PRIMA subretinal wireless photovoltaic microchip implantation in non-human primate and feline models

PURPOSE: To evaluate the surgical technique for subretinal implantation of two sizes of PRIMA photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials. METHODS: Cats and Macaca fascicularis primates with healthy retina underwent vitrectomy surgery and were implanted with subretinal wireless photovoltaic microchip at the macula/central retina. The 1.5mm PRIMA chip was initially studied in feline eyes. PRIMA implant (2mm,1.5mm sizes) arrays were studied in primates. Feasibility of subretinal chip implantation was evaluated with a newly-developed surgical technique, with surgical complications and adverse events recorded. RESULTS: The 1.5mm implant was placed in the central retina of 11 feline eyes, with implantation duration 43-106 days. The 1.5mm implant was correctly positioned into central macula of 11 primate eyes, with follow-up periods of minimum 6 weeks (n = 11), 2 years (n = 2), and one eye for 3 years. One primate eye underwent multi-chip 1.5mm implantation using two 1.5mm chips. The 2mm implant was delivered to 4 primate eyes. Optical coherence tomography confirmed correct surgical placement of photovoltaic arrays in the subretinal space in all 26 eyes. Intraoperative complications in primate eyes included retinal tear, macular hole, retinal detachment, and vitreous hemorrhage that resolved spontaneously. Postoperatively, there was no case of significant ocular inflammation in the 1.5mm implant group. CONCLUSIONS: We report subretinal implantation of 1.5mm and 2mm photovoltaic arrays in the central retina of feline and central macula of primate eyes with a low rate of device-related complications. The in vivo PRIMA implantation technique has been developed and refined for use for a 2mm PRIMA implant in ongoing human trials

Translational considerations in injectable cell-based therapeutics for neurological applications: concepts, progress and challenges

Significant progress has been made during the past decade towards the clinical adoption of cell-based therapeutics. However, existing cell-delivery approaches have shown limited success, with numerous studies showing fewer than 5% of injected cells persisting at the site of injection within days of transplantation. Although consideration is being increasingly given to clinical trial design, little emphasis has been given to tools and protocols used to administer cells. The different behaviours of various cell types, dosing accuracy, precise delivery, and cell retention and viability post-injection are some of the obstacles facing clinical translation. For efficient injectable cell transplantation, accurate characterisation of cellular health post-injection and the development of standardised administration protocols are required. This review provides an overview of the challenges facing effective delivery of cell therapies, examines key studies that have been carried out to investigate injectable cell delivery, and outlines opportunities for translating these findings into more effective cell-therapy interventions

Risk factors for iatrogenic retinal breaks induced by separation of posterior hyaloid face during 23-gauge pars plana vitrectomy

Purpose To describe the incidence and features of intraoperative retinal breaks caused by induction of posterior hyaloid face (PHF) separation during 23-gauge pars plana vitrectomy (PPV). Methods A prospective, consecutive, single surgeon, observational study of patients undergoing 23-gauge transconjunctival sutureless vitrectomy for macular pathology or floaters, was carried out between 2009 and 2011 at Calderdale Royal Hospital, UK. PHF separations were categorised as either suction induced or requiring membrane blue (DORC Limited) with suction (adherent). The outcome measure was dichotomised into retinal break or tear and no retinal break or tear. Forced entry and parsimonious multiple logistic regression analyses were conducted, using statistical software, to test for significance of association of the set of recorded factors and covariates with the dichotomised outcome measure. Results Data were collected and analysed from 137 patients. The incidence of iatrogenic retinal breaks associated with PHF separation during 23-gauge PPV was 18.2%. Under both forced entry and parsimonious multiple logistic regression models, the odds of a retinal break or tear reduce by about 3–4% for each increasing year of age. Findings also showed some substantive association in the forced entry model, with the odds of a retinal break or tear for adherent cases being around 3.8 times those for suction-only cases. Conclusions Mechanical detachment of the PHF represents an important risk factor in the formation of retinal breaks. Particular care should be taken to examine intraoperatively for iatrogenic breaks in order to prevent missed breaks and subsequent rhegmatogenous retinal detachments

Prevalence of age-related macular degeneration in Nakuru, Kenya: a cross-sectional population-based study.

BACKGROUND: Diseases of the posterior segment of the eye, including age-related macular degeneration (AMD), have recently been recognised as the leading or second leading cause of blindness in several African countries. However, prevalence of AMD alone has not been assessed. We hypothesized that AMD is an important cause of visual impairment among elderly people in Nakuru, Kenya, and therefore sought to assess the prevalence and predictors of AMD in a diverse adult Kenyan population. METHODS AND FINDINGS: In a population-based cross-sectional survey in the Nakuru District of Kenya, 100 clusters of 50 people 50 y of age or older were selected by probability-proportional-to-size sampling between 26 January 2007 and 11 November 2008. Households within clusters were selected through compact segment sampling. All participants underwent a standardised interview and comprehensive eye examination, including dilated slit lamp examination by an ophthalmologist and digital retinal photography. Images were graded for the presence and severity of AMD lesions following a modified version of the International Classification and Grading System for Age-Related Maculopathy. Comparison was made between slit lamp biomicroscopy (SLB) and photographic grading. Of 4,381 participants, fundus photographs were gradable for 3,304 persons (75.4%), and SLB was completed for 4,312 (98%). Early and late AMD prevalence were 11.2% and 1.2%, respectively, among participants graded on images. Prevalence of AMD by SLB was 6.7% and 0.7% for early and late AMD, respectively. SLB underdiagnosed AMD relative to photographic grading by a factor of 1.7. After controlling for age, women had a higher prevalence of early AMD than men (odds ratio 1.5; 95% CI, 1.2-1.9). Overall prevalence rose significantly with each decade of age. We estimate that, in Kenya, 283,900 to 362,800 people 50 y and older have early AMD and 25,200 to 50,500 have late AMD, based on population estimates in 2007. CONCLUSIONS: AMD is an important cause of visual impairment and blindness in Kenya. Greater availability of low vision services and ophthalmologist training in diagnosis and treatment of AMD would be appropriate next steps. Please see later in the article for the Editors' Summary