Olga Safrina, Irene Vorontsova, Paul J Donaldson, Thomas F Schilling
{"title":"Zebrafish Optical Development Requires Regulated Water Permeability by Aquaporin 0.","authors":"Olga Safrina, Irene Vorontsova, Paul J Donaldson, Thomas F Schilling","doi":"10.1167/iovs.65.11.42","DOIUrl":"https://doi.org/10.1167/iovs.65.11.42","url":null,"abstract":"<p><strong>Purpose: </strong>Optical development of the zebrafish eye relies on the movement of the highly refractive lens nucleus from an anterior to a central location in the optical axis during development. We have shown that this mechanism in turn depends on the function of Aquaporin 0a (Aqp0a), a multifunctional and extremely abundant protein in lens fiber cell membranes. Here, we probe the specific cellular functions necessary for rescuing lens nucleus centralization defects in aqp0a-/- null mutants by stable overexpression of an Aqp0 orthologue from a killifish, MIPfun.</p><p><strong>Methods: </strong>We test in vivo requirements for lens transparency and nucleus centralization of MIPfun for auto-adhesion, water permeability (Pf), and Pf sensitivity to regulation by Ca2+ or pH by overexpression of MIPfun mutants previously shown to have defects in these functions in vitro or in silico.</p><p><strong>Results: </strong>Water permeability of MIPfun is essential for rescuing lens transparency and nucleus centralization defects, whereas auto-adhesion is not. Furthermore, water permeability regulation by Ca2+ and pH appear residue-dependent, because some Ca2+-insensitive mutants fail to rescue, and pH-insensitive mutants only partially rescue defects. MIPfun lacking Pf sensitivity to both, Ca2+ and pH, also fails to rescue lens nucleus centralization.</p><p><strong>Conclusion: </strong>This study shows that regulation of water permeability by Aqp0 plays a key role in the centralization of the zebrafish lens nucleus, providing the first direct evidence for water transport in this aspect of optical development.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346862","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}
Tiffany DeVine,Gabriela Elizondo,Garen Gaston,Shannon J Babcock,Dietrich Matern,Mikhail S Shchepinov,Mark E Pennesi,Cary O Harding,Melanie B Gillingham
{"title":"iPSC-Derived LCHADD Retinal Pigment Epithelial Cells Are Susceptible to Lipid Peroxidation and Rescued by Transfection of a Wildtype AAV-HADHA Vector.","authors":"Tiffany DeVine,Gabriela Elizondo,Garen Gaston,Shannon J Babcock,Dietrich Matern,Mikhail S Shchepinov,Mark E Pennesi,Cary O Harding,Melanie B Gillingham","doi":"10.1167/iovs.65.11.22","DOIUrl":"https://doi.org/10.1167/iovs.65.11.22","url":null,"abstract":"PurposeProgressive choroid and retinal pigment epithelial (RPE) degeneration causing vision loss is a unique characteristic of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), a fatty acid oxidation disorder caused by a common c.1528G>C pathogenic variant in HADHA, the α subunit of the mitochondrial trifunctional protein (TFP). We established and characterized an induced pluripotent stem cell (iPSC)-derived RPE cell model from cultured skin fibroblasts of patients with LCHADD and tested whether addition of wildtype (WT) HAHDA could rescue the phenotypes identified in LCHADD-RPE.MethodsWe constructed an rAAV expression vector containing 3' 3xFLAG-tagged human HADHA cDNA under the transcriptional control of the cytomegalovirus (CMV) enhancer-chicken beta actin (CAG) promoter (CAG-HADHA-3XFLAG). LCHADD-RPE were cultured, matured, and transduced with either AAV-GFP (control) or AAV-HADHA-3XFLAG.ResultsLCHADD-RPE express TFP subunits and accumulate 3-hydroxy-acylcarnitines, cannot oxidize palmitate, and release fewer ketones than WT-RPE. When LCHADD-RPE are exposed to docosahexaenoic acid (DHA), they have increased oxidative stress, lipid peroxidation, decreased viability, and are rescued by antioxidant agents potentially explaining the pathologic mechanism of RPE loss in LCHADD. Transduced LCHADD-RPE expressing a WT copy of TFPα incorporated TFPα-FLAG into the TFP complex in the mitochondria and accumulated significantly less 3-hydroxy-acylcarnitines, released more ketones in response to palmitate, and were more resistant to oxidative stress following DHA exposure than control.ConclusionsiPSC-derived LCHADD-RPE are susceptible to lipid peroxidation mediated cell death and are rescued by exogenous HADHA delivered with rAAV. These results are promising for AAV-HADHA gene addition therapy as a possible treatment for chorioretinopathy in patients with LCHADD.","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249909","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}
Alessia Ruffini,Mariia Dvoriashyna,Andrea Govetto,Mario R Romano,Rodolfo Repetto
{"title":"A Mathematical Model of Interstitial Fluid Flow and Retinal Tissue Deformation in Macular Edema.","authors":"Alessia Ruffini,Mariia Dvoriashyna,Andrea Govetto,Mario R Romano,Rodolfo Repetto","doi":"10.1167/iovs.65.11.19","DOIUrl":"https://doi.org/10.1167/iovs.65.11.19","url":null,"abstract":"PurposeThis study aims to develop a mathematical model to elucidate fluid circulation in the retina, focusing on the movement of interstitial fluid (comprising water and albumin) to understand the mechanisms underlying exudative macular edema (EME).MethodsThe model integrates physiological factors such as retinal pigment epithelium (RPE) pumping, osmotic pressure gradients, and tissue deformation. It accounts for spatial variability in hydraulic conductivity (HC) across the retina and incorporates the structural role of Müller cells (MCs) in maintaining retinal stability.ResultsThe model predicts that tissue deformation is maximal at the center of the fovea despite fluid exudation from blood capillaries occurring elsewhere, aligning with clinical observations. Additionally, the model suggests that spatial variability in HC across the thickness of the retina plays a protective role against fluid accumulation in the fovea.ConclusionsDespite inherent simplifications and uncertainties in parameter values, this study represents a step toward understanding the pathophysiology of EME. The findings provide insights into the mechanisms underlying fluid dynamics in the retina and fluid accumulation in the foveal region, showing that the specific conformation of Müller cells is likely to play a key role.","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213055","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":"Administration of Nicotine Can Inhibit Myopic Growth in Animal Models.","authors":"Kate Thomson,Cindy Karouta,Regan Ashby","doi":"10.1167/iovs.65.11.29","DOIUrl":"https://doi.org/10.1167/iovs.65.11.29","url":null,"abstract":"PurposeWhile previously investigating the mechanism by which atropine inhibits ocular growth, we observed that stimulation of nicotinic receptors can inhibit experimental myopia. This study expands on that preliminary finding and investigates the safety and efficacy of nicotinic stimulation in the inhibition of ocular growth.MethodsNicotine's ability to inhibit form-deprivation myopia (FDM), following intravitreal injection (9 chicks per group) or topical application (6 chicks per group), was investigated over three doses. The ability of nicotine to inhibit lens-induced myopia (LIM) was also tested (in 12 chicks). For ocular safety, following 4 weeks of topical treatment with nicotine (n = 10), pupillary reflex, intraocular pressure, corneal curvature/thickness, lens thickness, retinal health (retinal thickness/cell apoptosis), as well as retinal function (electroretinogram recordings) were assessed. We also examined the effects of nicotine on non-ocular autonomic functions in both chicks (n = 5) and mice (n = 5).ResultsNicotine was observed to significantly inhibit the development of FDM in chicks when administered as an intravitreal injection (P < 0.05) or topical eye drops (P < 0.05), albeit not in a dose-dependent manner. Nicotine also inhibited LIM (P < 0.05) to a similar degree to that seen for FDM. Although ocular health was (for the most part) unaffected by nicotine, the highest topical dose induced a temporary reduction in cardiorespiratory output (P < 0.05).ConclusionsNicotine, administered as an intravitreal injection or topical eye drop, significantly inhibits the development of experimental myopia. Although the anti-myopic effects observed presently are interesting, the well-reported side effects (expanded on presently) and addictive properties of nicotine would preclude its clinical use.","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249885","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":"Delayed Surgical Reversal of Optic Nerve Compression Leads to Exponential Degeneration of Optic Nerve Fibers and Selective Sparing of the Small Fibers.","authors":"XiaoHui Jiang, Boyue Xu, Shuang Yao, Zhuowei Wang, Mingyue Liu, Yikui Zhang, Wencan Wu, Ende Wu","doi":"10.1167/iovs.65.11.40","DOIUrl":"https://doi.org/10.1167/iovs.65.11.40","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the effectiveness of surgical reversal of experimental optic nerve compression in treating persistent compressive optic neuropathy and to explore the relationship between surgical outcomes and the timing of the procedure.</p><p><strong>Methods: </strong>Surgical reversal procedures (decompression surgery) were conducted at five time intervals: 1, 3, and 7 days and 2 and 3 weeks following optic nerve compression in a rabbit model. The groups were labeled as DC-1d, DC-3d, DC-7d, DC-2w, and DC-3w, respectively. The study investigated changes in ganglion cell complex (GCC) thickness using spectral-domain optical coherence tomography and the percentage of surviving retinal ganglion cells (RGCs) through immunofluorescence staining and optic nerve axons stained with p-phenylenediamine at 4 weeks after decompression. Additionally, the area distribution of surviving axons was analyzed.</p><p><strong>Results: </strong>The decline in GCC thickness was halted following decompression. The remaining thickness of the GCC in group DC-1d was found to be statistically significantly higher at 2, 3, and 4 weeks postonset compared to the no-decompression group. Similarly, GCC thickness in group DC-3d was significantly higher at 3 and 4 weeks postonset. The percentage of surviving RGCs and axons at 4 weeks postonset exhibited an exponential correlation with the onset time of decompression, with R2 values of 0.72 and 0.78, respectively. The surviving axon area declined following delayed decompression.</p><p><strong>Conclusions: </strong>Persistent substantial compression on the optic nerve leads to exponential degeneration of the optic nerve, initially affecting larger optic nerve fibers. Early intervention aimed at relieving the compression on the optic nerve may offer potential benefits in mitigating the degenerative effects and conserving visual function.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346855","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}
Royston K Y Tan, Gim Yew Ng, Tin A Tun, Fabian A Braeu, Monisha E Nongpiur, Tin Aung, Michaël J A Girard
{"title":"Iris Morphological and Biomechanical Factors Influencing Angle Closure During Pupil Dilation.","authors":"Royston K Y Tan, Gim Yew Ng, Tin A Tun, Fabian A Braeu, Monisha E Nongpiur, Tin Aung, Michaël J A Girard","doi":"10.1167/iovs.65.11.7","DOIUrl":"10.1167/iovs.65.11.7","url":null,"abstract":"<p><strong>Purpose: </strong>To use finite element (FE) analysis to assess what morphologic and biomechanical factors of the iris and anterior chamber are more likely to influence angle narrowing during pupil dilation.</p><p><strong>Methods: </strong>The study consisted of 1344 FE models comprising the cornea, sclera, lens, and iris to simulate pupil dilation. For each model, we varied the following parameters: anterior chamber depth (ACD = 2-4 mm) and anterior chamber width (ACW = 10-12 mm), iris convexity (IC = 0-0.3 mm), iris thickness (IT = 0.3-0.5 mm), stiffness (E = 4-24 kPa), and Poisson's ratio (v = 0-0.3). We evaluated the change in (△∠) and the final dilated angles (∠f) from baseline to dilation for each parameter.</p><p><strong>Results: </strong>The final dilated angles decreased with a smaller ACD (∠f = 53.4° ± 12.3° to 21.3° ± 14.9°), smaller ACW (∠f = 48.2° ± 13.5° to 26.2° ± 18.2°), larger IT (∠f = 52.6° ± 12.3° to 24.4° ± 15.1°), larger IC (∠f = 45.0° ± 19.2° to 33.9° ± 16.5°), larger E (∠f = 40.3° ± 17.3° to 37.4° ± 19.2°), and larger v (∠f = 42.7° ± 17.7° to 34.2° ± 18.1°). The change in angles increased with larger ACD (△∠ = 9.37° ± 11.1° to 15.4° ± 9.3°), smaller ACW (△∠ = 7.4° ± 6.8° to 16.4° ± 11.5°), larger IT (△∠ = 5.3° ± 7.1° to 19.3° ± 10.2°), smaller IC (△∠ = 5.4° ± 8.2° to 19.5° ± 10.2°), larger E (△∠ = 10.9° ± 12.2° to 13.1° ± 8.8°), and larger v (△∠ = 8.1° ± 9.4° to 16.6° ± 10.4°).</p><p><strong>Conclusions: </strong>The morphology of the iris (IT and IC) and its innate biomechanical behavior (E and v) were crucial in influencing the way the iris deformed during dilation, and angle closure was further exacerbated by decreased anterior chamber biometry (ACD and ACW).</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132772","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}
Xiao Shang, Nathanael Urs Häner, Joel-Benjamin Lincke, Valentin Pfeiffer, Pascal Aurel Gubser, Martin Sebastian Zinkernagel, Jan Darius Unterlauft
{"title":"Long-Term Changes in Lamina Cribrosa Curvature Index After Trabeculectomy in Glaucomatous Eyes.","authors":"Xiao Shang, Nathanael Urs Häner, Joel-Benjamin Lincke, Valentin Pfeiffer, Pascal Aurel Gubser, Martin Sebastian Zinkernagel, Jan Darius Unterlauft","doi":"10.1167/iovs.65.11.3","DOIUrl":"10.1167/iovs.65.11.3","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate both short-term and long-term changes in the lamina cribrosa curvature index (LCCI) following trabeculectomy and investigate the factors influencing these changes.</p><p><strong>Methods: </strong>In this retrospective, observational study, 40 eyes of 40 patients with glaucoma who underwent trabeculectomy and had a follow-up of at least 2 years were included. Optic nerve head area was scanned by using spectral-domain optical coherence tomography before surgery (Pre_OP), within 6 months postoperatively (Post_OP1), and at the last visit (Post_OP2). LCCI values calculated from B-scan images at six different planes (0°, 30°, 60°, 90°, 120°, and 150°) and their mean values were compared. Univariate and multivariate linear regression analyses were used to identify the clinical factors associated with the amount of LCCI changes.</p><p><strong>Results: </strong>The mean follow-up time was 38.3 ± 16.8 months. At Post_OP1, the mean LCCI decreased from 9.28 ± 2.58 to 7.91 ± 2.57 (P < 0.001), and the mean intraocular pressure decreased from 22.0 ± 7.6 mm Hg to 12.2 ± 3.8 mm Hg (P = 0.001). At Post_OP2, the mean LCCI was maintained at 7.74 ± 2.49 (P = 0.56 when compared to Post_OP1 and P < 0.001 when compared to Pre_OP). The mean intraocular pressure was 12.6 ± 5.4 mm Hg (P = 0.67 when compared to Post_OP1 and P < 0.001 when compared to Pre_OP). Long-term LCCI changes were associated with baseline age (P = 0.04), spherical equivalent (P = 0.02), mean IOP during follow-ups (P = 0.02), and preoperative LCCI (P = 0.04).</p><p><strong>Conclusions: </strong>Glaucomatous eyes undergoing trabeculectomy demonstrated reductions in the LCCI after a mean follow-up of over 3 years. Greater long-term LCCI reduction was associated with younger age, lower mean IOP during follow-up period, greater spherical equivalent refractive error, and preoperative LCCI.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132773","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}
Baptiste Wilmet, Christelle Michiels, Jingyi Zhang, Jacques Callebert, José Alain Sahel, Serge Picaud, Isabelle Audo, Christina Zeitz
{"title":"Loss of ON-Pathway Function in Mice Lacking Lrit3 Decreases Recovery From Lens-Induced Myopia.","authors":"Baptiste Wilmet, Christelle Michiels, Jingyi Zhang, Jacques Callebert, José Alain Sahel, Serge Picaud, Isabelle Audo, Christina Zeitz","doi":"10.1167/iovs.65.11.18","DOIUrl":"10.1167/iovs.65.11.18","url":null,"abstract":"<p><strong>Purpose: </strong>To determine whether the Lrit3-/- mouse model of complete congenital stationary night blindness with an ON-pathway defect harbors myopic features and whether the genetic defect influences the recovery from lens-induced myopia.</p><p><strong>Methods: </strong>Retinal levels of dopamine (DA) and 3,4 dihydroxyphenylacetic acid (DOPAC) from adult isolated Lrit3-/- retinas were quantified using ultra performance liquid chromatography after light adaptation. Natural refractive development of Lrit3-/- mice was measured from three weeks to nine weeks of age using an infrared photorefractometer. Susceptibility to myopia induction was assessed using a lens-induced myopia protocol with -25 D lenses placed in front of the right eye of the animals for three weeks; the mean interocular shift was measured with an infrared photorefractometer after two and three weeks of goggling and after one and two weeks after removal of goggles.</p><p><strong>Results: </strong>Compared to wild-type littermates (Lrit3+/+), both DA and DOPAC were drastically reduced in Lrit3-/- retinas. Natural refractive development was normal but Lrit3-/- mice showed a higher myopic shift and a lower ability to recover from induced myopia.</p><p><strong>Conclusions: </strong>Our data consolidate the link between ON pathway defect altered dopaminergic signaling and myopia. We document for the first time the role of ON pathway on the recovery from myopia induction.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154086","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}
Salma El Emrani, Esther J S Jansen, Jelle J Goeman, Jacqueline U M Termote, Enrico Lopriore, Nicoline E Schalij-Delfos, Lotte E van der Meeren
{"title":"Enhancing the Retinopathy Of Prematurity Risk Profile Through Placental Evaluation of Maternal and Fetal Vascular Malperfusion.","authors":"Salma El Emrani, Esther J S Jansen, Jelle J Goeman, Jacqueline U M Termote, Enrico Lopriore, Nicoline E Schalij-Delfos, Lotte E van der Meeren","doi":"10.1167/iovs.65.11.9","DOIUrl":"10.1167/iovs.65.11.9","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the independent effect of uteroplacental malperfusion on the development of retinopathy of prematurity (ROP).</p><p><strong>Methods: </strong>This cohort study included 591 neonates with a gestational age (GA) ≤ 32 weeks or birthweight (BW) ≤ 1500 g. Clinical data was retrospectively collected and placentas were prospectively examined for maternal vascular malperfusion (e.g., abruption, infarct, distal villous hypoplasia, ischemia, and decidual necrosis) and fetal vascular malperfusion (e.g., thrombosis, fetal hypoxia, and hydrops parenchyma). The primary outcome was ROP. Secondary outcomes were GA, BW, small for gestational age (SGA), mechanical ventilation duration, postnatal corticosteroids, sepsis, and necrotizing enterocolitis.</p><p><strong>Results: </strong>Maternal vascular malperfusion was associated with higher GA, lower BW, and increased SGA rates, except placental abruption, which was associated with lower SGA rates. Fetal vascular malperfusion was associated with lower BW, increased SGA rates and lower duration of mechanical ventilation. Subgroup analysis of placentas without inflammation showed increased rates of distal villous hypoplasia (44% vs. 31%) and hydrops parenchyma (7% vs. 0%) in neonates with ROP. Multivariate regression analyses revealed three placenta factors to be independently associated with ROP: distal villous hypoplasia (OR = 1.7; 95% CI, 1.0-3.0), severe acute histological chorioamnionitis (OR = 2.1; 95% CI, 1.1-3.9) and funisitis (OR = 1.8; 95% CI, 1.0-3.1).</p><p><strong>Conclusions: </strong>Placental evaluation of distal villous hypoplasia, severe acute chorioamnionitis and funisitis is a novel and valuable addition to the ROP risk profile. Evaluation of these placental risk factors shortly after birth can aid in identifying high-risk infants in an earlier stage than currently possible.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132770","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}