Purpose
To evaluate the long‐term efficacy and safety of two minimally invasive glaucoma surgery implants with a subconjunctival drainage approach: the XEN45 Gel Stent® (Xen) implant and the ...PRESERFLO™ MicroShunt (MicroShunt).
Methods
Retrospective comparative case series of primary open‐angle glaucoma (POAG) patients with at least 6 months of follow‐up after a MicroShunt or Xen implantation augmented with mitomycin C.
Results
Forty‐one eyes of 31 patients underwent Xen implantation, and 41 eyes of 33 patients, MicroShunt implantation. Baseline characteristics were similar, except for more combined surgeries with phacoemulsification in the Xen group (37% vs. 2%). Mean baseline IOP ± standard deviation dropped from 19.2 ± 4.4 to 13.8 ± 3.8 mmHg (n = 26) in the Xen group and from 20.1 ± 5.0 to 12.1 ± 3.5 (n = 14) in the MicroShunt group at 24 months of follow‐up (p = 0.19, t‐test). The number of IOP‐lowering medications dropped from 2.5 ± 1.4 to 0.9 ± 1.2 in the Xen group and from 2.3 ± 1.5 to 0.7 ± 1.1 in the MicroShunt group. The probability of qualified success was 73% and 79% at 24 months of follow‐up for the Xen and MicroShunt groups, respectively. Postoperative complications were usually mild and self‐limiting. The number of bleb needling and secondary glaucoma surgery procedures was similar in both groups; however, in the Xen group more additional MicroPulse® transscleral cyclophotocoagulation procedures were performed.
Conclusion
Xen Gel Stent and PreserFlo MicroShunt implantations achieved comparable results in POAG eyes in terms of IOP‐lowering and surgical success, with a similar high safety profile.
To compare visual acuity, refraction, endothelial cell density (ECD), and complications after Descemet stripping automated endothelial keratoplasty (DSAEK) and ultrathin DSAEK (UT-DSAEK).
A ...multicenter, prospective, double-masked, randomized, controlled clinical trial.
From 66 patients with irreversible corneal endothelial dysfunction dues to Fuchs' dystrophy who enrolled from 4 tertiary medical centers in the Netherlands, 66 eyes were studied.
Participants were centrally randomized to undergo either UT-DSAEK or DSAEK, based on preoperative best spectacle-corrected visual acuity (BSCVA), recipient central corneal thickness, patient age, and recruitment center. Donor corneas were precut by a single cornea bank.
Participants underwent ophthalmic examinations preoperatively and 3, 6, and 12 months after the operation, including manifest refraction, BSCVA using an Early Treatment Diabetic Retinopathy Study chart, and endothelium imaging.
BSCVA 12 months postoperatively.
Preoperative BSCVA did not differ between patients undergoing DSAEK (0.35 logarithm of the minimum angle of resolution logMAR 95% confidence interval {CI} 0.27-0.43; n = 32) and UT-DSAEK (0.37 logMAR 95% CI 0.31-0.43; n = 34; P = 0.8). BSCVA was significantly better after UT-DSAEK compared with that after DSAEK at 3 months (0.17 logMAR 95% CI 0.13-0.21, n = 31 vs. 0.28 logMAR 95% CI 0.23-0.33, n = 31; P = 0.001), 6 months (0.14 logMAR 95% CI 0.10-0.18, n = 30 vs. 0.24 logMAR 95% CI 0.20-0.28, n = 30; P = 0.002), and 12 months (0.13 logMAR 95% CI 0.09-0.17, n = 33 vs. 0.20 logMAR 95% CI 0.15-0.25, n = 29; P = 0.03). Refraction, ECD loss (40% at 3 months; P < 0.001), donor loss (DSAEK n = 2 vs. UT-DSAEK n = 3 relative risk {RR} 1.4 {95% CI 0.24-7.5}; P = 0.7), and graft dislocation (DSAEK n = 5 vs. UT-DSAEK n = 5 RR 1.0 {95% CI 0.34-3.33}; P = 0.9) did not differ between UT-DSAEK and DSAEK. Donor thickness was significantly thinner for UT-DSAEK (101 μm 95% CI 93-110 μm; range 50-145 μm) than for DSAEK (209 μm 95% CI 196-222 μm; range 147-289 μm; P < 0.001).
This study indicates that compared with DSAEK, UT-DSAEK results in faster and better recovery of BSCVA with similar refractive outcomes, endothelial cell loss, and incidence of complications.
Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes ("ticking clock ...hypothesis"). Whether a similar phenomenon also applies to microvascular dysfunction is not known. We therefore tested the hypothesis that microvascular dysfunction is already present in prediabetes and is more severe in T2DM. To do so, we investigated the associations of prediabetes, T2DM, and measures of hyperglycemia with microvascular function measured as flicker light-induced retinal arteriolar dilation and heat-induced skin hyperemia.
In the Maastricht Study, a T2DM-enriched population-based cohort study (n=2213, 51% men, aged mean±standard deviation 59.7±8.2 years), we determined flicker light-induced retinal arteriolar %-dilation (Dynamic Vessel Analyzer), heat-induced skin %-hyperemia (laser-Doppler flowmetry), and glucose metabolism status (oral glucose tolerance test; normal glucose metabolism n=1269, prediabetes n=335, or T2DM n=609). Differences were assessed with multivariable regression analyses adjusted for age, sex, body mass index, smoking, physical activity, systolic blood pressure, lipid profile, retinopathy, estimated glomerular filtration rate, (micro)albuminuria, the use of lipid-modifying and blood pressure-lowering medication, and prior cardiovascular disease.
Retinal arteriolar %-dilation was (mean±standard deviation) 3.4±2.8 in normal glucose metabolism, 3.0±2.7 in prediabetes, and 2.3±2.6 in T2DM. Adjusted analyses showed a lower arteriolar %-dilation in prediabetes (B=-0.20, 95% confidence interval -0.56 to 0.15) with further deterioration in T2DM (B=-0.61 -0.97 to -0.25) versus normal glucose metabolism (P for trend=0.001). Skin %-hyperemia was (mean±standard deviation) 1235±810 in normal glucose metabolism, 1109±748 in prediabetes, and 937±683 in T2DM. Adjusted analyses showed a lower %-hyperemia in prediabetes (B=-46 -163 to 72) with further deterioration in T2DM (B=-184 -297 to -71) versus normal glucose metabolism (P for trend=0.001). In addition, higher glycohemoglobin A1c and fasting plasma glucose were associated with lower retinal arteriolar %-dilation and skin %-hyperemia in fully adjusted models (for glycohemoglobin A1c, standardized B=-0.10 -0.15 to -0.05, P<0.001 and standardized B=-0.13 -0.19 to -0.07, P<0.001, respectively; for fasting plasma glucose, standardized B=-0.09 -0.15 to -0.04, P<0.001 and standardized B=-0.10 -0.15 to -0.04, P=0.002, respectively).
Prediabetes, T2DM, and measures of hyperglycemia are independently associated with impaired microvascular function in the retina and skin. These findings support the concept that microvascular dysfunction precedes and thus may contribute to T2DM-associated cardiovascular disease and other complications, which may in part have a microvascular origin such as impaired cognition and heart failure.
Lutein: More than just a filter for blue light Kijlstra, Aize; Tian, Yuan; Kelly, Elton R. ...
Progress in retinal and eye research,
July 2012, 2012-Jul, 2012-7-00, 20120701, Letnik:
31, Številka:
4
Journal Article
Recenzirano
Lutein is concentrated in the primate retina, where together with zeaxanthin it forms the macular pigment. Traditionally lutein is characterized by its blue light filtering and anti-oxidant ...properties. Eliminating lutein from the diet of experimental animals results in early degenerative signs in the retina while patients with an acquired condition of macular pigment loss (Macular Telangiectasia) show serious visual handicap indicating the importance of macular pigment. Whether lutein intake reduces the risk of age related macular degeneration (AMD) or cataract formation is currently a strong matter of debate and abundant research is carried out to unravel the biological properties of the lutein molecule. SR-B1 has recently been identified as a lutein binding protein in the retina and this same receptor plays a role in the selective uptake in the gut. In the blood lutein is transported via high-density lipoproteins (HDL). Genes controlling SR-B1 and HDL levels predispose to AMD which supports the involvement of cholesterol/lutein transport pathways. Apart from beneficial effects of lutein intake on various visual function tests, recent findings show that lutein can affect immune responses and inflammation. Lutein diminishes the expression of various ocular inflammation models including endotoxin induced uveitis, laser induced choroidal neovascularization, streptozotocin induced diabetes and experimental retinal ischemia and reperfusion. In vitro studies show that lutein suppresses NF kappa-B activation as well as the expression of iNOS and COX-2. Since AMD has features of a chronic low-grade systemic inflammatory response, attention to the exact role of lutein in this disease has shifted from a local effect in the eye towards a possible systemic anti-inflammatory function.
Abstract
The aim of this study was to evaluate repeatability, reproducibility, and agreement of three commonly used tonometers in animal research (TonoLab, TonoVet, and TonoPEN AVIA) in a cohort of ...24 rabbits. Additionally, the impact of sedation on IOP was investigated in 21 New Zealand White rabbits with the TonoVet tonometer. Repeatability was determined using the coefficient of variation (CoV) for two observers. For the TonoLab (6.55%) and TonoVet (6.38%) the CoV was lower than for the TonoPEN AVIA (10.88%). The reproducibility was highest for the TonoVet (0.2 ± 3.3 mmHg), followed by the TonoLab (0 ± 12.89 mmHg) and lowest for the TonoPEN AVIA (− 1.48 ± 10.3 mmHg). The TonoLab and TonoVet showed the highest agreement (r = 0.85, R
2
= 0.73). After sedation, a significant IOP reduction (often > 25%) was observed. Our results show that among the three tonometers tested, the TonoVet tonometer is best for use in rabbits while the TonoLab should be avoided. The impact of sedation on IOP was substantial and should be taken into account during experimentation.
Loss of neurons in chronic neurodegenerative diseases may occur over a period of many years. Once initiated, neuronal cell death is accompanied by distinct phenotypic changes including cell ...shrinkage, neurite retraction, mitochondrial fragmentation, nuclear condensation, membrane blebbing and phosphatidylserine (PS) exposure at the plasma membrane. It is still poorly understood which events mark the point of no return for dying neurons. Here we analyzed the neuronal cell line SH-SY5Y expressing cytochrome C (Cyto.C)-GFP. Cells were exposed temporarily to ethanol (EtOH) and tracked longitudinally in time by light and fluorescent microscopy. Exposure to EtOH induced elevation of intracellular Ca
and reactive oxygen species, cell shrinkage, neurite retraction, mitochondrial fragmentation, nuclear condensation, membrane blebbing, PS exposure and Cyto.C release into the cytosol. Removing EtOH at predetermined time points revealed that all phenomena except Cyto.C release occurred in a phase of neuronal cell death in which full recovery to a neurite-bearing cell was still possible. Our findings underscore a strategy of treating chronic neurodegenerative diseases by removing stressors from neurons and harnessing intracellular targets that delay or prevent trespassing the point of no return.
Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular ...measures.
In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders.
Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation.
Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.
Purpose
To investigate central and peripheral corneal endothelial cell density (ECD) in relation to Baerveldt (BV) glaucoma drainage device (GDD) tube corneal (TC) distance.
Methods
Prospective study ...of all patients scheduled for glaucoma tube surgery with 36 months follow‐up. A BV GDD was inserted into the anterior chamber (AC). Anterior segment optical coherence tomography (AS‐OCT) scans were made to determine the TC distance. Central and peripheral ECD was measured, preoperatively and at 3, 6, 12, 24 and 36 months postoperatively.
Results
Fifty‐three eyes were included primary open‐angle glaucoma, (n = 13); secondary glaucoma, (n = 30); and primary angle‐closure glaucoma, (n = 10). Central ECD significantly decreased during follow‐up, with a mean decrease of 4.54% per year (p < 0.001), and 6.57% in the peripheral quadrant closest to the BV GDD tube (PQC, p < 0.001). In the PQC, a yearly decrease of 1.57% was shown after transiridial tube placement versus 7.43% after placement ‘free’ into the AC (p = 0.006). Endothelial cell (EC) loss was related to TC distance (mean 1.69 mm), with a central loss of 6.20% and 7.25% in the PQC per year with shorter TC distances, versus a central loss of 4.11% and 5.77% in the PQC per year with longer TC distances (outside mean ± 2SD, p < 0.001). A difference in EC loss by glaucoma subtype was not identified.
Conclusion
The TC distance is of significant influence on corneal ECD, a shorter TC distance causing more severe EC loss, especially in the PQC. Transiridial placement of the BV GDD tube seems safer than placement ‘free’ into the AC.
Recently, the level of growth differentiation factor 15 (GDF-15) in blood, was proposed as biomarker to detect mitochondrial dysfunction. In the current study, we evaluate this biomarker in ...open-angle glaucoma (OAG), as there is increasing evidence that mitochondrial dysfunction plays a role in the pathophysiology of this disease. Plasma GDF-15 concentrations were measured with ELISA in 200 OAG patients and 61 age-matched controls (cataract without glaucoma). The OAG patient group consisted of high tension glaucoma (HTG; n = 162) and normal tension glaucoma (NTG; n = 38). Groups were compared using the Kruskal-Wallis nonparametric test with Dunn's multiple comparison post-hoc correction. GDF-15 concentration was corrected for confounders identified with forward linear regression models. Before correcting for confounders, median plasma GDF-15 levels was significantly lower in the combined OAG group (p = 0.04), but not when analysing HTG and NTG patients separately. Forward linear regression analysis showed that age, gender, smoking and systemic hypertension were significant confounders affecting GDF-15 levels. After correction for these confounders, GDF-15 levels in OAG patients were no longer significantly different from controls. Subgroup analysis of the glaucoma patients did not show a correlation between disease severity and plasma GDF-15, but did reveal that for NTG patients, intake of dietary supplements, which potentially improve mitochondrial function, correlated with lower plasma GDF-15. The present study suggests that plasma GDF-15 is not suited as biomarker of mitochondrial dysfunction in OAG patients.
Neurodegenerative diseases are generally characterized clinically by the selective loss of a distinct subset of neurons and a slow progressive course. Mounting evidence in vivo indicates that large ...numbers of neurons pass through a long period of injury and dysfunction before the actual death of the cells. Whether these dying neurons can be rescued and return to a normal, functional state is uncertain. In the present study, we explored the reversibility of the neuronal cell death pathway at various stages by monitoring the dynamics of single cells with high-resolution live-cell spinning disk confocal microscopy in an in vitro neuronal cell death model. We exposed differentiated neuronal PC12 cells to ethanol as our cell death model. Results showed that exposure to 5% ethanol for 24 h induced cell death in >70% of the cells. Ethanol treatment for 3 h already induced cellular changes and damage such as reactive oxygen species generation, elevation of intracellular Ca2+ level, phosphatidylserine exposure, nuclear shrinkage, DNA damage, mitochondrial fragmentation and membrane potential loss, and retraction of neurites. These phenomena are often associated with programmed cell death. Importantly, after removing ethanol and further culturing these damaged cells in fresh culture medium, cells recovered from all these cell injuries and generated new neurites. Moreover, results indicated that this recovery was not dependent on exogenous NGF and other growth factors in the cell culture medium. Overall, our results suggest that targeting dying neurons can be an effective therapeutic strategy in neurodegenerative diseases.
PDF
