Investigative ophthalmology & visual science最新文献

{"title":"Statistical Model of Ocular Wavefronts With Accommodation.","authors":"María Mechó-García, María Arcas-Carbonell, Elvira Orduna-Hospital, Ana Sánchez-Cano, Norberto López-Gil, Rute J Macedo-de-Araújo, Miguel Faria-Ribeiro, Paulo Fernandes, José Manuel González-Méijome, Jos Rozema","doi":"10.1167/iovs.65.12.12","DOIUrl":"10.1167/iovs.65.12.12","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to determine the minimum number of orthonormal basis functions, applying Principal Component Analysis (PCA), to represent the most wavefront aberrations at different accommodation stages. The study also aims to generate synthetic wavefront data using these functions.</p><p><strong>Methods: </strong>Monocular wavefront data from 191 subjects (26.15 ± 5.56 years old) were measured with a Hartmann-Shack aberrometer, simulating accommodation from 0 diopters (D) to 5 D in 1 D steps. The wavefronts for each accommodative demand were rescaled for different pupil sizes: 4.66, 4.76, 4.40, 4.09, 4.07, and 3.68 mm. PCA was applied to 150 wavefront parameters (25 Zernike coefficients × 6 accommodation levels) to obtain eigenvectors for dimensional reduction. A total of 49 eigenvectors were modeled as a sum of 2 multivariate Gaussians, from which 1000 synthetic data sets were generated.</p><p><strong>Results: </strong>The first 49 eigenvectors preserved 99.97% of the original data variability. No significant differences were observed between the mean values and standard deviation of the generated and original 49 eigenvectors (two one-sided test [TOST], P > 0.05/49) and (F-test, P > 0.05/49), both with Bonferroni correction. The mean values of the generated parameters (1000) were statistically equal to those of the original data (TOST, P > 0.05/150). The variability of the generated data was similar to the original data for the most important Zernike coefficients (F-test, P > 0.05/150).</p><p><strong>Conclusions: </strong>PCA significantly reduces the dimensionality of wavefront aberration data across 6 accommodative demands, reducing the variable space by over 66%. The synthetic data generated by the proposed wavefront model for accommodation closely resemble the original clinical data.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"12"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Spliceosome Inhibition in SF3B1-Mutated Uveal Melanoma.","authors":"Josephine Q N Nguyen, Wojtek Drabarek, Aïsha M C H J Leeflang, Tom Brands, Thierry P P van den Bosch, Robert M Verdijk, Harmen J G van de Werken, Job van Riet, Dion Paridaens, Annelies de Klein, Erwin Brosens, Emine Kiliç","doi":"10.1167/iovs.65.12.11","DOIUrl":"10.1167/iovs.65.12.11","url":null,"abstract":"<p><strong>Purpose: </strong>Unfortunately, treatment of patients with uveal melanoma (UM) with metastatic disease is limited. Twenty percent of patients with UM harbor a mutation in the splicing factor gene SF3B1, suggesting that aberrant spliceosome function plays a vital role in tumorigenesis. Splicing inhibitors exploit the preferential sensitivity of spliceosome-compromised leukemic cells to these compounds.</p><p><strong>Methods: </strong>We studied the effect of the splicing inhibitor E7107 using two UM cell lines and ex vivo cultured SF3B1- and BAP1-mutated primary UM tumor slices. These UM cell lines and ex vivo tumor slices were exposed for 24 hours to different concentrations of E7107. Tumor slices were stained with hematoxylin and eosin (H&E) and incubated with BAP1, MelanA, MIB-1, and caspase-3 antisera.</p><p><strong>Results: </strong>The E7107-exposed UM cell lines exhibited decreased cell viability and increased apoptosis, with the greatest effect on SF3B1-mutated UM cells. A similar effect on UM tumor slices was observed upon exposure to E7107. Additionally, RNA was isolated for differential isoform expression analysis. No significant difference in isoform usage was found genome-wide. However, specific genes were differentially expressed after E7107 treatment in the SF3B1-mutated samples. Moreover, E7107 had the greatest effect on intron retention.</p><p><strong>Conclusions: </strong>This study indicates/suggests that mutated SF3B1 UM cells are more sensitive to the splicing inhibitor E7107 than wild-type SF3B1 UM cells.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"11"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMNAT1 Is Essential for Human iPS Cell Differentiation to the Retinal Lineage.","authors":"Hiroshi Kuribayashi, Toshiro Iwagawa, Akira Murakami, Takeshi Kawamura, Yutaka Suzuki, Sumiko Watanabe","doi":"10.1167/iovs.65.12.37","DOIUrl":"https://doi.org/10.1167/iovs.65.12.37","url":null,"abstract":"<p><strong>Purpose: </strong>The gene encoding nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), a nicotinamide adenine dinucleotide synthetase localized in the cell nucleus, is a causative factor in Leber's congenital amaurosis, which is the earliest onset type of inherited retinal degeneration. We sought to investigate the roles of NMNAT1 in early retinal development.</p><p><strong>Methods: </strong>We used human induced pluripotent stem cells (hiPSCs) and established NMNAT1-knockout (KO) hiPSCs using CRISPR/cas9 technology to reveal the roles of NMNAT1 in human retinal development.</p><p><strong>Results: </strong>NMNAT1 was not essential for the survival and proliferation of immature hiPSCs; therefore, we subjected NMNAT1-KO hiPSCs to retinal organoid (RO) differentiation culture. The expression levels of immature hiPSC-specific genes decreased in a similar manner after organoid culture initiation up to 2 weeks in the control and NMNAT1-KO. Neuroectoderm-specific genes were induced in the control and NMNAT1-KO organoids within a few days after starting the organoid culture; PAX6 and TUBB3 were higher in NMNAT1-KO organoids up to 7 days than in the control organoids. However, the induction of genes involving retinal early development, such as RAX, which was induced at around day 10 in this culture, was considerably reduced in NMNAT1-KO organoids. Morphological examination also showed failure of retinal primordial structure formation, which became visible at around 2 weeks of the control culture, in the NMNAT1-KO organoids. Decreased intracellular NAD levels and poly(ADP-ribosyl)ation were observed in NMNAT1-KO organoids at 7 to 10 days of the culture. Mass spectrometry analysis of inhibited proteins in the poly(ADP-ribosyl)ation pathway identified poly(ADP-ribosyl)ation of poly(ADP-ribose) polymerase 1 (PARP1) as a major protein.</p><p><strong>Conclusions: </strong>These results indicate that NMNAT1 was dispensable for neural lineage differentiation but essential for the commitment of retinal fate differentiation in hiPSCs. The NMNAT1-NAD-PARP1 axis may play a critical role in the appropriate development of human retinal lineage differentiation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"37"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Evaluation of the Genetic Basis of Keratoconus: New Perspectives for Clinical Translation.","authors":"Miriam Cerván-Martín, Inmaculada Higueras-Serrano, Sara González-Muñoz, Andrea Guzmán-Jiménez, Blas Chaves-Urbano, Rogelio J Palomino-Morales, Arancha Poo-López, Luis Fernández-Vega-Cueto, Jesús Merayo-Lloves, Ignacio Alcalde, Lara Bossini-Castillo, F David Carmona","doi":"10.1167/iovs.65.12.32","DOIUrl":"10.1167/iovs.65.12.32","url":null,"abstract":"<p><strong>Purpose: </strong>Keratoconus (KC) is a corneal disorder with complex etiology, apparently involving both genetic and environmental factors, characterized by progressive thinning and protrusion of the cornea. We aimed to identify novel genetic regions associated with KC susceptibility, elucidate relevant genes for disease development, and explore the translational implications for therapeutic intervention and risk assessment.</p><p><strong>Methods: </strong>We conducted a genome-wide association study (GWAS) that integrated previously published data with newly generated genotyping data from an independent European cohort. To evaluate the clinical translation of our results, we performed functional annotation, gene prioritization, polygenic risk score (PRS), and drug repositioning analyses.</p><p><strong>Results: </strong>We identified two novel genetic loci associated with KC, with rs2806689 and rs807037 emerging as lead variants (P = 1.71E-08, odds ratio [OR] = 0.88; P = 1.93E-08, OR = 1.16, respectively). Most importantly, we identified 315 candidate genes influenced by confirmed KC-associated variants. Among these, MINK1 was found to play a pivotal role in KC pathogenesis through the WNT signaling pathway. Moreover, we developed a PRS model that successfully differentiated KC patients from controls (P = 7.61E-16; area under the curve = 0.713). This model has the potential to identify individuals at high risk for developing KC, which could be instrumental in early diagnosis and management. Additionally, our drug repositioning analysis identified acetylcysteine as a potential treatment option for KC, opening up new avenues for therapeutic intervention.</p><p><strong>Conclusions: </strong>Our study provides valuable insights into the genetic and molecular basis of KC, offering new targets for therapy and highlighting the clinical utility of PRS models in predicting disease risk.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"32"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Short- and Long-Term Perceptual Learning of Clinical Dynamic Visual Acuity Test.","authors":"Xiaobing Wang, Mingxin Yan, Jingmin Li, Yuexin Wang","doi":"10.1167/iovs.65.12.43","DOIUrl":"10.1167/iovs.65.12.43","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the short- and long-term learning effect of dynamic visual acuity (DVA) tests.</p><p><strong>Methods: </strong>Participants between 18 and 30 years with corrected to normal visual acuity were enrolled in this study. Three repeated sessions were performed, with 15 minutes and 15 days' intervals between sessions. Each session included 9 DVA tests of horizontal, vertical, and diagonal motions of E optotypes at 20, 40, and 80 degrees per second (dps). The short- and long-term learning effects were analyzed from repeated DVA tests.</p><p><strong>Results: </strong>Of the 58 enrolled participants, the mean age was 23.1 ± 2.1 years. DVA significantly varied among motion types and velocities (P < 0.05, respectively). There was a significant short-term learning effect for 20 (P = 0.004), 40 (P < 0.001), and 80 (P = 0.014) dps DVA test of horizontal motion, 40 dps DVA test of vertical (P = 0.003), and diagonal motion (P = 0.036). The long-term learning effect was detected in the 40 dps diagonal motion DVA test (P = 0.015). The short- and long-term learning effects were positively associated with initial DVA in most combinations of motion type and velocity tests (P < 0.05, respectively). The short- (P = 0.031) and long-term (P = 0.024) learning effect of 80 dps horizontal motion DVA test was greater in male than female participants.</p><p><strong>Conclusions: </strong>There is a significant short-term learning effect in the DVA test of various motion types, but the long-term learning effect was rarely observed, and it is greater in participants with worse initial DVA.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"43"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Performance for Detection of Glaucomatous Structural Damage Using Pixelwise Analysis of Retinal Thickness Measurements.","authors":"Hongli Yang, Juan Reynaud, Glen P Sharpe, Dawn Jennings, Cindy Albert, Trinity Holthausen, Xiue Jiang, Shaban Demirel, Steven L Mansberger, Marcelo T Nicolela, Stuart K Gardiner, Balwantray C Chauhan, Claude F Burgoyne, Brad Fortune","doi":"10.1167/iovs.65.12.17","DOIUrl":"10.1167/iovs.65.12.17","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the diagnostic accuracy of thickness measurements of individual and combined macular retinal layers to discriminate 188 glaucomatous and 148 glaucoma suspect eyes from 362 healthy control (HC) eyes on a pixel-by-pixel basis.</p><p><strong>Methods: </strong>For this retrospective study, we manually corrected the segmentations of posterior pole optical coherence tomography (OCT) scans to determine the thickness of the nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), the ganglion cell complex (GCC), and the total neural retina (TR). For each eye, the total number of pixels with thickness values less than the fifth percentile of the HC distribution was used to create a receiver operating characteristic (ROC) curve for each layer and for layer combinations.</p><p><strong>Results: </strong>Using total abnormal pixel count criteria to discriminate glaucoma from HC eyes, the individual layers with the highest area under the ROC curve (AUC) were the NFL and GCL; IPL performance was significantly lower (P < 0.05). GCC had a significant higher AUC (94.3%) than individual the AUC of the NFL (92.3%) (P = 0.0231) but not higher than AUC of the GCL (93.4%) (P = 0.3487). The highest AUC (95.4%) and sensitivity (85.1%) at 95% specificity was found for the Boolean combination of NFL or GCL. The highest AUC is not significantly higher (P = 0.0882) than the AUC of the GCC but the highest sensitivity is significantly higher than the sensitivity of the GCC. This pattern was similar for discriminating between suspect and HC eyes (P = 0.0356).</p><p><strong>Conclusions: </strong>Using pixel-based methods, the diagnostic accuracy of NFL and GCL exceeded that of IPL and TR. GCC had equivalent performance as NFL and GCL. The specific spatial locations within the posterior pole that exhibit best performance vary depending on which layer is being assessed. Recognizing this dependency highlights the importance of considering multiple layers independently, as they offer complementary information for effective and comprehensive diagnosis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"17"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Effect of Aldosterone or Mineralocorticoid Receptor Overexpression on Retinal Inflammation.","authors":"Bastien Leclercq, Dan Mejlachowicz, Linxin Zhu, Laurent Jonet, Chadi Mehanna, Marianne Berdugo, Theano Irinopoulou, Fréderic Jaisser, Min Zhao, Francine Behar-Cohen","doi":"10.1167/iovs.65.12.39","DOIUrl":"https://doi.org/10.1167/iovs.65.12.39","url":null,"abstract":"<p><strong>Purpose: </strong>Overactivation of the mineralocorticoid receptor (MR) pathway is proinflammatory and contributes to the pathogenesis of diabetic retinopathy and of age-related macular degeneration. Excess of aldosterone, the specific MR ligand, is known to stimulate the production of proinflammatory cytokines and chemokines in extrarenal tissues and cells. In the RPE/choroid complex, aldosterone upregulated genes encoding proteins of the inflammatory response and downregulated genes encoding proteins involved in synaptic activity and neurotransmitters. Yet, cortisol, which is the main MR ligand in the eye, is a potent anti-inflammatory endogenous glucocorticoid. The aim of the present work was to better understand the role of MR activation in retinal inflammation either by acute injection of aldosterone or overexpression of the receptor.</p><p><strong>Methods: </strong>We first analyzed the retinal transcriptomic regulation induced by acute intraocular injection of aldosterone in the rat. Then, we used a transgenic rat overexpressing human MR (hMR) to also conduct retinal transcriptomic analysis as well as histological evaluation of the retina, retinal pigment epithelium and choroid.</p><p><strong>Results: </strong>Our results show that acute intravitreal injection of aldosterone is highly proinflammatory, upregulating pathways related to microglial activation, oxidative stress, cell death, and downregulating pathways related to glial/neuronal cells activity and proper neurotransmission. On the other hand, hMR overexpression mediates a low-grade inflammation in the retina, associated with notable choroidal inflammation and choroidal neuropathy.</p><p><strong>Conclusions: </strong>Consequences of hMR overexpression or aldosterone-injection on retinal transcriptome reveal very distinct pathological mechanisms, with only a few common genes regulated, most of them not being regulated in the same way. Although aldosterone is highly proinflammatory in the retina, MR overactivation in its physiologic milieu mediates a low-grade inflammation in the neural retina.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"39"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A First-Passage Model of Intravitreal Drug Delivery and Residence Time-Influence of Ocular Geometry, Individual Variability, and Injection Location.","authors":"Patricia Lamirande, Eamonn A Gaffney, Michael Gertz, Philip K Maini, Jessica R Crawshaw, Antonello Caruso","doi":"10.1167/iovs.65.12.21","DOIUrl":"https://doi.org/10.1167/iovs.65.12.21","url":null,"abstract":"<p><strong>Purpose: </strong>Standard of care for various retinal diseases involves recurrent intravitreal injections. This motivates mathematical modeling efforts to identify influential factors for ocular drug residence time, aiming to minimize administration frequency. We sought to describe the vitreal diffusion of therapeutics in nonclinical species frequently used during drug development assessments. In human eyes, we investigated the impact of variability in vitreous cavity size and eccentricity, and in injection location, on drug disposition.</p><p><strong>Methods: </strong>Using a first-passage time approach, we modeled the transport-controlled distribution of two standard therapeutic protein formats (Fab and IgG) and elimination through anterior and posterior pathways. Anatomical three-dimensional geometries of mouse, rat, rabbit, cynomolgus monkey, and human eyes were constructed using ocular images and biometry datasets. A scaling relationship was derived for comparison with experimental ocular half-lives.</p><p><strong>Results: </strong>Model simulations revealed a dependence of residence time on ocular size and injection location. Delivery to the posterior vitreous resulted in increased vitreal half-life and retinal permeation. Interindividual variability in human eyes had a significant influence on residence time (half-life range of 5-7 days), showing a strong correlation to axial length and vitreal volume. Anterior exit was the predominant route of drug elimination. Contribution of the posterior pathway displayed a 3% difference between protein formats but varied between species (10%-30%).</p><p><strong>Conclusions: </strong>The modeling results suggest that experimental variability in ocular half-life is partially attributed to anatomical differences and injection site location. Simulations further suggest a potential role of the posterior pathway permeability in determining species differences in ocular pharmacokinetics.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"21"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying the Functional Relationship Between Visual Acuity and Contrast Sensitivity Function.","authors":"Zhong-Lin Lu, Yukai Zhao, Luis Andres Lesmes, Michael Dorr","doi":"10.1167/iovs.65.12.33","DOIUrl":"10.1167/iovs.65.12.33","url":null,"abstract":"<p><strong>Purpose: </strong>Studies have reported that individuals with certain ocular disorders may have significant decreases in contrast sensitivity function (CSF) despite having normal or near normal visual acuity (VA). This study seeks to elucidate this phenomenon by investigating the relationship between VA and CSF.</p><p><strong>Methods: </strong>We analyzed data from 14 eyes tested with Electronic Early Treatment Diabetic Retinopathy and quantitative CSF under four Bangerter foil conditions (n = 56). From the CSF data, we estimated peak gain, peak frequency, and contrast sensitivity acuity (CSA). We explored the correlations between VA and various CSF parameters and evaluated five predictive models of VA using CSA alone and in combination with additional CSF parameters through ridge regression.</p><p><strong>Results: </strong>We found that similar VA scores can correspond with markedly different CSFs and observed significant correlations among all CSF parameters and between VA and each CSF parameter (all P < 0.001). The most effective predictive model, incorporating CSA and peak gain, explained 90.97% of the variance with a root mean squared error of 0.0676 logMAR, which is comparable with the average standard deviation of the VA scores (0.0627 logMAR) and accounted for 38.6% of the residual variance not explained by the CSA-alone model.</p><p><strong>Conclusions: </strong>This study offers the first empirical inference of the quantitative relationship between VA and CSF, suggesting that various CSF parameter combinations can yield identical VA. This might help to explain why some clinical populations with normal or near-normal VA exhibit significant CSF deficits and calls for further research in different clinical settings.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"33"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Assessment of Retinal Microvasculature in Preclinical Alzheimer's Disease.","authors":"Katie R Curro, Ruth M A van Nispen, Anouk den Braber, Elsmarieke M van de Giessen, Jacoba A van de Kreeke, H Stevie Tan, Pieter-Jelle Visser, Femke H Bouwman, Frank D Verbraak","doi":"10.1167/iovs.65.12.2","DOIUrl":"10.1167/iovs.65.12.2","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate if changes in vessel density (VD) and the foveal avascular zone (FAZ) occur in the preclinical phase of Alzheimer's disease (pAD) over time.</p><p><strong>Methods: </strong>Optical coherence tomography angiography (OCTA) was used to image VD and FAZ at baseline and for a follow-up period of 2 years. Positron emission tomography (PET) was used to determine the amyloid beta (Aβ) status of participants.</p><p><strong>Results: </strong>The VD and FAZ of 148 participants (54% female) were analyzed at baseline and follow-up (mean time between measurements, 2.24 ± 0.35 years). The mean age of the participants was 68.3 ± 6.0 years at baseline and 70.3 ± 5.9 years at follow-up. Participants were divided into three groups: control group, participants who had negative Aβ status at both measurements (Aβ-, n = 116); converter group, participants who transitioned from negative to positive between baseline and follow-up (Aβ-+, n = 18); and participants who were consistently positive at both visits (Aβ++, n = 14). The VD of both Aβ+ groups demonstrated non-significant increases over time in both macula and optic nerve head (ONH) regions. The Aβ- group was found to be significantly higher in both ONH and macular regions. The VD of the Aβ++ group was significantly higher in the macula inner and outer rings compared to the Aβ-+ and Aβ- groups. No significant change was found in FAZ values over time.</p><p><strong>Conclusions: </strong>Alterations in VD seem to manifest already in pAD, exhibiting distinct variations between the ONH and macula. Further longitudinal studies with a longer follow-up design and known amyloid pathology should be undertaken to validate these observations.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"2"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}