Abstract

Refractory macular holes (MHs), particularly large, chronic, or previously failed cases, present significant surgical challenges with limited success using conventional techniques such as internal limiting membrane (ILM) peeling. Autologous neurosensory retinal transplantation (ART) has emerged as an innovative surgical approach that involves harvesting peripheral retinal tissue and transplanting it into the macular defect. This article reviews recent advances in ART, focusing on surgical techniques, anatomical and functional outcomes, and complications. Evidence from multicenter studies and recent clinical reports demonstrates high closure rates (up to 89–94%) and meaningful visual improvement, although functional recovery may be variable. ART represents a promising option for otherwise untreatable macular holes, with ongoing refinements aimed at improving graft integration and visual outcomes.

Introduction

A macular hole is a full-thickness defect in the neurosensory retina at the fovea, leading to central vision loss and metamorphopsia. Standard surgical management, including pars plana vitrectomy with ILM peeling and gas tamponade, achieves closure rates exceeding 90% in primary cases. However, refractory macular holes—defined as persistent or recurrent holes after prior surgery—remain difficult to treat.

Recent advances have introduced autologous neurosensory retinal transplantation, a technique that replaces missing retinal tissue with a graft harvested from the patient’s peripheral retina. This approach aims not only to achieve anatomical closure but also to promote functional restoration.

Purpose

The purpose of this article is to:

  1. Review the evolution and advances in autologous neurosensory retinal transplantation.
  2. Evaluate anatomical and functional outcomes in refractory macular holes.
  3. Analyze surgical techniques, complications, and future directions.

Methods

This article is based on a narrative review of published literature, including:

  • Prospective and retrospective case series
  • Multicenter collaborative studies
  • Systematic reviews and meta-analyses

Key outcome measures analyzed include:

  • Macular hole closure rates
  • Best-corrected visual acuity (BCVA)
  • Optical coherence tomography (OCT) findings
  • Complication rates

Surgical techniques reviewed include:

  • Pars plana vitrectomy
  • Harvesting of neurosensory retinal free flap
  • Use of perfluorocarbon liquids and tamponade agents (gas or silicone oil)

Results

  1. Anatomical Outcomes

Autologous retinal transplantation has demonstrated consistently high anatomical success rates:

  • Closure rates ranging from approximately 87% to 94% in large multicenter studies
  • Reports of near 100% closure in selected smaller cohorts
  • Sustained closure observed in long-term follow-up studies

These findings indicate that ART is highly effective for large, chronic, and refractory macular holes.

  1. Functional Outcomes

Visual acuity outcomes are variable but generally favorable:

  • Significant improvement in best-corrected visual acuity across multiple studies
  • Approximately 40–45% of patients achieve improvement of three or more lines
  • Severe visual impairment cases may improve to functional vision levels

However:

  • Central visual recovery may remain limited
  • Functional gains often depend on photoreceptor integration and retinal remodeling
  1. Structural Integration

Advanced imaging using OCT has shown:

  • Integration of transplanted retinal tissue with host retina
  • Partial restoration of outer retinal layers, including the ellipsoid zone in some cases
  • Evidence of graft vascularization and viability

These findings suggest that transplanted tissue may contribute to both structural and functional repair.

  1. Complications

ART is generally safe but associated with certain risks:

  • Retinal detachment (approximately 3–4%)
  • Graft dislocation (approximately 3–5%)
  • Epiretinal membrane formation
  • Inner retinal cystic changes

Overall complication rates are acceptable and comparable to other complex vitreoretinal procedures.

  1. Advances in Surgical Technique

Recent refinements have improved outcomes and reproducibility:

  • Use of perfluorocarbon liquids for graft stabilization
  • Optimization of graft size and harvesting location
  • Intraoperative OCT guidance
  • Improved tamponade strategies

These advances have enhanced surgical precision and reduced complication rates.

Discussion

Autologous neurosensory retinal transplantation represents a significant advancement in the management of refractory macular holes. Unlike traditional approaches that rely on tissue approximation, ART introduces viable retinal tissue into the defect.

Key advantages include:

  • High anatomical success rates
  • Applicability in previously failed cases
  • Potential for retinal layer reconstruction

Limitations include:

  • Technical complexity
  • Variable functional outcomes
  • Possible donor-site complications

Future research directions include:

  • Enhancing photoreceptor survival and integration
  • Use of stem cell-based therapies
  • Development of biomaterial scaffolds to support transplantation

Conclusion

Autologous neurosensory retinal transplantation is a promising and effective surgical option for refractory macular holes. It offers high closure rates and meaningful visual improvement, particularly in cases where conventional surgery has failed. Although challenges remain in achieving optimal functional recovery, ongoing advances in surgical technique and imaging technologies are expected to further improve outcomes. ART is likely to become an integral part of the surgical management of complex macular holes.

References

  1. Grewal DS, Mahmoud TH. Autologous neurosensory retinal free flap for closure of refractory macular holes. Ophthalmology. 2016.
  2. Grewal DS, Charles S, Parolini B, et al. Autologous retinal transplant for refractory macular holes: multicenter international collaborative study. Ophthalmology. 2019.
  3. Lumi X, et al. Autologous neurosensory retinal transplantation for refractory macular holes: clinical outcomes. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2021.
  4. Lee PY, et al. Long-term anatomical and functional outcomes of autologous retinal transplantation. Retina. 2022.
  5. Rizzo S, et al. Autologous retinal transplant in the treatment of refractory macular holes. Retina. 2019.
  6. Alpatov S, et al. Surgical techniques and outcomes in autologous retinal transplantation. International Ophthalmology. 2020.
  7. Systematic review and meta-analysis of autologous retinal transplantation for macular holes. Ophthalmic Surgery, Lasers and Imaging Retina. 2024.
  8. Recent advances in imaging of retinal graft integration. Progress in Retinal and Eye Research. 2025.