AAO: Autologous retinal transplant for larger macular holes gaining traction

Reviewed by Tamer Mahmoud, MD, PhD

Autologous retinal transplant (ART) for macular holes, a relatively new procedure, is providing anatomic hole closure in the vast majority of cases of large macular holes as well as increases in visual acuity (VA).

In addition to the macular hole closure, the keys to better final outcomes were ellipsoidal band reconstitution and alignment of the neurosensory layers.

In this procedure, which was developed by Tamer Mahmoud, MD, PhD, an autologous neurosensory retinal free flap is harvested and moved over the hole to cover the hole gap and connect to surrounding macular tissue for large holes in which the mean minimal linear diameter exceeded 800 μm in the study.

Dr. Mahmoud, a professor of ophthalmology at Oakland University William Beaumont School of Medicine, and Associated Retinal Consultants in Royal Oak, MI, presented the information at the American Academy of Ophthalmology’s virtual 2020 annual meeting on behalf of the ART Team Study.

ART trial/results
In a multicenter, international, case series in which 33 surgeons participated, 130 eyes of 130 patients (women, 58%; mean age, 63±6.3 years) underwent ART to treat their macular holes. All patients underwent a pars plana vitrectomy and ART during the study from January 2017 through December 2019.

Dr. Mahmoud and his colleagues sought to determine the anatomic and functional outcomes of ART for the surgical repair of primary and refractory macular holes and macular hole retinal detachment (MHRD). This study is in press in Ophthalmology.¹

Of the 130 patients, 35 (27%) had primary macular holes and 76 (58%) had refractory macular holes. Among the patients, 19 (15%) also had a MHRD, that was recurrent in 13 cases, and 12 of the 19 patients had a recurrent MHRD and had undergone previous internal limiting membrane (ILM) peeling. The mean number of surgeries that the patients had undergone previously was 1.6±0.2 (ILM peeling and flaps).

Dr. Mahmoud recounted that the patients’ mean preoperative axial length was 24.6 ± 3.2 mm, the mean maximal hole diameter 1,470 ± 160 μm, and the mean minimal hole diameter 840 ± 94 μm. The preoperative logarithm of the minimum angle of resolution best-corrected VA (logMAR BCVA) was 1.37 ± 0.12 (~20/500).

The graft type was a 90% neurosensory retina without the choroid that was harvested in 45% of cases superiorly, 17% inferonasally, 11% superotemporally, 8% each superonasally, and inferiorly, 7% temporally, and 4% inferotemporally.

In 84% of cases, the harvest site was posterior to the equator and in 16% anterior to the equator. Most grafts (70%) ranged in size from 0 to 1 disc diameter (DD), 29% from 1 to 2 DD, and 1% 2 to 3 DD.

When the grafts were positioned in the eyes, 81% were placed preretinally and the remainder subretinally. The mean follow-up time was 8.6 ± 0.8 months.

The reconstitution of the external limiting membrane and the ellipsoidal zone is important to the success of the procedure.

“In this study, we introduced the term “ANL” or alignment of the neurosensory layers,” Dr. Mahmoud said. “When the graft is first moved to the hole area, vertical lines are seen on optical coherence tomography [OCT] between the graft and surrounding macular tissue.”

Dr. Mahmoud noted that within the first few weeks, those lines gradually fade and details of graft layers can be detected and those align with similar layers in the surrounding host macular tissue, plexiform to plexiform, nuclear to nuclear, etc.

“We feel this is remarkable as the macular tissue recognizes the retinal tissue and may try to connect to respective layers creating that integration of the retinal transplant, which reflects on better visual outcomes,” he said.

The final postoperative logMAR BCVA improved significantly (p<0.001) to 1.05 ± 0.09 (~20/225), with 29% of patients gaining more than 5 lines of vision and 43% gaining 3 lines of vision.

Subgroup analysis
Fifteen (12%) patients had a final VA of 20/50 or better; among these, a third had a primary macular hole and two-thirds a refractory macular hole.

The mean preoperative BCVA in this subgroup was 0.848 ± 0.219 (~20/125) and the mean final BCVA was 0.308±0.079 (~20/40), a difference that reached significance (p<0.001).

Two-thirds gained more than 3 lines and 40% more than 5 lines; all of these holes closed. In addition, two-thirds had a complete ellipsoidal zone.

According to Dr. Mahmoud, the global study reflects the initial experience worldwide, with most surgeons sharing their initial experiences.

“With better understanding of prognostic factors and refinement of surgical techniques developed throughout this collaboration, anatomic closure can be achieved in most large macular holes, which would reflect on better visual outcomes,” he said. “This also paves the way to further research the role of peripheral retina into acquiring macular function and its potential in many macular diseases.”

The postoperative complications included 5 cases of retinal detachment, 5 cases of ART graft dislocation, and 2 cases of subretinal perfluoro-N-octane. Endophthalmitis was suspected in 1 case. There were 5 cases of ART graft dislocation (3.9%).

Dr. Mahmoud enumerated the main study points, including that the preoperative diagnosis (p = 0.026) and preoperative VA were associated significantly (p < 0.001) with the postoperative VA, and that the macular hole closure (p < 0.001), reconstitution of the ellipsoid zone band (p=0.02), and alignment of neurosensory layers (p = 0.01) on OCT were associated with better final VA.

The results showed a high rate of closure (89%) of the macular holes and 95% in MHRD. The gains in VA were substantial, in that 29% of cases had at least a 5-line gain in visual acuity and 43% had at least a 3-line gain in visual acuity.

“The higher final levels of VA were associated significantly with macular hole closure (p < 0.001), reconstitution of the ellipsoid zone band (p = 0.02), and alignment of the neurosensory layers (p = 0.01) on OCT images,” Dr. Mahmoud concluded.

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Tamer Mahmoud, MD, PhD
E: tmahmoud@arcpc.net​
Dr. Mahmoud has no financial interest in this subject matter.

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Reference
1. Moysidis SN, Koulisis N, Adrean SD, et al. Autologous retinal transplantation for primary and refractory macular holes, and macular hole retinal detachments: The Global Consortium. Ophthalmology 2020; Published online: October 9, 2020.