Retinal visual prostheses (“bionic eyes”) have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration.Trial RegistrationClinicaltrials.gov NCT01603576
A wide-field retinal prosthesis was stable and well tolerated during long-term suprachoroidal implantation in a cat model. The surgical approach was reproducible and overall safe.
Diabetic retinopathy (DR) is a retinal microvascular disease characterized by inflammatory and angiogenic pathways. In this study, we evaluated NLRP3 inflammasome in a double transgenic mouse model, Akimba (Ins2AkitaxVEGF+/−), which demonstrates hyperglycemia, vascular hyperpermeability and neovascularization seen in the proliferative DR. Retinal structural integrity, vascular leakage and function were examined by fundus photography, fluorescein angiography, optical coherence tomography, retinal flat mounts, laser speckle flowgraphy (LSFG), and electroretinography in Akimba and its parental strains, Akita (Ins2Akita) and Kimba (trVEGF029) mice. Inflammatory mechanisms involving NLRP3 inflammasome were investigated using real time-PCR, immunohistochemistry, ELISA and western blots. We observed an increased vascular leakage, reduced retinal thickness, and function in Akimba retina. Also, Akimba retina depicts decreased relative flow volume measured by LSFG. Most importantly, high levels of IL-1β along with increased NLRP3, ASC, and Caspase-1 at mRNA and protein levels were observed in Akimba retina. However, the in vivo functional role remains undefined. In conclusion, increased activation of macroglia (GFAP), microglia (Iba-1 and OX-42) and perivascular macrophages (F4/80 and CD14) together with pro-inflammatory (IL-1β and IL-6) and pro-angiogenic markers (PECAM-1, ICAM-1, VEGF, Flt-1, and Flk-1), suggested a critical role for NLRP3 inflammasome in the Akimba mouse model depicting advanced stages of DR pathogenesis.
Purpose: We compared measurements of central retinal sensitivity on a portable, lowcost tablet device to the established method of microperimetry in age-related macular degeneration (AMD).Methods: A customized test designed to measure central retinal sensitivity (within the central 18 radius) on a tablet device was developed using an open-source platform called PsyPad. A total of 30 participants with AMD were included in this study, and all participants performed a practice test on PsyPad, followed by four tests of one eye and one test of the other eye. Participants then underwent standardized microperimetry examinations in both eyes. Results:The average test duration on PsyPad was 53.9 6 7.5 seconds, and no significant learning effect was observed over the examinations performed (P ¼ 1.000). The coefficient of repeatability of central retinal sensitivity between the first two examinations on PsyPad was 61.76 dB. The mean central retinal sensitivity was not significantly different between PsyPad (25.7 6 0.4 dB) and microperimetry (26.1 6 0.4 dB, P ¼ 0.094), and the 95% limits of agreement between the two measures were between À4.12 and 4.92 dB. Conclusions:The measurements of central retinal sensitivity can be performed effectively using a tablet device, displaying reasonably good agreement with those obtained using the established method of microperimetry.Translational Relevance: These findings highlight the potential of tablet devices as low-cost and portable tools for developing and performing visual function measures that can be easily and widely implemented.
PURPOSE. To evaluate rod function longitudinally in intermediate age-related macular degeneration subjects with reticular pseudodrusen (RPD) and without RPD (AMD). METHODS. Retinal sensitivities (505 and 625 nm) during dark adaptation, at 14 locations within the central 128 macula were obtained after photobleaching at baseline and 12-month visits. Pointwise sensitivity differences between both stimuli were used to assess static rod function, while rod intercept time (RIT) and rod recovery rate (RRR) were used to evaluate dynamic function. Changes in function over time were compared between groups. RESULTS. A total of 23 controls, 12 AMD, and 13 RPD cases were followed-up. At baseline, the RPD group had significantly worst static and dynamic rod function compared to AMD and control groups. Static function in AMD was similar to controls. Static and dynamic function across the central 128 was consistent in controls; however, it was most impaired at 48 compared to 128 eccentricity in disease groups. Over 12 months, no AMD cases progressed clinically and static function in AMD improved (P 0.04), but remained unchanged in control and RPD groups (P ‡ 0.17). The RRR for control and RPD groups remained stable, while the AMD group deteriorated, but only at 128 (P ¼ 0.02). The RIT was stable in AMD (P ¼ 0.75) and RPD (P ¼ 0.71) groups but improved in the control group (P ¼ 0.002). CONCLUSIONS. A decrease in RRR was detected over 12 months at 128 eccentricity in the AMD group. Evaluating changes in rod function requires testing at multiple locations including the peripheral macula.
METHODS. In this cross-sectional study, retinal sensitivities within the central 248 retina were obtained twice using a dark-adapted chromatic perimeter, both with 505-and 625-nm stimuli. Tests were performed after 30 minutes of dark-adaptation either with or without a preceding photobleach. Multimodal imaging was performed to grade AMD and SDD status, and other retinal changes considered being risk factors for progression to late AMD. The sensitivity difference between both stimuli was used to assess rod function. The average point wise sensitivity difference (PWSD) was compared among the study groups.RESULTS. Twenty-nine control subjects and 20 iAMD without SDD and 17 iAMD with SDD cases were recruited. The average PWSD of the SDD group was significantly reduced (more with photobleach) compared with that of the control (P < 0.001) and no-SDD groups (P < 0.001), but only within the central 88. The average PWSD of the non-SDD group was also reduced compared with the control group but only for measurements with photobleach (P ¼ 0.020). There was no difference in average PWSD between the presence and absence of hyperreflective foci and/or nascent geographic atrophy in iAMD eyes without SDD (P ¼ 0.60) or with SDD (P ¼ 0.12).CONCLUSIONS. iAMD eyes with SDD are associated with worse static rod function compared with eyes without SDD. The greatest abnormality in rods is observed within the central 88 and when tested with a preceding photobleach.
Citation: Luu CD, Dimitrov PN, Wu Z, et al. Static and flicker perimetry in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2013;54:3560-3568. DOI:10.1167/ iovs.12-10465 PURPOSE. The relationship between clinical severity of age-related macular degeneration (AMD) and macular function has not been well established. In this study, we investigated the correlation between clinical severity and functional deficits as detected by static and flicker perimetry.METHODS. This cross-sectional study consisted of 279 AMD subjects and 24 control participants. AMD subjects were allocated into 1 of 10 AMD severity groups depending on the status of the designated study eye and the fellow eye, as assessed by color fundus photographs. Visual acuity, and static and flicker perimetry were tested on one eye during the same session. The geometric means, SDs, and percentage of abnormal eyes of static and flicker sensitivity of each AMD severity group were determined and compared. CONCLUSIONS. Static and flicker perimetry were affected similarly across the spectrum of AMD severity, and methods appeared to be valid techniques for assessing retinal sensitivity in AMD once drusen > 125 lm are present, but before the development of late AMD.
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