Peripapillary and macular vessel density (VD) are reduced in myopic non-glaucomatous eyes, the dynamic range of VD may be decreased by myopia, and whether VD measurement has the potential in differentiating stages of glaucoma severity in patients with myopic glaucoma remains questionable. This observational, cross-sectional study aimed to clarify the changes in peripapillary and macular VDs in preperimetric glaucoma (PPG) and primary open-angle glaucoma in the early, moderate, and late stages. A total of 1228 eyes from 661 participants (540 normal, 67 PPG, and 521 glaucomatous) were included. Participants underwent free blood tests at the internal medicine clinic to retrieve systemic data. Patients with glaucoma were grouped by disease severity, defined by glaucomatous visual field mean defect, including early-(224 eyes), moderate-(103 eyes), and late-stage glaucoma (194 eyes), and further divided into advanced (158 eyes) and terminal glaucoma (36 eyes). Macular VD, peripapillary VD, circumpapillary retinal nerve fiber layer (cpRNFL) thickness, and ganglion cell complex (GCC) thickness were evaluated and divided into superior and inferior parts. One-way analysis of variance was performed, followed by Tukey’s post-hoc test. The peripapillary VD was significantly different between the healthy and PPG groups and the early-, moderate-, and late-stage glaucoma subgroups (all p < 0.001). Peripapillary VD measurements are helpful in differentiating the various stages of glaucoma even in patients with myopic glaucoma. Full article

In glaucoma, macular optical coherence tomography (OCT) typically shows a thinning of the three inner segments and OCT-angiography (OCTA) a reduction of the vascular density (VD). It is still unclear if glaucoma directly affects macular VD. This retrospective study included 31 glaucoma patients of early and moderate stage (GS1, GS2, Mills et al.) and 39 healthy individuals. Macular segments’ thickness and superficial and deep plexus vascular density (VD) were obtained using spectral-domain OCT and OCTA, respectively. One-way analysis of variance (ANOVA) was used to compare healthy controls and glaucoma patients according to their glaucoma stage. Using correlation analyses, the association between glaucoma and either OCT or OCTA parameters was evaluated. A glaucoma stage-stratified linear regression analysis was then performed. Inner macular segment and whole retinal thickness were reduced in GS1 and GS2 patients compared to healthy controls (e.g., ganglion cell layer GCL: controls: 47.9 ± 7.4, GS1: 45.8 ± 5.1, GS2: 30.6 ± 9.4, ANOVA: p < 0.0001). Regarding OCTA-parameters, the VD of both segmentation levels was reduced in glaucoma patients, particularly when comparing GS2 patients with controls (superficial plexus: p = 0.004) and GS2 with GS1 (p = 0.0008). Linear regression revealed an association between these parameters and the presence of glaucoma (for superior plexus: R² = 0.059, p = 0.043). Finally, a correlation between macular segment thickness and VD was observed, but with a strength increasing with glaucoma severity (GCL and superior plexus VD: controls: R² = 0.23, GS1 R² = 0.40, GS2 R² = 0.76). Despite the glaucoma-independent correlation between macular segment thickness and VD, disease severity strengthens this correlation. This consideration suggests that glaucoma directly influences OCT and OCTA parameters individually. Full article

Purpose: The aim of this study is too correlate the sensitivity and thickness values of intraretinal layers at macula in healthy eyes and primary open-angle glaucoma (POAG) eyes. Methods: The thickness of different intraretinal segmentations was estimated by means of optical coherence tomography (OCT) Spectralis (Heidelberg, Engineering, Inc., Heidelberg, Germany) with the posterior pole analysis program 8 × 8 in 91 eyes from 91 patients (60 with glaucoma and 31 healthy patients). Macular sensitivity was also measured with an MP-1 microperimeter (Nidek Instruments, Inc Padova, Italy) with a customized, 36-stimulus pattern adjusted to an anatomical correspondence with the OCT grid. Correlations were calculated by using Spearman’s rho and the results were represented in color maps. Results: Significant structure–function correlations were much more frequent in the glaucoma group than in control group. In general terms, associations were positive for inner retinal layers but negative correlations were also found for the inner nuclear layer and outer retinal layer in glaucoma. Conclusions: In general terms, significant structure–function correlations for different intraretinal layers are higher and wider in POAG eyes than in healthy eyes. Inner and outer retinal layers behave differently in terms of the structure–function relationship in POAG as assessed by microperimetry and OCT. Full article

Cytokine- and chemokine-mediated signalling is involved in the neuroinflammatory process that leads to retinal ganglion cell (RGC) damage in glaucoma. Substances with anti-inflammatory properties could decrease these cytokines and chemokines and thus prevent RGC death. The authors of this study analysed the anti-inflammatory effect of a hydrophilic saffron extract standardized to 3% crocin content, focusing on the regulation of cytokine and chemokine production, in a mouse model of unilateral laser-induced ocular hypertension (OHT). We demonstrated that following saffron treatment, most of the concentration of proinflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-17), anti-inflammatory cytokines (IL-4 and IL-10), Brain-derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), and fractalkine were unaffected in response to laser-induced OHT in both the OHT eye and its contralateral eye. Only IL-6 levels were significantly increased in the OHT eye one day after laser induction compared with the control group. These results differed from those observed in animals subjected to unilateral OHT and not treated with saffron, where changes in cytokine levels occurred in both eyes. Therefore, saffron extract regulates the production of proinflammatory cytokines, VEGF, and fractalkine induced by increasing intraocular pressure (IOP), protecting the retina from inflammation. These results indicate that saffron could be beneficial in glaucoma by helping to reduce the inflammatory process. Full article

To evaluate the effects of an acrobatic gymnastics (AG) training session on intraocular pressure (IOP), a familiarization session was employed to confirm the participant’s suitability for the study. Forty-nine gymnasts (63.27% females, 18–40 years old) voluntarily agreed to participate. As age, sex, baseline IOP, and central corneal thickness (CCT) were considered as potential predictors of the IOP variations, in the second session measurements of the above parameters were taken before and after 90 min of AG. A mixed-factorial analysis of variance evaluated differences. Linear regression was conducted to potentially predict the IOP variation with the exercise. After the scheduled exercise, highly significant (p < 0.001, effect size: 0.73) reductions in IOP, but no significant changes in CCT (p = 0.229), were observed. IOP was significantly modified in males, older than 25 years, and subjects with baseline IOP > 14 mmHg (p ≤ 0.001, effect sizes: 0.57–1.02). In contrast, the IOP of females, younger participants, and subjects with baseline IOP ≤ 14 mmHg was not significantly modified (p = 0.114). With the regression analyses, we concluded that both sex and baseline IOP levels were significant predictors of the IOP fluctuation with AG. These findings could be of interest for gymnasts, coaches, ophthalmologists, and/or optometrists in the prevention and control of risk factors associated with glaucoma. Full article

Obesity contributes to multiple systemic disorders; however, extensive discussion regarding obesity and open-angle glaucoma (OAG) remains limited, and conclusions in the existing literature diverge. This study aims to analyze the risk of OAG among obese adults in Taiwan. In this study, adults (aged ≥18 years) with a diagnostic code of obesity or morbid obesity registered in the Longitudinal Health Insurance Database (LHID) 2000 and LHID2005 from 1 January 2001 to 31 December 2010 were included. All adults were traced until the diagnosis of OAG, the occurrence of death, or 31 December 2013. Risk of OAG was significantly higher in obese adults than in non-obese adults after multivariable adjustment (adjusted hazard ratio (aHR): 1.43 (95% confidence interval (CI) 1.11–1.84)/aHR: 1.54 (95% CI 1.23–1.94) in the LHID2000/LHID2005). Both databases demonstrated that young obese adults (aged ≤40 years) had a remarkably increased risk of OAG compared with young non-obese adults (aHR 3.08 (95% CI 1.82–5.21)/aHR 3.81 (95% CI 2.26–6.42) in the LHID2000/LHID2005). This two-database matched-cohort study suggests that obese adults have an increased risk of OAG. In young adults, in particular, obesity could be a potential risk factor of OAG. Full article

Background: Laguna-ONhE is an application for the colorimetric analysis of optic nerve images, which topographically assesses the cup and the presence of haemoglobin. Its latest version has been fully automated with five deep learning models. In this paper, perimetry in combination with Laguna-ONhE or Cirrus-OCT was evaluated. Methods: The morphology and perfusion estimated by Laguna ONhE were compiled into a “Globin Distribution Function” (GDF). Visual field irregularity was measured with the usual pattern standard deviation (PSD) and the threshold coefficient of variation (TCV), which analyses its harmony without taking into account age-corrected values. In total, 477 normal eyes, 235 confirmed, and 98 suspected glaucoma cases were examined with Cirrus-OCT and different fundus cameras and perimeters. Results: The best Receiver Operating Characteristic (ROC) analysis results for confirmed and suspected glaucoma were obtained with the combination of GDF and TCV (AUC: 0.995 and 0.935, respectively. Sensitivities: 94.5% and 45.9%, respectively, for 99% specificity). The best combination of OCT and perimetry was obtained with the vertical cup/disc ratio and PSD (AUC: 0.988 and 0.847, respectively. Sensitivities: 84.7% and 18.4%, respectively, for 99% specificity). Conclusion: Using Laguna ONhE, morphology, perfusion, and function can be mutually enhanced with the methods described for the purpose of glaucoma assessment, providing early sensitivity. Full article

Purpose: To evaluate and compare corneal hysteresis (CH), corneal resistance factor (CRF), and central corneal thickness (CCT), measurements were taken between a healthy population (controls), patients diagnosed with glaucoma (DG), and glaucoma suspect patients due to ocular hypertension (OHT), family history of glaucoma (FHG), or glaucoma-like optic discs (GLD). Additionally, Goldmann-correlated intraocular pressure (IOPg) and corneal-compensated IOP (IOPcc) were compared between the different groups of patients. Methods: In this prospective analytical-observational study, a total of 1065 patients (one eye of each) were recruited to undergo Ocular Response Analyzer (ORA) testing, ultrasound pachymetry, and clinical examination. Corneal biomechanical parameters (CH, CRF), CCT, IOPg, and IOPcc were measured in the control group (n = 574) and the other groups: DG (n = 147), FHG (n = 78), GLD (n = 90), and OHT (n = 176). We performed a variance analysis (ANOVA) for all the dependent variables according to the different diagnostic categories with multiple comparisons to identify the differences between the diagnostic categories, deeming p < 0.05 as statistically significant. Results: The mean CH in the DG group (9.69 mmHg) was significantly lower compared to controls (10.75 mmHg; mean difference 1.05, p < 0.001), FHG (10.70 mmHg; mean difference 1.00, p < 0.05), GLD (10.63 mmHg; mean difference 0.93, p < 0.05) and OHT (10.54 mmHg; mean difference 0.84, p < 0.05). No glaucoma suspects (FHG, GLD, OHT groups) presented significant differences between themselves and the control group (p = 1.00). No statistically significant differences were found in the mean CRF between DG (11.18 mmHg) and the control group (10.75 mmHg; mean difference 0.42, p = 0.40). The FHG and OHT groups showed significantly higher mean CRF values (12.32 and 12.41 mmHg, respectively) than the DG group (11.18 mmHg), with mean differences of 1.13 (p < 0.05) and 1.22 (p < 0.001), respectively. No statistically significant differences were found in CCT in the analysis between DG (562 μ) and the other groups (control = 556 μ, FHG = 576 μ, GLD = 569 μ, OHT = 570 μ). The means of IOPg and IOPcc values were higher in the DG patient and suspect groups than in the control group, with statistically significant differences in all groups (p < 0.001). Conclusion: This study presents corneal biomechanical values (CH, CRF), CCT, IOPg, and IOPcc for diagnosed glaucoma patients, three suspected glaucoma groups, and a healthy population, using the ORA. Mean CH values were markedly lower in the DG group (diagnosed with glaucoma damage) compared to the other groups. No significant difference was found in CCT between the DG and control groups. Unexpectedly, CRF showed higher values in all groups than in the control group, but the difference was only statistically significant in the suspect groups (FHG, GLD, and OHT), not in the DG group. Full article

We analyzed the vascular densities (VDs) of the optic disc areas in eyes with normal-tension glaucoma (NTG) according to their branch retinal vessel occlusion (BRVO) status. The VDs of the optic discs and peripapillary areas of 68 NTG patients with BRVO (BRVO group; BRVO eyes and fellow eyes) and 37 patients with NTG alone (control eyes) were measured on angiographic images obtained via swept-source optical coherence tomography angiography. VDs were compared among groups and correlations were assessed. The VD of the optic disc large vessel was the highest in BRVO eyes, followed by the fellow eyes and controls (all P < 0.05). Conversely, small and medium vessel VD was in the opposite order (all P < 0.05). Large vessel VD was negatively correlated with small and medium vessel VD (r = −0.697, P < 0.001). Peripapillary VD was lower in the BRVO eyes than in the control and fellow eyes (P < 0.001 and P = 0.861, respectively). In conclusion, significant changes in the distribution of VDs for optic disc larger vessel and small and medium vessels were observed in both eyes of NTG patients with BRVO, compared to NTG patients without BRVO. Full article

Purpose: To investigate the association of decreased vessel density (VD) in the deep peripapillary region and structural features of the lamina cribrosa (LC). Materials and Methods: 70 eyes of glaucoma suspects with enlarged cup-to-disc ratio were scanned and 51 eyes with adequate image quality were included in this study. All subjects had localized VD defects in the deep layer but intact VD in the superficial layer around the peripapillary region using optical coherence tomography angiography (OCTA). Only single-hemizone OCTA results from one eye of each subject had to fulfill the distinctive feature mentioned above to perform inter-eye and inter-hemizone comparisons. The thickness and depth of the LC, and prelaminar thickness were measured using enhanced depth imaging OCT (EDI-OCT). Paired t-tests were performed to evaluate differences in measurements of the LC and prelaminar thickness within each individual. p-values lower than 0.05 was considered to be statistically significant. Results: Eyes with deep VD defects in the peripapillary region in OCTA had thinner LC than the fellow eyes. The hemizone with the deep VD defects in the peripapillary region had a thinner LC and a deeper depth of LC than the other hemizone in the same eye. According to logistic regression analysis, a thin LC was a significant factor associated with deep VD defect in the peripapillary region. Conclusions: Glaucoma suspect eyes with deep VD defects in the peripapillary area exhibited structural differences in the LC. The structural changes of the LC was associated with the vessel density in the deep peripapillary layer at the stage of suspected glaucoma. Full article

Glaucoma has no cure and is a sight-threatening neurodegenerative disease affecting more than 100 million people worldwide, with primary open angle glaucoma (POAG) being the most globally prevalent glaucoma clinical type. Regulation of gene expression and gene networks, and its multifactorial pathways involved in glaucoma disease are landmarks for ophthalmic research. MicroRNAs (miRNAs/miRs) are small endogenous non-coding, single-stranded RNA molecules (18–22 nucleotides) that regulate gene expression. An analytical, observational, case-control study was performed in 42 patients of both sexes, aged 50 to 80 years, which were classified according to: (1) suffering from ocular hypertension (OHT) but no glaucomatous neurodegeneration (ND) such as the OHT group, or (2) have been diagnosed of POAG such as the POAG group. Participants were interviewed for obtaining sociodemographic and personal/familial records, clinically examined, and their tear samples were collected and frozen at 80 °C until processing for molecular-genetic assays. Tear RNA extraction, libraries construction, and next generation sequencing were performed. Here, we demonstrated, for the first time, the differential expression profiling of eight miRNAs when comparing tears from the OHT versus the POAG groups: the miR-26b-5p, miR-152-3p, miR-30e-5p, miR-125b-2-5p, miR-224-5p, miR-151a-3p, miR-1307-3p, and the miR-27a-3p. Gene information was set up from the DIANA-TarBase v7, DIANA-microT-CDS, and TargetScan v7.1 databases. To build a network of metabolic pathways, only genes appearing in at least four of the following databases: DisGeNet, GeneDistiller, MalaCards, OMIM PCAN, UniProt, and GO were considered. We propose miRNAs and their target genes/signaling pathways as candidates for a better understanding of the molecular-genetic bases of glaucoma and, in this way, to gain knowledge to achieve optimal diagnosis strategies for properly identifying HTO at higher risk of glaucoma ND. Further research is needed to validate these miRNAs to discern the potential role as biomarkers involved in oxidative stress, immune response, and apoptosis for the diagnosis and/or prognosis of OHT and the prevention of glaucoma ND. Full article

(1) Purpose: To assess the main corneal response differences between normal and subclinical keratoconus (SCKC) with a Corvis^® ST device. (2) Material and Methods: We selected 183 eyes of normal patients, of a mean age of 33 ± 9 years and 16 eyes of patients with SCKC of a similar mean age. We measured best corrected visual acuity (BCVA) and corneal topography with a Pentacam HD device to select the SCKC group. Biomechanical measurements were performed using the Corvis^® ST device. We carried out a non-parametric analysis of the data with SPSS software (Wilcoxon signed rank-test). (3) Results: We found statistically significant differences between the control and SCKC groups in some corneal biomechanical parameters: first and second applanation time (p = 0.05 and p = 0.02), maximum deformation amplitude (p = 0.016), highest concavity radius (p = 0.007), and second applanation length and corneal velocity ((p = 0.039 and p = 0.016). (4) Conclusions: Our results show that the use of normalised biomechanical parameters provided by noncontact tonometry, combined with a discriminant function theory, is a useful tool for detecting subclinical keratoconus. Full article

Oxidative stress and neuroinflammation are involved in the pathogenesis and progression of glaucoma. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in inflammation and oxidative stress genes on the risk of glaucoma, the patients’ clinical characteristics and the glaucoma phenotype. In total, 307 patients with primary open-angle glaucoma or ocular hypertension were enrolled. The control group included 339 healthy Slovenian blood donors. DNA was isolated from peripheral blood. Genotyping was performed for SOD2 rs4880, CAT rs1001179, GPX1 rs1050450, GSTP1 rs1695, GSTM1 gene deletion, GSTT1 gene deletion, IL1B rs1143623, IL1B rs16944, IL6 rs1800795 and TNF rs1800629. We found a nominally significant association of GSTM1 gene deletion with decreased risk of ocular hypertension and a protective role of IL1B rs16944 and IL6 rs1800629 in the risk of glaucoma. The CT and TT genotypes of GPX1 rs1050450 were significantly associated with advanced disease, lower intraocular pressure and a larger vertical cup–disc ratio. In conclusion, genetic variability in IL1B and IL6 may be associated with glaucoma risk, while GPX and TNF may be associated with the glaucoma phenotype. In the future, improved knowledge of these pathways has the potential for new strategies and personalised treatment of glaucoma. Full article

We evaluated the effects of ripasudil on the distal aqueous outflow tract in patients with open-angle glaucoma (OAG) who underwent a 360° suture trabeculotomy ab interno followed by ripasudil treatment beginning 1 month postoperatively. We compared 27 of these patients, by using propensity score analysis, with 27 patients in a matched control group who had no ripasudil treatment. We assessed the changes in the mean intraocular pressure (IOP) and the relationship between the IOP changes and background factors. All eyes had a complete 360° Schlemm’s canal incision and phacoemulsification. The mean IOP at 1 and 3 months after ripasudil administration were significantly reduced by −1.7 ± 1.9 mmHg (p < 0.0001) and −1.3 ± 2.3 mmHg (p = 0.0081) in the ripasudil group, respectively, but IOP in the control group was not significantly reduced. The IOP reduction was significantly associated with the IOP before ripasudil treatment (p < 0.001). In conclusion, the use of ripasudil for patients with OAG after circumferential incision of the Schlemm’s canal produced significant IOP reductions. Ripasudil may affect the distal outflow tract, thereby leading to the IOP reduction. Full article

Some discrepancies have been observed in the diagnostic efficacy of multifocal visual evoked potential (mfVEP) when evaluating visual field defects in glaucoma patients. Therefore, we evaluated the diagnostic precision of the mfVEP in glaucoma to find its best diagnostic indicator. A systematic review and meta-analysis of quantitative studies published up to 1 April 2021 was performed. The methodological quality of the included articles was assessed. Publication bias analysis and heterogeneity tests were performed. The sensitivity, specificity and diagnostic odds ratio were calculated. The area under the curve (AUC) was calculated using the summary of receiver operating characteristics curve. Six studies with a total of 241 patients were included according to the inclusion and exclusion criteria. The AUC was 0.98. There was no evidence of publication bias or threshold effect. The pooled sensitivity and pooled specificity of the mfVEP amplitude for detection of visual field defects in all studies was 0.93 and 0.89, respectively. The positive and negative likelihood ratios of mfVEP amplitude were 6.56 and 0.08, respectively. The amplitude of mfVEP showed a good diagnostic precision in the prediction of visual field defects. Interocular mfVEP amplitude analysis can be a good diagnostic indicator for visual field study. Full article