Marten E. Brelen

Creating a meaningful visual perception in blind volunteers by optic nerve stimulation

A blind volunteer, suffering from retinitis pigmentosa, has been chronically implanted with an optic nerve visual prosthesis. Vision rehabilitation with this volunteer has concentrated on the development of a stimulation strategy according to which video camera images are converted into stimulation pulses. The aim is to convey as much information as possible about the visual scene within the limits of the devices capabilities. Pattern recognition tasks were used to assess the effectiveness of the stimulation strategy. The results demonstrate how even a relatively basic algorithm can efficiently convey useful information regarding the visual scene. By increasing the number of phosphenes used in the algorithm, better performance is observed but a longer training period is required. After a learning period, the volunteer achieved a pattern recognition score of 85% at 54 s on average per pattern. After nine evaluation sessions, when using a stimulation strategy exploiting all available phosphenes, no saturation effect has yet been observed.

Vision rehabilitation in the case of blindness.

This article examines the various vision rehabilitation procedures that are available for early and late blindness. Depending on the pathology involved, several vision rehabilitation procedures exist, or are in development. Visual aids are available for low vision individuals, as are sensory aids for blind persons. Most noninvasive sensory substitution prostheses as well as implanted visual prostheses in development are reviewed. Issues dealing with vision rehabilitation are also discussed, such as problems of biocompatibility, electrical safety, psychosocial aspects, and ethics. Basic studies devoted to vision rehabilitation such as simulation in mathematical models and simulation of artificial vision are also presented. Finally, the importance of accurate rehabilitation assessment is addressed, and tentative market figures are given.

Association of Genetic Variants with Polypoidal Choroidal Vasculopathy: A Systematic Review and Updated Meta-analysis.

TOPIC A systematic review and meta-analysis of the genetic association with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD). CLINICAL RELEVANCE To identify genetic biomarkers that are potentially useful for genetic diagnosis of PCV and for differentiating PCV from nAMD. METHODS We performed a literature search in EMBASE, PubMed, Web of Science, and the Chinese Biomedical Database for PCV genetic studies published before February 6, 2015. We then conducted a meta-analysis of all polymorphisms that had sufficient genotype/allele data reported in ≥2 studies and estimated the summary odds ratio (OR) and 95% confidence intervals (CIs) for PCV. We also compared the association profiles between PCV and nAMD, and performed a sensitivity analysis. RESULTS A total of 66 studies were included in the meta-analysis, involving 56 polymorphisms in 19 genes/loci. In total, 31 polymorphisms in 10 genes/loci (age-related maculopathy susceptibility 2 [ARMS2], high-temperature requirement factor A1 [HTRA1], complement factor H [CFH], complement component 2 [C2], CFB, RDBP, SKIV2L, CETP, 8p21, and 4q12) were significantly associated with PCV. Another 25 polymorphisms in 13 genes (ARMS2, HTRA1, C2, CFB, ELN, LIPC, LPL, ABCA1, VEGF-A, TLR3, LOXL1, SERPING1, and PEDF) had no significant association. Twelve polymorphisms at the ARMS2-HTRA1 locus showed significant differences between PCV and nAMD. The sensitivity analysis validated the significance of our analysis. CONCLUSIONS This study revealed 31 polymorphisms in 10 genes/loci that contribute to PCV susceptibility. Among them, ARMS2-HTRA1 also showed allelic diversity between PCV and nAMD. Our results confirm the gene variants that could affect the phenotypic expressions of PCV and nAMD.

Measurement of evoked potentials following electrical stimulation of the human optic nerve

PURPOSE To examine the visual evoked potentials (VEP) and electroretinograms (ERG) generated during electrical stimulation of the human optic nerve using the optic nerve visual prosthesis. METHODS Two volunteers blind from retinitis pigmentosa (RP) and with no light perception each received a chronically implanted optic nerve visual prosthesis. Cortical evoked potentials were recorded using 16 scalp electrodes, and antidromic ERGs were obtained using DTL electrodes while the optic nerve was electrically stimulated. The results were compared with flash and eye surface electrical stimulation results in normal-sighted control subjects. RESULTS The VEPs obtained in our two volunteers with implants had a waveshape similar to that obtained in normal-sighted volunteers during flash stimulation, but latency was reduced by approximately 25 ms. The VEPs recorded during surface eye stimulation are similar in both normal-sighted and RP volunteers. The VEPs were compared at sub- and supra-threshold stimulation strength and with different electrode configurations. Finally, the antidromic ERG recordings obtained in our implanted volunteers show a unique inner retinal potential generated by retrograde stimulation of the eye from the optic nerve. CONCLUSIONS Evoked potentials can be used to examine how a visual prosthesis generates visual sensations. This provides an objective means to investigate various aspects of the visual prostheses.

Anti-TNF-alpha reduces the inflammatory reaction associated with cuff electrode implantation around the sciatic nerve.

Extraneural cuff electrodes have been extensively used to investigate the nervous system. Their implantation is, however, associated with epineurial fibrosis, fiber loss, limited reproducibility of recordings and variability in stimulating conditions. It has recently been shown that TNF-alpha is involved in nerve alterations after electrode implantation. This study investigated whether a peri-operative anti-TNF-alpha treatment could modify the inflammation and fibrosis associated with cuff electrode implantation. Morphometrical and immunohistochemical methods were used to show that a single systemic injection of TNF-alpha neutralizing antibodies is sufficient to reduce the early inflammatory events, but not the long lasting fibrotic reaction.

Vision rehabilitation with the optic nerve visual prosthesis

A blind volunteer with retinitis pigmentosa has been chronically implanted with an optic nerve visual prosthesis. The axons of retinal ganglion cells have been successfully activated by electrical stimuli to evoke many distinct phosphenes over a large portion of the visual field. No sensations other than visual have been elicited. Controlled electrical stimulation of the optic nerve proved able to convey visual information useful for the localization and discrimination of objects.

Determinants of Quantitative Optical Coherence Tomography Angiography Metrics in Patients with Diabetes

Early microvascular damage in diabetes (e.g. capillary nonperfusion and ischemia) can now be assessed and quantified with optical coherence tomography-angiography (OCT-A). The morphology of vascular tissue is indeed affected by different factors; however, there is a paucity of data examining whether OCT-A metrics are influenced by ocular, systemic and demographic variables in subjects with diabetes. We conducted an observational cross-sectional study and included 434 eyes from 286 patients with diabetes. Foveal avascular zone (FAZ) area, FAZ circularity, total and parafoveal vessel density (VD), fractal dimension (FD), and vessel diameter index (VDI) from the superficial capillary plexus OCT-angiogram were measured by a customized automated image analysis program. We found that diabetic retinopathy (DR) severity was associated with increased FAZ area, decreased FAZ circularity, lower VD, lower FD, and increased VDI. Enlarged FAZ area was correlated with shorter axial length and thinner central subfield macular thickness. Decreased FAZ circularity was correlated with a reduction in visual function. Decreased VD was correlated with thinner macular ganglion-cell inner plexiform layer. Increased VDI was correlated with higher fasting glucose level. We concluded that the effects of ocular and systemic factors in diabetics should be taken into consideration when assessing microvascular alterations via OCT-A.

EFFECTS OF REDUCING SUBMANDIBULAR BLOOD FLOW ON SECRETORY RESPONSES TO PARASYMPATHETIC STIMULATION IN ANAESTHETIZED CATS

Submandibular secretory responses to stimulation of the parasympathetic chorda‐lingual nerve were investigated in five anaesthetized cats before, during and after withdrawal of blood (ca 20 ml kg−1) in order to investigate the consequences of a reduced blood flow through the gland. Stimulation at different frequencies (2, 4, 6 and 8 Hz) evoked a frequency‐dependent increase in the flow of submandibular saliva, sodium concentration, electrolyte and protein output. When the blood pressure was reduced (by about 50%) there was a significant reduction in submandibular blood flow and the secretion of both saliva and protein during stimulation. Under each set of conditions the flow of saliva was linearly related to the blood flow through the gland. It is concluded that submandibular secretory responses to electrical stimulation of the parasympathetic innervation can be significantly attenuated when the blood flow through the gland is reduced under the conditions employed in this study.

Diabetes mellitus and risk of age-related macular degeneration: a systematic review and meta-analysis.

Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious consequences, and diabetic retinopathy (DR) is the main ophthalmic complication. DR and AMD are different diseases and we seek to explore the relationship between diabetes and AMD. MEDLINE, EMBASE, and the Cochrane Library were searched for potentially eligible studies. Studies based on longitudinal cohort, cross-sectional, and case-control associations, reporting evaluation data of diabetes as an independent factor for AMD were included. Reports of relative risks (RRs), hazard ratios (HRs), odds ratio (ORs), or evaluation data of diabetes as an independent factor for AMD were included. Review Manager and STATA were used for the meta-analysis. Twenty four articles involving 27 study populations were included for meta-analysis. In 7 cohort studies, diabetes was shown to be a risk factor for AMD (OR, 1.05; 95% CI, 1.00–1.14). Results of 9 cross-sectional studies revealed consistent association of diabetes with AMD (OR, 1.21; 95% CI, 1.00–1.45), especially for late AMD (OR, 1.48; 95% CI, 1.44–1.51). Similar association was also detected for AMD (OR, 1.29; 95% CI, 1.13–1.49) and late AMD (OR, 1.16; 95% CI, 1.11–1.21) in 11 case-control studies. The pooled ORs for risk of neovascular AMD (nAMD) were 1.10 (95% CI, 0.96–1.26), 1.48 (95% CI, 1.44–1.51), and 1.15 (95% CI, 1.11–1.21) from cohort, cross-sectional and case-control studies, respectively. No obvious divergence existed among different ethnic groups. Therefore, we find diabetes a risk factor for AMD, stronger for late AMD than earlier stages. However, most of the included studies only adjusted for age and sex; we thus cannot rule out confounding as a potential explanation for the association. More well-designed prospective cohort studies are still warranted to further examine the association.

Ethnic differences in the association of SERPING1 with age-related macular degeneration and polypoidal choroidal vasculopathy.

Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of irreversible blindness in developed countries. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in the serpin peptidase inhibitor, clade G, member 1 (SERPING1) gene with neovascular AMD and PCV. Two haplotype-tagging SNPs, rs1005510 and rs11603020, of SERPING1 were genotyped in 708 unrelated Chinese individuals: 200 neovascular AMD, 233 PCV and 275 controls. A meta-analysis was also performed for all reported associations of SERPING1 SNPs with AMD and PCV. None of the tagging SNPs had a significant association with neovascular AMD or PCV (P > 0.05) in our study cohort. The meta-analyses showed that the most-studied SNP rs2511989 was not significantly associated with all forms of AMD, neovascular AMD, or PCV in East Asians (P = 0.98, 0.93 and 0.30, respectively) but was associated with AMD in Caucasians (P = 0.04 for all AMD and 0.004 for neovascular AMD). Therefore, the results of our study and meta-analysis suggest that SERPING1 is not a major genetic component of AMD or PCV in East Asians but is a genetic risk factor for AMD in Caucasians, providing evidence for an ethnic diversity in the genetic etiology of AMD.