Developing and validating a clinlabomics-based machine-learning model for early detection of retinal detachment in patients with high myopia.

BACKGROUND: Retinal detachment (RD) is a vision-threatening disorder of significant severity. Individuals with high myopia (HM) face a 2 to 6 times higher risk of developing RD compared to non-myopes. The timely identification of high myopia-related retinal detachment (HMRD) is crucial for effective treatment and prevention of additional vision impairment. Consequently, our objective was to streamline and validate a machine-learning model based on clinical laboratory omics (clinlabomics) for the early detection of RD in HM patients. METHODS: We extracted clinlabomics data from the electronic health records for 24,440 HM and 5607 HMRD between 2015 and 2022. Lasso regression analysis assessed fifty-nine variables, excluding collinear variables (variance inflation factor > 10). Four models based on random forest, gradient boosting machine (GBM), generalized linear model, and Deep Learning Model were trained for HMRD diagnosis and employed for internal validation. An external test of the models was done. Three random data sets were further processed to validate the performance of the diagnostic model. The primary outcomes were the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUCPR) to diagnose HMRD. RESULTS: Nine variables were selected by all models. Given the AUC and AUCPR values across the different sets, the GBM model was chosen as the final diagnostic model. The GBM model had an AUC of 0.8550 (95%CI = 0.8322-0.8967) and an AUCPR of 0.5584 (95%CI = 0.5250-0.5879) in the training set. The AUC and AUCPR in the internal validation were 0.8405 (95%CI = 0.8060-0.8966) and 0.5355 (95%CI = 0.4988-0.5732). During the external test evaluation, it reached an AUC of 0.7579 (95%CI = 0.7340-0.7840) and an AUCPR of 0.5587 (95%CI = 0.5345-0.5880). A similar discriminative capacity was observed in the three random data sets. The GBM model was well-calibrated across all the sets. The GBM-RD model was implemented into a web application that provides risk prediction for HM individuals. CONCLUSION: GBM algorithms based on nine features successfully predicted the diagnosis of RD in patients with HM, which will help ophthalmologists to establish a preliminary diagnosis and to improve diagnostic accuracy in the clinic.

Development and validation of predictive models for myopia onset and progression using extensive 15-year refractive data in children and adolescents.

BACKGROUND: Global myopia prevalence poses a substantial public health burden with vision-threatening complications, necessitating effective prevention and control strategies. Precise prediction of spherical equivalent (SE), myopia, and high myopia onset is vital for proactive clinical interventions. METHODS: We reviewed electronic medical records of pediatric and adolescent patients who underwent cycloplegic refraction measurements at the Eye & Ear, Nose, and Throat Hospital of Fudan University between January 2005 and December 2019. Patients aged 3-18 years who met the inclusion criteria were enrolled in this study. To predict the SE and onset of myopia and high myopia in a specific year, two distinct models, random forest (RF) and the gradient boosted tree algorithm (XGBoost), were trained and validated based on variables such as age at baseline, and SE at various intervals. Outputs included SE, the onset of myopia, and high myopia up to 15 years post-initial examination. Age-stratified analyses and feature importance assessments were conducted to augment the clinical significance of the models. RESULTS: The study enrolled 88,250 individuals with 408,255 refraction records. The XGBoost-based SE prediction model consistently demonstrated robust and better performance than RF over 15 years, maintaining an R2 exceeding 0.729, and a Mean Absolute Error ranging from 0.078 to 1.802 in the test set. Myopia onset prediction exhibited strong area under the curve (AUC) values between 0.845 and 0.953 over 15 years, and high myopia onset prediction showed robust AUC values (0.807-0.997 over 13 years, with the 14th year at 0.765), emphasizing the models' effectiveness across age groups and temporal dimensions on the test set. Additionally, our classification models exhibited excellent calibration, as evidenced by consistently low brier score values, all falling below 0.25. Moreover, our findings underscore the importance of commencing regular examinations at an early age to predict high myopia. CONCLUSIONS: The XGBoost predictive models exhibited high accuracy in predicting SE, onset of myopia, and high myopia among children and adolescents aged 3-18 years. Our findings emphasize the importance of early and regular examinations at a young age for predicting high myopia, thereby providing valuable insights for clinical practice.

Recent advances in corneal neovascularization imaging.

Corneal neovascularization (CoNV) is a vision-threatening ocular disease commonly secondary to infectious, inflammatory, and traumatic etiologies. Slit lamp photography, in vivo confocal microscopy, angiography, and optical coherence tomography angiography (OCTA) are the primary diagnostic tools utilized in clinical practice to evaluate the vasculature of the ocular surface. However, there is currently a dearth of comprehensive literature that reviews the advancements in imaging technology for CoNV administration. Initially designed for retinal vascular imaging, OCTA has now been expanded to the anterior segment and has shown promising potential for imaging the conjunctiva, cornea, and iris. This expansion allows for the quantitative monitoring of the structural and functional changes associated with CoNV. In this review, we emphasize the impact of algorithm optimization in anterior segment-optical coherence tomography angiography (AS-OCTA) on the diagnostic efficacy of CoNV. Through the analysis of existing literature, animal model assessments are further reported to investigate its pathological mechanism and exhibit remarkable therapeutic interventions. In conclusion, AS-OCTA holds broad prospects and extensive potential for clinical diagnostics and research applications in CoNV.

Exploration of the pathophysiology of high myopia via proteomic profiling of human corneal stromal lenticules.

This study aimed to investigate the underlying pathophysiology of high myopia by analyzing the proteome of human corneal stromal lenticule samples obtained through small incision lenticule extraction (SMILE). A total of thirty-two patients who underwent SMILE were included in the study. Label-free quantitative proteomic analysis was performed on corneal stromal lenticule samples, equally representing high myopia (n = 10) and low myopia (n = 10) groups. The identified and profiled lenticule proteomes were analyzed using in silico tools to explore biological characteristics of differentially expressed proteins (DEPs). Additionally, LASSO regression and random forest model were employed to identify key proteins associated with the pathophysiology of high myopia. The DEPs were found to be closely linked to immune activation, extracellular matrix, and cell adhesion-related pathways according to gene ontology analysis. Specifically, decreased expression of COL1A1 and increased expression of CDH11 were associated with the pathogenesis of high myopia and validated by western blotting (n = 6) and quantitative real time polymerase chain reaction (n = 6). Overall, this study provides evidence that COL1A1 and CDH11 may contribute to the pathophysiology of high myopia based on comparative proteomic profiling of human corneal stromal lenticules obtained through SMILE.

Study on the biological properties of SMILE-derived corneal stromal lenticules after long-term cryopreservation in nutrient capsules.

PURPOSE: To investigate the long-term preservation effects of nutrient capsules on the physiological activity, collagen fiber structure and transmittance of corneal stromal lenticules derived from small incision lenticule extraction (SMILE). METHODS: A new nutrient capsule was constructed for long-term preservation of SMILE-derived corneal stromal lenticules. The lenticules were randomly divided into 99% anhydrous glycerol, and hydrogel nutrient capsules. After preserving for 1 year at -80 °C, lenticules were compared with fresh lenticules. The optical transmittance, tissue morphology, ultrastructure, cells activity and immunogenicity of the lenticules was detected and compared between different groups. RESULTS: The rate of apoptotic cells was significantly higher in the glycerol group compared with the nutrient capsule group (P < 0.0001). More viable cells were present in the lenticules after nutrient capsule preservation compared to the glycerol group (P = 0.0003). The mean transmittance of the lenticules in the glycerol group (50 ± 18%) was significantly lower (P = 0.0008) compared to the control group (75 ± 11%), and the lenticules transmittance of the nutrient capsule group (64 ± 15%) after long-term preservation was not significantly different (P = 0.23) compared to the control group. The structure of HE staining showed that the collagen fibers in the nutrient capsule group were arranged in parallel and neatly, and a few cavitation vesicles were visible inside the tissue. There was no significant difference in the number of lenticular collagen fibers in the nutritional capsule group compared to the fresh lenticule group (P = 0.06). HLA-DR, HLA-ABC, CD45, CD25 and CD69 expression was low in all groups of lenticules after preservation. CONCLUSIONS: Nutrient capsules can preserve lenticules for a long time and maintain the transmission structure and cells activity of lenticules.

Early regional changes in retina and choroid of chicks following monocular hemifield form deprivation.

To investigate regional changes in the chick retina and choroid after hemifield form deprivation (HFD). Ten chicks were randomly and equally divided into a temporal retinal deprivation (TRD) and nasal retinal deprivation (NRD) group. HFD was induced with half-lateral translucent plastic goggles in the right eye; the left eye was kept untreated. Swept-source optical coherence tomography (SS-OCT) images obtained at 0, 3, and 72 hours (h) were analyzed using customized software. After 72 h of TRD, the retinal thickness (RT) of the treated eyes was significantly less than that of the fellow eyes in the temporal (P = 0.034) rather than the nasal (P = 0.083) region. In the NRD group, the RT of the treated eyes was thinner in both the nasal and temporal regions than that of the fellow eyes (P < 0.01). The RT alterations were more pronounced in the temporal (Δ = -16.86 ± 7.14 µm) than in the nasal (Δ = -13.44 ± 4.83 µm) region after 72-h TRD (P = 0.036), whereas the opposite was observed in the NRD group (P = 0.008). The choroidal thickness (ChT) of the treated eyes was less in both the nasal and temporal regions than that of the fellow eyes in both groups after 72-h treatment (P < 0.01). The ChT alterations were more pronounced in the temporal (Δ = -2.48 ± 8.95 µm) than in the nasal (Δ = 23.65 ± 13.58 µm) region after 72-h TRD (P = 0.021), whereas the NRD group showed the opposite effect (P = 0.019). HFD in chicks can lead to retinal and choroidal thinning in the corresponding regions.

Characteristics of disk halo size and its correlation with lenticule quality in small incision lenticule extraction for moderate to high myopia.

PURPOSE: To investigate changes in disk halo size after small incision lenticule extraction (SMILE) and the correlation between halo size and lenticule quality in moderate to high myopia. METHODS: Thirty eyes of 30 consecutive patients (mean age, 24.9 ± 4.5 years; mean spherical equivalent, -6.85 ± 1.18 D) undergoing SMILE were included in this prospective study. Lenticule surface quality was accessed with a scanning electron microscopy by a scoring system. Halo size was measured preoperatively and at 1, 3, and 6 months postoperatively. Multiple linear regression analysis was performed to explore associations between halo size and a range of factors, including lenticule quality. RESULTS: Disk halo size increased slightly at 1 month and then recovered continually from 3 to 6 months postoperatively, with no difference between halo size during the preoperative period and at 6 months postoperatively (P > 0.05). One month after SMILE, halo size (1 cd/m2, 5 cd/m2) was associated only with uncorrected distance visual acuity (P ≤ 0.004). A halo size of 5 cd/m2 at 3 months postoperatively correlated with the anterior surface quality of the lenticule (P = 0.046). At 6 months postoperatively, a halo size of 1 cd/m2 was associated only with the baseline, accounting for 11.9% of the variability (P = 0.041); no correlations were found for the halo size of 5 cd/m2. CONCLUSIONS: Disk halo size after SMILE was enlarged at an early stage postoperatively and subsequently declined to the baseline level during a 6-month follow-up. The quality of the lenticule surface influenced halo size changes in the early phase.

Correlation between mental status and prevalence of asthenopia in Chinese college students.

BACKGROUND: The purpose of this study was to identify the possible association between mental status and the risk of self-reported asthenopia among college students in China. METHODS: Ten thousand students were randomly assessed in the study using a self-reported asthenopia questionnaire. Their demographic characteristics and mental status were recorded. Univariate analysis was performed to preliminarily select potential risk and protective factors. Then, multivariate logistic regression was used to estimate odds ratios for the selected risk factors of interest. RESULTS: Among the 8370 students who completed the survey, the prevalence of asthenopia was 61.0%. Multivariate analysis revealed a significant relationship between asthenopia and depressive symptoms (OR 1.511 95% CI: 1.350-1.691), obsessive-compulsive symptoms (OR 1.477, 95% CI: 1.338-1.632), gender and study load. The place college students spent their off-hours (OR 0.841, 95% CI: 0.784-0.902) was found to be the strongest factor for decreasing the occurrence of asthenopia complaints. CONCLUSION: Asthenopia appears common in Chinese college students. In addition to depressive symptoms, we should pay attention to obsessive-compulsive symptoms when considering means of preventing asthenopia. Harmonious social relationships, outdoor off-hour activities and exercising more than three times per week are crucial to relieving visual fatigue. Further study is still needed in this area.

A Brillouin microscopy analysis of the crystalline lenses of Chinese adults with myopia.

To evaluate lenticular biomechanical and geometric parameters in Chinese adults with myopia and identify relevant factors using Brillouin microscopy (BM) and Pentacam. The biomechanical and geometric properties of the ocular lenses of Chinese adults with myopia were quantified using BM. Anterior segment images were acquired using a Pentacam. Correlated factors including age, sex, spherical equivalent (SE), intraocular pressure (IOP), axial length (AL), white-to-white ratio (WTW), central corneal thickness (CCT), anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) were analyzed. We studied 65 eyes from 65 participants (mean age, 25.23 ± 6.12 years). Width of Top Plateau (WTP), Width of Bottom Plateau (WBP), Slope of Anterior Cortex (SAC), Slope of Posterior Cortex (SPC), and Height of Plateau (Height) metrics obtained using BM showed mean values of 2.597 ± 0.393 mm, 4.310 ± 0.535 mm, 1.344 ± 0.549 GPa/mm, -1.343 ± 0.480 GPa/mm, and 3.373 ± 0.048 GPa, respectively. No significant correlation was found between these parameters and sex, SE, IOP, CCT, ACA, or Height. Interestingly, WBP (r = 0.467, P < 0.001), SAC (r = 0.412, P = 0.001), and SPC (r = -0.280, P = 0.024) were significantly associated with age, and an age-related increase of WBP (slope of 35.36 ± 10.08 µm per year) was identified. Both ACD and ACV showed significant correlations with SAC (r = 0.329 and 0.380, P = 0.008 and 0.002, respectively), but not with SPC. BM provided a novel perspective on lenticular biomechanical and geometric properties in Chinese adults with myopia, which correlated with age, AL, WTW, ACD, and ACV.

ASSOCIATION OF TESSELLATION DENSITY WITH PROGRESSION OF AXIAL LENGTH AND REFRACTION IN CHILDREN: An Artificial Intelligence-Assisted 4-Year Study.

PURPOSE: To investigate fundus tessellation density (TD) and its association with axial length (AL) elongation and spherical equivalent (SE) progression in children. METHODS: The school-based prospective cohort study enrolled 1,997 individuals aged 7 to 9 years in 11 elementary schools in Mojiang, China. Cycloplegic refraction and biometry were performed at baseline and 4-year visits. The baseline fundus photographs were taken, and TD, defined as the percentage of exposed choroidal vessel area in the photographs, was quantified using an artificial intelligence-assisted semiautomatic labeling approach. After the exclusion of 330 ineligible participants because of loss to follow-up or ineligible fundus photographs, logistic models were used to assess the association of TD with rapid AL elongation (>0.36 mm/year) and SE progression (>1.00 D/year). RESULTS: The prevalence of tessellation was 477 of 1,667 (28.6%) and mean TD was 0.008 ± 0.019. The mean AL elongation and SE progression in 4 years were 0.90 ± 0.58 mm and -1.09 ± 1.25 D. Higher TD was associated with longer baseline AL (ß, 0.030; 95% confidence interval: 0.015-0.046; P < 0.001) and more myopic baseline SE (ß, -0.017; 95% confidence interval: -0.032 to -0.002; P = 0.029). Higher TD was associated with rapid AL elongation (odds ratio, 1.128; 95% confidence interval: 1.055-1.207; P < 0.001) and SE progression (odds ratio, 1.123; 95% confidence interval: 1.020-1.237; P = 0.018). CONCLUSION: Tessellation density is a potential indicator of rapid AL elongation and refractive progression in children. TD measurement could be a routine to monitor AL elongation.

Measurement of the distance between corneal apex and pupil center in patients following small-incision lenticule extraction or implantable collamer lens implantation and its correlation with the surgical-induced astigmatism.

BACKGROUND: To investigate the change in the distance between corneal apex and pupil center after small-incision lenticule extraction (SMILE) or implantable collamer lens (ICL) implantation and its correlation with surgical-induced astigmatism (SIA). METHODS: This study included patients who had undergone SMILE (n = 112) or ICL implantation (n = 110) to correct myopia and myopic astigmatism. The angle kappa was measured using a Scheimpflug imaging device (Pentacam) and represented as Cartesian values between the pupil center and the corneal vertex (X, Y) and chord u ([Formula: see text]orientation), and was compared pre- and post-operative. RESULTS: Following SMILE, the magnitude of chord u[Formula: see text]) significantly increased in both eyes (Wilcoxon signed-rank test, OD: P<0.001; OS: P=0.007), while no significant change was observed in the orientation. A significant correlation was found between the J0 component of SIA and the change in the magnitude of chord u for both eyes (OD: R2=0.128, P<0.001; OS: R2=0.033, P=0.004). After ICL implantation, the orientation of the chord u was significantly different in the right eye (Wilcoxon signed-rank test, P = 0.008), and the Y-intercept significantly decreased in both eyes (Wilcoxon signed-rank test, P<0.001). A significant correlation was found between J0 of SIA and the change in the magnitude of chord u for the right eyes (R2=0.066, P=0.002). A significant correlation was found between J45 of SIA and the change in the magnitude of chord u for the left eyes (R2=0.037, P=0.044). CONCLUSIONS: The magnitude of the chord u increased following the SMILE procedure, whereas the Y-intercept significantly decreased after ICL implantation. SIA was related to the change in the magnitude of chord u.

Correlation analysis of angles κ and α with the refraction and anterior segment parameters in children.

AIM: To investigate the correlation of angles α and κ with the refractive and biological parameters in children. METHODS: This case-series study included 438 eyes of 219 children (males/females = 105/114, age: 3-15 years). Ocular biometric parameters, including axial length, corneal radius of curvature (CR), white-to-white distance (WTW), angle κ and angle α, were measured using IOL Master 700; auto-refraction were assessed under cycloplegia. The eyes were assigned to different groups based on CR, WTW, and gender to compare the angles α and κ, and analyze the correlations between the differences of biological parameters on angles α and κ. RESULTS: The means of axial length, CR, WTW, angle α, and angle κ were 23.24 ± 1.14 mm, 7.79 ± 0.27 mm, 11.68 ± 0.41 mm, 0.45 ± 0.25 mm, and 0.27 ± 0.22 mm, respectively. Angle α was correlated with CR and WTW (fixed effect coefficient [FEC] = 0.237, p = 0.015; FEC = -0.109, p = 0.003; respectively), and angle κ also correlated with CR and WTW (FEC = 0.271, p = 0.003; FEC = -0.147, p < 0.001, respectively). Comparing subgroups, the large CR and small WTW group had larger angles α (0.49 ± 0.27 vs. 0.41 ± 0.21, p < 0.001; 0.46 ± 0.27 vs. 0.44 ± 0.21, p < 0.05, respectively) and κ (0.29 ± 0.25 vs. 0.24 ± 0.15, p < 0.01; 0.29 ± 0.25 vs. 0.26 ± 0.19, p < 0.05, respectively). The differences in interocular angles α and κ showed correlation with interocular WTW (r = - 0.255, p < 0.001; r = - 0.385, p < 0.001). Eyes with smaller WTW tended to have larger angle κ (0.28 ± 0.27 vs. 0.25 ± 0.15, p < 0.05). CONCLUSION: The size of angle α/κ may be correlated to CR and WTW, and a larger WTW eye may suggest a smaller angle κ compared with the fellow eye.

Association between major discrimination and deficit accumulation in African American cancer survivors: The Detroit Research on Cancer Survivors Study.

BACKGROUND: Discrimination can adversely affect health and accelerate aging, but little is known about these relationships in cancer survivors. This study examines associations of discrimination and aging among self-identified African American survivors. METHODS: A population-based sample of 2232 survivors 20-79 years old at diagnosis were enrolled within 5 years of breast (n = 787), colorectal (n = 227), lung (n = 223), or prostate (n = 995) cancer between 2017 and 2022. Surveys were completed post-active therapy. A deficit accumulation index measured aging-related disease and function (score range, 0-1, where <0.20 is robust, 0.20 to <0.35 is pre-frail, and 0.35+ is frail; 0.06 is a large clinically meaningful difference). The discrimination scale assessed ever experiencing major discrimination and seven types of events (score, 0-7). Linear regression tested the association of discrimination and deficit accumulation, controlling for age, time from diagnosis, cancer type, stage and therapy, and sociodemographic variables. RESULTS: Survivors were an average of 62 years old (SD, 9.6), 63.2% reported ever experiencing major discrimination, with an average of 2.4 (SD, 1.7) types of discrimination events. Only 24.4% had deficit accumulation scores considered robust (mean score, 0.30 [SD, 0.13]). Among those who reported ever experiencing major discrimination, survivors with four to seven types of discrimination events (vs. 0-1) had a large, clinically meaningful increase in adjusted deficits (0.062, p < .001) and this pattern was consistent across cancer types. CONCLUSION: African American cancer survivors have high deficit accumulated index scores, and experiences of major discrimination were positively associated with these deficits. Future studies are needed to understand the intersectionality between aging, discrimination, and cancer survivorship among diverse populations.

Epigenetic aging in older breast cancer survivors and noncancer controls: preliminary findings from the Thinking and Living with Cancer Study.

BACKGROUND: Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes. METHODS: Nonmetastatic breast cancer survivors (n = 89) enrolled prior to systemic therapy and frequency-matched controls (n = 101) ages 62 to 84 years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age [EEA], PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy-Cognitive Function) and physical (Medical Outcomes Study Short Form-12) function assessments at approximately 24 to 36 and 60 months after enrollment. Mixed-effects models tested survivor-control differences in epigenetic aging, adjusting for age and comorbidities; models for functional outcomes also adjusted for racial group, site, and cognitive reserve. RESULTS: Survivors were 1.04 to 2.22 years biologically older than controls on Horvath, EEA, GrimAge, and DunedinPACE measures (p = .001-.04) at approximately 24 to 36 months after enrollment. Survivors exposed to chemotherapy were 1.97 to 2.71 years older (p = .001-.04), and among this group, an older EEA related to worse self-reported cognition (p = .047) relative to controls. An older epigenetic age related to worse physical function in all women (p < .001-.01). Survivors and controls showed similar epigenetic aging over time, but Black survivors showed accelerated aging over time relative to non-Hispanic White survivors. CONCLUSION: Older breast cancer survivors, particularly those exposed to chemotherapy, showed greater epigenetic aging than controls that may relate to worse outcomes. If replicated, measurement of biological aging could complement geriatric assessments to guide cancer care for older women.

Plasma levels of interleukin-6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study.

BACKGROUND: Immune activation/inflammation markers (immune markers) were tested to explain differences in neurocognition among older breast cancer survivors versus noncancer controls. METHODS: Women >60 years old with primary breast cancer (stages 0-III) (n = 400) were assessed before systemic therapy with frequency-matched controls (n = 329) and followed annually to 60 months; blood was collected during annual assessments from 2016 to 2020. Neurocognition was measured by tests of attention, processing speed, and executive function (APE). Plasma levels of interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor α (TNF-α), and interferon γ were determined using multiplex testing. Mixed linear models were used to compare results of immune marker levels by survivor/control group by time and by controlling for age, racial/ethnic group, cognitive reserve, and study site. Covariate-adjusted multilevel mediation analyses tested whether survivor/control group effects on cognition were explained by immune markers; secondary analyses examined the impact of additional covariates (e.g., comorbidity and obesity) on mediation effects. RESULTS: Participants were aged 60-90 years (mean, 67.7 years). Most survivors had stage I (60.9%) estrogen receptor-positive tumors (87.6%). Survivors had significantly higher IL-6 levels than controls before systemic therapy and at 12, 24, and 60 months (p ≤ .001-.014) but there were no differences for other markers. Survivors had lower adjusted APE scores than controls (p < .05). Levels of IL-6, IL-10, and TNF-α were related to APE, with IL-6 explaining part of the relationship between survivor/control group and APE (p = .01). The magnitude of this mediation effect decreased but remained significant (p = .047) after the consideration of additional covariates. CONCLUSIONS: Older breast cancer survivors had worse long-term neurocognitive performance than controls, and this relationship was explained in part by elevated IL-6.

Validating the PROMIS cognitive function short form in cancer survivors.

PURPOSE: The Patient-Reported Outcome Measurement Information System Cognitive Function Short Form 8a  (PROMIS Cog) could provide a shorter, useful alternative to the often used Functional Assessment of Cancer Therapy - Cognition (FACT-Cog) in research and clinical care. This study aimed to determine the convergent validity and internal reliability of the PROMIS Cog in 3 separate samples of breast cancer survivors and to explore clinical cut points. METHODS: Data from three samples of breast cancer survivors were used for this secondary analysis. Convergent validity was determined by evaluating correlation strength among the derived PROMIS Cog and measures of depression, anxiety, stress, fatigue, sleep, loneliness, the FACT-Cog . Clinical cut-points for the PROMIS Cog were determined by plotting the receiver operating characteristic curves. RESULTS: 3 samples of breast cancer survivors (N = 471, N = 132, N = 90) were included. Absolute values of correlations demonstrating convergent validity ranged from 0.21 to 0.82, p's < 0.001, and were comparable to correlations with the full FACT-Cog 18 item perceived cognitive impairments (PCI) scale. ROC curve plots indicated a clinical cut off < 34 for the combined sample. CONCLUSION: The 8-item PROMIS Cog demonstrated good convergent validity and internal reliability in breast cancer survivors, comparable to the 18-item FACT-Cog PCI. The PROMIS Cog 8a is a brief self-report measure that can be easily incorporated into cancer-related cognitive impairment research designs or used in clinical settings.

Targeting choroidal vasculopathy via up-regulation of tRNA-derived fragment tRF-22 expression for controlling progression of myopia.

BACKGROUND: Myopia has emerged as a major public health concern globally, which is tightly associated with scleral extracellular matrix (ECM) remodeling and choroidal vasculopathy. Choroidal vasculopathy has gradually been recognized as a critical trigger of myopic pathology. However, the precise mechanism controlling choroidal vasculopathy remains unclear. Transfer RNA-derived fragments (tRFs) are known as a novel class of small non-coding RNAs that plays important roles in several biological and pathological processes. In this study, we investigated the role of tRF-22-8BWS72092 (tRF-22) in choroidal vasculopathy and myopia progression. METHODS: The tRF-22 expression pattern under myopia-related stresses was detected by qRT-PCR. MTT assays, EdU incorporation assays, Transwell migration assays, and Matrigel assays were conducted to detect the role of tRF-22 in choroidal endothelial cell function in vitro. Isolectin B4 staining and choroidal sprouting assay ex vivo were conducted to detect the role of tRF-22 in choroidal vascular dysfunction in vivo. Immunofluorescent staining, western blot assays and ocular biometric parameters measurement were performed to examine whether altering tRF-22 expression in choroid affects scleral hypoxia and ECM remodeling and myopia progression in vivo. Bioinformatics analysis and luciferase activity assays were conducted to identify the downstream targets of tRF-22. RNA-sequencing combined with m6A-qPCR assays were used to identify the m6A modified targets of METTL3. Gain-of-function and Loss-of-function analysis were performed to reveal the mechanism of tRF-22/METTL3-mediated choroidal vascular dysfunction. RESULTS: The results revealed that tRF-22 expression was significantly down-regulated in myopic choroid. tRF-22 overexpression alleviated choroidal vasculopathy and retarded the progression of myopia in vivo. tRF-22 regulated choroidal endothelial cell viability, proliferation, migration, and tube formation ability in vitro. Mechanistically, tRF-22 interacted with METTL3 and blocked m6A methylation of Axin1 and Arid1b mRNA transcripts, which led to increased expression of Axin1 and Arid1b. CONCLUSIONS: Our study reveals that the intervention of choroidal vasculopathy via tRF-22-METTL3- Axin1/Arid1b axis is a promising strategy for the treatment of patients with myopic pathology.

LncRNA-XR_002792574.1-mediated ceRNA network reveals potential biomarkers in myopia-induced retinal ganglion cell damage.

BACKGROUND: Long noncoding RNAs (lncRNAs) play a key role in the occurrence and progression of myopia. However, the function of lncRNAs in retinal ganglion cells (RGCs) in the pathogenesis of myopia is still unknown. The aim of our study was to explore the lncRNA-mediated competing endogenous RNA (ceRNA) network in RGCs during the development of myopia. METHODS: RNA sequencing was performed to analyze lncRNA and mRNA expression profiles in RGCs between guinea pigs with form-deprived myopia (FDM) and normal control guinea pigs, and related ceRNA networks were constructed. Then, potentially important genes in ceRNA networks were verified by qRT‒PCR, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore biological functions in the RGCs of FDM guinea pigs. The important genes and related signaling pathways were further verified by qRT‒PCR, immunohistochemistry, immunofluorescence and Western blot in myopia in FDM guinea pigs, FDM mice, and highly myopic adults. RESULTS: The distribution of RGCs was uneven, the number of RGCs was decreased, and RGC apoptosis was increased in FDM guinea pigs. In total, 873 lncRNAs and 2480 mRNAs were determined to be differentially expressed genes in RGCs from normal control and FDM guinea pigs. Via lncRNA-mediated ceRNA network construction and PCR verification, we found that lncRNA-XR_002792574.1 may be involved in the development of myopia through the miR-760-3p/Adcy1 pathway in RGCs. Further verification in FDM guinea pigs, FDM mice, and highly myopic adults demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to cGMP/PKG, the apelin signaling pathway and scleral remodeling. CONCLUSION: We demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to myopia. On the one hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis might inhibit the cGMP/PKG and apelin signaling pathways in RGCs, thereby causing RGC damage in myopia. On the other hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis may cause myopic scleral remodeling through the ERK-MMP-2 pathway. These findings may reveal novel potential targets in myopia and provide reference value for exploration and development of gene editing therapeutics for hereditary myopia.

Defocus-induced spatial changes in choroidal thickness of chicks observed by wide-field swept-source OCT.

Choroid has been claimed to be of importance during ocular development. However, how the choroid responds spatially to different visual cues has not been fully understood. The aim of this study was to investigate defocus-induced spatial changes in choroidal thickness (ChT) in chicks. Eight 10-day-old chicks were fitted monocularly with -10 D or +10 D lenses (day 0), which were removed seven days later (day 7). The ChT was measured on days 0, 7, 14, and 21 using wide-field swept-source optical coherence tomography (SS-OCT) and analyzed with custom-made software. Comparisons of the ChT in the central (1 mm), paracentral (1-3 mm), and peripheral (3-6 mm) ring areas and the ChT in the superior, inferior, nasal, and temporal regions were conducted. Axial lengths and refractions were also evaluated. In the negative lens group, the global ChT of the treated eyes was significantly less than that of the fellow eyes on day 7 (interocular difference: 179.28 ± 25.94 µm, P = 0.001), but thicker on day 21 (interocular difference: 241.80 ± 57.13 µm, P = 0.024). These changes were more pronounced in the central choroid. The superior-temporal choroid changed more during induction but less during recovery. In the positive lens group, the ChT of both eyes increased on day 7 and decreased on day 21, with most changes occurring in the central region, too. The inferior-nasal choroid of the treated eyes changed more during induction but less during recovery. These results provide evidence for regionally asymmetric characteristics of the choroidal response to visual cues and insights into the underlying mechanisms of emmetropization.

Corneal biomechanical stiffness and histopathological changes after in vivo repeated accelerated corneal cross-linking in cat eyes.

Corneal cross-linking (CXL) has been proved efficiency for treating progressive keratoconus and other corneal ectasia diseases by stabilizing corneal geometry and biomechanics. However, the necessity of repeated CXL treatment in patients is unknown. This study aimed to investigate corneal biomechanical stiffness and change in corneal histopathological characteristics after repeated accelerated CXL (A-CXL) in cat eyes. A-CXL was performed with 0.1% riboflavin applied for 10 min, followed by ultraviolet A irradiation at 30 mW/cm2 for 3 min at 365 nm in 15 domestic cats. Corneas (n = 30) were divided into three groups: one-time accelerated corneal cross-linking (A-CXL*1 group), repeated accelerated corneal cross-linking (A-CXL*2 group), and an untreated control group. In A-CXL*2 group, A-CXL was repeated at 1-month intervals. In vivo ocular examinations were performed pre- and postoperatively. Biomechanical analysis was performed using a biotester biaxial testing system. We used the Mooney-Rivlin strain-energy function to describe corneal material properties. No infection in any case after A-CXL was observed. Biomechanical tests showed that the stress-strain curves of the two A-CXL groups were significantly different from those of the control group (P < 0.01), whereas stress-strain curve of the A-CXL*2 group was similar to that of the A-CXL*1 group (P > 0.05). Delayed epithelial healing and haze were observed 1 month after surgery. Stromal demarcation line depth measured with anterior spectral-domain optical coherence tomography was 187.6 ± 20.4 and 197.1 ± 11.5 µm for the A-CXL*1 and A-CXL*2 groups, respectively (P > 0.05). These results show that A-CXL can increase corneal biomechanics in cat eyes. The biomechanical enhancement of cat corneas treated with repeated A-CXL at 1-month intervals was similar to that of performing a one-time A-CXL. Repeated cross-linking procedures at short intervals may increase the risk of adverse reactions, and more caution should be taken in clinical applications.