Investigative ophthalmology & visual science最新文献

{"title":"Individual-Eye Pharmacokinetics of Intravitreal Ranibizumab: Linking Ocular Geometry to Drug Retention Using MRI and Modeling.","authors":"Patricia Lamirande, Eamonn A Gaffney, Michael Gertz, Basil Künnecke, Thomas Bielser, Andreas Bruns, Jessica R Crawshaw, Uwe Wessels, Antonella Rampazzo, Philip K Maini, Antonello Caruso","doi":"10.1167/iovs.67.12.31","DOIUrl":"10.1167/iovs.67.12.31","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to quantify the influence of ocular geometry on intravitreal (IVT) ranibizumab pharmacokinetics (PKs) in rabbits by integrating magnetic resonance imaging (MRI)-derived geometries, diffusion-based modeling, and PK measurements.</p><p><strong>Methods: </strong>MRI was performed to obtain detailed ocular geometries in 39 New Zealand White (NZW) rabbits. Ranibizumab PKs were assessed in the same animals by serial aqueous humour (AH) sampling following single or three 0.5 mg doses. Individual eye parameters were estimated using profile likelihood analysis. A mean first passage time model was developed to predict ocular half-life as a function of eye size and injection location. Simplified ocular models parameterized by axial length (AL) were constructed to assess whether reduced anatomic representations capture population-level trends.</p><p><strong>Results: </strong>MRI-derived vitreous geometries enabled quantification of inter-eye anatomic variability. The study cohort of adult rabbits exhibited a limited range of AL and vitreous volume compared to human variability. Modeling predicted increased ocular half-life with eye size, a trend reproduced by simplified AL-based models. Experimentally estimated half-lives ranged between 2.8 and 4.9 days and showed weak correlation to AL and vitreous volume. The population mean half-life was 3.67 days, consistent with previous results.</p><p><strong>Conclusions: </strong>This study provides a quantitative framework for analyzing IVT PKs at the level of individual eyes. Modeling predicts that ocular geometry influences drug elimination, and this relationship was also detected experimentally in rabbits, albeit over a limited anatomic range. Greater variability in human eye size may therefore contribute to interindividual PK differences and warrants further investigation, as it may inform personalized dosing strategies.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"31"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193824","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":"Temporal Transcriptomic Profiling Reveals DECTIN-1-Mediated Immune Responses in Acanthamoeba Keratitis.","authors":"Jinding Pang, Zhenyu Wei, Yuheng Zhang, Yuan Wei, Qingquan Shi, Qiankun Chen, Zijun Zhang, Sitong Shen, Bo Peng, Ahyan Ilman Qudsi, Sizhe Ji Wu, Qingfeng Liang","doi":"10.1167/iovs.67.12.25","DOIUrl":"10.1167/iovs.67.12.25","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the dynamic immune response and the role of DECTIN-1 in Acanthamoeba keratitis (AK).</p><p><strong>Methods: </strong>The AK mouse model was established, and corneal tissue samples were collected at 1, 3, and 7 days post-infection (dpi). Transcriptomic profiling was performed to analyze differentially expressed genes and enriched Gene Ontology terms. Immune cell infiltration was estimated using ImmuCellAI-mouse. The expression of DECTIN-1 and associated signaling molecules was validated using quantitative PCR, immunostaining, and Western blotting. In vitro experiments were conducted to assess DECTIN-1 expression in human corneal epithelial cells (HCECs).</p><p><strong>Results: </strong>AK progression was characterized by dynamic changes, with peak inflammatory responses at 3 dpi. Immune infiltration analysis revealed early innate immune activation followed by adaptive immune involvement at later stages. Temporal transcriptome analysis identified DECTIN-1 as a significantly upregulated gene throughout disease progression. Activation of the DECTIN-1/SYK/NF-κB signaling pathway was associated with increased expression of pro-inflammatory cytokines. In vitro experiments confirmed that Acanthamoeba directly induced DECTIN-1 expression in HCECs.</p><p><strong>Conclusions: </strong>DECTIN-1 was dynamically upregulated during AK and may play a potential role in mediating innate immune responses and shaping immune cell dynamics. These findings provided new insights into AK pathogenesis and indicated DECTIN-1 as a potential therapeutic target.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"25"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181263","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":"Association Between Ellipsoid Zone Area and Fixation Stability in Macular Telangiectasia Type 2.","authors":"Kensington A Hatcher, Thomas M Aaberg, Joanna Yankey, Eleonora M Lad, Razek G Coussa, Robert Kissling, Muna I Bitar","doi":"10.1167/iovs.67.12.57","DOIUrl":"10.1167/iovs.67.12.57","url":null,"abstract":"<p><strong>Purpose: </strong>To determine whether ellipsoid zone (EZ) area loss, a biomarker of photoreceptor degeneration, is associated with fixation stability in macular telangiectasia type 2 (MacTel).</p><p><strong>Methods: </strong>This retrospective analysis included 212 adults from two Phase 3 trials of revakinagene taroretcel-lwey for MacTel. EZ area loss was quantified with optical coherence tomography. Fixation stability (P1 index) was measured by microperimetry. Linear and logistic regressions evaluated associations between EZ area loss and P1 over 24 months. A median split stratified the population to evaluate whether baseline EZ area loss influenced the therapeutic effect of the implant versus sham. A receiver operating characteristic analysis identified a structural threshold for unstable fixation.</p><p><strong>Results: </strong>EZ area loss was significantly associated with reduced fixation stability at baseline (P = 0.002) and month 24 (P = 0.01). Each 1-mm² increase in EZ area loss doubled the odds of poor fixation stability (defined as a P1 <80%) (odds ratio, 2.07; P = 0.047). P1 change did not significantly differ between the treatment and sham groups. In exploratory analyses, stratification by median baseline EZ area loss, despite a nonsignificant treatment-by-baseline interaction (P = 0.17), revealed a greater decline in fixation stability in sham-treated eyes (mean, -3.8%) versus the implant group (+0.6%). The receiver operating characteristic analysis identified an EZ area loss threshold of 1.075 mm² for unstable fixation.</p><p><strong>Conclusions: </strong>Greater EZ area loss is associated with poorer fixation stability in MacTel. An EZ area loss threshold of ∼1 mm² may serve as an exploratory marker of fixation instability risk, though this threshold requires independent validation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"57"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267547","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":"Single-Cell Sequencing Reveals Androgen Deficiency Arrests Meibocyte Differentiation and Impairs EMC-Mediated Lipid Metabolism.","authors":"Shenchuan Qian, Zihao Liu, Mike Pan, Meiling Zhu, Juan Li, Yuyang Fu, Qian Li, Zhiwei Zha, Ying Feng, Wei Chen","doi":"10.1167/iovs.67.12.46","DOIUrl":"10.1167/iovs.67.12.46","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the cellular dynamics of androgen-deficient meibomian gland dysfunction (MGD) and to elucidate the molecular mechanisms limiting the structural regenerative efficacy of topical dihydrotestosterone (DHT) treatment.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) was performed on meibomian glands from sham-operated controls, castrated mice, and castrated mice receiving topical 0.08% DHT. We performed comparative analyses to quantify changes in cell composition, reconstruct differentiation trajectories, and systematically profile alterations in metabolic pathways and organelle homeostasis networks.</p><p><strong>Results: </strong>Castration arrested meibocyte differentiation and redirected cell fate commitment. Pseudotime trajectory analysis revealed a pronounced shift from the meibocyte lineage toward ductal and progenitor fates, accompanied by comprehensive downregulation of lipogenic genes (e.g., Fasn, Awat2). This fate reprogramming was coupled with disrupted endoplasmic reticulum (ER) homeostasis, including suppression of the ER membrane protein complex (EMC) and impaired lipid assembly machinery. Topical DHT treatment partially restored meibocyte differentiation but failed to fully recover gland morphology. Furthermore, rapid metabolic reactivation following DHT treatment outpaced ER capacity recovery, inducing proteostatic stress.</p><p><strong>Conclusions: </strong>Androgen deficiency drives MGD through dual mechanisms: reprogramming of meibocyte cell fate toward non-lipogenic lineages and suppression of EMC-mediated stabilization of ER-resident lipogenic enzymes. The resulting temporal mismatch between lipogenic reactivation and ER capacity recovery upon DHT treatment induces proteostatic stress, limiting the efficacy of androgen monotherapy and identifying the EMC-ER axis as a candidate therapeutic target for combinatorial intervention.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"46"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244732","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":"Association Between Extrafoveal Paravascular Retinoschisis and Central Retinal Vessel Trunk Dragging in High Myopia.","authors":"Jost B Jonas, Rahul A Jonas, Ya Xing Wang, Songhomitra Panda-Jonas","doi":"10.1167/iovs.67.12.7","DOIUrl":"10.1167/iovs.67.12.7","url":null,"abstract":"<p><strong>Purpose: </strong>To assess occurrence and associations of myopic extrafoveal paravascular retinoschisis (EPR).</p><p><strong>Methods: </strong>Using optical coherence tomographic images of the optic disc and macula, taken in the population-based Beijing Eye Study, we assessed prevalence and associations of parapapillary retinoschisis.</p><p><strong>Results: </strong>The study included 3336 individuals (3336 eyes) with a mean age of 64.2 ± 9.6 years (range, 50-93) and a mean axial length of 23.4 ± 1.2 mm (range, 20.16-30.88). EPR prevalence (34/3336, 1.0%; 95% confidence interval [CI], 0.6-1.4) increased from 1/3046 (0.03%) to 8/173 (4.6%; 95% CI, 1-8), 4/74 (5.4%; 95% CI, 0-11), 10/25 (40%; 95% CI, 19-61), and 11/18 (61%; 95% CI, 36-86) with axial lengths of ≤25.0 mm, 25.01 to 26.0 mm, 26.01 to 27.0 mm, 27.01 to 28.0 mm, and >28.0 mm, respectively. Higher EPR prevalence was associated (multivariable analysis) with higher prevalence of central retinal vessel trunk dragging (CRVTD) (odds ratio [OR] = 8.81; 95% CI, 3.02-25.7; P < 0.001) and longer axial length (OR = 2.97; 95% CI, 2.27-3.89; P < 0.001; Nagelkerke R2 = 0.55), or alternatively with longer fovea-optic disc center distance (OR = 2.79; 95% CI, 1.55-5.03; P < 0.001). In a nonlinear manner, EPR prevalence increased steeply beyond an axial length of 25.5 mm and a fovea-disc center distance of 5.5 mm. These relationships were complemented by univariate associations between EPR prevalence and temporal retinal vessel straightening, smaller angle kappa, higher myopic macular degeneration stage and prevalence, and larger parapapillary beta zone and gamma zone.</p><p><strong>Conclusions: </strong>EPR was a common feature in eyes with severe/high axial myopia and was mainly associated with CRVTD and longer axial length or fovea-disc center distance. As a hypothesis, EPR, contrary to myopic foveoschisis, may be due to a stretching of the temporal large retinal vessels in highly myopic eyes, related to the fovea-disc distance elongation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"7"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109673","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":"Latent Correlations Between Longitudinal Systemic Complement Factors and Geographic Atrophy Growth Rate.","authors":"Talisa E de Carlo Forest, Nathan C Grove, Nicholas Cordaro, Yoga Advaith Veturi, Brandie D Wagner, Niranjan Manoharan, Andres Lisker-Cervantes, Benjamin Bearce, Steve McNamara, Anne Lynch, Jayashree Kalpathy-Cramer, Alan G Palestine, Marc Mathias, V Michael Holers, Naresh Mandava","doi":"10.1167/iovs.67.12.69","DOIUrl":"https://doi.org/10.1167/iovs.67.12.69","url":null,"abstract":"<p><strong>Purpose: </strong>Investigate associations between square root-transformed (SQRT) geographic atrophy (GA) growth rate and longitudinal systemic complement levels in non-neovascular AMD.</p><p><strong>Methods: </strong>Prospective longitudinal cohort study of patients with GA in the University of Colorado AMD Registry enrolled from August 2014 to September 2022, with ≥1month of follow-up imaging through April 2023. Systemic complement factor level ratios (Bb/Factor B, Ba/Factor B, Factor H, Factor I, C4b/C4, C3a/C3, C3b/C3, sC5b-9/C5) were collected approximately annually. SQRT GA growth rate was quantified on fundus autofluorescence. Correlations between GA growth rate and longitudinal biomarker levels were evaluated using a Bayesian hierarchical joint model.</p><p><strong>Results: </strong>One hundred fifty-five eyes from 88 patients were included. Average SQRT GA growth rate was 0.27mm/year over a mean of 3.3 years and was positively associated with female sex. Ba/Factor B (correlation [credible interval {CrI}]:0.35, 95% CrI: 0.02 to 0.64), and Bb/Factor B (0.20, 95% CrI: -0.086 to 0.48) demonstrated posterior distributions largely above zero, consistent with a positive association. Posterior distributions for Factor I (-0.08, 95% CrI: -0.35 to 0.20) and C3a/C3 (-0.14, 95% CrI: -0.44 to 0.18) were centered below zero, whereas those for Factor H (0.09, 95% CrI: -0.20 to 0.37) and sC5b-9/C5 (0.09, 95% Crl: -0.19 to 0.37) were centered above zero.</p><p><strong>Conclusions: </strong>Systemic alternative pathway biomarkers demonstrated the strongest positive associations with GA growth rate. The pattern of associations in this exploratory analysis supports a hypothesis-generating framework in which differences in alternative pathway regulation may be associated with heterogeneity in GA progression. Future larger studies are needed for external validation of this hypothesis-generating work.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"69"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267597","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":"Temporal Deletion of AP-2β in Postnatal Mice Demonstrates Distinct Roles in Anterior Angle Development and Intraocular Pressure Homeostasis.","authors":"Lindsey M Kukoly, Aysha Jamal, Japnit Dham, Serosh Khawaja, Monica Akula, Trevor Williams, Judith A West-Mays, Aftab Taiyab","doi":"10.1167/iovs.67.12.70","DOIUrl":"https://doi.org/10.1167/iovs.67.12.70","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate how the loss of activating protein 2β (AP-2β) in either the early postnatal or adult mouse eye affects the trabecular meshwork (TM) and intraocular pressure (IOP) homeostasis.</p><p><strong>Methods: </strong>UbCreERT2+/-; Tfap2b-/lox; tdTomatolox/+ (UbCre/AP-2β-KO or mutant) and UbCreERT2+/-; Tfap2b+/lox; tdTomatolox/+ (control) pups were exposed to tamoxifen via intraperitoneal injection once daily from postnatal day 4 (P4) to P7 and were euthanized at P14. To investigate adult tissue, tamoxifen exposure occurred from P22 to P25. IOP measurements were taken at P40, P60, or P90 followed by euthanasia. Hematoxylin and eosin (H&E), immunohistochemistry (IHC) and transmission electron microscopy (TEM) were performed to assess the TM, retinal ganglion cells (RGCs), and retinal inflammation.</p><p><strong>Results: </strong>Loss of AP-2β in early postnatal (P4 to P7) mice showed a partially closed iridocorneal angle and absence of the TM and Schlemm's canal (SC); however, loss of AP-2β in adult mice (P22-P25) produced an open-angle phenotype with preserved outflow pathway structures. Despite maintaining an open-angle phenotype, these mutant mice demonstrated elevated IOP. Ultrastructural analysis revealed flattened vacuoles surrounding the SC, along with pigment dispersion and disrupted extracellular matrix architecture. Additionally, increased IOP was associated with a significant RGC loss, reduced retinal thickness, and increased retinal inflammation.</p><p><strong>Conclusions: </strong>Early postnatal loss of AP-2β resulted in impaired development of aqueous outflow structures. Loss of AP-2β in adult mice showed an open-angle phenotype, elevated IOP, and marked retinal abnormalities. Together, these outcomes reveal a dual requirement for AP-2β in anterior angle development and TM and IOP homeostasis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"70"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149286802","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":"Layer-Specific Associations of Axial Length With Retinal and Choroidal Thickness: A Nationally Representative Population-Based Study.","authors":"Min-Ji Kim, Dah Hyun Ryu, Mingui Kong","doi":"10.1167/iovs.67.12.26","DOIUrl":"10.1167/iovs.67.12.26","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize layer-specific, potentially non-linear associations between axial length (AL) and macular ganglion cell-inner plexiform layer (GCIPL), peripapillary retinal nerve fiber layer (RNFL), outer-retinal, and subfoveal choroidal thickness (SFCT) in a nationally representative sample of Korean adults.</p><p><strong>Methods: </strong>Cross-sectional analysis of the Korea National Health and Nutrition Examination Survey 2017-2021. Right eyes of adults ≥19 years with AL and optical coherence tomography measurements were included; eyes with major retinal or optic-nerve disease or implausible measurements were excluded. Survey-weighted spline regression tested non-linearity by a design-based nested comparison adjusted for age and sex. Ocular magnification, refractive error, and intraocular pressure were addressed in sensitivity analyses.</p><p><strong>Results: </strong>Among 9867 participants (mean age 42.6 years; AL 24.4 mm), AL was associated with all four layers (all P < 0.001). GCIPL was nonlinear (P < 0.001), steepening at longer AL, and remained so after adjustment for magnification and refractive error. The RNFL association was not robust to magnification correction: a keratometry-based correction moved the slope from -2.2 to +0.2 µm/mm (P = 0.48), and an axial-length-only factor reversed it, indicating over-correction. Outer retina was essentially preserved (≈-0.4 µm/mm), whereas SFCT showed the largest, approximately linear association (≈-31.8 µm/mm). Excluding ocular hypertension did not change the findings.</p><p><strong>Conclusions: </strong>The apparent RNFL thinning with longer AL was largely attributable to scan-circle magnification rather than tissue thinning. The other layers differed in form: a non-linear GCIPL association and a large, approximately linear choroidal reduction, with outer-retinal preservation. Interpretation should account for AL, magnification, and functional form across layers.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"26"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181823","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":"Quantitation of Stromal Distortion Across the Full Depth of Keratoconic Corneas.","authors":"Poncia Nyembo Kasongo, Djida Ghoubay, Jean-Marc Allain, Malika Hamrani, Cristina Georgeon, Vincent Borderie, Gaël Latour, Marie-Claire Schanne-Klein","doi":"10.1167/iovs.67.12.58","DOIUrl":"10.1167/iovs.67.12.58","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed at gaining new insights into the pathophysiology of keratoconus by providing a comprehensive and quantitative characterization of stromal structural alterations throughout the full thickness of keratoconic corneas and in regions both proximal to and distant from the cone.</p><p><strong>Methods: </strong>Complementary three-dimensional imaging techniques were combined in a pilot exploratory series of four keratoconic and four control human corneas: clinical spectral-domain optical coherence tomography, highly-resolved line-field confocal optical coherence tomography and second harmonic generation (SHG) microcopy. Several structural metrics were computed from SHG images using automatic image analysis pipelines.</p><p><strong>Results: </strong>Quantitative SHG imaging revealed striking structural shifts in keratoconic corneas compared to healthy controls. Most notably, we observed a significant rise in normalized striation Endpoints (P = 0.008) and End/Branch ratio (P = 0.015), consistent with the presence of wavy lamellae and the loss of the plywood-like structure found in control corneas. Importantly, these structural markers remained consistent in both the cone and outside the cone regions. Quantitative processing of collagen orientation revealed a single widely-spread orientation as opposed to two main orthogonal orientations in control corneas, and slight shifts in orientation between superimposed lamellae rather than the abrupt changes observed in control corneas.</p><p><strong>Conclusions: </strong>We provide new quantitative data on the structural alterations associated with keratoconus that could serve as useful biomarkers for earlier detection. Our findings are consistent with a decreased stromal stiffness and an increase in the corneal birefringence. They are also in favor of a global stromal disorder rather than a purely localized disorder.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"58"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267552","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":"Quantitative Fundus Autofluorescence in Geographic Atrophy Secondary to AMD: Comparison With Stargardt Disease, PRPH2-Associated Retinal Dystrophies, and Healthy Controls.","authors":"Maximilian Pawloff, Marlene Hollaus, Luca Schwarzenbacher, Günther Weigert, Magdalena Baratsits, Stefan Sacu, Markus Ritter, Gregor S Reiter","doi":"10.1167/iovs.67.12.50","DOIUrl":"10.1167/iovs.67.12.50","url":null,"abstract":"<p><strong>Purpose: </strong>To analyze differences in quantitative fundus autofluorescence (qAF) between geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and other diseases associated with macular atrophy including Stargardt disease (STGD), and autosomal-dominant PRPH2-associated retinal dystrophies (PRPH2).</p><p><strong>Methods: </strong>Patients with GA, STGD, PRPH2, and healthy subjects were included in this cross-sectional study. The qAF was assessed using a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference. Mean qAF values were obtained using the standardized qAF Delori pattern (qAF8). Care was taken to remove areas of atrophy within the qAF8 pattern. Mixed models were calculated to compare disease groups, correcting for age, and evaluate possible associations between qAF8 and macular atrophy size.</p><p><strong>Results: </strong>Two hundred eight eyes from 118 patients (87 GA, 22 STGD, 10 PRPH2, 89 healthy controls) were analyzed. There were significant differences in qAF8 between the groups (P < 0.001). GA patients showed significantly reduced qAF8 values compared to healthy controls (P < 0.001), STGD patients (P < 0.001), and PRPH2 patients (P < 0.001). STGD patients demonstrated significantly elevated qAF8 values compared to healthy controls (P < 0.001). PRPH2 patients did not differ from healthy controls (P = 0.3). GA and PRPH2 demonstrated nominal inverse correlations with increasing atrophy area, whereas STGD showed a significant positive correlation. Lens status was confounded completely with disease group and thus could not be tested as an independent covariate. Univariately, lens status was associated with qAF8 (P < 0.001), whereas age was not significant in the final model (P = 0.4).</p><p><strong>Conclusions: </strong>The qAF8 varies significantly between eyes with macular atrophy due to GA secondary to AMD, STGD and PRPH2-associated retinal dystrophy. Although age was included as covariate, residual confounding cannot entirely be excluded due to the partial overlap in age distributions of cohorts. Lens status could not be adjusted for because it was completely confounded with disease group. This noninvasive, objectively acquired data may serve as an adjunctive biomarker to support diagnosis, prognosis, counselling and management in these degenerative disorders, pending further validation in balanced cohorts.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"50"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244736","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}