Regenerative Therapy by Suprachoroidal Cell Autograft in Dry Age-related Macular Degeneration: Preliminary In Vivo Report

Summary

The goal of this study is to assess whether the suprachoroidal graft of adipose-derived stem cells included in the stromal vascular fraction and platelets derived from platelet-rich plasma by the Limoli Retinal Restoration Technique can improve visual acuity and retinal sensitivity responses in eyes affected by dry age-related macular degeneration.

Abstract

This study is aimed at examining whether a suprachoroidal graft of autologous cells can improve best corrected visual acuity (BCVA) and responses to microperimetry (MY) in eyes affected by dry Age-related Macular Degeneration (AMD) over time through the production and secretion of growth factors (GFs) on surrounding tissue. Patients were randomly assigned to each study group. All patients were diagnosed with dry AMD and with BCVA equal to or greater than 1 logarithm of the minimum angle of resolution (logMAR). A suprachoroidal autologous graft by Limoli Retinal Restoration Technique (LRRT) was carried out on group A, which included 11 eyes from 11 patients. The technique was performed by implanting adipocytes, adipose-derived stem cells obtained from the stromal vascular fraction, and platelets from platelet-rich plasma in the suprachoroidal space. Conversely, group B, including 14 eyes of 14 patients, was used as a control group. For each patient, diagnosis was verified by confocal scanning laser ophthalmoscope and spectral domain-optical coherence tomography (SD-OCT). In group A, BCVA improved by 0.581 to 0.504 at 90 days and to 0.376 logMAR at 180 days (+32.20%) postoperatively. Furthermore, MY test increased by 11.44 dB to 12.59 dB at 180 days. The different cell types grafted behind the choroid were able to ensure constant GF secretion in the choroidal flow. Consequently, the results indicate that visual acuity (VA) in the grafted group can increase more than in the control group after six months.

Introduction

Cell therapy, consisting of the systemic or local injection of stem/progenitor cells in the injured area to treat multiple chronic disorders, has drawn close attention in the last decade¹. Since the 1990s, growth factors (GFs) have been studied for their potentially therapeutic role in retinal atrophy². In fact, many human cells can produce GFs, which are specific proteins that are able to block or slow down apoptosis, i.e., the programmed death of cells³.

It is known that dry age-related macular degeneration (AMD) is an atrophic retinal disease where gradual a....

Protocol

The study protocol was approved by the Ethics Committee of the Low Vision Academy and all subjects signed a written consent in accordance with the Helsinki Declaration. This research study has received ethical approval from both Loughborough and Sheffield Universities.

NOTE: The inclusion and exclusion criteria of dry age-related macular degeneration patients to receive suprachoroidal autologous graft by Limoli Retinal Restoration Technique (LRRT) is described in Table 1.

1. Diagnosis of Dry Age-related Macular Degeneration Patients

1. Ascertain the diagnosis with confocal scanning laser....

Results

Using the procedure presented here, two groups of dry AMD-affected patients, with BCVA equal to or greater than 1 logarithm of the minimum angle of resolution (logMAR), were enrolled in the study. Group A, including 11 eyes of 11 patients, received suprachoroidal autologous graft by Limoli Retinal Restoration Technique (LRRT), whereas group B, including 14 eyes of 14 patients, was used as a control group.

Student's t-test and th.......

Discussion

The primary purpose of this study was to evaluate whether the suprachoroidal graft of adipocytes, ADSCs in SVF, and PRP could improve VA and retinal sensitivity in dry AMD-affected eyes over time. Another main objective was to demonstrate possible therapeutic effects of these cells, based on the recent literature, since several preclinical studies have suggested that GF-based therapy could be useful for patient care in several diseases.

In fact, some studies have shown that autologous human in.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Blunt cannula, 3 mm.	Mentor, Santa Barbara, CA.
Luer-LokTM syringe.	BD Biosciences, Franklin Lakes, NJ.
Regen-BCT tube.	RegenKit; RegenLab, Le Mont-sur-Lausanne, CH.
Centrifuge	RegenPRP Centri. RegenLab, Le Mont-sur-Lausanne, CH.
BD Venflon Pro Safety 22G x 1.00 inch (0.9 mm x 25 mm).	BD Biosciences, Franklin Lakes, NJ.
SPSS Statistics Version 19.0	IBM Corp., Armonk, NY, USA.
Confocal scanning laser ophthalmoscope	Nidek Inc, Fremont, CA	Nidek F10
Cirrus 5000 Spectral Domain-Optical Coherence Tomography	Carl Zeiss Meditec AG, Jena, Germany	SD-OCT
Maia 100809 Microperimetry	CenterVue S.p.A., Padua, Italy
Ocular electrophysiology electromedical system,	C.S.O., S.r.l., Scandicci, Italy		Retimax for ERG