Showing papers in "Current Eye Research in 2023"

OCTA Biomarker Search in Patients with nAMD: Influence of Retinal Fluid on Time-Dependent Biomarker Response

Abstract: Purpose Previous studies have identified a link between optical coherence tomography (OCT)-derived and OCT angiography (OCTA)-based parameters in patients with neovascular AMD (nAMD); the latter may serve as direct biomarkers for macular neovascularization (MNV) activity. The aim of this study was to assess the individual influence of retinal thickness (RT) as well as intra- and sub-retinal fluid (IRF, SRF) presence on the treatment response over time as assessed by previously identified OCTA-derived MNV vascular parameters.Methods During the first 3 months of anti-VEGF therapy patients were prospectively followed. RT, SRF and IRF were determined from SSOCT/A (PlexElite, Zeiss) images and using the semi-automated AngioTool software, vessel area (VA), total vessel length (TVL), total number of junctions (TNJ), junction density (JD), vessel density (VD) as well as MNV area were exported. IRF and SRF were identified manually on OCT volume scans .The associations between RT, IRF, and SRF and SSOCTA vascular parameters were analyzed using linear mixed models.Results 31 eyes of 31 patients with treatment-naïve and OCTA-positive nAMD MNV were included in this analysis. VA, TVL, TNJ, and MNV area show a statistically significant change over time in response to anti-VEGF treatment, even after correcting for the presence of SRF, IRF, or RT (all p < 0.05). This is not the case for JD and VD (both p > 0.05).Conclusions OCTA-based parameters VA, TVL, TNJ, and MNVarea show a strong response to anti-VEGF therapy over time, independent of the presence of IRF, SRF or RT. We conclude that the above listed OCTA parameters could contribute to our understanding of MNV biology and to guide individualized treatment in the future.Trial registry The authors confirm that all ongoing and related trials are registered. ClinicalTrials.gov Number: NCT02521142

Design and Baseline Data of the Diabetes Registration Study: Guangzhou Diabetic Eye Study

Abstract: Abstract Purpose The incidence and risk factors for diabetic retinopathy (DR) in southern China remain unclear. This project aims to explore the onset and progression of DR and their determinants through a prospective cohort in South China. Methods The Guangzhou Diabetic Eye Study (GDES) recruited patients with type 2 diabetic registered in the community health centers in Guangzhou, China. Comprehensive examinations were performed including visual acuity, refraction, ocular biometry, fundus imaging, blood and urine tests. Results A total of 2305 eligible patients were included in the final analysis. In total, 14.58% of the participants had any DR and 4.25% had vision-threatening DR (VTDR), among which 76 (3.30%), 197 (8.55%), 45 (1.95%) and 17 (0.74%) were classified as mild NPDR, moderate NPDR, severe NPDR and PDR, respectively. There were 93 (4.03%) patients with diabetic macular edema (DME). The presence of any DR was independently associated with a longer duration of DM, higher degree of HbA1c, insulin treatment, higher average arterial pressure, higher concentration of serum creatinine, presence of urinary microalbumin, older age, and lower body mass index (BMI) (all p < 0.001). For VTDR, seven factors were significant: older age, a longer duration of DM, higher concentration of HbA1c, use of insulin, lower BMI, higher concentration of serum creatinine, and high albuminuria (all p < 0.05). These factors were also independently associated with DME (all p < 0.001). Conclusion The GDES is the first large-scale prospective cohort study of the diabetic population in southern China, which will help to identify novel imaging and genetic biomarkers for DR in this population.

Impact of Lens Opacity on Optical Coherence Tomography Angiography Metrics.

Abstract: PURPOSE To evaluate the impact of lens opacity on the reliability of optical coherence tomography angiography metrics and to find a vessel caliber threshold that is reproducible in cataract patients. METHODS A prospective cohort study of 31 patients, examining one eye per patient, by applying 3 × 3 mm macular optical coherence tomography angiography before (18.94 ± 12.22 days) and 3 months (111 ± 23.45 days) after uncomplicated cataract surgery. We extracted superficial (SVC) and deep vascular plexuses (DVC) for further analysis and evaluated changes in image contrast, vessel metrics (perfusion density, flow deficit and vessel-diameter index) and foveal avascular area (FAZ). RESULTS After surgery, the blood flow signal in smaller capillaries was enhanced as image contrast improved. Signal strength correlated to average lens density defined by objective measurement in Scheimpflug images (Pearson's r: -.40, p: .027) and to flow deficit (r= -.70, p < .001). Perfusion density correlated to the signal strength index (r = .70, p < .001). Vessel metrics and FAZ area, except for FAZ area in DVC, were significantly different after cataract surgery, but the mean change was approximately 3-6%. A stepwise approach in extracting vessels according to their pixel caliber showed a threshold of > 6 pixels caliber (∼20-30 µm) was comparable before and after lens removal. CONCLUSION In patients with cataract, OCTA vessel metrics should be interpreted with caution. In addition to signal strength, contrast and pixel properties can serve as supplementary quality metrics to improve the interpretation of OCTA metrics. Vessels with ∼20-30 µm in caliber seem to be reproducible.

Bootstrap Outlier Identification in Clinical Datasets for Lens Power Formula Constant Optimization

Abstract: Abstract Purpose Bootstrapping is a modern technique widely used in statistics to evaluate the performance of model parameters. The purpose of this study was to develop a strategy to identify and eliminate outliers in a dataset used for optimizing formula constants for lens power calculation. Methods In a dataset with N = 888 clinical cases treated with a monofocal aspherical intraocular lens (XC1/XY1, Hoya) constants for the SRKT, Haigis and Castrop formula were optimized and the prediction error PE calculated. The PE was bootstrapped NB = 1000 times, and the mean and trimmed mean of the bootstrapped PE were derived to generate the Bootlier plot showing the probability density function of the mean minus trimmed mean. With outliers this Bootlier plot shows some multimodality, and a Bootlier Index was extracted as a measure for multimodality. Outliers were removed from the tails of the PE distribution in a stepwise fashion until the Bootlier Index fell below a threshold of 0.001. Results With the entire dataset the mean/SD/median/mean absolute/root mean squared PE using the optimized formula constants were -0.0045/0.44415/0.0134/0.3406/0.4412 dpt with SRKT, 0.0065/0.3711/-0.0056/0.2830/0.3710 dpt with Haigis, and 0.0034/0.3452/0.0023/0.2683/0.3451 dpt with the Castrop formula. After identifying and removing outliers the respective metrics for the PE were -0.0036/0.4028/0.0134/0.3205/0.4026 dpt for the SRKT (13 cases removed), 0.0050/0.3375/-0.0056/0.2656/0.3373 dpt with Haigis (11 cases removed), and 0.0035/0.3168/0.0023/0.2531/0.3166 dpt with Castrop (11 cases removed). The multimodality in the Bootlier plots was reduced from 0/0.1567/0.0587/0.0258/0.0007/0 with SRKT, 0/0.0981/0.0261/0.0202/0.0003/0 with Haigis, and 0.0006/0.0006/0.0161/0.0191/0.0005/0 with Castrop for the entire dataset to values below 1e-3 for trimming both tails of the PE distribution by ⅛, ¼, ½, 1, 2.5, and 5% respectively. Conclusion We were able to prove that bootstrapping with outlier identification based on Bootlier plots and the Bootlier Index is a powerful tool to clean a dataset of outliers for formula constant optimization.

Glabridin Inhibits <i>Aspergillus fumigatus</i> Growth and Alleviate Inflammation Mediated by Dectin-2 and NLRP3 Inflammasome

Abstract: Purpose The research was used to uncover the mechanism of glabridin in Aspergillus fumigatus keratitis in anti-fungus and anti-inflammation.Methods In vitro, RAW 264.7 cells were infected with A. fumigatus with incubation of glabridin in different concentrations. Real-time quantitative polymerase chain reaction (RT‑qPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were used to assess the inflammatory severe and alternation with the intervention of Dectin-2 siRNA and glabridin. In vivo, A. fumigatus keratitis mouse models were established by spore intra-stromal injection and treated with glabridin or PBS. And disease scores, inflammatory mediators, and periodic acid-schiff (PAS) staining were exhibited to demonstrate the therapeutic efficiency of glabridin in vivo. Morphological interference assay monitored fungal germination. Scanning and transmission electron microscopy were used to observe the growth of fungi.Results In RAW 264.7 cells and mouse keratitis models, noncytotoxic 16 μg/mL glabridin showed significant inhibition in the expression of Dectin-2, NLRP3, Caspase-1, IL-1β, and TNF-α after A. fumigatus infection, almost similar to the intervention of Dectin-2 siRNA. PAS staining illustrated the reduced hyphal distribution in cornea stroma with glabridin treatment. Glabridin remarkably inhibited A. fumigatus growth through delaying germination and disrupting the integrity of the hyphae membrane.Conclusion Glabridin plays an anti-inflammatory role in A. fumigatus challenge via suppression of the Dectin-2 and NLRP3 inflammasome, and plays an anti-fungal role through delaying germination and changing the hyphal integrity.KEY MESSAGESGlabridin plays an anti-inflammatory role in A. fumigatus infection of RAW264.7 cells in a concentration-dependent manner and through Dectin-2 mediation.Glabridin decreases fungal distribution and inflammation in mouse A. fumigatus keratitis.Glabridin inhibits A. fumigatus growth by delaying germination and disrupting cellular structure in vitro.

Long-Term Activity and Safety of a Low-Dose Hydrocortisone Tear Substitute in Patients with Dry Eye Disease

Abstract: A clinical trial was conducted to evaluate the activity of a new artificial tear containing hyaluronic acid (HA) and low-dose hydrocortisone to control dry-eye disease (DED) symptoms.a randomized, controlled, double-masked study was carried out at the Ocular Surface and Dry Eye Center, "Luigi Sacco" University Hospital (Milan, Italy), between June 2020 and June 2021. The study involved patients with DED for at least 6 months. After an initial 7-day treatment with corticosteroid, the treatment with the new artificial tear (four-times a day for 6 months) was compared with a control HA solution.A total of 40 patients were considered. We observed a significant improvement in the frequency and intensity of DED symptoms in both groups. After corticosteroid discontinuation, the maintenance of the therapeutic advantage was observed only in the treatment group, which also showed a significant improvement of the tear film break-up time (p ≤ 0.05) and infiltrated macrophages (p < 0.05). A significant reduction in fluorescein and Lissamine staining (p < 0.05) was observed in the treatment group, suggesting damage reduction at both corneal and conjunctival levels. Intraocular pressure did not change at the end of the treatment period and was maintained within the normal range, sustaining the product's safety.Our findings support the prolonged use of the new eye drop with low-dose hydrocortisone, also in the DED initial stages, to prevent the degenerating towards a chronic condition (http://www.isrctn.com/ISRCTN16288419).

Refractive Outcome After Corneal Lenticule Implantation Ex Vivo Non-Human Study

Abstract: Abstract Purpose To evaluate changes in corneal refractive parameters after implantation of a stromal lenticule of different thickness. We assume that the refractive outcome depends on the optical power of the used lenticule. Methods We conducted an ex-vivo non-human study on 33 normotonic porcine eyeballs divided into two groups, for 4D and 8D human lenticule implantation. Corneal stromal lenticules were obtained as a by-product from a laser procedure ReLEx SMILE. We evaluated corneal refractive parameters measured on Oculus Pentacam© device before and immediately after the intrastromal lenticule implantation. Results There was no statistically significant difference in corneal refractive parameters between the eyeball groups before lenticule implantation. In both groups, the intrastromal implantation in the depth of 300um led to a significant increase of central corneal pachymetry and corneal anterior steepening. In the 4D group the average central corneal pachymetry increased from 903 ± 124.59 to 1230 ± 148.99 (p = 0.0022) and in 8D group from 733.35 ± 69.60 to 1109 ± 161.64 (p = 0.0008). Induced changes in other studied parameters were not statistically significant, Kmax changed from 45.57 ± 2.78 to 72.07 ± 16.83 (p = 0.0094) and Km front from 40.72 ± 1.60 to 48.87 ± 5.83 (p = 0.0037) in 4D group and in the 8D group average Kmax increased from 42.22 ± 1.54 to 62.95 ± 12.67 (p = 0.0001) and K2 front 40.46 ± 1.64 to 51.51 ± 9.63 (p = 0.0037). There were no significant differences in refractive changes between the 4D and 8D groups after lenticule implantation. Conclusion Intrastromal corneal lenticule implantation induces changes in corneal refractive parameters. In both groups, the implantation induced a significant increase of an anterior corneal steepening without any significant influence on posterior corneal flattening. Corneal lenticule implantation did not lead to any significant change of corneal astigmatism. However, in order to have more precise data for future clinical applications we need to continue with the experiments and verify the results on human corneas.

Visual Outcomes Early after Implantable Collamer Lens V4c Implantation in Different Preoperative Spectacle Correction: Full Correction vs. Under Correction

Abstract: Abstract Purpose To investigate visual outcomes early after implantable collamer lens (ICL) V4c implantation between patients with fully corrected and under-corrected spectacles preoperatively. Methods Patients who implanted ICL V4c were divided into the full correction (46 eyes/23 patients) and under-correction groups (48 eyes/24 patients) based on preoperative differences between the spherical diopter of the spectacles and the actual spherical diopter. Refractive outcomes, scotopic pupil size, higher-order aberrations, and subjective visual outcomes as assessed using a validated questionnaire were compared between the two groups 3 months postoperatively. Moreover, the relationships between the severity of haloes and postoperative ocular or ICL parameters were analyzed. Results At the 3-month follow-up, the efficacy indices in the full correction and under-correction groups were 0.99 ± 0.12 and 1.00 ± 0.10, respectively; the safety indices were 1.15 ± 0.16 and 1.15 ± 0.15, respectively. Total-eye spherical aberration (p < 0.0001) and internal spherical aberration (p = 0.0005) were significantly different pre- and post-operatively in the under-correction group, while no differences were found in the full correction group. Total-eye spherical aberration (p = 0.002) and the severity of haloes (p = 0.03) were postoperatively different between the two groups. The severity of haloes was associated with postoperative spherical aberration (total-eye spherical aberration: r = −0.32, p = 0.002; internal spherical aberration: r = −0.24, p = 0.02). Conclusion Good efficacy, safety, predictability, and stability were obtained early after surgery regardless of preoperative spectacle correction. Patients in the under-correction group possessed a shift to negative spherical aberration and reported greater severity of haloes at the 3-month follow-up. Haloes were the most common visual symptoms after ICL V4c implantation and the severity of them was correlated with postoperative spherical aberration.

Ophthalmic Manifestations of Unilateral Coronal Synostosis.

Abstract: PURPOSE To summarize the ophthalmic manifestations of unilateral coronal synostosis patients. METHODS We performed a literature search in the electronic database of PubMed, CENTRAL, Cochrane, and Ovid Medline guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement for studies evaluating ophthalmic manifestations of unilateral coronal synostosis. RESULTS Unilateral coronal synostosis, also called unicoronal synostosis, may be mistaken for deformational plagiocephaly, an asymmetric skull flattening common in newborns. Characteristic facial features, however, distinguish the two. Ophthalmic manifestations of unilateral coronal synostosis include a "harlequin deformity", anisometropic astigmatism, strabismus, amblyopia, and significant orbital asymmetry. The astigmatism is greater on the side opposite the fused coronal suture. Optic neuropathy is uncommon unless unilateral coronal synostosis accompanies more complex multi-suture craniosynostosis. In many cases, surgical intervention is recommended; without intervention, skull asymmetry and ophthalmic disorders tend to worsen with time. Unilateral coronal synostosis can be managed by early endoscopic stripping of the fused suture and helmeting through a year of age or by fronto-orbital-advancement at approximately 1 year of age. Several studies have demonstrated that anisometropic astigmatism, amblyopia, and severity of strabismus are significantly lower after earlier intervention with endoscopic strip craniectomy and helmeting compared to treatment by fronto-orbital-advancement. It remains unknown whether the earlier timing or the nature of the procedure is responsible for the improved outcomes. As endoscopic strip craniectomy can only be performed in the first few months of life, early recognition of the facial, orbital, eyelid, and ophthalmic characteristics by consultant ophthalmologists enables expeditious referral and optimized ophthalmic outcomes. CONCLUSION Timely identification of craniofacial and ophthalmic manifestations of infants with unilateral coronal synostosis is important. Early recognition and prompt endoscopic treatment appears to optimize ocular outcomes.

Dynamic Changes in Retinal Vessel Diameters and Arteriovenous Ratio within 10 Days of Birth

Abstract: Abstract Purpose This study monitored the dynamic changes in retinal vascular width and the AVR in full-term neonates within 1–10 days of birth. Methods It was conducted at hospitals in the Anhui province from October 2020 to March 2022. A total of 700 full-term, healthy infants were chosen randomly within 10 days of birth, and the Star Pupil Medical Cloud Data System (XBDS) was used to collect fundus images. Infants within 6 days of birth were grouped into groups one to six, while those within the 7th to 10th days were grouped into group seven. The fundus photographs were imported into Image-Pro-Plus (IPP) software. The optic disc diameter was measured. The retinal artery and vein’s diameter was measured at a distance between 0.5- and 1.0-disc diameter from the optic disc’s margin. The AVR was also calculated. Finally, each group’s retinal vessel diameters and AVR were compared separately to show their dynamic changes. Results There were differences in the retinal artery diameter between groups one and two, three and four, four and five, and five and six. For retinal vein diameter, there were differences between groups one and two and groups six and seven. There were also differences in the AVR between all groups. In addition, there was a significant positive correlation between the small retinal artery and vein diameters. Conclusion The retinal artery and vein diameters and AVR in neonates change dynamically during the first 10 days of life. The AVR undergoes the most dramatic change daily and is considerably smaller than the AVR in adults. Hence, this study found that the external environment undergoes significant changes following birth that affect the microcirculation. Then, the retinal central vascular system undergoes similar emergency and adaptive alterations.

Clinical and Pathological Features of Primary Orbital Liposarcoma in Chinese Patients.

Abstract: PURPOSE Liposarcomas are rare in the orbit. We analyzed a series of primary liposarcomas to determine the features unique to the orbit. METHODS Records from 10 Chinese patients treated for primary orbital liposarcoma at Beijing Tongren Hospital, Capital Medical University, between September 2009 and September 2020 were reviewed. RESULTS This cohort included four men and six women with age of onset ranging from 18 to 80 years. The pathology was myxoid liposarcoma in five patients, dedifferentiated liposarcoma in two patients, well-differentiated liposarcoma and pleomorphic liposarcoma in one patient each, and dedifferentiated liposarcoma and well-differentiated liposarcoma co-existing in one case. Magnetic resonance imaging (MRI) revealed a well-defined, irregular, or lobulated mass in the orbit, which contained components that were suppressible in the fat-suppression sequence, as well as components that were enhanced by gadolinium enhancement. Nine patients relapsed after surgery, with a mean recurrence of 2.44, and one patient was lost to follow-up. The interval between treatment and first recurrence ranged from 4 months to 16 years; 55.6% of patients with orbital liposarcoma relapsed within one year. Three patients underwent local excision alone, four patients underwent excision combined with radiotherapy, and three patients underwent exenteration. Half of the patients were misdiagnosed in the pathologic diagnosis after their first or multiple surgeries. No distant metastasis, death from tumors, or invasion of adjacent organs was observed after 21-150 months of follow-up. CONCLUSION Orbital liposarcoma is easily misdiagnosed and prone to recurrence; however, MRI findings may help identify orbital liposarcoma prior to surgery. The optimal treatment choice remains to be discussed.

Association of Tear Cytokine Concentrations with Symptoms and Signs of Dry Eye Disease: Baseline Data from the Dry Eye Assessment and Management (DREAM) Study

Abstract: Abstract Purpose To describe tear concentrations of IL-1β, Il-6, IL-8, IL-10, IL-17A, IFNγ and TNFα in tears, collected by microcapillaries, and their correlation with symptoms and signs in subjects with dry eye disease (DED) in the DREAM Study. Methods Cytokine levels of patients with moderate to severe DED were determined using a magnetic bead assay. Scores for Ocular Surface Disease Index, corneal and conjunctival staining, tear break-up time (TBUT), and Schirmer’s test were obtained using standardized procedures. Associations of cytokines with each other and signs/symptoms were assessed with Spearman correlation coefficients (r). Results Assay results from 131 patient samples from 10 sites with tear volumes ≥ 4 ul were analyzed. Cytokine concentrations did not correlate with each other in a generally acknowledged pro-inflammatory/anti-inflammatory pattern, such as proinflammatory IL-17A and IFNγ were not inversely correlated to anti-inflammatory cytokine IL-10, and cytokines did not correlate with DED symptoms. Lower corneal staining was correlated with higher concentrations of IL-17A (r= −0.24, p = 0.006), IL-10 (r= −0.25, p = 0.005) and IFNγ (r= −0.33, p = 0.0001). Higher concentrations of IFNγ were associated with lower conjunctival staining (r= −0.18, p = 0.03). Higher concentrations of IL-17A were associated with higher TBUT scores (r = 0.19 p = 0.02). Conclusions Cytokines IL-10, IL-17A and IFNγ were highly correlated with each other but weakly correlated with some DED signs. No key cytokines or definitive expression patterns were identified in this study of moderate to severe DED patients. Further studies addressing various biases, including methodological and sampling biases, and standardization of methodology for inter-laboratory consistency are needed to confirm and establish pathological and clinical relevance of tear cytokines in DED.

Effects of Punctal Occlusion on Ocular Itching and Conjunctival Redness Associated with Allergic Conjunctivitis.

Abstract: PURPOSE Punctal occlusion using punctal plugs has been successfully used to treat the signs and symptoms of dry eye disease. However, the effects of punctal occlusion on the symptoms of allergic conjunctivitis (AC) have been less well documented. There is some concern among clinicians that punctal occlusion may make signs/symptoms of allergic conjunctivitis worse by trapping allergens on the eye. The objective of this post hoc analysis was to address this question and thus assess the effect of punctal occlusion alone on ocular itching and conjunctival redness associated with AC. METHODS This was a pooled post hoc analysis of three randomized, double-blind, placebo insert-controlled clinical trials in subjects with AC. Enrolled subjects were generally healthy adults with ocular allergies and a positive skin test reaction to perennial and/or seasonal allergens. The study used a modified version of the traditional conjunctival allergen challenge (CAC) model, which included multiple, repeated allergen challenges following placement of the intracanalicular insert. Subjects were rechallenged on Days 6, 7 and 8; Days 13, 14 and 15; and Days 26, 27 and 28. RESULTS The data set included 128 subjects that were administered placebo. Baseline mean (SD) ocular itching and conjunctival redness scores were 3.52 (0.44) and 2.97 (0.39), respectively. On post-insertion Days 7, 14 and 28, mean itching scores were 2.62, 2.26 and 1.91, respectively, representing 26%, 36% and 46% itching reductions, respectively (p < 0.001). On Days 7, 14 and 28, mean conjunctival redness scores were 1.98, 1.90, and 2.08, respectively, representing 33%, 36%, and 30% redness reductions, respectively (p < 0.001). CONCLUSIONS Based on this post hoc pooled analysis, punctal occlusion with a resorbable hydrogel intracanalicular insert did not worsen ocular itching or conjunctival redness in this patient population.

Effect of Internal Limiting Membrane Peeling or Not on Blood Flow Signal in Macular Area of Diabetic Patients with Preretinal Membrane

Abstract: Abstract Purpose To study the effect of intraoperative internal limiting membrane (ILM) peeling on the macular vascular structure in patients with diabetic epiretinal membrane (ERM). Methods Patients with diabetic ERM were divided into an ERM + ILM peeling group (18 eyes) and an ERM peeling group (19 eyes), all of whom underwent standard vitrectomy and were followed up until 6 months postoperatively. Best-corrected visual acuity (BCVA), Central macular thickness (CMT), Vessel density (VD) and vessel length density (VLD) of the superficial as well as deep retinal capillary plexus were compared between the two groups. Results There was no significant difference in BCVA (p = .188, .410, .901, .916) and CMT (p = .164, .128, .110, .105) between the two groups at the week 1, month 1, month 3 and month 6 after operation. In the superficial capillary plexus (SCP), the change in VD (p = .106) and VLD (p = .438) was not affected by ILM peeling, and there was no significant difference in VD (p = .154, .063, .100, .162) and VLD (p = .386, .263, .431, .391) between the two groups during the four follow-up after operation. For the deep capillary plexus (DCP), there was an effect of ILM peeling on the changes in VD (p = .024) and VLD (p = .012), ILM peeling delayed the recovery time of the VD and VLD; The VD (p = .026, .000, .003) and VLD (p = .005, .000, .000) of ERM + ILM peeling group were lower than those of ERM peeling group from the month 1 to the month 6 after operation. Conclusion Intraoperative peeling of the ILM in patients with diabetic ERM delayed the improvement of blood flow signal in the DCP but did not affect the recovery of postoperative BCVA and CMT.

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Abstract: This article refers to:Using the Chick Embryo Model to Examine the Effects of Hypoxia Pre-conditioning of Uveal Melanoma Cells on Tumor Growth and Metastasis

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Abstract: This article refers to:Enhanced Detection of Reticular Pseudodrusen on Color Fundus Photos by Image Embossing

The relationship between Kiritsu-Meijin-derived autonomic function parameters and visual-field defects in eyes with open-angle glaucoma.

Abstract: Purpose: This retrospective cross-sectional study aimed to investigate the association between autonomic parameters measured using the Kiritsu-Meijin device and visual-field defects in patients with open-angle glaucoma (OAG).Methods: A total of 79 eyes of 42 patients with OAG were enrolled in this study. Kiritsu-Meijin testing comprised three phases: sitting, standing, and sitting again (2 minutes, 2 minutes, and 1 minute, respectively). Continuous electrocardiograms were recorded for five minutes. Autonomic parameters were extracted from the resulting data and analyzed, including activity, balance, reaction, switchover, and recovery; these are 5 representative parameters derived from Kiritsu-Meijin testing. Correlations between these parameters and mean deviation (MD) from Humphrey visual field testing were determined. Additionally, we used a linear mixed-effects model to observe sectoral differences in the relationship between TD and the Kiritsu-Meijin parameters. In this study, we focused on superior, central, and inferior TD.Results: Significant positive correlations were observed between activity, balance, and recovery and MD values (β = 0.29-0.38, P < 0.05). The β value between activity and inferior TD was higher than that between activity and superior TD (β = 0.22, P < 0.05). Balance did not show any sectoral differences (P > 0.05). Recovery was more strongly associated with central to inferior TD than superior TD (β = 0.17-0.25, P < 0.05).Conclusion: Our findings suggest that in patients with OAG, lower activity and recovery are associated with more severe central and/or inferior visual field defects in the superior quadrant. These results imply that measurements of autonomic function made with the Kiritsu-Meijin device may have clinical utility in the management of glaucoma.

Electroacupuncture Reduces Ocular Surface Neuralgia in Dry-Eyed Guinea Pigs by Inhibiting the Trigeminal Ganglion and Spinal Trigeminal Nucleus Caudalis P2X3R-PKC Signaling Pathway

Abstract: Abstract Purpose To observe the effects of electroacupuncture on ocular surface neuralgia and the P2X3R-PKC signaling pathway in guinea pigs with dry eye. Methods A dry eye guinea pig model was established by subcutaneous injection of scopolamine hydrobromide. Guinea pigs were monitored for body weight, palpebral fissure height, number of blinks, corneal fluorescein staining score, phenol red thread test, and corneal mechanical perception threshold. Histopathological changes and mRNA expression of P2X3R and protein kinase C in the trigeminal ganglion and spinal trigeminal nucleus caudalis were observed. We performed a second part of the experiment, which involved the P2X3R-specific antagonist A317491 and the P2X3R agonist ATP in dry-eyed guinea pigs to further validate the involvement of the P2X3R-protein kinase C signaling pathway in the regulation of ocular surface neuralgia in dry eye. The number of blinks and corneal mechanical perception threshold were monitored before and 5 min after subconjunctival injection and the protein expression of P2X3R and protein kinase C was detected in the trigeminal ganglion and spinal trigeminal nucleus caudalis of guinea pigs. Results Dry-eyed guinea pigs showed pain-related manifestations and the expression of P2X3R and protein kinase C in the trigeminal ganglion and spinal trigeminal nucleus caudalis was upregulated. Electroacupuncture reduced pain-related manifestations and inhibited the expression of P2X3R and protein kinase C in the trigeminal ganglion and spinal trigeminal nucleus caudalis. Subconjunctival injection of A317491 attenuated corneal mechanoreceptive nociceptive sensitization in dry-eyed guinea pigs, while ATP blocked the analgesic effect of electroacupuncture. Conclusions Electroacupuncture reduced ocular surface sensory neuralgia in dry-eyed guinea pigs, and the mechanism of action may be associated with the inhibition of the P2X3R-protein kinase C signaling pathway in the trigeminal ganglion and spinal trigeminal nucleus caudalis by electroacupuncture.

Comparison of retinal and choroidal microvasculature changes in monocular amblyopic and non-amblyopic eyes following short-term patch occlusion treatment.

Abstract: PURPOSE Our objective was to investigate whether there were differences in the short-term changes of retinal and choroidal microvasculature between amblyopic and non-amblyopic eyes after patch occlusion treatment in patients with monocular amblyopia. Additionally, we aimed to determine if these changes were associated with improvements in clinical parameters. METHODS We conducted a retrospective, longitudinal paired-eye case-control study by analyzing the medical records of patients under the age of 12 who had monocular amblyopia and underwent patch occlusion treatment for a duration of 2 to 12 months. Using optical coherence tomography angiography images, we compared the foveal avascular zone width, retinal blood vessel density (VD), choroidal thickness (CT), and choroidal vascularity index (CVI) in amblyopic and non-amblyopic eyes before and after patch occlusion treatment. We analyzed the correlations between the aforementioned parameters and changes in best-corrected visual acuity (BCVA) and stereopsis. RESULTS Overall, 114 eyes from 57 patients were enrolled. At baseline, parafoveal superficial plexus VD, foveal and parafoveal deep capillary plexus VD (DCPD) were lower by 0.994 ± 3.312% (P=0.026), 2.403 ± 8.273% (P=0.033), and 2.469 ± 4.095% (P<0.001), respectively; CT was thicker by 30.6 ± 90.7 μm (P = 0.014); and CVI was higher by 1.920 ± 3.432% (P < 0.001) in the amblyopic eyes than in the non-amblyopic eyes. Following short-term patch occlusion treatment, foveal and parafoveal DCPD increased by 1.264 ± 3.829% (P = 0.017) and 1.028 ± 3.662% (P = 0.036), respectively, CT thinned by 15.5 ± 51.5 μm (P = 0.019), and CVI decreased by 1.296 ± 3.997% (P = 0.018) in the amblyopic eyes. Following patch occlusion treatment, as the foveal DCPD decreased and CVI increased, the BCVA improved (P = 0.017 and 0.035, respectively). CONCLUSION Following patch occlusion treatment, increased foveal DCPD and decreased CVI were associated with improved BCVA.

Optical Coherence Tomography Angiography Demonstrates Strain and Volume Effects on Optic Disk and Peripapillary Vasculature Caused by Horizontal Duction

Abstract: Abstract Purpose The optic nerve mechanically loads the eye during ocular rotation, thus altering the configuration of the disk and peripapillary tissues. We used optical coherence tomography (OCT) angiography (OCTA) to investigate mechanical strains and volume changes in disk and peripapillary blood vessels during horizontal duction. Methods Structural OCT and OCTA were performed centered on optic disks; imaging was repeated in central gaze, and in 30° ab- and adduction. By an algorithm employing point-set registration of 3 D features, we developed a novel approach for measuring disk strains, and strains and volumes of the blood vessels associated with horizontal duction. Repeatability was demonstrated in each gaze position. Results 19 eyes of 10 healthy adults of average age 37 ± 15 (standard deviation, SD) years were imaged. The method was validated by demonstrating numerically consistent vascular volumes and strains for repeated imaging under identical conditions. Compared with central gaze, vascular volume increased by 5.2 ± 4.1% in adduction. Adduction and abduction caused strains of 3.0 ± 1.6% and 2.6 ± 1.8% in the optic disk, whereas blood vessels showed greater strains of 8.1 ± 1.3% and 8.2 ± 1.7%. Decomposition of strain components depending on directionality and regions demonstrated that adduction induces significant net tensile strains, suggesting traction exerted by the optic nerve. The decomposition also showed that nasotemporal compressive strains are larger in temporal hemidisks than nasal hemidisks. The Bruch’s membrane opening was significantly compressed horizontally in adduction by 1.1% (p = .009). Conclusion This novel analysis combining structural OCT and OCTA demonstrates that optic disk compression during adduction is associated with disk and vascular strains much larger than reported for intraocular pressure elevation and pulsatile perfusion, as well as compressing the disk and increasing peripapillary vascular volume. These changes may be relevant to the pathogenesis of optic nerve and retinal vascular disorders.

Laser-Activated Chitosan Adhesive for Replacing Corneal Sutures

Abstract: Corneal sutures provide point-to-point apposition of wound edges but do not hermetically seal penetrating wounds. 1 Leaking corneal wounds carry the risk of sight-threatening infective endophthalmitis. Suture application also damages adjacent healthy corneal tissue, cause astigmatism, foreign body reactions

Beneficial Effects of Plasma Rich in Growth Factors (PRGF) Versus Autologous Serum and Topical Insulin in Ocular Surface Cells

Abstract: Abstract Purpose In the last few decades, several blood derived products such as platelet-rich plasma (PRP), plasma rich in growth factors (PRGF) and autologous serum (AS) have been used for the treatment of ocular surface disorders. Recently, insulin has been proposed to be used as an alternative for the treatment of ocular surface diseases. The aim of this study was to evaluate the biological potential of PRGF eye drops in comparison with AS and insulin on ocular surface cells. Methods Blood from three healthy young donors was collected to obtain autologous serum (AS) eye drops and plasma rich in growth factors (PRGF) eye drops. Insulin (Actrapid®) was diluted at 1 and 0.2 IU/mL. The biological potential of PRGF, AS and insulin was assessed by proliferation in HCE, HK and HConF cells. Wound healing assay was performed in HCE cells after incubation with the different treatments. HConF and HK cells were differentiated to myofibroblast after treatment with 2.5 ng/mL of TGF-β1 and then incubated with all treatments. Results PRGF eye drops induced significantly higher proliferation rate compared to AS or insulin in HConF and HK cells, but not in HCE cells. In addition, the percentage of wound healing area was significantly reduced after PRGF treatment in comparison with AS or insulin treatment. Furthermore, PRGF significantly reduced the number of myodifferentiated cells compared to AS and insulin at both concentrations analyzed. Conclusion The results obtained in the present study show that PRGF increases the biological activity of the ocular surface cells and reduces the expression of fibrosis marker compared to insulin or AS. Translational relevance The present study suggests that plasma rich in growth factors eye drops are a more effective therapy than insulin and autologous serum eye drops for the treatment of ocular surface diseases.

Simvastatin attenuates glucocorticoid-induced human trabecular meshwork cell dysfunction via YAP/TAZ inactivation.

Abstract: PURPOSE Impairment of the trabecular meshwork (TM) is the principal cause of increased outflow resistance in the glaucomatous eye. Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ) are emerging as potential mediators of TM cell/tissue dysfunction. Furthermore, YAP/TAZ activity was recently found to be controlled by the mevalonate pathway in non-ocular cells. Clinically-used statins block the mevalonate cascade and were shown to improve TM cell pathobiology; yet, the link to YAP/TAZ signaling was not investigated. In this study, we hypothesized that simvastatin attenuates glucocorticoid-induced human TM (HTM) cell dysfunction via YAP/TAZ inactivation. METHODS Primary HTM cells were seeded atop or encapsulated within bioengineered extracellular matrix (ECM) hydrogels. Dexamethasone was used to induce a pathologic phenotype in HTM cells in the absence or presence of simvastatin. Changes in YAP/TAZ activity, actin cytoskeletal organization, phospho-myosin light chain levels, hydrogel contraction/stiffness, and fibronectin deposition were assessed. RESULTS Simvastatin potently blocked pathologic YAP/TAZ nuclear localization/activity, actin stress fiber formation, and myosin light chain phosphorylation in HTM cells. Importantly, simvastatin co-treatment significantly attenuated dexamethasone-induced ECM contraction/stiffening and fibronectin mRNA and protein levels. Sequential treatment was similarly effective but did not match clinically-used Rho kinase inhibition. CONCLUSIONS YAP/TAZ inactivation with simvastatin attenuates HTM cell pathobiology in a tissue-mimetic ECM microenvironment. Our data may help explain the association of statin use with a reduced risk of developing glaucoma via indirect YAP/TAZ inhibition as a proposed regulatory mechanism.

Outcomes of Laser Retinopexy for Retinal Tears in Pseudophakic Eyes with Multifocal Versus Monofocal Intraocular Lenses: A Matched Cohort Study

Abstract: Abstract Purpose Performing laser retinopexy through multifocal intraocular lenses may be challenging due to aberrations of the peripheral retinal view. This study investigated the influence of multifocal versus monofocal intraocular lenses on outcomes of laser retinopexy for retinal tears. Methods Pseudophakic eyes (multifocal and monofocal intraocular lenses) that underwent in-office laser retinopexy for retinal tears, with a minimum follow-up of 3 months, were retrospectively analyzed. Eyes with multifocal intraocular lenses were matched to controls with monofocal intraocular lenses in a 1:2 ratio for age, gender, number, and location of retinal tears. The main outcome measure was the rate of complications. Results We included 168 eyes in the study. Fifty-six eyes (51 patients) with multifocal intraocular lenses were matched with 112 eyes (112 patients) with monofocal intraocular lenses. The mean follow-up was 26 months. Baseline characteristics were similar between two groups. No significant differences were noted in the rate of successful laser retinopexy without additional procedures (91% vs. 86% at 3 months and 79% vs. 74% during follow-up, in the multifocal intraocular lens and monofocal intraocular lens group, respectively). No significant differences were observed in the rate of subsequent rhegmatogenous retinal detachment (multifocal, 4% vs. monofocal, 6%, p=.716) or need for additional laser retinopexy for new tears (14% vs. 15%; p=.939). The surgery rates for vitreous hemorrhage (0% vs. 3%; p=.537), epiretinal membrane (2% vs. 2%; p=.553), and vitreous floaters (5% vs. 2%, p=.422) were not significantly different. Visual outcomes were also similar. Conclusion Multifocal intraocular lenses did not appear to negatively impact the outcomes of in-office laser retinopexy for retinal tears.

Correlation and Level of Agreement Between the Ocular Surface Disease Index and the Symptom Assessment iN Dry Eye Questionnaires: A Survey-Based Study.

Abstract: PURPOSE The Ocular Surface Disease Index (OSDI) is the most frequently used dry eye disease (DED) questionnaire, and the Symptom Assessment iN Dry Eye (SANDE) is the simplest and quickest to apply. We analyze the correlation and level of agreement between these two questionnaires in a large DED heterogeneous population to evaluate their performance and potential interchangeability. METHODS Prospective, multicenter longitudinal survey-based study performed on patients diagnosed with DED by 99 ophthalmologists from 20/32 Mexican states. Questionnaires were applied in two consecutive visits to analyze the correlation between OSDI and SANDE to evaluate patients with DED clinically. Level of agreement was evaluated with Bland-Altman analysis, and internal consistency of instruments was evaluated individually and combined with Cronbach's alpha index. RESULTS 3421 patients studied: 1996 (58.3%) women and 1425 (41.7%) men, aged 49.5 ± 15.4 years; 995 (29.1%) patients had aqueous-deficient, 1086 (31.7%) evaporative, and 1340 (39.2%) mixed DED subtypes. Normalized baseline scores were 53.7 (OSDI) and 54.1 (SANDE). After 36.3 ± 24.4 days between visits, scores were reduced to 25.2 (OSDI) and 21.8 (SANDE) points (p<.001). A positive correlation between questionnaires was found at baseline (R = 0.592; p<.001), follow-up (R = 0.543; p<.001) and change between visits (R = 0.630; p<.001). Using both questionnaires together improved the overall reliability of symptom evaluation at baseline (α = 0.7), follow-up (α = 0.7), and both (α = 0.7), compared to individual application (OSDI α = 0.5, SANDE α = 0.6)-the same improvements applied to all DED subtypes. Bland-Altman analysis revealed a differential bias of -0.41% at baseline and +3.6% at follow-up visits between OSDI and SANDE. CONCLUSIONS We validated the correlation (high precision) between questionnaires in a large-scale population, demonstrating improved reliability (high accuracy) in evaluating DED when used together, challenging their interchangeable use. These results open a venue to improve recommendations toward a more precise and accurate diagnostic and therapeutic evaluation of DED by using OSDI and SANDE concurrently.

Investigation of Choroidal Blood Flow and Thickness Changes Induced by Near Work in Young Adults.

Abstract: PURPOSE This research aimed to determine the effects of near work on macular choroidal blood flow and thickness in young adults. METHODS A total of 109 participants (19-28 years old) were recruited from Capital Medical University in China. The participants spent 40 min reading a book text at a distance of 33 cm. Swept-source optical coherence tomography/optical coherence tomography angiography (SS-OCT/OCTA) was performed to measure the changes in choriocapillaris perfusion area (CCPA) and choroidal thickness (ChT) after 40 min of near work. The SS-OCT/OCTA data covered an area of 6 mm × 6 mm, which centered on the fovea. RESULTS The baseline ChT and CCPA before near work were negatively correlated with AL, while positively correlated with the magnitude of spherical equivalent (p < .001). Total CCPA decreased significantly by 6 mm × 6 mm macular area after near work compared to that before near work (24.26 ± 1.96 vs. 24.63 ± 1.61 mm2, p<.001). The macular ChT was lower after 40 min of reading than that before 40 min of reading, but no significant difference was observed (302.25 ± 77.69 vs. 304.92 ± 79.73 μm, p = .078). The extent of choroidal thinning was significantly positively correlated with the magnitude of CCPA reduction (p < .001). The decline in CCPA after near work was significantly positively correlated with axial length (AL; p < .001). CONCLUSION This study demonstrated that near work significantly decreased CCPA. The extent of CCPA reduction after near work was associated with higher severity of myopia and choroidal thinning. The baseline CCPA and ChT decreased gradually with AL.

MD2 Inhibits Choroidal Neovascularization via Antagonizing TLR4/MD2 Mediated Signaling Pathway

Abstract: Abstract Purpose To explore the pathological mechanism of Toll-like receptor 4 (TLR4) mediating neovascular age-related macular degeneration (nAMD) and the potential role of the TLR4 coreceptor myeloid differentiation protein 2 (MD2). Methods In the study, we inhibited MD2 with the chalcone derivative L2H17 and we utilized a laser-induced choroidal neovascularization (CNV) mouse model and Tert-butyl hydroperoxide (TBHP)-challenged rhesus choroid-retinal endothelial (RF/6A) cells to assess the effect of MD2 blockade on CNV. Results Inhibiting MD2 with L2H17 reduced angiogenesis in CNV mice, and significantly protected against retinal dysfunction. In retina and choroid/retinal pigment epithelium (RPE) tissues, L2H17 reduced phospho-ERK, phospho-P65 but not phospho-P38, phospho-JNK, and reduced the transcriptional levels of IL-6, TNF-α, ICAM-1 but not VCAM-1. L2H17 could protect RF/6A against TBHP-induced inflammation, oxidative stress, and apoptosis, via inhibiting the TLR4/MD2 signaling pathway and the following downstream mitogen-activated protein kinase (MAPK) and nuclear transcription factor-κB (NF-κB) activation. Conclusions Inhibiting MD2 with L2H17 significantly reduced CNV, suppressed inflammation, and oxidative stress by antagonizing TLR4/MD2 pathway in an MD2-dependent manner. MD2 may be a potential therapeutic target and L2H17 may offer an alternative treatment strategy for nAMD.

Effect of the Presence of Silicone Oil in the Anterior Chamber After Complicated Retinal Detachment Surgery on Corneal Morphology by In Vivo Confocal Microscopy.

Abstract: PURPOSE This study evaluated the corneal endothelium, stromal keratocytes, subbasal nerve number and density in patients with silicone oil transferred to the anterior camera after pseudophakic complicated retinal detachment surgery by in vivo laser scanning confocal microscopy (IVLSCM). METHODS Sequential measurements were made by IVLSCM between 3-6 months after surgery in two groups of patients: a) with silicon oil migration (Group 1) and without silicone oil migration (Group 2). RESULTS A total of 63 cases (Group 1: 32 and Group 2: 31) were examined. The mean ages of patients were 65 ± 12 and 61 ± 11 and M/F ratio was 18/14 and 17/14, respectively. Mean intraocular pressures were 16.60 ± 4.60 and 15.75 ± 5.70 mm Hg, respectively. Changes were detected by IVLSCM mostly on the superior part of the cornea. A significant decrease in endothelial cell density and the number was detected in group 1 (2072 ± 116.2 cells/mm2 vs 2752 ± 512.3 cells/mm2; p < 0.001). Significant increases in posterior keratocyte density and stromal hyperreflective deposits were observed in group 1 (887 ± 45.8 cells/mm2 vs 725 ± 65.8 cells/mm2; p < 0.001). A significant negative correlation was observed between the size of stromal deposits and endothelial cell density (r=-0.758; p < 0.001). The number and density of corneal subbasal nerves were significantly lower in group 1 (1.8 ± 0.8 and 4.8 ± 1.2 vs 420 ± 101 and 701 ± 112 µm/square; p < 0.001). CONCLUSION IVLSCM is a useful tool for the early detection of corneal abnormalities caused by silicone oil injection. This study verified silicone oil's detrimental effect on the corneal endothelium and revealed stromal changes in the anterior chamber, which we believe can be also been associated with the presence of silicone oil.

CD44 Drives M1 Macrophage Polarization in Diabetic Retinopathy.

Abstract: PURPOSE Diabetic retinopathy is a typical complication of diabetes, which can facilitate the risk of blindness in severe cases. We sought to determine the function of CD44 in inflammatory responses of human retinal microvascular endothelial cells (HRMECs) and macrophage polarization during diabetic retinopathy (DR). METHODS The hub genes were tested based on two datasets from the Gene Expression Omnibus database. Gene Ontology and pathway enrichment analysis was conducted on the base of differentially expressed genes (DEGs). The infiltration score and infiltration of the immune cells were assessed, and the link between key genes and macrophages was analyzed. The role of CD44 in HRMECs and macrophage polarization was determined by quantitative reverse transcription polymerase chain reaction, western blot, cell counting kit-8, Enzyme-linked immunosorbent assay, flow cytometry, and immunofluorescence. RESULTS DEGs were enriched in several pathways linked to DR, such as cellular response to retinoic acid, retinol metabolic process, retina homeostasis, PI3K-AKT signaling pathway, and leukocyte transendothelial migration. A total of 144 DEGs were identified by up-regulation both in GSE102485 and GSE160306. Moreover, the infiltration of macrophages was greater in the DR group than that in the control group. We highlighted an obvious increase in the expression of CD44 and CD86 in patients with DR, and distinct positive associations were found between levels of macrophages and levels of CD44 and CD86. Furthermore, CD44 expression was substantially increased in HRMECs under high glucose (HG) conditions and CD44 knockdown markedly inhibited HG-induced inflammatory responses of HRMECs. HG-induced HRMECs remarkably influenced M1 polarization of macrophages, but CD44 knockdown significantly nullified this effect. CONCLUSIONS CD44 influenced the advancement of DR via meditating M1 polarization of macrophages. Our findings could enhance the understanding of the mechanism of DR, which might offer a therapeutic target for DR patients.

Comparing Common Retinal Vessel Caliber Measurement Software with an Automatic Deep Learning System.

Abstract: PURPOSE To compare the Retina-based Microvascular Health Assessment System (RMHAS) with Integrative Vessel Analysis (IVAN) for retinal vessel caliber measurement. METHODS Eligible fundus photographs from the Lingtou Eye Cohort Study were obtained alongside their corresponding participant data. Vascular diameter was automatically measured using IVAN and RMHAS software, and intersoftware variations were assessed by intra-class correlation coefficients (ICC), and 95% confidence intervals (CIs). Scatterplots and Bland-Altman plots assessed the agreement between programs, and a Pearson's correlation test assessed the strength of associations between systemic variables and retinal calibers. An algorithm was proposed to convert measurements between software for interchangeability. RESULTS ICCs between IVAN and RMHAS were moderate for CRAE and AVR (ICC; 95%CI)(0.62; 0.60 to 0.63 and 0.42; 0.40 to 0.44 respectively) and excellent for CRVE (0.76; 0.75 to 0.77). When comparing retinal vascular calibre measurements between tools, mean differences (MD, 95% confidence intervals) in CRAE, CRVE, and AVR were 22.34 (-7.29 to 51.97 µm),-7.01 (-37.68 to 23.67 µm), and 0.12 (-0.02 to 0.26 µm), respectively. The correlation of systemic parameters with CRAE/CRVE was poor and the correlation of CRAE with age, sex, systolic blood pressure, and CRVE with age, sex, and serum glucose were significantly different between IVAN and RMHAS (p < 0.05). CONCLUSIONS CRAE and AVR correlated moderately between retinal measurement software systems while CRVE correlated well. Further studies confirming this agreeability and interchangeability in large-scale datasets are needed before softwares are deemed comparable in clinical practice.