COMBINED AUTOLOGOUS TRANSPLANTATION OF NEUROSENSORY RETINA, RETINAL PIGMENT EPITHELIUM, AND CHOROID FREE GRAFTS

Abstract

Purpose: To evaluate the feasibility and initial functional and anatomical outcomes of transplanting a full-thickness free graft of choroid and retinal pigment epithelium (RPE), along with neurosensory retina in advanced fibrosis and atrophy associated with end-stage exudative age-related macular degeneration with and without a concurrent refractory macular hole.

Methods: During vitrectomy, an RPE-choroidal and neurosensory retinal free graft was harvested in nine eyes of nine patients. The RPE-choroidal and neurosensory retinal free graft was either placed subretinally (n = 5), intraretinally to cover the foveal area inside an iatrogenically induced macular hole over the RPE-choroidal graft (n = 3) or preretinally (n = 1) without a retinotomy wherein both free grafts were placed over the concurrent macular hole. Silicone oil endotamponade was used in all cases.

Results: Mean follow-up was 7 ± 5.5 months (range 3-19). The mean preoperative visual acuity was ∼count fingers (logarithm of the minimum angle of resolution = 2.11, range 2-3), which improved to ∼20/800 (logarithm of the minimum angle of resolution 1.62 ± 0.48, range 0.7-2, P = 0.04). Vision was stable in 5 eyes (55.6%) and improved in 4 eyes (44.4%). Reading ability improved in 5 eyes (55.6%). Postoperative complications were graft atrophy (n = 1), epiretinal membrane (n = 1), and dislocation of neurosensory retina-choroid-RPE free graft (n = 1).

Conclusion: Combined autologous RPE-choroid and neurosensory retinal free graft is a potential surgical alternative in eyes with end-stage exudative age-related macular degeneration, including concurrent refractory macular hole.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Tamer Mahmoud reports participation in an advisory board for Dutch Ophthalmic (Exeter, NH), Alimera, and Spark Therapeutics. Research support as investigator for Genentech. Dr Grewal reports participation in an advisory board for Allergan and Regeneron. No other disclosures were reported.

Figures

Figure 1

Exudative age related macular degeneration (AMD) with a disciform scar covering the macular region (A). OCT shows cystic intraretinal fluid overlying the subretinal hyperreflective material with loss of the outer retinal layers (B red arrow). Six months after surgery, the retinal pigment epithelium (RPE)-choroid graft is visualized in the center of the macular region (C, yellow arrow) and the RPE-choroid graft temporal harvest site is flat (white asterisk). The peripheral superotemporal harvesting site of the retinal graft is not visible in the picture. Postoperative OCT (D) shows the RPE-choroid graft, with rounded hyporeflective spaces due to dilatation of choroidal vessels inside the RPE-choroid graft (white arrows). The neurosensory retinal graft appears well integrated between the native macula, and the RPE-choroid graft separated by a hyper-reflective line (yellow arrows). The retinal layers are not well recognizable. There is resolution of the intraretinal fluid. The silicone oil reflex is visible. Postoperative fluorescein angiography (FA) and Indocyanine Green (ICG) Angiography images (E) showing the complete revascularization of the choroidal graft. Dynamic ICG angiography revealed choroidal vessels starting at the margin of the graft. Feeder vessels of the choroidal patch seemed to grow in sites of contacts of the choroidal graft with healthy and original underlying choroidal vasculature (yellow arrow).

Figure 2

Patient with advanced exudative AMD (A) with RPE atrophy in the macular region (white arrow). OCT (C) showing lamellar macular hole configuration with a very thin residual foveal floor, significant loss of outer retinal layers and RPE atrophy (red arrow), overlying intraretinal fluid and subretinal hyporeflective spaces. Postoperative photograph 1 month after surgery (B) showing the choroidal-RPE graft in the center of the macular region and the neurosensory retinal graft covering the macular hole (yellow arrow). The temporal harvest site of the neurosensory retinal graft is shown with the white asterisk. Postoperative OCT 3 months after surgery (D) showing RPE-choroidal patch in the macula area, with rounded hyporeflective round spaces due to dilatation of choroidal vessels inside the graft (white arrows). The neurosensory retinal graft (yellow arrow) appears well integrated into the macular hole and is partly lying over the original retina, separated by a hyper-reflective line. Postoperative OCT angiography (E, scan area 6 x 6 mm) 3 months after surgery. The choroidal graft (yellow arrows) is visualized on the en face images at the level of the outer retina and choriocapillaris. The superficial and deep retinal vasculature appear grossly preserved in the area of the original overlying neurosensory retina (white arrows), however the scan is limited by artifact and segmentation errors.

Figure 3

OCT (A) showing advanced exudative AMD with subretinal hyperreflective material, extensive loss of outer retinal layers and overlying cystic intraretinal fluid. Postoperative OCT (B) showing the RPE-choroid graft in the macula area, with a dome-shaped elevation nasally due to dilatation of choroidal vessels and an irregular surface secondary to contraction (white arrows). The neurosensory retinal free graft appears well integrated with the original retina (yellow arrow), and there is resolution of the intraretinal fluid. Postoperative fundus photograph (C) showing the RPE-choroidal free graft and the neurosensory retinal graft in the center of the macular region (yellow arrow). The harvest sites of the neurosensory retinal free graft (white arrow) and the RPE-choroid free graft (white asterisk) are seen temporally.

Figure 4

Postoperative fundus photograph showing the RPE-choroidal free graft in the center of the macula (A. white arrow). The neurosensory retinal free graft is under the native retina. The temporal harvest site of RPE-choroidal patch and the superotemporal harvest site of the retinal patch are not visible. Preoperative OCT showing advanced exudative AMD with subretinal hyperreflective material, loss of outer retinal layers and overlying cystic intraretinal fluid (B). Postoperative OCT (C) showing the RPE-choroid graft in the macula area, with a dome-shaped aspect due to dilatation of choroidal vessels and an irregular surface secondary to contraction of the RPE-choroid graft (white arrows). The neurosensory retinal free graft is well integrated between the native retina and the RPE-choroidal graft, separated by a hyper-reflective line, (yellow arrow) and there is relative preservative of the retinal architecture. OCT angiography (D, scan area 6 x 6 mm) shows the area of the RPE-Choroid graft seen on the outer retina and choriocapillaris slabs (yellow arrows). While the superficial capillary plexus is relatively well preserved (left white arrow), the deep capillary plexus which is likely in the area of the neurosensory graft (right white arrow) is not well visualized. The scan is however limited by artifact and segmentation errors.

Figure 5

Fundus photograph after surgery (A) showing the RPE-choroid free graft in the center of the macular region with the overlying neurosensory retinal graft (white arrow). The harvest sites of the RPE-choroid free graft temporally and the neurosensory retinal free graft superotemporally are not visible in the picture. Preoperative OCT (B, left) showing an atrophic macular area with loss of the outer retinal layers and highly reflective subretinal material (red arrow). Postoperative OCT (B, right) showing the RPE-choroid graft with dilatation of choroidal vessels and an irregular surface (white arrows). The choroidal patch is vascularized as shown by the ovoidal dark hyporeflective spaces. The intraretinal neurosensory retinal free graft appears well integrated (yellow arrow) with some inner retinal boundaries visible overlying the RPE-choroidal free graft. Postoperative microperimety (C) and fixation maps (4-2 strategy). The area of fixation was at superotemporal border of the retinal free graft (yellow arrow) overlying the area of the choroidal graft. There was a dense scotoma with complete loss of sensitivity, however there are areas of low sensitivity along on the retinal free graft, in the superotemporal, nasal and temporal sides and over the choroidal graft (white arrows).

Figure 6

74-year-old female with end-stage CNV that progressed to a fibrovascular scar with OCT showing lamellar macular hole like configuration with very thin residual fovea and loss of retinal layers, outer retinal tabulation (white asterisk) and subretinal hyperreflective subretinal material (red arrow). Postoperative ultra-wide-field fundus photograph showing the RPE-choroid graft in the center of the macular region and the neurosensory retinal graft covering the macular hole (yellow arrow). The harvest site of the retinal graft (white arrow) and area of RPE-choroid graft (white asterisk) are seen temporally. Postoperative OCT 5 months after combined RPE-choroid free graft and intraretinal retinal graft (C). The RPE-choroid graft is vascularized as shown by the ovoidal dark hyporeflective spaces. The intraretinal retina graft is integrated in the surrounding retina. Postoperative microperimetry (D) showing fixation if on the area of the choroid graft and close to the nasal margin of the retinal graft. Fixation is stable with P2= 75%. The sensitivity map shows a spot of sensitivity over the choroid and retina grafts. Vision improved from 2 to 0.7 logMAR.

Figure 7

76-year-old M with exudative age related macular degeneration with a concurrent large macular hole refractory to prior internal limiting membrane removal and chorioretinal scarring from prior retinal detachment repair. Preoperative OCT (A, middle) shows a large refractory macular hole with 2400-micron largest basal diameter and 1600-micron inner opening diameter. Following a combined autologous neurosensory retinal and choroidal free graft with silicone oil tamponade (B), post-operative day 1 OCT (C) shows the choroidal graft plugging the macular hole, the neurosensory retinal graft had dislocated. Postoperative photograph at 1 month shows the choroidal free graft covering the macular hole, free graft harvest site and a silicone oil tamponade. OCT at 2 months (C) and shows improved integrated of the choroidal free graft tissue in the macular hole with surrounding retinal tissue. Fluorescein angiogram (C, right) shows blockage from the subretinal heme, staining around the choroidal graft site and no leakage. The subretinal hemorrhage resolved. OCT at 12 months shows resolution of subretinal fluid and further improved integration of the choroidal free graft with the retinal tissue and closure of the macular hole and ICG shows blockage in the area of the choroidal graft with no abnormal vascular complex or leakage. The vision was improved from HM preoperative to 20/200E@1 meter 12 months postoperatively with subjective improvement as well.