{"title":"Associations of Retinal Vessel Geometry and Optical Coherence Tomography Angiography Metrics With Choroidal Metrics in Diabetic Retinopathy.","authors":"Dae Joong Ma, Seong Mi Kim, Ji Min Choi","doi":"10.1167/iovs.65.13.31","DOIUrl":"10.1167/iovs.65.13.31","url":null,"abstract":"<p><strong>Purpose: </strong>To elucidate the mechanism underlying changes in choroidal metrics (choroidal thickness [CT], choroidal vascularity index [CVI], and choriocapillaris [CC] flow deficit [FD]) observed in diabetic retinopathy (DR) and examine the association of choroidal metrics with both retinal vessel geometry and optical coherence tomography angiography (OCTA) metrics.</p><p><strong>Methods: </strong>Overall, 133 eyes of 133 patients were analyzed retrospectively. Retinal vessel geometry parameters were assessed using semiautomated software. The OCTA metrics and CT were calculated using automated algorithms provided by the manufacturer, whereas the CVI and CC-FD were calculated using ImageJ software from the binarized choroid B-scan image and the CC slab provided by the manufacturer, respectively. To assess the associations among choroidal metrics, retinal vessel geometry, and OCTA metrics, multivariable regression analyses were performed while controlling for clinical features and DR severity.</p><p><strong>Results: </strong>In the multivariable linear regression analysis, CT (β = -399.84; P = 0.014) and CVI (β = -2.34; P = 0.021) showed significant associations with the arteriole-venule ratio, which is a ratio of central retinal arteriolar equivalent caliber with respect to central retinal venular equivalent caliber. The CC-FD showed a significant association with the fractal dimension of retinal arteriolar network (β = -2.90; P = 0.040). In contrast, the OCTA metrics showed no significant association with the choroidal metrics.</p><p><strong>Conclusions: </strong>The CT, CVI, and CC-FD in patients with DR were associated with retinal arteriolar geometry parameters rather than OCTA metrics, which indicates an association between choroidal changes and hemodynamic alterations in retinal arterioles and venules.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"31"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638969","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":"Adult Myopia Progression.","authors":"Noel A Brennan, Xu Cheng, Mark A Bullimore","doi":"10.1167/iovs.65.13.49","DOIUrl":"10.1167/iovs.65.13.49","url":null,"abstract":"<p><strong>Purpose: </strong>To explore evidence for myopic shift between the ages of 20 and 50 years.</p><p><strong>Methods: </strong>Three usable sets of data with long-term adult refractive progression were identified: (1) US population-based prevalence data for those 18 to 24 years of age in 1971 and 1972 and 45 to 54 years of age from 1999 to 2004; a logit transformation of prevalence values at different refractive error thresholds allowed estimation of myopic progression in this group. (2) German clinical data describing 5- to 10-year progression for different refractive error groupings across 5-year age bands from 20 to 49 years; these were extracted, adjusted, and analyzed. (3) Five-year progression rates with similar breakdown of age and refractive error groups as the German data but in a Japanese clinical population.</p><p><strong>Results: </strong>Estimates of progression between 20 and 50 years for the given studies were: (1) -1.1, -1.4, and -1.9 diopters (D) for baseline refractive errors of -1, -3, and -6 D, respectively; (2) a range from -1.0 to -2.9 D, increasing with degree of baseline myopia; (3) a weighted average of -1.0 D for males and -0.9 D for females but with decreasing progression with increasing myopia. In all studies, average progression rates fell with increasing age, with most progression occurring between 20 and 30 years.</p><p><strong>Conclusions: </strong>All three studies provide evidence of around -1 D myopia progression between the ages of 20 and 50 years. This has implications for intervention to slow progression during adulthood, as well as projections of visual impairment associated with myopia.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"49"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah E Quillen, Elizabeth C Kimball, Kelsey A Ritter-Gordy, Liya Du, Zhuochen Yuan, Mary E Pease, Salaheddine Madhoun, Thao D Nguyen, Thomas V Johnson, Harry A Quigley, Ian F Pitha
{"title":"The Mechanisms of Neuroprotection by Topical Rho Kinase Inhibition in Experimental Mouse Glaucoma and Optic Neuropathy.","authors":"Sarah E Quillen, Elizabeth C Kimball, Kelsey A Ritter-Gordy, Liya Du, Zhuochen Yuan, Mary E Pease, Salaheddine Madhoun, Thao D Nguyen, Thomas V Johnson, Harry A Quigley, Ian F Pitha","doi":"10.1167/iovs.65.13.43","DOIUrl":"10.1167/iovs.65.13.43","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to delineate the neuroprotective mechanisms of topical 2% ripasudil (Rip), a Rho kinase (ROCK) inhibitor.</p><p><strong>Methods: </strong>In 340 mice, scheduled 2% Rip or balanced salt solution (BSS) saline drops were intermittently, unilaterally delivered. Intracameral microbead glaucoma (GL) injection increased intraocular pressure (IOP) from 1 day to 6 weeks (6W), whereas other mice underwent optic nerve (ON) crush. Retinal ganglion cell (RGC) loss was assessed using retinal wholemount anti-RNA Binding Protein with Multiple Splicing (RBPMS) labeling and ON axon counts. Axonal transport was quantified with β-amyloid precursor protein (APP) immunolocalization. Micro-Western (Wes) analysis quantified protein expression. Immunofluorescent expression of ROCK pathway molecules, quantitative astrocyte structural changes, and ON biomechanical strains (explanted eyes) were evaluated. ROCK activity assays were conducted in separate ON regions.</p><p><strong>Results: </strong>At 6W GL, mean RGC axon loss was 6.6 ± 13.3% in Rip and 36.3 ± 30.9% in BSS (P = 0.04, n = 10/group). RGC soma loss after crush was lower with Rip (68.6 ± 8.2%) than BSS (80.5 ± 5.7%, P = 0.006, n = 10/group). After 6W GL, RGC soma loss was lower with Rip (34 ± 5.0%) than BSS (51 ± 8.1%, P = 0.03, n = 10/group). Axonal transport of APP within the unmyelinated ON (UON) was unaffected by Rip. Maximum principal mechanical strains increased similarly in Rip and BSS-treated mice. Retinal ROCK 1 and 2 activity was reduced by Rip in GL eyes. The pROCK2/ROCK2 protein ratio rose in the retina of BSS GL eyes, but not in Rip GL eyes.</p><p><strong>Conclusions: </strong>Topical Rip reduced RGC loss in GL and ON crush, with suppression of ROCK signaling in the retina and ON. The neuroprotection mechanisms appear to involve effects on both RGC and astrocyte responses to IOP elevation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"43"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675060","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}
Dong Liang, Bei Du, Tsz-Wing Leung, Zhuzhu Liu, Qiang Su, Nan Jin, Ziyu Zhang, Mingguang He, Hua Yan, Ruihua Wei, Chea-Su Kee
{"title":"Impact of Astigmatism on Axial Elongation in School-Age Children: A Five-Year Population-Based Study in Tianjin, China.","authors":"Dong Liang, Bei Du, Tsz-Wing Leung, Zhuzhu Liu, Qiang Su, Nan Jin, Ziyu Zhang, Mingguang He, Hua Yan, Ruihua Wei, Chea-Su Kee","doi":"10.1167/iovs.65.13.45","DOIUrl":"10.1167/iovs.65.13.45","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the progression rates of axial length (AXL) among school-age children with baseline astigmatism and spherical ametropia.</p><p><strong>Methods: </strong>Annual vision screenings were conducted at seven schools in Tianjin, China, from 2018 to 2022. Ocular biometry and non-cycloplegic autorefraction were collected. Children 5 to 16 years old without any myopia interventions were included and categorized by their baseline astigmatism magnitude (control, low, or high) and axis orientation (with the rule [WTR], against the rule [ATR], or oblique). Additionally, children were classified by baseline spherical ametropia (compound hyperopic, compound myopic, or other). Annual AXL progression rates of right eyes were calculated using regression models and compared across different types of astigmatism and spherical ametropia.</p><p><strong>Results: </strong>A total of 10,732 Chinese children (baseline age, 9.26 ± 2.42 years; follow-up duration, 2.63 ± 1.01 years) were included and divided into a younger cohort (age < 11 years; n = 7880) and an older cohort (age ≥ 11 years; n = 2852). Across both age groups and all astigmatism magnitudes, ATR astigmatism exhibited the most rapid AXL progression, followed by oblique and WTR astigmatism. Two-way ANCOVA of the combined cohort revealed that both high-magnitude and ATR astigmatism were significantly associated with AXL progression (P ≤ 0.018). However, the impact of astigmatism on AXL progression varied depending on baseline spherical ametropia, as high-magnitude and ATR astigmatism increased AXL progression in compound myopic eyes but decreased progression in compound hyperopic eyes.</p><p><strong>Conclusions: </strong>Both baseline magnitude and axis orientation of astigmatism are significantly associated with axial elongation in children. However, these associations may vary with spherical ametropia, with differential patterns being observed between compound hyperopic and myopic eyes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"45"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolomic Profiling of Open-Angle Glaucoma Etiologic Endotypes: Tohoku Multi-Omics Glaucoma Study.","authors":"Akiko Hanyuda, Yoshihiko Raita, Takahiro Ninomiya, Kazuki Hashimoto, Naoko Takada, Kota Sato, Jin Inoue, Seizo Koshiba, Gen Tamiya, Akira Narita, Masato Akiyama, Kazuko Omodaka, Satoru Tsuda, Yu Yokoyama, Noriko Himori, Yasuko Yamamoto, Takazumi Taniguchi, Kazuno Negishi, Toru Nakazawa","doi":"10.1167/iovs.65.13.44","DOIUrl":"10.1167/iovs.65.13.44","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate biologically meaningful endotypes of open-angle glaucoma (OAG) by applying unsupervised machine learning to plasma metabolites.</p><p><strong>Methods: </strong>This retrospective longitudinal cohort study enrolled consecutive patients aged ≥20 years with OAG at Tohoku University Hospital from January 2017 to January 2020. OAG was confirmed based on comprehensive ophthalmic examinations. Among the 523 patients with OAG with available clinical metabolomic data, 173 patients were longitudinally followed up for ≥2 years, with available data from ≥5 reliable visual field (VF) tests without glaucoma surgery. We collected fasting blood samples and clinical data at enrollment and nuclear magnetic resonance spectroscopy to profile 45 plasma metabolites in a targeted approach. After computing a distance matrix of preprocessed metabolites with Pearson distance, gap statistics determined the optimal number of OAG endotypes. Its risk factors, clinical presentations, metabolomic profiles, and progression rate of sector-based VF loss were compared across endotypes.</p><p><strong>Results: </strong>Five distinct OAG endotypes were identified. The highest-risk endotype (endotype B) showed a significant faster progression of central VF loss (P = 0.007). Compared with patients with other endotypes, those with endotype B were more likely to have a high prevalence of dyslipidemia, cold extremities, oxidative stress, and low OAG genetic risk scores. Pathway analysis of metabolomic profiles implicated altered fatty acid and ketone body metabolism in this endotype, with 34 differentially enriched pathways (false discovery rate [FDR] < 0.05).</p><p><strong>Conclusions: </strong>Integrated metabolomic profiles identified five distinct etiologic endotypes of OAG, suggesting pathological mechanisms related with a high-risk group of central vision loss progression in the Japanese population.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"44"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675764","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":"Optimization of HITI-Mediated Gene Insertion for Rhodopsin and Peripherin-2 in Mouse Rod Photoreceptors: Targeting Dominant Retinitis Pigmentosa.","authors":"Akishi Onishi, Yuji Tsunekawa, Michiko Mandai, Aiko Ishimaru, Yoko Ohigashi, Junki Sho, Kazushi Yasuda, Keiichiro Suzuki, Juan Carlos Izpisua Belmonte, Fumio Matsuzaki, Masayo Takahashi","doi":"10.1167/iovs.65.13.38","DOIUrl":"10.1167/iovs.65.13.38","url":null,"abstract":"<p><strong>Purpose: </strong>Among the genome-editing methods for repairing disease-causing mutations resulting in autosomal dominant retinitis pigmentosa, homology-independent targeted integration (HITI)-mediated gene insertion of the normal form of the causative gene is useful because it allows the development of mutation-agnostic therapeutic products. In this study, we aimed for the rapid optimization and validation of HITI-treatment gene constructs of this approach in developing HITI-treatment constructs for various causative target genes in mouse models of retinal degeneration.</p><p><strong>Methods: </strong>We constructed the Cas9-driven HITI gene cassettes in plasmid vectors to treat the mouse Rho gene. A workflow utilizing in vivo electroporation was established to validate the efficacy of these constructs. Single-cell genotyping was conducted to evaluate allelic donor gene insertion. The therapeutic potency of HITI-treatment plasmid and adeno-associated virus (AAV) vectors was examined by section immunohistochemistry and optomotor response (OMR) in Rho+/P23H mutant mice. We also targeted mouse Prph2 to examine the workflow.</p><p><strong>Results: </strong>The optimized HITI-treatment constructs for mouse Rho genes achieved gene insertion in 80% to 90% of transduced mouse rod photoreceptor cells. This construct effectively suppressed degeneration and induced visual restoration in mutant mice. HITI-treatment constructs for the Rhodopsin gene demonstrated efficacy in AAV vectors and are adaptable for the mouse Prph2 gene locus.</p><p><strong>Conclusions: </strong>The study showcases a workflow for the rapid optimization and validation of highly effective HITI-treatment gene constructs against dominant-negative inheritance in inherited retinal dystrophy. These findings suggest the potential utility of this approach in developing HITI-treatment constructs for various target genes, advancing gene therapy products for diverse genetic disorders.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"38"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647892","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":"De-Differentiation of Corneal Epithelial Cells Into Functional Limbal Epithelial Stem Cells After the Ablation of Innate Stem Cells.","authors":"Yijian Li, Lingling Ge, Bangqi Ren, Xue Zhang, Zhiyuan Yin, Hongling Liu, Yuli Yang, Yong Liu, Haiwei Xu","doi":"10.1167/iovs.65.13.32","DOIUrl":"10.1167/iovs.65.13.32","url":null,"abstract":"<p><strong>Purpose: </strong>Regeneration after tissue injury is often associated with cell fate plasticity, which restores damaged or lost cells. Here, we examined the de-differentiation of corneal epithelial cells (CECs) into functional limbal epithelial stem cells (LESCs) after the ablation of innate stem cells.</p><p><strong>Methods: </strong>The regeneration of LESCs after the ablation of innate LESCs was identified by a set of markers: ApoE+/Cx43low/CK12-. CK14-CreERT2 or Slc1a3-CreERT mice were crossed with reporter mice to trace the fate of CECs. YAP-TEAD inhibitor verteporfin (VTP) and LATS inhibitor TRULI were used to examine the role of Hippo/YAP pathway in the de-differentiation of CECs.</p><p><strong>Results: </strong>LESCs-ablation cornea showed to be functionally normal, including the maintenance of corneal transparency, prevention of conjunctivalization, and wound healing rate equivalent to that of normal cornea. ApoE+/Cx43low/CK12- LESCs regenerated at the limbus at 6 days after the ablation of innate stem cells, and maintained for at least 6 months. Corneal epithelial lineage tracing showed that CECs migrated back to the limbus after the ablation of innate stem cells, and de-differentiated into active and quiescent LESCs (aLESCs and qLESCs), which participated in corneal epithelial homeostasis and wound healing, respectively, like their innate counterparts. However, when the limbus niche was destroyed by NaOH (1 M, 5 seconds), CECs that occupied the limbus could not de-differentiate into ApoE+/Cx43low/CK12- LESCs and cornea developed into conjunctivalization. In addition, the protein level and activity of YAP increased at the early stage (1-2 days) after the ablation of limbal epithelium, and decreased when the de-differentiation occurred. The YAP-TEAD inhibitor VTP promoted the de-differentiation, whereas LATS inhibitor TRULI inhibited the de-differentiation of CECs. However, the persistent activation of YAP prevented the de-differentiation of CECs after an additional NaOH burn to the limbal stroma, and VTP could not rescue the capacity of CECs to de-differentiate into LESCs.</p><p><strong>Conclusions: </strong>These results reveal the de-differentiation of CECs into functional LESCs after the ablation of innate stem cells, and suggest potential role of Hippo/YAP pathway in the de-differentiation of CECs in vivo.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"32"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638971","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}
XiaoBo Zheng, Chong Wang, YiWen Fan, YuXin Hong, Han Bao, ErChi Zhang, Yi Jin, Peng Yang, LingQiao Li, JunJie Wang, ShiHao Chen, Ahmed Elsheikh, FangJun Bao
{"title":"Restoration of Corneal Stiffness in Rabbits Following Withdrawal of Travoprost.","authors":"XiaoBo Zheng, Chong Wang, YiWen Fan, YuXin Hong, Han Bao, ErChi Zhang, Yi Jin, Peng Yang, LingQiao Li, JunJie Wang, ShiHao Chen, Ahmed Elsheikh, FangJun Bao","doi":"10.1167/iovs.65.13.35","DOIUrl":"10.1167/iovs.65.13.35","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate if the effect of travoprost on corneal material stiffness could be restored after drug withdrawal.</p><p><strong>Methods: </strong>Seventy-two rabbits were randomly allocated into three groups: medicine (M), medicine withdrawal (MW), and blank (B). Within the M and MW groups, treatment with travoprost was administered to the right eyes (MT and MWT) over a period of 12 weeks. Subsequently, the M group was killed, but the MW group underwent an additional 12-week period for treatment withdrawal. No treatment was given to the contralateral eyes (MC and MWC) in the M and MW groups. A separate blank control (BC) group remained untreated for the entire 24-week duration. In each group, corneas from 18 rabbits were tested mechanically under inflation conditions to estimate their tangent modulus (Et). The corneas of the remaining six rabbits underwent electron microscopy analysis, which focused on fibril diameter and interfibrillar spacing.</p><p><strong>Results: </strong>Central corneal thickness (CCT) of the treated eyes (MT and MWT groups) decreased with 12 weeks of travoprost treatment (P < 0.05). The CCT in the MWT group increased after 12 weeks of withdrawal but was still lower than that in the BC group (P < 0.05). The Et of the MT group was significantly lower than that of the MC group at mean tissue stresses of 2, 4, and 6 kPa (P < 0.05). Conversely, no significant difference in Et values was observed between the MWT, MWC, and BC groups, indicating recovery after treatment cessation. Furthermore, the stromal interfibrillar spacing of the treated MT group was significantly larger (P < 0.05) than that of the control MC group, but no disparity was noted among the MWT, MWC, and BC groups following treatment withdrawal. Additionally, there were no significant differences in the mean diameter of collagen fibrils among all groups (all P > 0.05).</p><p><strong>Conclusions: </strong>Travoprost treatment appears to soften corneal tissue, decrease tissue thickness, and reduce the density of stromal collagen fibers by increasing the interfibrillar spacing. These changes were partially reversed after treatment cessation. Travoprost could further inhibit corneal growth, so its use in childhood and adolescence should be carefully considered. Additionally, the effect of travoprost in reducing corneal stiffness may lead to underestimations of intraocular pressure (IOP) measurement and hence overestimations in the effect of treatment in lowering IOP.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"35"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638880","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}
Saman Ebrahimi, Phillip Bedggood, Yifu Ding, Andrew Metha, Prosenjit Bagchi
{"title":"A High-Fidelity Computational Model for Predicting Blood Cell Trafficking and 3D Capillary Hemodynamics in Retinal Microvascular Networks.","authors":"Saman Ebrahimi, Phillip Bedggood, Yifu Ding, Andrew Metha, Prosenjit Bagchi","doi":"10.1167/iovs.65.13.37","DOIUrl":"10.1167/iovs.65.13.37","url":null,"abstract":"<p><strong>Purpose: </strong>To present a first principle-based, high-fidelity computational model for predicting full three-dimensional (3D) and time-resolved retinal microvascular hemodynamics taking into consideration the flow and deformation of individual blood cells.</p><p><strong>Methods: </strong>The computational model is a 3D fluid-structure interaction model based on combined finite volume/finite element/immersed-boundary methods. Three in silico microvascular networks are built from high-resolution in vivo motion contrast images of the superficial capillary plexus in the parafoveal region of the human retina. The maximum tissue area represented in the model is approximately 500 × 500 µm2, and vessel lumen diameters ranged from 5.5 to 25 µm covering capillaries, arterioles, and venules. Blood is modeled as a suspension of individual blood cells, namely, erythrocytes (RBC), leukocytes (WBC), and platelets in plasma. An accurate and detailed biophysical modeling of each blood cell and their flow-induced deformation is considered. A physiological, pulsatile boundary condition corresponding to an average cardiac cycle of 0.9 second is used.</p><p><strong>Results: </strong>Detailed quantitative data and analysis of 3D retinal microvascular hemodynamics are presented, and their relationship to RBC flow dynamics is illustrated. Blood velocity is shown to have temporal oscillations superimposed on the background pulsatile variation, which arise because of the way RBCs partition at vascular junctions, causing repeated clogging and unclogging of vessels. Temporal variations in RBC velocity and hematocrit are anti-correlated in a given vessel, but their time-averaged distributions are positively correlated across the network. Whole blood velocity is 65% to 85% of RBC velocity, with the discrepancy related to the formation of an RBC-free region, adjacent to the vascular endothelium and typically 0.8 to 1.8 µm thick. The 3D velocity and RBC concentration profiles are shown to be oppositely skewed with respect to each other, because of the way that RBCs \"hug\" the apex of each bifurcation. RBC deformation is predicted to have biphasic behavior with respect to vessel diameter, with minimal cell length for vessels approximately 7 µm in diameter. The wall shear stress (WSS) exhibits a strongly 3D distribution with local regions of high value and gradient spanning a range of 10 to 80 dyn/cm2. WSS is highest where there is faster flow, greater curvature of the vessel wall, capillary bifurcations, and at locations of RBC crowding and associated thinning of the cell-free layer.</p><p><strong>Conclusions: </strong>This study highlights the usefulness of high-fidelity cell-resolved modeling to obtain accurate and detailed 3D, time-resolved retinal hemodynamic parameters that are not readily available through noninvasive imaging approaches. The results presented are expected to complement and enhance the interpretation of in vivo data, as well as open new avenu","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"37"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638968","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}
Archayeeta Rakshit, Debasmita Majhi, Katrina L Schmid, Vivek Warkad, David A Atchison, Ann L Webber
{"title":"Fine Motor Skills, Reading Speed, and Self-Reported Quality of Life in Adults With Amblyopia and/or Strabismus.","authors":"Archayeeta Rakshit, Debasmita Majhi, Katrina L Schmid, Vivek Warkad, David A Atchison, Ann L Webber","doi":"10.1167/iovs.65.13.48","DOIUrl":"10.1167/iovs.65.13.48","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to assess fine motor skills and reading proficiency in adults with amblyopia and/or strabismus, and to determine how these relate to clinical measures of vision and self-reported vision-related quality of life.</p><p><strong>Methods: </strong>Fine motor skills (Manual dexterity - Bruininks-Oseretsky Test of Motor Proficiency [BOT-2]) and reading performance (International Reading Speed Texts [IReST]) were assessed in 23 adults with non-strabismic amblyopia, 20 with non-amblyopic strabismus, 52 with both amblyopia and strabismus, and 19 with normal visual development. Visual acuity and binocular function score (BFS), obtained from stereoacuity and presence/absence of suppression, were also determined. Vision-related quality of life was assessed with the Amblyopia and Strabismus Questionnaire (A&SQ) in those with amblyopia and/or strabismus. Statistical analysis included ANOVA and multiple regression models.</p><p><strong>Results: </strong>Participants with amblyopia and/or strabismus exhibited poorer performance in all five manual dexterity sub-items and the overall standardized score (P < 0.05). The reading rate was significantly slower across all amblyopia/strabismus groups (P < 0.05). Poorer fine motor skills and slower reading performance were associated with each other (R = 0.29). Clinical visual characteristics (visual acuity [VA], BFS, and presence of strabismus) explained 39% of the variance in fine motor skills score (R2 = 0.39), however, these explained only 6% of the variance in reading speed (R2 = 0.06). Self-report of functional ability related most to BFS, whereas psychosocial impact related to the presence of strabismus. The clinical and functional characteristics predicted 4% of the variance in functional impact score (R2 = 0.038) and explained 16% of the variance in psychosocial impact score (R2 = 0.16).</p><p><strong>Conclusions: </strong>The functional and psychosocial effects of amblyopia and strabismus are common and persist into adulthood, with outcomes inadequately accounted for by clinical measures of vision.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"48"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}