Is Encelto (revakinagene taroretcel-lwey) implantation medically necessary for the treatment of idiopathic macular telangiectasia type 2 (MacTel)?

Encelto (Revakinagene Taroretcel-lwey) for Idiopathic Macular Telangiectasia Type 2

Encelto is medically necessary for appropriately selected patients with MacTel type 2 who meet all four FDA-approved criteria, as it is the only approved treatment that slows photoreceptor loss by approximately 55% over 24 months in this progressive disease that otherwise leads to inevitable vision decline. 1, 2

Disease Context and Natural History

MacTel type 2 is a bilateral neurodegenerative macular disease that causes progressive photoreceptor loss and vision decline without any previously available treatment options. 3 The natural history demonstrates:

• Average vision loss of 2 lines by 5 years and 4 lines by 10 years in untreated patients 4
• Progressive retinal atrophy with characteristic ellipsoid zone (EZ) breaks that expand over time 2
• No effective treatment existed for the nonproliferative stage prior to Encelto approval 5

FDA-Approved Indication and Required Criteria

Encelto received FDA approval in March 2025 as the first and only treatment for MacTel type 2, making it medically necessary when patients meet all four criteria simultaneously: 1

Criterion 1: Confirmed MacTel Type 2 Diagnosis

The patient must demonstrate fluorescein leakage (the pathognomonic angiographic finding) plus at least one of these features: 3

• Hyperpigmentation >500 microns from foveal center
• Retinal opacification (graying of involved retina)
• Crystalline deposits (refractile deposits in superficial retina)
• Right-angle vessels (blunted venules)
• Inner/outer lamellar cavities (intraretinal hyporeflective spaces on OCT)

Criterion 2: Ellipsoid Zone Break Size

EZ area loss must measure between 0.16 mm² and 2.00 mm² on spectral domain-OCT. 2 This range defines the therapeutic window where treatment efficacy was demonstrated in phase 3 trials—patients outside this range were not studied and should not receive treatment.

Criterion 3: Visual Acuity Threshold

BCVA must be 54 letters or better (20/80 or better) on ETDRS chart at screening. 2 This ensures patients have sufficient remaining visual function to benefit from slowing photoreceptor loss.

Criterion 4: Imaging Quality Requirements

The patient must have steady fixation and sufficiently clear ocular media for quality OCT imaging and photographs. 2 This is essential for accurate EZ measurement and treatment monitoring.

Evidence of Efficacy

Two identical phase 3 trials (NTMT-03-A and NTMT-03-B) demonstrated statistically significant reduction in photoreceptor loss: 2

• NTMT-03-A: Encelto reduced EZ loss by 0.091 mm²/24 months compared to sham (P<0.001), representing approximately 55% slowing of progression
• NTMT-03-B: Encelto reduced EZ loss by 0.049 mm²/24 months compared to sham (P=0.02), representing approximately 31% slowing of progression
• Both trials showed consistent benefit in the primary endpoint of slowing photoreceptor degeneration 2

Safety Profile and Manageable Adverse Events

The treatment has a favorable risk-benefit profile with no increase in serious adverse events compared to sham: 2

• Miosis: Occurred in 17% (NTMT-03-A) and 14% (NTMT-03-B) of treated patients versus 0% in sham groups
• Delayed dark adaptation: Occurred in 17% (NTMT-03-A) and 24% (NTMT-03-B) of treated patients versus 0-2% in sham groups
• No difference in BCVA loss ≥15 letters between treatment and sham groups
• No difference in treatment-emergent serious adverse events between groups

These side effects are manageable and do not outweigh the benefit of slowing inevitable vision loss in this progressive disease. 2

Treatment Administration

Encelto is a one-time intravitreal implant per affected eye containing 200,000-440,000 allogeneic RPE cells expressing recombinant human ciliary neurotrophic factor. 1 The single-dose administration provides sustained neuroprotective effect over the 24-month study period without need for repeated injections. 2

Documentation Requirements for Authorization

The insurance denial cited lack of clinical documentation—only email communication was provided. To meet medical necessity, the following must be documented:

• Office visit note with complete ophthalmic examination findings
• Fluorescein angiography report demonstrating characteristic leakage pattern 3
• SD-OCT measurements with calculated EZ area loss between 0.16-2.00 mm² 2
• ETDRS visual acuity testing showing 54 letters or better (20/80 or better) 2
• Assessment of fixation stability and media clarity for imaging quality 2
• Treatment plan justification for sequential bilateral treatment if both eyes qualify

Critical Pitfall to Avoid

Do not delay treatment once all criteria are met. MacTel type 2 is relentlessly progressive, and the natural history shows continuous photoreceptor loss over time. 4 Unlike conditions where observation is reasonable, there is no spontaneous improvement in MacTel type 2, and waiting results in irreversible vision loss that cannot be recovered even with subsequent treatment. 3, 5 The phase 3 trials demonstrated that Encelto slows but does not stop progression, making early intervention within the therapeutic window (EZ loss 0.16-2.00 mm²) essential for preserving remaining photoreceptors. 2