Real-World Experience with Revakinagene Taroretcel-lwey (Encelto) for MacTel: First Year Insights on Patient Selection and Surgical Technique
核心洞察
Revakinagene taroretcel-lwey (搜索) (Encelto (搜索)) is the first and only FDA-approved treatment for macular telangiectasia type 2 (搜索) (MacTel), using encapsulated cell therapy to deliver ciliary neurotrophic factor to the retina.
A systematic review of five studies (498 eyes) found CNTF therapy slows retinal degeneration as measured by ellipsoid zone discontinuity, though functional gains such as BCVA improvements remain mixed.
Charles Wykoff, MD, PhD, reports that real-world patient selection requires symptomatic patients with documented progression, confirmed EZ loss, and absence of active neovascularization.
Macular telangiectasia type 2 (搜索) (MacTel), a bilateral neurodegenerative disease characterized by neurosensory and macular capillary network atrophy, has long been an underdiagnosed and historically undertreated condition. That landscape shifted with the FDA approval of revakinagene taroretcel-lwey (搜索) (Encelto (搜索); Neurotech Pharmaceuticals (搜索)), the first and only approved therapy for MacTel. Now, one year into real-world commercial use, clinicians are refining their approach to patient selection, surgical technique, and outcome expectations.
Charles Wykoff, MD, PhD, director of research at Retina Consultants of Texas, performed the first commercial Encelto (搜索) implantation outside of a clinical trial and recently offered a detailed account of how the first year of real-world experience has shaped his clinical practice. He emphasized that FDA approval has meaningfully accelerated education efforts among referring physicians and general ophthalmologists, addressing what has been a significant gap in disease recognition.
Encapsulated Cell Therapy: A Novel Drug Delivery Platform
Encelto (搜索) employs encapsulated cell therapy (ECT) technology to continuously deliver therapeutic doses of ciliary neurotrophic factor (CNTF) to the retina. The implantable device represents a departure from conventional intravitreal injections, offering sustained protein delivery through a surgically placed, titanium-anchored system.
A recent systematic review published in Retina, which analyzed five studies reporting on 498 eyes of 422 patients, found that CNTF therapy appears to slow retinal degeneration, specifically in terms of ellipsoid zone (EZ) discontinuity. One randomized-controlled trial of 99 eyes demonstrated decreased progression of retinal degeneration and reduced decline in reading speed in implant-treated eyes compared to sham-treated eyes. An uncontrolled Phase I safety trial demonstrated good tolerance, with no significant differences in visual acuity or retinal sensitivity between treated and untreated eyes over 36 months, though five participants experienced persistent miosis in the implanted eye.
"OCT mapping of EZ discontinuity detects structural changes before mesopic microperimetry identifies retinal sensitivity loss in MacTel," the review authors wrote. "Using OCT to determine outcomes may prevent the potential exclusion of early defects or disease of the outer retina over mesopic function as a measure of retinal degeneration."
Structural Benefits, Mixed Functional Gains
While structural benefits are consistently identified across studies, functional gains have been mixed. Some data indicate preserved reading speed in treated patients, while other functional measures—such as best-corrected visual acuity (BCVA) and patient-reported outcomes—have not shown significant differences compared to sham-treated groups.
Reported adverse effects are typically limited to miosis and delayed dark adaptation, and no severe complications such as endophthalmitis, retinal breaks, or detachments were observed. Wykoff echoed this safety profile, describing the therapy as "fascinating and remarkably well tolerated in this population of patients." Known adverse events to counsel patients on include miosis, delayed dark adaptation, and the rare risk of device extrusion or intraocular tissue damage.
Patient Selection: Two Core Requirements
Wykoff stressed that eligibility for Encelto (搜索) requires two core conditions: the patient must be symptomatic, and they must be experiencing documented progression. A confirmed MacTel diagnosis with EZ loss on imaging and absence of active neovascularization are also required. He actively avoids implanting patients on anti-VEGF therapy for neovascular complications and uses tools including the Amsler grid and microperimetry to confirm progression in patients who appear clinically stable.
Crucially, Wykoff is direct with patients that revakinagene taroretcel-lwey (搜索) is not intended to improve vision—only to slow the rate of photoreceptor loss. This expectation-setting is a cornerstone of his clinical approach.
Surgical Technique Within Existing Repertoire
Wykoff described the implantation procedure as well within the retina surgeon's existing technical repertoire, typically not requiring a vitrectomy machine. The key steps include a 7 × 7 mm conjunctival peritomy placed inferotemporally, a 3-mm sclerotomy approximately 3.75 mm posterior to the surgical limbus, and fixation of the titanium loop with a double-armed 9-0 polypropylene suture, with wound closure using buried 9-0 nylon sutures.
The primary technical challenge, he noted, is managing the fine 9-0 polypropylene suture, which is prone to kinking. In patients with bilateral disease interested in receiving bilateral implantation, Wykoff typically implants the worse-seeing eye first.
Limitations and Future Directions
The systematic review authors acknowledged several limitations. Data synthesis was primarily narrative due to the heterogeneity of study designs and reporting methods, which prevented a formal meta-analysis. Additionally, although MacTel is a bilateral disease, reporting outcomes based on a sample of bilateral and unilateral eyes poses a risk of bias. "A more robust approach would involve using statistical techniques that account for inter-eye correlations," the authors wrote. "Furthermore, extending study duration beyond 24 months could reveal greater divergence in outcomes between CNTF-treated and sham-treated eyes."
The authors highlighted the need for further, long-term and larger-scale trials to better understand the therapy's long-term efficacy and its potential impact on other disease features, such as retinal cavitations and choroidal neovascularization.
Wykoff expressed enthusiasm for ECT as a broader drug delivery platform, noting its potential for delivering other therapeutic proteins beyond CNTF, signaling that the technology underlying Encelto (搜索) may have applications well beyond MacTel.