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Novel clinical findings in autosomal recessive NR2E3-related retinal dystrophy
摘要： Purpose To evaluate the clinical phenotype of autosomal recessive NR2E3-related retinal dystrophy. Methods We retrospectively studied 11 patients carrying out at least 2 NR2E3 mutations; they had undergone comprehensive ophthalmological examination, fundus photography, optical coherence tomography, electrophysiological testing, and visual field at the Regional Reference Center for Hereditary Retinal Degenerations of the Eye Clinic in Florence. Results Five females and six males with a diagnosis of NR2E3-related retinal dystrophy were included in the study. All patients complained of nyctalopia. Visual acuity ranged from 0.00 logMAR to hand motion. Two patients presented bull’s eye maculopathy, and one of these was characterized by a triple hyper-autofluorescent ring at the fundus autofluorescence examination. Three patients showed small yellowish dots and spots at the mid-periphery. One patient was characterized by widespread subretinal drusenoid deposits (SDD) at the posterior pole. Four patients showed vitreous abnormalities. Optical coherence tomography (OCT) examinations detected variable degrees of abnormal retinal lamination and schitic changes. Seven patients were compound heterozygous and four were homozygous for mutations in NR2E3. Conclusions Our study confirmed high variable phenotype in autosomal recessive NR2E3-related retinal dystrophy. Bull’s eye maculopathy, subretinal drusenoid deposits, and foveal hypoplasia represent novel clinical findings in NR2E3-related retinal dystrophy. Macular involvement was detectable in all the patients, and the abnormal foveal avascular zone (FAZ) supports the role of NR2E3 in retinal development.
关键词： Retinal dystrophy,Foveal hypoplasia,Retinitis pigmentosa,Subretinal drusenoid deposits,Autosomal recessive disease,Goldmann-Favre,NR2E3
更新于2025-09-23 15:23:52
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Characterization of Rod Function Phenotypes Across a Range of Age-Related Macular Degeneration Severities and Subretinal Drusenoid Deposits
摘要： PURPOSE. To examine spatial changes in rod-mediated function in relationship to local structural changes across the central retina in eyes with a spectrum of age-related macular degeneration (AMD) disease severity. METHODS. Participants were categorized into five AMD severity groups based on fundus features. Scotopic thresholds were measured at 14 loci spanning 6° to 18° along the vertical meridian from one eye of each of 42 participants (mean = 71.7 ± 9.9 years). Following a 30% bleach, dark adaptation was measured at eight loci (4° to 12°). Rod intercept time (RIT) was defined from the time to detect a ?3.1 log cd/m2 stimulus. RITslope was defined from the linear fit of RIT with decreasing retinal eccentricity. The presence of subretinal drusenoid deposits (SDD), ellipsoid (EZ) band disruption, and drusen at the test loci was evaluated using optical coherence tomography. RESULTS. Scotopic thresholds indicated greater rod function loss in the macula, which correlated with increasing AMD group severity. RITslope, which captures the spatial change in the rate of dark adaptation, increased with AMD severity (P < 0.0001). Three rod function phenotypes emerged: RF1, normal rod function; RF2, normal scotopic thresholds but slowed dark adaptation; and RF3, elevated scotopic thresholds with slowed dark adaptation. Dark adaptation was slowed at all loci with SDD or EZ band disruption, and at 32% of loci with no local structural changes. CONCLUSIONS. Three rod function phenotypes were defined from combined measurement of scotopic threshold and dark adaptation. Spatial changes in dark adaptation across the macula were captured with RITslope, which may be a useful outcome measure for functional studies of AMD.
关键词： age-related macular degeneration,RIT,SDD,scotopic thresholds,dark adaptation,rod intercept time,subretinal drusenoid deposits,AMD
更新于2025-09-23 15:22:29
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In vitro reliability testing and in vivo lifespan estimation of wireless Pixium Vision PRIMA photovoltaic subretinal prostheses suggest prolonged durability and functionality in clinical practice
摘要： Objective. Retinal implants have the potential to restore some sight in patients with retinal degeneration. The PRIMA implant’s novel design features simpler insertion and no transscleral cabling or extraocular components. This in vitro study investigated PRIMA’s durability under real time and accelerated conditions and estimated the device’s lifespan in vivo. Approach. Two potential failure modes were examined: corrosion and overstimulation. Real-time aging was tested using implants immersed in balanced saline solution (BSS) at 37°C, mimicking the intraocular environment. Accelerated aging was examined at 77°C (Arrhenius theory). Confirmatory testing of acceleration factor was performed using different temperatures (37°C-87°C) and weakened implant coatings. The effect of repeated maximum stimulation was tested using a pulsed infrared laser (6x acceleration factor). Data were used to estimate device lifespan. Main results. 175 implants were tested for up to 33 months. No corrosion or water ingress was observed after approximately 20 accelerated years. A pixel failure rate of 0.15% was recorded after 10 accelerated years’ stimulation. The derived lifespan estimation for the PRIMA implant was 27.0 years with a reliability of 90% (95% confidence interval). Significance. The PRIMA implant was found to be robust, with in vitro reliability of at least ten years. The PRIMA implant shows durability and functionality for clinically relevant timespans under similar environmental conditions to the human eye. These results require in vivo confirmation.
关键词： implant corrosion,reliability,retinal prosthesis,lifespan,subretinal
更新于2025-09-23 15:21:01
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Influence of Axial Length on Thickness Measurements Using Spectral-Domain Optical Coherence Tomography
摘要： The purpose of this study was to assess the in?uence of axial length on spectral-domain optical coherence tomography (SD-OCT) thickness measurements in patients with subretinal visual implants. Data from eight emmetropic pseudophakic eyes of eight patients with subretinal visual implants were analyzed retrospectively. These patients participated in the monocentric part of a multicenter trial. The axial length was measured in three short (<22.5 mm), three medium (22.51–25.50 mm), and two long (>25.52 mm) eyes. Using Heidelberg Spectralis, the known thickness of a subretinal implant microchip (70 lm) was measured on 15 images per eye with SD-OCT, using the software calipers. The mean axial length was 20.8 6 0.8 mm in short eyes, 23.3 6 0.4 mm in medium eyes, and 26.3 6 0.5 mm in long eyes. We found in short eyes, in medium eyes, and in long eyes a mean value of microchip thickness measurements from SD-OCT of 82.9 6 1.4 lm, 70.5 6 1.3 lm, and 64.2 6 1.3 lm, respectively. The thickness measurements decreased in SD-OCT measurements with longer axial lengths signi?cantly (P < 0.0001). Axial length in?uences SD-OCT thickness measurements. Our ?ndings demonstrate accuracy of the scaling in SD-OCT thickness measurements in emmetropic medium eyes. Caution is recommended when comparing the measured values of short and long eyes with the normative database of the instrument. There is a need for larger sample-size studies to con?rm our results.
关键词： subretinal visual implant,spectral-domain optical coherence tomography (SD-OCT),axial length,Heidelberg Spectralis,in vivo measurement
更新于2025-09-23 15:21:01
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Changes in Retinal Layer Thickness in the?Contralateral Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration
摘要： To evaluate the thickness of the outer retinal layers and its relationship with visual function in fellow eyes of participants with unilateral neovascular age-related macular degeneration (AMD). Design: Longitudinal study. Participants: We enrolled 105 subjects with unilateral neovascular AMD from 3 clinical centers in Europe. Methods: The fellow eye, without advanced AMD, was selected for the study. Subjects were followed up with visits occurring every 6 months for 2 years. Spectral domain optical coherence tomography volume scans were collected at 3 clinical sites, in Belfast, Northern Ireland; Coimbra, Portugal; and Milan, Italy. Detailed manual segmentation of outer retinal layers was performed using the custom-designed and validated grading software 3D OCTOR. Thickness measurements for neurosensory retina, photoreceptor layer (PRL) outer segments, retinal pigment epithelium plus drusen (RPEtdrusen) complex, and choroidal layers from each sector of the standard macular grid were obtained. Measures of vison were distance visual acuity, near visual acuity, Smith-Kettlewell Institute low-luminance acuity score, and reading speed. Subjects were grouped based on the presence or absence of subretinal drusenoid deposits (SDDs) for further analysis. Main Outcome Measures: Change in thickness of retinal layers and change in measures of vision. Results: In all, 85 eyes were included in the analysis. The average duration of follow-up was 20.5 (cid:2) 5.8 months. By the ?nal visit, the RPEtdrusen complex was signi?cantly thinner when compared with baseline (29.7 mm vs. 34.09 mm; P ? 0.03). Low-luminance de?cit was signi?cantly worse at the ?nal visit (P < 0.001) and correlated with PRL outer segment thickness (r ? 0.33; P ?0.02). The RPEtdrusen complex was signi?cantly thicker in eyes with SDDs compared with that in those without SDDs (30.67 mm vs. 28.64 mm; P ? 0.02). PRL outer segments became signi?cantly thinner over time in eyes with SDDs compared with those in eyes without SDDs. Conclusions: The RPEtdrusen complex layer becomes thinner over time in fellow eyes of subjects with unilateral neovascular AMD. The rate of PRL outer segment thinning was higher in eyes with SDDs than in eyes without SDDs. These ?ndings are preliminary steps in the identi?cation of early biomarkers for detecting and monitoring the progression of AMD. Ophthalmology Retina 2018;-:1e10 a 2018 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology
关键词： spectral domain optical coherence tomography,visual function,retinal layer thickness,subretinal drusenoid deposits,age-related macular degeneration
更新于2025-09-23 15:21:01
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Electrical activation of degenerated photoreceptors in blind mouse retina elicited network-mediated responses in different types of ganglion cells
摘要： Electrical (e-) stimulation is explored in schemes to rescue the vision of blind people, e.g. those affected by Retinitis Pigmentosa (RP). We e-activated subretinally the surviving degenerated photoreceptors (d-Phrs) of the rd1 mouse (RP model) and evoked visual responses in the blind retina. The e-stimulation was applied with a single platinum/iridium electrode. The d-Phrs (calcium-imaging) and ganglion cells (GC) activity (MEA-recording) were recorded in simultaneous multilayer recordings. The findings of this study confirm that the d-Phrs responded to e-stimulation and modulated the retinal network-activity. The application of blockers revealed that the synaptic interactions were dependent on voltage-gated calcium channels and mediated by the transmitters glutamate and GABA. Moreover, the gap junctions coupled networks promoted the lateral-spread of the e-evoked activity in the outer (~60 μm) and inner (~120 μm) retina. The activated GCs were identified as subtypes of the ON, OFF and ON-OFF classes. In conclusion, d-Phrs are the ideal interface partners for implants to elicit enhanced visual responses at higher temporal and spatial resolution. Furthermore, the retina’s intact circuity at the onset of complete blindness makes it a tempting target when considering the implantation of implants into young patients to provide a seamless transition from blinding to chip-aided vision.
关键词： blind retina,MEA recording,subretinal implant,gap junctions,glutamate,rd1 mouse,calcium imaging,ganglion cells,GABA,electrical stimulation,Retinitis Pigmentosa,degenerated photoreceptors
更新于2025-09-19 17:15:36
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Statement of the BVA, the DOG, and the RG on treatment of choroidal neovascularization in diseases other than neovascular age-related macular degeneration; Stellungnahme des BVA, der DOG und der RG zur Therapie chorioidaler Neovaskularisationen bei anderen Erkrankungen als der neovaskul?ren altersabh?ngigen Makuladegeneration (Englische Version);
摘要： Choroidal neovascularizations (CNV) occur not only in age-related macular degeneration (AMD), but also in numerous other macular and retinal disorders of varying etiology and, if left untreated, can cause irreversible visual loss. The diagnosis of CNV as well as the indication for treatment should be made in the same way as in neovascular AMD: On initial diagnosis: best-corrected visual acuity, fundus examination, optical coherence tomography (OCT), and fluorescein angiography. At follow-up: best-correct visual acuity, fundus examination, OCT, and, depending on findings, fluorescein angiography. Active CNV should be treated with intravitreal operative medication (IVOM) using vascular endothelial growth factor (VEGF) inhibitors if patients have visual acuity of at least 0.05 or if there is sufficient reason to assume that visual acuity could increase to over 0.05 under treatment. Underlying disorders can include, e.g., high myopia, angioid streaks, central serous chorioretinopathy, active and inactive uveitis of varying etiology, including retinochoroiditis, chorioretinitis, and choroiditis, eye injuries, retinal dystrophies, e.g., best disease and pattern dystrophies, idiopathic CNV, subretinal masses (osteomas, hamartomas, nevi). If CNV is not present as a complication in the above-mentioned disorders, IVOM with VEGF inhibitors should not be performed. Ranibizumab and aflibercept are approved in Germany for the treatment of CNV secondary to pathologic myopia. Ranibizumab has been approved in Germany since 12/2016 for the treatment of CNV in disorders other than neovascular AMD and pathologic myopia irrespective of the underlying disease. The other VEGF inhibitors, aflibercept and bevacizumab, can be used off-label. Due to its overall significantly poorer treatment results, photodynamic therapy (PDT) should only be used in exceptional cases and extrafoveal localization. After one initial intravitreal administration of VEGF inhibitors, further CNV activity should be monitored monthly for the first 6 months (see point 2). In the case of persisting or recurrent activity, repeated IVOM should be performed. Depending on disease course, the follow-up interval might be extended 6 months after the last IVOM. In individual justified cases (e.g., patients requiring frequent re-injections), a different treatment regimen (e.g., treat and extend) can be considered in the further course. If visual acuity drops below 0.05 on anti-VEGF treatment, or no further positive treatment outcome is expected (e.g., in the presence of atrophy and/or fibrosis), treatment should be discontinued, unless there is a clear possibility that visual acuity could increase again to over 0.05 under treatment. If no improvement is seen under therapy with a certain VEGF inhibitor, or if deterioration occurs, one can consider switching to an alternative VEGF inhibitor.
关键词： Choroidal neovascularization,Myopia,Retinal dystrophies,Ranibizumab,VEGF inhibitors,Uveitis,Idiopathic CNV,Central serous chorioretinopathy,Angioid streaks,Photodynamic therapy,Subretinal tumors,Aflibercept,Bevacizumab,Eye injuries
更新于2025-09-19 17:15:36
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[IEEE 2019 IEEE 62nd International Midwest Symposium on Circuits and Systems (MWSCAS) - Dallas, TX, USA (2019.8.4-2019.8.7)] 2019 IEEE 62nd International Midwest Symposium on Circuits and Systems (MWSCAS) - A CMOS 256-Pixel Self-Photovoltaics-Powered Subretinal Prosthetic Chip with Wide Image Dynamic Range and Shared Electrodes and Its In Vitro Experimental Results on Rd1 Mice
摘要： A self-photovoltaics-powered CMOS 256-pixel implantable chip with wide image dynamic range and shared electrodes is proposed and fabricated for subretinal prostheses. The infra-red (IR) light is incident only on photovoltaic cells of the chip whereas the visible light is mainly incident on pixels. The proposed adaptive background cancellation circuit (ABCC) is adopted to increase the image dynamic range so that the subretinal chip can adapt for different surrounding illuminances. Moreover, the bi-directional sharing electrodes (BDSEs) is used to increase electrode size under the same chip area and boost the stimulation charges to 11.4 nC. The functions of the chip have been successfully validated with both electrical measurement and in vitro patch clamp experiments with the retinas of Rd1 mice.
关键词： subretinal prostheses,CMOS image sensor,implantable chip
更新于2025-09-19 17:13:59
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PRIMA subretinal wireless photovoltaic microchip implantation in non-human primate and feline models
摘要： 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.
关键词： photovoltaic microchip,primate model,PRIMA,feline model,surgical technique,subretinal implantation
更新于2025-09-19 17:13:59
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Intraocular pharmacokinetics of antia??vascular endothelial growth factor agents by intraoperative subretinal versus intravitreal injection in silicone oila??filled eyes of proliferative diabetic retinopathy: a randomized controlled pilot study
摘要： Purpose: Intraoperative subretinal anti-vascular endothelial growth factor (VEGF) injections have been used clinically in some case, but the pharmacokinetic characteristics have not yet been determined. In this pilot study, we investigate the pharmacokinetic parameters of anti-VEGF agents by intraoperative subretinal or intravitreal injection in silicone oil (SiO)-filled eyes of patients with proliferative diabetic retinopathy (PDR). Methods: Randomized controlled trial including 13 patients (16 eyes) with PDR underwent pars plana vitrectomy (PPV) with SiO tamponade and randomly received a subretinal (8 eyes) or intravitreal (8 eyes) conbercept injection (0.5 mg/0.05 ml) intraoperatively. Aqueous humour (AH) was obtained on the 1st, 3rd, 7th, 10th, 14th, 21st and 28th day after the injection. Drug concentrations in the AH were determined by enzyme-linked immunosorbent assay (ELISA). The last best-corrected visual acuity (BCVA) was examined 6 months postoperatively. Results: The clearance rate of anti-VEGF agents by subretinal injection was reduced in vitrectomized eyes with SiO tamponade (p < 0.05). With the same drug dose, subretinal injection (5.49 (cid:1) 6.11 lg/ml) resulted in higher drug concentrations in the AH when compared with intravitreal injection (0.42 (cid:1) 0.46 lg/ml, p = 0.001) 4 weeks after the treatment. The mean residence time last (MRT0-t) by subretinal injection (11.57 (cid:1) 0.83 days) was significantly longer than the mean MRT0-t by intravitreal injection (7.10 (cid:1) 1.00 days, p < 0.001). A self-paired analysis showed that subretinal injection led to the BCVA improvement by +28.59 letters 6 months postoperatively (p = 0.028) while the BCVA did not improve significantly by intravitreal injection (p = 0.715). Conclusions: The drug maintenance phase was prolonged by intraoperative subretinal injection in SiO-filled eyes of PDR. The results suggest that subretinal injection might be a valuable treatment option for the management of PDR.
关键词： proliferative diabetic retinopathy,pharmacokinetics,subretinal injection,anti-VEGF agents,pars plana vitrectomy
更新于2025-09-16 10:30:52