Patient‐specific determination of change in ocular spherical aberration to improve near and intermediate visual acuity of presbyopic eyes

2018 ◽  
Vol 12 (4) ◽  
pp. e201800259 ◽  
Author(s):  
Naren Shetty ◽  
Shruti Kochar ◽  
Prajakta Paritekar ◽  
Pablo Artal ◽  
Rohit Shetty ◽  
...  
2019 ◽  
Vol 4 (1) ◽  
pp. e000273
Author(s):  
Irina Balikova ◽  
Laurence Postelmans ◽  
Brigitte Pasteels ◽  
Pascale Coquelet ◽  
Janet Catherine ◽  
...  

ObjectiveAge-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response.Methods and analysisA retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort.ResultsAssociation with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction.ConclusionIdentifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mohammad Miraftab ◽  
Hassan Hashemi ◽  
Mohammadreza Aghamirsalim ◽  
Shiva Fayyaz ◽  
Soheila Asgari

Abstract Background The refractive surgeries induce corneal higher order aberrations (C-HOAs). In this study, change of C-HOAs after small-incision lenticule extraction (SMILE) compared to femtosecond assisted laser in situ keratomileusis (femto-LASIK), and to photorefractive keratectomy with mitomycin-C (PRK) under photopic and mesopic conditions. Methods In this prospective study, age, gender, and apical corneal thickness (ACT) matched cases with moderate myopia [spherical equivalent (SE) 3.00 to 6.00D) to high myopia (SE > 6.00D)] were enrolled. In addition to visual acuity and refraction, total C-HOA, coma, spherical aberration (SA), and trefoil in the 3- and 6-mm zones were measured before and 3 and 6 months after surgery. Results Overall, 372 moderate myopia cases (124 eyes of 124 individuals in each surgical group) and 171 high myopia cases (57 eyes of 57 individuals in each surgical group) were enrolled. At baseline, the differences in age, gender, ACT, uncorrected and corrected visual acuity, and SE were not statistically significant between subgroups of surgical methods within each myopia group (all P > 0.05). At 12 months, in the moderate myopia group, there was less increase in 6-mm zone total C-HOA, coma, and SA with SMILE compared to the other groups (all P < 0.05). In the high myopia group, there was greater increase in photopic total C-HOA and trefoil and less increase in mesopic SA with SMILE (all P < 0.05). Conclusions In correction of moderate myopia, SMILE has better results in mesopic condition. In high myopia correction, femto-LASIK and PRK have better results in photopic and SMILE in mesopic condition.


2021 ◽  
Vol 22 (8) ◽  
pp. 4009
Author(s):  
Maik Liedtke ◽  
Christin Völkner ◽  
Alexandra V. Jürs ◽  
Franziska Peter ◽  
Michael Rabenstein ◽  
...  

Niemann-Pick type C2 (NP-C2) disease is a rare hereditary disease caused by mutations in the NPC2 gene. NPC2 is a small, soluble protein consisting of 151 amino acids, primarily expressed in late endosomes and lysosomes (LE/LY). Together with NPC1, a transmembrane protein found in these organelles, NPC2 accomplishes the exclusion of cholesterol; thus, both proteins are essential to maintain cellular cholesterol homeostasis. Consequently, mutations in the NPC2 or NPC1 gene result in pathophysiological accumulation of cholesterol and sphingolipids in LE/LY. The vast majority of Niemann-Pick type C disease patients, 95%, suffer from a mutation of NPC1, and only 5% display a mutation of NPC2. The biochemical phenotype of NP-C1 and NP-C2 appears to be indistinguishable, and both diseases share several commonalities in the clinical manifestation. Studies of the pathological mechanisms underlying NP-C2 are mostly based on NP-C2 animal models and NP-C2 patient-derived fibroblasts. Recently, we established induced pluripotent stem cells (iPSCs), derived from a donor carrying the NPC2 mutations c.58G>T/c.140G>T. Here, we present a profile of pathophysiological in vitro features, shared by NP-C1 and NP-C2, of neural differentiated cells obtained from the patient specific iPSCs. Profiling comprised a determination of the NPC2 protein level, detection of cholesterol accumulation by filipin staining, analysis of oxidative stress, and determination of autophagy. As expected, the NPC2-deficient cells displayed a significantly reduced amount of NPC2 protein, and, accordingly, we observed a significantly increased amount of cholesterol. Most notably, NPC2-deficient cells displayed only a slight increase of reactive oxygen species (ROS), suggesting that they do not suffer from oxidative stress and express catalase at a high level. As a site note, comparable NPC1-deficient cells suffer from a lack of catalase and display an increased level of ROS. In summary, this cell line provides a valuable tool to gain deeper understanding, not only of the pathogenic mechanism of NP-C2, but also of NP-C1.


1985 ◽  
Vol 12 (9) ◽  
pp. 493-496 ◽  
Author(s):  
P. Traldi ◽  
S. Daolio ◽  
B. Pelli ◽  
R. Maffei Facino ◽  
M. Carini

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