Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration.

Age-related macular degeneration (AMD) remains a major cause of blindness, with dysfunction and loss of retinal pigment epithelium (RPE) central to disease progression. We engineered an RPE patch comprising a fully differentiated, human embryonic stem cell (hESC)-derived RPE monolayer on a coated, synthetic basement membrane. We delivered the patch, using a purpose-designed microsurgical tool, into the subretinal space of one eye in each of two patients with severe exudative AMD. Primary endpoints were incidence and severity of adverse events and proportion of subjects with improved best-corrected visual acuity of 15 letters or more. We report successful delivery and survival of the RPE patch by biomicroscopy and optical coherence tomography, and a visual acuity gain of 29 and 21 letters in the two patients, respectively, over 12 months. Only local immunosuppression was used long-term. We also present the preclinical surgical, cell safety and tumorigenicity studies leading to trial approval. This work supports the feasibility and safety of hESC-RPE patch transplantation as a regenerative strategy for AMD.

Long-term Repeatability and Reproducibility of Phosphene Characteristics in Chronically Implanted Argus II Retinal Prosthesis Subjects.

PURPOSE: Previously published literatures of acute studies on few subjects have shown contradictory evidence on the reproducibility and characteristics of the elicited phosphenes, despite using the same stimulating parameters with epiretinal electrode arrays. In this study, we set out to investigate the long-term repeatilibity and reproducibility of phosphenes in subjects chronically implanted with the Argus II retinal prosthesis (Second Sight Medical Products, Inc., Sylmar, CA, USA). DESIGN: Retrospective interventional case series and reliability study. METHODS: Six Argus II subjects of >5 years implantation from a single site participated. The 4-electrode cluster ("quad") closest to fovea was stimulated in each subject with a fixed biphasic current. Perceived phosphenes were depicted relative to subjective visual field center. The stimulus was applied at reducing time intervals from 20 minutes to 1 second. Two sets of stimulations were performed on the same day and 2 further sets repeated on a separate visit >1 week apart. RESULTS: Each subject depicted phosphenes of consistent shapes and sizes, and reported seeing the same colors with the fixed stimulating parameters, irrespective of the interstimuli intervals. However, there is a wide intersubject variation in the phosphene characteristics. Four subjects drew phosphenes in the same visual field quadrant, as predicted by the quad-fovea location. Two subjects depicted phosphenes in the same hemifield as the expected locations. CONCLUSION: Phosphenes for each subject were consistently reproducible in all our chronically implanted subjects. This has important implications in the development of long-term pixelated prosthetic vision for future devices.

Punctal function in lacrimal drainage: the 'pipette sign' and functional ectropion.

BACKGROUND: The aim was to assess the movements of the inferior punctum during blinking and discuss pertinent clinical applications. METHODS: This is a prospective, non-comparative observational case-series examining the function of inferior punctum during blinking using video recordings of the blinking action at the slitlamp with slow-motion analysis and comparison. RESULTS: In all 56 eyes of 28 patents, supero-medial movement of the lower punctum toward the medial canthus, together with a medially directed protrusion of the inferior punctum was noted. It was also noted that the punctum blanched during this projectile movement compared to the rest of the lid margin. Simultaneous posterior rotation of the punctum was also observed in 48 eyes (85.7 per cent; 23 right eyes and 25 left eyes), resulting in apposition of the punctum to the lacus lacrimalis. In eight eyes (14.3 per cent; five right eyes and three left) from six patients, co-existence of medial punctal ectropion led to failure of internal rotation of the punctum during blinking, even though punctal 'pipette formation' was preserved. These six patients all suffered from epiphora in the affected eyes. The presence of 'pipette' formation was calculated to have a sensitivity of 80 per cent and specificity of 100 per cent for punctal ectropion in our series. A two-tailed Fisher exact test showed that based on our 56 eyes, these results were statistically significant (p < 0.0001). CONCLUSIONS: The inferior punctum plays an active and important role in the drainage of tears by the mechanism of supero-medial movement and medially directed protrusion ('pipetting action'), failure of which contributes to epiphora. This is a highly specific sign and should be sought in the evaluation of epiphora, even in the absence of frank ectropion. In punctual stenosis where location of the punctal orifice is proving difficult, inducing the pipette sign will help in its identification.

A review and update on the current status of retinal prostheses (bionic eye).

INTRODUCTION/BACKGROUND: The Argus® II is the first retinal prosthesis approved for the treatment of patients blind from retinitis pigmentosa (RP), receiving CE (Conformité Européenne) marking in March 2011 and FDA approval in February 2013. Alpha-IMS followed closely and obtained CE marking in July 2013. Other devices are being developed, some of which are currently in clinical trials. SOURCES OF DATA: A systematic literature search was conducted on PubMED, Google Scholar and IEEExplore. AREAS OF AGREEMENT: Retinal prostheses play a part in restoring vision in blind RP patients providing stable, safe and long-term retinal stimulation. AREAS OF CONTROVERSY: Objective improvement in visual function does not always translate into consistent improvement in the patient's quality of life. Controversy exists over the use of an external image-capturing device versus internally placed photodiode devices. GROWING POINTS: The alpha-IMS, a photovoltaic-based retinal prosthesis recently obtained its CE marking in July 2013. AREAS TIMELY FOR DEVELOPING RESEARCH: Improvement in retinal prosthetic vision depends on: (i) improving visual resolution, (ii) improving the visual field, (iii) developing an accurate neural code for image processing and (iv) improving the biocompatibility of the device to ensure longevity.