Transplants and AMD
Researchers report promising results with human embryonic stem cell-based tissue transplantation
Ongoing follow-up of patients in a phase I clinical study supports the safety, feasibility, efficiency and stability of a novel tissue transplantation approach as a regenerative therapeutic strategy for age-related macular degeneration (AMD), reported Dr Odysseas Georgiadis, at the 18th EURETINA Congress in Vienna, Austria.
Speaking on behalf of The London Project to Cure Blindness team, Dr Georgiadis described the procedure, which involves submacular transplantation of a sheet consisting of a fully differentiated, human embryonic stem cell (hESC)-derived retinal pigment epithelium (RPE) monolayer on a coated, synthetic basement membrane. Graft delivery is performed using a purpose-designed surgical tool. He reported encouraging outcomes from follow-up to 18 months in the two patients treated so far.
“Late AMD is considered amenable to cell replacement therapy because it manifests with irreversible cell loss. Although previous surgical approaches, such as macular translocation and autologous RPE transplantation, provided proof of principle for cell replacement, their complexity highlighted the need for an easily accessible cell source and a more feasible surgical paradigm,” said Dr Georgiadis, Moorfields Eye Hospital, London, England.
“Our ultimate goal is to establish a new therapeutic paradigm, applicable to the large number of patients that suffer from untreatable forms of AMD and a broader spectrum of retinal degenerative diseases.”
The two patients enrolled in the study – a 60-year-old woman and an 84-year-old man – had severe neovascular AMD and recent rapid vision decline associated with a submacular haemorrhage and/or RPE tear. Both had failed anti-VEGF treatment. Dr Georgiadis reported successful delivery and survival of the graft with resulting regeneration of the RPE-BM structure and rescue and preservation of photoreceptor function.
The first patient had a BCVA of 10 ETDRS letters before surgery, reached 39 ETDRS letters at 12 months and maintained this 29-letter gain at month 18. The second patient had eight ETDRS letters BCVA at baseline, gained 21 ETDRS letters at month 12 and maintained a 27-letter BCVA at month 18.
Significant improvements were also seen in other functional tests. Reading speed increased from five to 84 words per minute in the first patient and from zero to 49 words per minute in the second patient. Contrast sensitivity also improved. In addition, both patients had a stable on-the-graft fixation during the first year that was maintained through month 18 in the second patient, while the first patient lost some of the stability. Microperimetry testing showed both patients had significant improvement in the light sensitivity of the retinal area treated with the hESC-RPE sheet.
A comprehensive battery of imaging tests is being used to evaluate structure. At 18 months, the transplants retained a stable position under the macula and fairly homogenous pigmentation that changed slightly with time, corresponding to functional outcomes. Fundus fluorescein angiography showed the transplants sustained background choroidal perfusion with no signs of disease recurrence in the grafted area.
Scanning with SD-OCT showed the transplants gave a stable “double-layer” outer retinal signal and that neurosensory retina segmentation was maintained over the transplant with positive signals of photoreceptor survival. Both transplants emitted autofluorescence and in vivo cellular imaging with adaptive optics technology showed the presence of cones over the transplant.
“Consolidating our outcomes, we identified direct associations between improvements in structural and functional assessments,” said Dr Georgiadis.
“Loci of good light sensitivity in the microperimetry were found to have preserved and even pigmentation combined with good blood perfusion, autofluorescence and signals of photoreceptor survival in the OCT and adaptive optics imaging.”
There were no significant safety concerns. Three serious adverse events – conjunctival dehiscence, retinal detachment and corticosteroid-induced worsening of diabetes – were managed without sequelae.
“There were no adverse events related to the transplant, and most importantly, no signs of local or distal uncontrolled proliferation of the implanted cells,” Dr Georgiadis said.
Going forward, the researchers are planning to recruit more patients in this study, and in the future to proceed with new studies including patients with dry AMD.
The London Project to Cure Blindness is a partnership between Professor Lyndon da Cruz, Moorfields Eye Hospital/University College London, and Professor Pete Coffey, University College London.
Odysseas Georgiadis: firstname.lastname@example.org