Rather, it is a primary neurodegenerative disease of Müller glial cells. Loss of Müller cell footplates in the fovea leads to secondary depletion of macular xanthophyll pigments (lutein and zeaxanthin), progressive photoreceptor apoptosis, and tertiary microvascular ectasia and cavitation.
• Multimodal Clinical Features:
  • Biomicroscopy: Subtle loss of retinal transparency (grayish opalescence) often most prominent to the temporal juxtafoveolar area; superficial refractile crystalline deposits in ~50% of eyes; dilated, blunted right-angled venules that plunge perpendicularly into deep retinal layers; late stellate hyperpigmentation plaques (pigment hyperplasia).
  • Absence of Lipid: In sharp contrast to MacTel Type 1 and diabetic retinopathy, prominent lipid hard exudates are completely absent in uncomplicated MacTel Type 2.
  • Optical Coherence Tomography (SD-OCT): Demonstrates the characteristic "ILM Drape"—the internal limiting membrane remains structurally intact, draping over empty, hyporeflective cavitations in the inner and outer retina without overall retinal thickening. Focal disruption of the ellipsoid zone (EZ) and external limiting membrane occurs, progressing to full-thickness macular holes (which lack surrounding subretinal fluid cuffs).
  • Fluorescein Angiography: Early telangiectatic capillary dilatation limited to the temporal perifoveolar network; late diffuse ectatic hyperfluorescent staining without classical petaloid cystoid pooling.
  • Confocal Blue Reflectance: Reveals a distinct, oval zone of hyper-reflectance centered temporally to the fovea.
  • Dual-Wavelength Autofluorescence: Demonstrates characteristic loss of normal central luteal pigment absorption.
• Complications & Therapy:
  • Non-Neovascular Stage: Anti-VEGF is not routine treatment for the non-neovascular neurodegeneration; avoid destructive macular laser. Neither addresses the underlying photoreceptor loss. Emerging therapy: Encapsulated cell biodelivery implants secreting Ciliary Neurotrophic Factor (CNTF / NT-501) significantly slow photoreceptor loss.
  • Neovascular Stage: Secondary subretinal choroidal/retinal neovascularisation (SRNV / CNV) develops in ~10% to 15% of eyes, causing acute subretinal haemorrhage. Unlike the non-neovascular phase, secondary CNV responds dramatically to intravitreal anti-VEGF injections.

Radiation Retinopathy & Radiation Optic Neuropathy

Radiation retinopathy is a delayed-onset, slowly progressive, occlusive microangiopathy resulting from exposure of the retina to ionizing radiation.

Etiology & Dosimetry

• Radiation Sources:
  1. Ophthalmic Plaque Brachytherapy: Iodine-125 ($^{125}\text{I}$), Ruthenium-106 ($^{106}\text{Ru}$), or Palladium-103 ($^{103}\text{Pd}$) episcleral plaques utilized for the treatment of uveal melanoma, circumscribed choroidal haemangioma, or retinoblastoma.
  2. External Beam Radiotherapy (EBRT) & Particle Beam Therapy: Proton beam irradiation, stereotactic radiosurgery (Gamma Knife / CyberKnife), or fractionated EBRT for head, neck, paranasal sinus, nasopharyngeal, or orbital malignancies.
• Radiation Threshold & Latency:
  • Risk depends on total dose, fractionation, irradiated retinal volume, tumour location, diabetes and other treatment. Published series do not establish one universally safe retinal threshold or a fixed retinopathy percentage for every eye receiving the same nominal dose.
  • Latency Period: Characteristically delayed, with clinical manifestations typically emerging between 6 months and 3 years (peak onset at 18 to 36 months) post-irradiation.
  • Accelerating Factors: Systemic hypertension, diabetes mellitus, and concurrent chemotherapy (e.g., 5-fluorouracil, cisplatin) significantly lower the radiation tolerance threshold and accelerate disease onset.

Molecular Pathology & Fundus Features

Ionizing radiation induces double-stranded DNA breaks in slowly dividing vascular endothelial cells, provoking cellular senescence, endothelial swelling, and apoptosis. The microvascular sequelae are clinically and angiographically identical to diabetic retinopathy:

• Clinical Signs: Cotton-wool spots (nerve fibre layer infarcts), microaneurysms, telangiectatic vessels, intraretinal flame and blot haemorrhages, hard exudates, and radiation macular oedema (RMO).
• Proliferative Complications: Extensive capillary non-perfusion on fluorescein angiography stimulates secondary neovascularisation of the disc (NVD), retina (NVE), and iris (rubeosis iridis), leading to vitreous haemorrhage and tractional retinal detachment.
• Radiation Optic Neuropathy (RON): Occurs when the anterior optic nerve receives $>50\,\text{Gy}$; presents with sudden, painless, catastrophic visual loss, swollen hyperaemic optic disc, peripapillary splinter haemorrhages, and subsequent optic atrophy.

Evidence-Based Management Protocols

1. Intravitreal Anti-VEGF Therapy: First-line treatment for radiation macular oedema (RMO). Anti-VEGF injections (aflibercept, ranibizumab, bevacizumab) administered on a proactive treat-and-extend schedule significantly decrease central foveal thickness and stabilize visual acuity.
2. Prophylactic Anti-VEGF Therapy: Selected cohort evidence supports scheduled injections after plaque treatment in defined populations. Interpret the comparator, follow-up and visual endpoint; this does not establish one compulsory prophylactic regimen for all forms of ocular irradiation.
3. Intravitreal Dexamethasone Implants: Effective adjuvant therapy, particularly in vitrectomised or refractory eyes.
4. Laser: Treat retinal neovascularisation and selected severe ischaemic complications according to specialist assessment. Nonperfusion alone does not impose a universal prophylactic laser rule.

Management Depends on Stage and Jurisdiction

Selected Coats disease without leakage threatening vision can be observed; leaking telangiectasia may need laser or cryotherapy, and detached retinas may require specialised drainage or surgery. Stage alone does not prescribe an identical operation. MacTel type 2 is primarily neurodegenerative with characteristic vascular and outer-retinal changes; anti-VEGF is used for associated neovascular complications, not routine treatment of non-neovascular cavitation. ENCELTO, an encapsulated cell implant delivering ciliary neurotrophic factor, received US FDA approval for adults with idiopathic MacTel type 2 on 5 March 2025. This is a US authorisation, not proof of European availability; verify local access. See the FDA approval. Radiation injury depends on dose, fractionation, field and latency; preventive injection series do not guarantee absence of retinopathy.