Outer retinal degeneration in a non-human primate model using temporary intravitreal tamponade with N-methyl-N-nitrosourea in cynomolgus monkeys.

Objective:The main objective of this study was to induce and evaluate drug-dose-dependent outer retinal degeneration in cynomolgus monkeys by application of N-methyl-N-nitrosourea (MNU).Approach:Intravitreal temporary tamponade induced outer retinal degeneration with MNU solutions (2-3 mg ml-1) after vitrectomy in five cynomolgus monkeys. Optical coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinography (ffERG), and visual evoked potentials (VEP) were performed at baseline and weeks 2, 6, and 12 postoperatively. At week 12, OCT angiography, histology, and immunohistochemistry were performed.Main results:Outer retinal degeneration was observed in four monkeys, especially in the peripheral retina. Anatomical and functional changes occurred at week 2 and persisted until week 12. FAF images showed hypoautofluorescence dots, similar to AF patterns seen in human retinitis pigmentosa. Hyperautofluorescent lesions in the pericentral area were also observed, which corresponded to the loss of the ellipsoid zone on OCT images. OCT revealed thinning of the outer retinal layer adding to the loss of the ellipsoid zone outside the vascular arcade. Histological findings confirmed that the abovementioned changes resulted from a gradual loss of photoreceptors from the perifovea to the peripheral retina. In contrast, the inner retina, including ganglion cell layers, was preserved. Functionally, a decrease or extinction of scotopic ffERGs was observed, which indicated rod-dominant loss. Nevertheless, VEPs were relatively preserved.Significance:Therefore, we can conclude that temporary exposure to intravitreal MNU tamponade after vitrectomy induces rod-dominant outer retinal degeneration in cynomolgus monkeys, especially in the peripheral retina.

Retinal Prostheses and Artificial Vision

In outer retinal degenerative diseases such as retinitis pigmentosa, choroideremia, and geographic atrophy, 30% of the ganglion cell layer in the macula remains intact. With subretinal and epiretinal prostheses, these inner retinal cells are stimulated with controlled electrical current by either a microphotodiode placed in the subretinal area or a microelectrode array tacked to the epiretinal region. As the patient learns to interpret the resulting phosphene patterns created in the brain through special rehabilitation exercises, their orientation, mobility, and quality of life increase. Implants that stimulate the lateral geniculate nucleus or visual cortex are currently being studied for diseases in which the ganglion cells and optic nerve are completely destroyed.

The use of Argus® II retinal prosthesis by blind subjects to achieve localisation and prehension of objects in 3-dimensional space.

BACKGROUND: The Argus® II retinal prosthesis system has entered mainstream treatment for patients blind from Retinitis Pigmentosa (RP). We set out to evaluate the use of this system by blind subjects to achieve object localisation and prehension in 3-dimensional space. METHODS: This is a single-centre, prospective, internally-controlled case series involving 5 blind RP subjects who received the Argus® II implant. The subjects were instructed to visually locate, reach and grasp (i.e. prehension) a small white cuboid object placed at random locations on a black worktop. A flashing LED beacon was attached to the reaching index finger (as a finger marker) to assess the effect of enhanced finger visualisation on performance. Tasks were performed with the prosthesis switched "on" or "off" and with the finger marker switched "on" or "off". Forty-eight trials were performed per subject. Trajectory of each subject's hand movement during the task was recorded by a 3D motion-capture unit (Qualysis®, see supplementary video) and analysed using a MATLAB script. RESULT: Percentage of successful prehension±standard deviation was: 71.3 ± 27.1 % with prosthesis on and finger marker on; 77.5 ± 24.5 % with prosthesis on and finger marker off; 0.0 ± 0.0 % with prosthesis off and finger marker on, and 0.00 ± 0.00 % with prosthesis off and finger marker off. The finger marker did not have a significant effect on performance (P = 0.546 and 1, Wilcoxon Signed Rank test, with prosthesis on and off respectively). With prosthesis off, none of the subjects were able to visually locate the target object and no initiation of prehension was attempted. With prosthesis on, prehension was initiated on 82.5 % (range 59-100 %) of the trials with 89.0 % (range 66.7-100 %) achieving successful prehension. CONCLUSION: Argus® II subjects were able to achieve object localisation and prehension better with their prosthesis switched on than off.

Epiretinal prosthesis for outer retinal degenerative diseases / 国际眼科杂志(Guoji Yanke Zazhi)

·Age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are common outer retinal degenerative problems, which are also the predominant causes of most blinding retinal diseases. Retinal prosthesis is a promising solution for such photoreceptor degeneration diseases.Most of current concepts for a retinal prosthesis are based on neuronal electrical stimulation. In the past twenty years, retinal prosthesis has been developed in two different directions: epiretinal prosthesis and subretinal prosthesis. Each prosthesis technique has its advantages and disadvantages. For epiretinal prosthesis, it is easier to be implanted and has the advantage of keeping most of the electronics in the vitreous cavity, off the retinal surface, which greatly helps in dissipating the heat generated by the implant device. In this paper, a brief overview of retinal prostheses concepts is introduced. After that, several important aspects of epiretinal electrical stimulation will be discussed. Moreover, some practical epiretinal prosthesis devices developed by researchers in United States, Germany and Japan in the past have been reviewed. We hope that the devices will be used widely in the near future.