The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer ...retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP.
Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II.
Thirty participants in 10 centers in the United States and Europe.
The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina.
The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks.
Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks.
The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada.
Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 ...people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation.
The study is a multicenter, single-arm, prospective clinical trial.
There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision).
The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina.
The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests.
A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments.
The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.
Docosahexaenoic acid (DHA) was supplemented in a single-site, placebo-controlled, randomized clinical trial designed to slow vision loss associated with X-linked retinitis pigmentosa (XLRP); the DHAX ...Trial. We previously reported no significant differences between supplemented and placebo groups in intent-to-treat analysis of primary ERG outcomes. Assessed herein are hypothesis-generating measures of ancillary visual function outcomes in participants fully adhering to trial protocol.
Male participants with XLRP (range, 7-31 years) received 30 mg DHA/kg/d (n = 29) or placebo (n = 22) for 4 years. Visual outcomes were measured annually and red blood cell (RBC) DHA determined every 6 months.
Oral DHA supplementation increased mean RBC-DHA levels by 4-fold (P < 0.0001) over placebo. No group differences in progression were found for visual acuity (P = 0.11), shape discrimination (P = 0.18), or fundus appearance (P = 0.70). Optical coherence tomography (OCT) became available during year 2 of the trial; no group differences were seen in ellipsoid zone constriction (P = 0.87) over 2 years. Yearly rates of progression were reduced for dark-adapted thresholds (P = 0.06) and visual field sensitivity for foveal, macular, peripheral, total, and ellipsoid zone regions by DHA supplementation (P = 0.039, P = 0.031, P < 0.0001, P < 0.0001, and P = 0.033). Rates of visual field sensitivity decline were dependent on RBC-DHA (P = 0.046 to <0.0001).
Supplementation of DHA significantly elevated blood DHA levels and reduced the rate of progression in final dark-adapted thresholds and visual field sensitivity. From the relationship between RBC-DHA and the rate of field sensitivity loss, we can extrapolate that an RBC-DHA level of 17% could minimize the decline in field sensitivity. (ClinicalTrials.gov number, NCT00100230.)
Docosahexaenoic acid (DHA) continues to be evaluated and recommended as treatment and prophylaxis for various diseases. We recently assessed efficacy of high-dose DHA supplementation to slow vision ...loss in patients with X-linked retinitis pigmentosa (XLRP) in a randomized clinical trial. Because DHA is a highly unsaturated fatty acid, it could serve as a target for free-radical induced oxidation, resulting in increased oxidative stress. Biosafety was monitored during the 4-year trial to determine whether DHA supplementation was associated with identifiable risks.
Males (n = 78; 7-31 years) meeting entry criteria were enrolled. The modified intent-to-treat cohort (DHA = 33; placebo = 27) adhered to the protocol ≥ 1 year. Participants were randomized to an oral dose of 30 mg/kg/d DHA or placebo plus a daily multivitamin. Comprehensive metabolic analyses were assessed for group differences. Treatment-emergent adverse events including blood chemistry metabolites were recorded.
By year 4, supplementation elevated plasma and red blood cell-DHA 4.4- and 3.6-fold, respectively, compared with the placebo group (P < 0.00001). Over the trial duration, no significant differences between DHA and placebo groups were found for vitamin A, vitamin E, platelet aggregation, antioxidant activity, lipoprotein cholesterol, or oxidized LDL levels (all P > 0.14). Adverse events were transient and not considered severe (e.g., gastrointestinal GI irritability, blood chemistry alterations). One participant was unable to tolerate persistent GI discomfort.
Long-term, high-dose DHA supplementation to patients with XLRP was associated with limited safety risks in this 4-year trial. Nevertheless, GI symptoms should be monitored in all patients taking high dose DHA especially those with personal or family history of GI disturbances. (ClinicalTrials.gov number, NCT00100230.).
Low docosahexaenoic acid (DHA) in X-linked retinitis pigmentosa (XLRP) may influence retinal function. The goals of this study were to elevate blood DHA levels and determine the effect on the rate of ...disease progression.
In a 4-year prospective randomized clinical trial, male patients with XLRP (mean age = 16 years; range = 4–38 years) received DHA (400 mg/d; n = 23; +DHA group) or placebo (n = 21) capsules.
Red blood cell (RBC)-DHA concentrations were assessed every 6 months. Full-field cone electroretinograms (ERGs; the primary outcome measure), visual acuity, dark-adaptation, visual fields, rod ERGs, and fundus photos were recorded annually.
In the +DHA group, RBC-DHA increased 2.5-fold over placebo levels (70 vs 28 mg DHA/l). Repeated measures analysis of variance for cone ERG showed a significant main effect of year (
P < .0001) but not of group (
P = .16). Preservation of cone ERG function correlated with RBC-DHA (
P = .018), and there was less change in fundus appearance in the +DHA group (
P = .04). Neither visual acuity nor visual fields were changed. In subset analysis, DHA supplementation was beneficial in reducing rod ERG functional loss in patients aged <12 years (
P = .040) and preserving cone ERG function in patients ≥12 years (
P = .038).
Although DHA-supplemented patients had significantly elevated mean RBC-DHA levels, the rate of cone ERG functional loss was not significantly different between groups. Supplemental analyses provided evidence for a DHA benefit and a direction for subsequent investigations.
Retinopathy of prematurity is a leading cause of childhood blindness. It is a disease of the developing retinal vasculature in premature infants. Mild forms regress with little or no loss of visual ...function; however, more severe forms can lead to retinal scarring and visual loss in the neonatal period. The pathogenesis of the disorder is controversial, but it seems to be related to the infant's environment.
Exposure to light was suggested as a cause of retinopathy of prematurity in the earliest description of this condition,
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but later studies revealed no association between light exposure and the disease.
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Subsequently, the . . .
We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10⁻⁷⁵), ARMS2 (P < ...10⁻⁵⁹), C2/CFB (P < 10⁻²⁰), C3 (P < 10⁻⁹), and CFI (P < 10⁻⁶). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 x 10⁻¹¹), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 x 10⁻⁷; CETP, P = 7.4 x 10⁻⁷) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c--associated alleles near LPL (P = 3.0 x 10⁻³) and ABCA1 (P = 5.6 x 10⁻⁴). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.
Vascularisation of the macula takes place between 24 and 27 weeks post-conception. Preterm birth may affect the formation of the foveal avascular zone (FAZ) and foveal depression, and displacement of ...inner retinal layers away from the incipient fovea.
To examine whether vascular abnormalities accompany an inner retinal abnormality, and whether they are coincident.
High-density spectral domain optical coherence tomography volume scans were obtained from 24 preterm children and 34 full-term controls (5-16 years). Matlab programs were used to quantify total retinal thickness, thickness of individual retinal layers and metrics of foveal morphology. Summed voxel projections for the ganglion cell layer-inner nuclear layer were used to identify the FAZ.
Preterm children had significantly smaller FAZ diameters than controls (p<0.0001). The foveal pits of preterm children were significantly shallower and less steep (p<0.0001) and total retinal thickness at the fovea was significantly increased (p<0.0001) compared to controls. The ganglion cell layer-inner plexiform layer and outer nuclear layer were significantly (p≤0.0001) thicker in preterm children than in controls.
Preterm birth results in abnormal foveal vascularisation, a failure of the inner retinal neurons to migrate away from the fovea, and an elevated outer nuclear layer ratio. The spatial coincidence of inner retinal and vascular abnormalities in preterm children supports the hypothesis that aspects of foveal development are interdependent.
Purpose To examine the visual acuity development of extremely low birth weight children and to determine factors that are predictive of long-term outcome. Methods This is a prospective observational ...longitudinal cohort study of children with birth weight less than 1001 g. One hundred thirty-nine children were recruited. Retinopathy of prematurity (ROP) examinations were graded according to the International Classification for ROP. Grating acuity was assessed monocularly with Teller acuity cards. All children were assessed before 24 months corrected age; 123 of the cohort had a grating acuity assessment at over 3 years. For the children who were capable, an assessment of recognition acuity was measured with the Electronic Visual Acuity system. Results Data are presented for the right eye and the ages reported are adjusted for prematurity to allow comparison with normative data. Initial grating acuity was compared with the late grating and recognition acuity, but in both cases analysis showed no statistically significant association. However, the relative risk analysis showed that, if the slope was abnormal, there was a 5.5 times higher risk of abnormal recognition acuity. Eyes with zone 1 disease were associated with a worse visual acuity outcome, but zone 1 disease also occurred more frequently in children with lower birth weight and gestational age. Conclusions Early measurements of visual acuity may be misleading in terms of the visual prognosis. The factor that was most predictive of a poor late visual acuity outcome was the rate of development, as calculated by the slope of the early visual acuity measurements.
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