Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals.

PURPOSE: To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. DESIGN: Cross-sectional analysis. PARTICIPANTS: Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study). METHODS: We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements. MAIN OUTCOME MEASURE: Proportion of patients with POAG after stratification according to the GRS. RESULTS: We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35-8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79-9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure (r = 0.08: P = 4.0 × 10-4) and vertical cup-to-disc ratio (r = 0.11; P = 4.0 × 10-6). CONCLUSIONS: The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effectiveness of remote risk-based monitoring and potential benefits for combination with direct data capture.

BACKGROUND: In recent years, alternative monitoring approaches, such as risk-based and remote monitoring techniques, have been recommended instead of traditional on-site monitoring to achieve more efficient monitoring. Remote risk-based monitoring (R2BM) is a monitoring technique that combines risk-based and remote monitoring and focuses on the detection of critical data and process errors. Direct data capture (DDC), which directly collects electronic source data, can facilitate R2BM by minimizing the extent of source documents that must be reviewed and reducing the additional workload on R2BM. In this study, we evaluated the effectiveness of R2BM and the synergistic effect of combining R2BM with DDC. METHODS: R2BM was prospectively conducted with eight participants in a randomized clinical trial using a remote monitoring system that uploaded photographs of source documents to a cloud location. Critical data and processes were verified by R2BM, and later, all were confirmed by on-site monitoring to evaluate the ability of R2BM to detect critical data and process errors and the workload of uploading photographs for clinical trial staff. In addition, the reduction of the number of uploaded photographs was evaluated by assuming that the DDC was introduced for data collection. RESULTS: Of the 4645 data points, 20.9% (n = 973, 95% confidence interval = 19.8-22.2) were identified as critical. All critical data errors corresponding to 5.4% (n = 53/973, 95% confidence interval = 4.1-7.1) of the critical data and critical process errors were detectable by R2BM. The mean number of uploaded photographs and the mean time to upload them per visit per participant were 34.4 ± 11.9 and 26.5 ± 11.8 min (mean ± standard deviation), respectively. When assuming that DDC was introduced for data collection, 45.0% (95% confidence interval = 42.2-47.9) of uploaded photographs for R2BM were reduced. CONCLUSIONS: R2BM can detect 100% of the critical data and process errors without on-site monitoring. Combining R2BM with DDC reduces the workload of R2BM and further improves its efficiency.

The relationship between equol production status and normal tension glaucoma.

PURPOSE: Equol is metabolized by intestinal bacteria from soy isoflavones and is chemically similar to estrogen. Dietary habits, such as consumption of soy products, influence equol production. A relationship between glaucoma and estrogen has been identified; here, we investigated the relationship between equol production status and glaucoma in Japan. METHODS: We recruited 68 normal-tension glaucoma (NTG) patients (male to female ratio 26:42, average age 63.0 ± 7.6 years) and 31 controls (male to female ratio 13:18, average age 66.0 ± 6.3 years) from our hospital. All women included were postmenopausal. Urinary equol concentration was quantified with the ELISA method. MD was calculated based on the Humphrey visual field. The association between MD and equol was analyzed with Spearman's rank correlation coefficient. The Mann-Whitney U test was used to compare the equol-producing (> 1 µM) and non-producing (< 1 µM) subjects. We also investigated the association between equol and glaucoma with a logistic regression analysis. RESULTS: There was a significant association between equol and MD (r = 0.36, P < 0.01) in the NTG patients. Glaucoma, represented by MD, was significantly milder in the equol-producing subjects than the non-equol producing subjects (P = 0.03). A multivariate analysis revealed the independent contributions of equol, cpRNFLT, and IOP to MD (P = 0.03, P = 0.04, and P < 0.01, respectively). CONCLUSION: Our results suggest that equol, acting through estrogen receptor-mediated neuroprotective effects, might be involved in suppressing the progression of NTG. This result also adds to evidence that glaucoma may be influenced by lifestyle.

SH-SY5Y human neuronal cells with mutations of the CDKN2B-AS1 gene are vulnerable under cultured conditions.

Glaucoma is a common cause of blindness worldwide. Genetic effects are believed to contribute to the onset and progress of glaucoma, but the underlying pathological mechanisms are not fully understood. Here, we set out to introduce mutations into the CDKN2B-AS1 gene, which is known as being the closely associated with glaucoma, in a human neuronal cell line in vitro. We introduced gene mutations with CRISPR/Cas9 into exons and introns into the CDKN2B-AS1 gene. Both mutations strongly promoted neuronal cell death in normal culture conditions. RNA sequencing and pathway analysis revealed that the transcriptional factor Fos is a target molecule regulating CDKN2B-AS1 overexpression. We demonstrated that gene mutation of CDKN2B-AS1 is directly associated with neuronal cell vulnerability in vitro. Additionally, Fos, which is a downstream signaling molecule of CDKN2B-AS1, may be a potential source of new therapeutic targets for neuronal degeneration in diseases such as glaucoma.

Comparative features of superior versus inferior hemisphere microvasculature dropout in open-angle glaucoma.

PURPOSE: This study aimed to investigate differences in microvasculature dropout (MvD) between the superior and inferior hemispheres in glaucoma patients. STUDY DESIGN: Retrospective and cross-sectional. METHODS: Fifty-eight eyes of 58 open-angle glaucoma patients (age 61.12 ± 10.19 years, mean deviation - 7.32 ± 6.36 dB) were included. MvD was detected with en face images from swept-source optical coherence tomography angiography. Blood flow at the optic nerve head was measured with laser speckle flowgraphy, represented as the mean blur rate in tissue (MBRT). Logistic and linear regression models adjusted for age, intraocular pressure, axial length, and circumpapillary retinal nerve fiber layer thickness were used to investigate the relationship between various factors and MvD angle in each hemisphere. RESULTS: The presence of inferior MvD was related to peripapillary atrophy-ß area (odds ratio = 14.10 [2.49-234.00], P = 0.019). Superior MvD angle was significantly related to MBRT in the superior quadrant (ß = -0.31 [- 0.60 - -0.02], P = 0.037). Inferior MvD angle was significantly related to peripapillary atrophy-ß area (ß = 0.49 [0.21-0.77], P = 0.001). CONCLUSIONS: Only superior MvD demonstrated a significant relationship with reduced ocular blood flow. In contrast, inferior MvD was associated with mechanical stress. These findings may suggest a potential difference in pathophysiology between superior and inferior MvD.

New Dihydropyridine Derivative Attenuates NF-κB Activation via Suppression of Calcium Influx in a Mouse BV-2 Microglial Cell Line.

Activated microglia contribute to many neuroinflammatory diseases in the central nervous system. In this study, we attempted to identify an anti-inflammatory compound that could suppress microglial activation. We performed high-throughput screening with a chemical library developed at our institute. We performed a luciferase assay of nuclear factor-kappa B (NF-κB) reporter stable HT22 cells and identified a compound that was confirmed to inhibit the anti-inflammatory response in BV2 microglial cells. The selected dihydropyridine derivative can suppress the expression response of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor (TNF), as well as NF-κB phosphorylation and nuclear translocation, and reduce the intracellular calcium level. Thus, our identified compound has a potential role in suppressing microglial activation and may contribute to the development of a new therapeutic molecule against neuroinflammatory diseases.

Mobile infrared slit-light scanner for rapid eye disease screening.

Purpose: Timely detection and treatment of visual impairments and age-related eye diseases are essential for maintaining a longer, healthier life. However, the shortage of appropriate medical equipment often impedes early detection. We have developed a portable self-imaging slit-light device utilizing NIR light and a scanning mirror. The objective of our study is to assess the accuracy and compare the performance of our device with conventional nonportable slit-lamp microscopes and anterior segment optical coherence tomography (AS-OCT) for screening and remotely diagnosing eye diseases, such as cataracts and glaucoma, outside of an eye clinic. Approach: The NIR light provides an advantage as measurements are nonmydriatic and less traumatic for patients. A cross-sectional study involving Japanese adults was conducted. Cataract evaluation was performed using photographs captured by the device. Van-Herick grading was assessed by the ratio of peripheral anterior chamber depth to peripheral corneal thickness, in addition to the iridocorneal angle using Image J software. Results: The correlation coefficient between values obtained by AS-OCT, and our fabricated portable scanning slit-light device was notably high. The results indicate that our portable device is equally reliable as the conventional nonportable slit-lamp microscope and AS-OCT for screening and evaluating eye diseases. Conclusions: Our fabricated device matches the functionality of the traditional slit lamp, offering a cost-effective and portable solution. Ideal for remote locations, healthcare facilities, or areas affected by disasters, our scanning slit-light device can provide easy access to initial eye examinations and supports digital eye healthcare initiatives.

Changes in ocular blood flow in patients with neovascular age-related macular degeneration after intravitreal injection of ranibizumab biosimilar and brolucizumab.

PURPOSE: To assess ocular blood flow (OBF) changes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injections of ranibizumab biosimilar (IVRbs) or brolucizumab (IVBr). METHODS: This retrospective longitudinal study included 43 eyes of 43 patients (74.5 ± 9.8 years old, male to female ratio 31:12) with nAMD treated with IVBr (29 eyes) or IVRbs (14 eyes). OBF in the optic nerve head (ONH) and choroid (Ch) was measured with laser speckle flowgraphy (Softcare Co., Ltd., Fukutsu, Japan) before and one month after treatment. Changes in mean blur rate (MBR) before and after each treatment were tested using Wilcoxon's signed-rank tests and mixed-effect models for repeated measures. RESULTS: In the IVBr group, MBR was significantly reduced in both the ONH and Ch (p < 0.01). In contrast, the IVRbs group showed no significant change in MBR in either the ONH or Ch (p = 0.56, p = 1). The linear mixed effect model showed a significant interaction between time and anti-VEGF drugs for MBR in both the ONH and Ch (ONH: p = 0.04; Ch: p = 0.002). A post hoc pairwise comparison of estimated marginal means showed that MBR decreased significantly only after IVBr (p < 0.001). CONCLUSION: Our findings suggest that the short-term impact on OBF varies depending on the drug used for nAMD.

Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases.

BACKGROUND: As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases. METHODS: We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines. RESULTS: A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases. CONCLUSION: A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.

Sector-specific Association of Intraocular Pressure Dynamics in Dark-room Prone Testing and Visual Field Defect Progression in Glaucoma.

PURPOSE: To investigate sectoral differences in the relationship between intraocular pressure (IOP) dynamics during dark-room prone testing (DRPT) and visual field (VF) defect progression in primary open-angle glaucoma (POAG) patients. DESIGN: Retrospective, longitudinal study. PARTICIPANTS: This retrospective study included 116 eyes of 84 POAG patients who underwent DRPT and had at least 5 reliable VF tests conducted over a more than 2-year follow-up period. We excluded eyes with mean deviation worse than -20 dB or a history of intraocular surgery or laser treatment. METHODS: Average total deviation (TD) was calculated in the superior, central, and inferior sectors of the Humphrey 24-2 or 30-2 program. During DRPT, IOP was measured in the sitting position, and after 60 minutes in the prone position in a dark room, IOP was measured again. The relationship between IOP change during DRPT, IOP after DRPT, and TD slope in each quadrant was analyzed with a linear mixed-effects model, adjusting for other potential confounding factors. MAIN OUTCOME MEASURES: Total deviation slope in each quadrant, IOP change during DRPT, and IOP after DRPT. RESULTS: Intraocular pressure after DRPT and IOP change during DRPT were 18.16 ± 3.42 mmHg and 4.92 ± 3.12 mmHg, respectively. Superior TD slope was significantly associated with both IOP after DRPT (ß = -0.28, P = 0.003) and IOP change during DRPT (ß = -0.21, P = 0.029), while central (ß = -0.05, P = 0.595; ß = -0.05; P = 0.622) and inferior (ß = 0.05, P = 0.611; ß = 0.01, P = 0.938) TD slopes were not. CONCLUSION: Dark-room prone testing might be a useful test to predict the risk of superior VF defect progression in eyes with POAG. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The Relationship Between Artificial Intelligence-Assisted OCT Angiography-Derived Foveal Avascular Zone Parameters and Visual-Field Defect Progression in Eyes with Open-Angle Glaucoma.

Purpose: To investigate clinical factors associated with foveal avascular zone (FAZ) parameters obtained using OCT angiography (OCTA) with assistance from a previously developed artificial intelligence (AI) platform in eyes with open-angle glaucoma (OAG). Design: Retrospective longitudinal. Participants: This study followed up 885 eyes of 558 patients with OAG for ≥ 2 years; all eyes underwent ≥ 5 Humphrey visual-field (VF) tests and had 3.0 × 3.0 mm macular OCTA scans available. Methods: Average total deviation (TD) in the superior, superocentral, inferocentral, and inferior sectors of the Humphrey 24-2 program was calculated. We collected 3.0 × 3.0 mm macular OCTA images from each patient and used a previously developed AI platform with these images to obtain FAZ parameters, including FAZ area, FAZ circularity index (CI), and FAZ perimeter. Multivariable linear mixed-effects models were used to analyze the relationship between FAZ parameters, TD or TD slope in each quadrant, and systemic factors, adjusting for potential confounding factors, including axial length. Main Outcome Measures: Ophthalmic and systemic variables, FAZ parameters, and TD or TD slope in each quadrant. Results: The multivariable model showed that FAZ parameters were correlated with both TD and TD slope in the inferocentral quadrant (ß = -0.244 - 0.168, P < 0.001). Both upper-half and lower-half FAZ parameters were better associated with TD-inferocentral and TD-inferocentral slope than TD-superocentral or TD-superocentral slope in terms of ß size and statistical significance, indicating that there was no evident vertical anatomical correspondence between TD in the central quadrant and FAZ parameters. Foveal avascular zone area enlargement was associated with female gender (ß = 0.242, P = 0.003). Loss of FAZ circularity was associated with both aging and comorbid sleep apnea syndrome (SAS) (yes: 1, no: 0) (ß = -0.188, P < 0.001; ß = -0.261, P = 0.031, respectively). Foveal avascular zone perimeter elongation was associated with aging and female gender (ß = 0.084, P = 0.040; ß = 0.168, P = 0.042, respectively). Conclusions: Artificial intelligence-assisted OCTA-measured FAZ enlargement and irregular shape might be good markers of ocular hypoperfusion and associated inferocentral VF defect progression in eyes with OAG. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Uric acid-driven NLRP3 inflammasome activation triggers lens epithelial cell senescence and cataract formation.

Excessive uric acid (UA) is associated with age-related cataract. A previous study showed that a high UA level in the aqueous humor stimulated the senescence of lens epithelial cells (LECs), leading to cataract progression. To better understand the underlying mechanisms, we investigated UA-driven senescence in human lens tissue samples obtained during surgery, rat lens organ cultures, and in vivo experiments, using senescence-associated ß-galactosidase (SA-ß-gal) staining, electronic microscopy, Western blotting, and histological analyses. Initially, we identified markedly higher expressions of NLRP3 and caspase-1 in the lens capsules of hyper-uricemic patients compared to normo-uricemic patients. This increase was accompanied by a significant rise in the SA-ß-gal positive rate. We next built a cataract model in which rat lenses in an organ culture system were treated with an increasing dosage of UA. Notably, opacification was apparent in the lenses treated with 800 µM of UA starting on the fifth day. Mechanistically, UA treatment not only significantly induced the expression of NLRP3, caspase-1, and IL-1ß, but also upregulated the levels of SA-ß-gal and the senescence regulators p53 and p21. These effects were fully reversed, and lens opacification was ameliorated by the addition of MCC950, a selective NLRP3 antagonist. Moreover, an in vivo model showed that intravitreal UA injection rapidly induced cataract phenotypes within 21 days, an effect significantly mitigated by co-injection with MCC950. Together, our findings suggest that targeting the UA-induced NLRP3 inflammasome with MCC950 could be a promising strategy for preventing cataract formation associated with inflammageing.

Effects of Deep Optic Nerve Head Structures on Bruch's Membrane Opening- Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer.

PURPOSE: To explore the effects of deep optic nerve head (ONH) structures on Bruch's membrane opening (BMO)-minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in healthy eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred five healthy eyes of 141 subjects (mean ± standard deviation of age and axial length (AXL): 46.9 ± 10.0 years and 24.79 ± 1.15 mm) were enrolled. Best fit multivariable linear mixed models identified factors associated with BMO-MRW and pRNFLT. Explanatory variables included age, gender, AXL, BMO and anterior scleral canal opening (ASCO) area and ovality, magnitude of BMO and ASCO shift, peripapillary choroidal thickness, lamina cribrosa (LC) parameters, prelaminar thickness, and peripapillary scleral (PPS) angle. RESULTS: Thinner BMO-MRW was associated with older age, smaller ASCO/BMO offset magnitude, larger BMO area, thinner prelaminar thickness, deeper LC, and thinner pRNFLT (P = .011, <.001, .004, <.001, <.001, <.001 respectively). Thinner pRNFLT was associated with shorter AXL, smaller ASCO area, a more posteriorly bowed PPS, shallower LC and thinner BMO-MRW. (P = .030, .002, .035, .012, <.001 respectively) CONCLUSIONS: BMO-MRW and pRNFLT were influenced by several deep ONH structures such as BMO and ASCO position shift, BMO or ASCO area, prelaminar thickness, PPS bowing and LC depth in addition to patient characteristics such as age and AXL. The degree and/or direction of associations varied between deep ONH structures and BMO-MRW or pRNFLT. Despite both BMO-MRW and pRNFLT being surrogate parameters for RGC loss, a complex relationship with ONH deep-layer morphology was indicated.

Vitreous Surgery for Giant Temporal Intrachoroidal Cavitation.

A 50-year-old woman had visual disturbance in her left eye. Optical coherence tomography (OCT) revealed an epiretinal membrane (ERM) and a giant peripapillary intrachoroidal cavitation (ICC). Best-corrected visual acuity (BCVA) was 15/50 in the left eye with central visual field (VF) impairment. We performed vitrectomy with internal limiting membrane "stuffing" into the sinkhole, as well as peeling of the ERM. One year after surgery, even though ocular blood flow had decreased and the VF impairment had worsened, OCT demonstrated that the ICC had completely disappeared, and BCVA had improved to 25/50. Although this technique can increase BCVA, the potential surgical risk of exacerbating VF impairment calls for careful consideration on a case-by-case basis. [Ophthalmic Surg Lasers Imaging Retina 2024;55:231-234.].

The Effect of ß-Blocker Eye Drops on Pulse Rate, Ocular Blood Flow, and Glaucoma Progression: A Retrospective Longitudinal Study.

INTRODUCTION: Our study was conducted to determine factors associated with the effectiveness of a ß-blocker eye drop add-on in altering pulse rate (PR) in glaucoma patients. METHODS: This retrospective study examined 236 eyes of 138 patients who received a ß-blocker eye drop add-on during follow-up. Patients were included if at least one PR measurement was available both before and after the add-on was started. We collected data on ophthalmic parameters: longitudinal PR; longitudinal choroidal blood flow, represented by laser speckle flowgraphy-measured mean blur rate (MBR); and diacron-reactive oxygen metabolites (d-ROMs). We used a multivariable linear mixed-effects model to investigate the effectiveness of the ß-blocker eye drop add-on in altering PR and examined factors contributing to a larger PR alteration after the add-on was started by analyzing the effect on PR of the interaction term between the add-on and clinical factors. We used the k-means method to classify the patients. RESULTS: The ß-blocker eye drop add-on reduced PR (- 7.61 bpm, P < 0.001). Female gender, higher PR when the add-on was started, lower central corneal thickness, and a higher d-ROM level were associated with greater reduction in PR (P < 0.05). In a cluster of patients with these clinical features, choroidal MBR increased by + 3.42% when we adjusted for change over time; MD slope, which represents the speed of glaucoma progression, improved by + 0.64 dB/year (P < 0.05). CONCLUSIONS: We identified a glaucoma subgroup in which PR decreased, choroidal blood flow increased, and glaucoma progression slowed after a ß-blocker eye drop add-on was started.

Relationship between nailfold capillaroscopy parameters and the severity of diabetic retinopathy.

PURPOSE: To determine whether non-invasive measurements of the nailfold capillaries (NCs) are associated with the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: Eighty-three eyes of 83 patients with type 2 diabetes were enrolled. Sixty-three age-matched non-diabetic subjects served as controls. Diabetic patients were classified by the severity of their DR: non-DR (NDR), non-proliferative DR (NPDR), and proliferative DR (PDR). We used nailfold capillaroscopy to measure NC parameters, including number, length, width, and turbidity. RESULTS: Four NC parameters in the diabetic patients were significantly lower than in the controls (all P < 0.001). There was a statistically significant decrease in the NC parameters along with the increasing severity of DR (number: P = 0.02; all others: P < 0.001). Logistic regression analysis revealed that combining the systemic characteristics of age, sex, systolic blood pressure, estimated glomerular filtration rate, hemoglobin A1c level, and history of hypertension and dyslipidemia could indicate the presence of DR and PDR (the area under the receiver operating characteristic curve [AUC] = 0.81, P = 0.006; AUC = 0.87, P = 0.001, respectively). Furthermore, the discriminative power of DR was significantly improved (P = 0.03) by adding NC length to the systemic findings (AUC = 0.89, P < 0.001). CONCLUSION: NC measurement is a simple and non-invasive way to assess the risk of DR and its severity.

Factors associated with intrachoroidal cavitation and sinkhole formation in eyes with glaucomatous visual-field defects.

PURPOSE: To investigate factors associated with intrachoroidal cavitation (ICC) and sinkhole formation in eyes with glaucomatous visual-field defects. METHODS: This retrospective, cross-sectional study enrolled a total of 2808 eyes of 1482 patients who were diagnosed/treated for glaucoma and underwent swept-source optical coherence tomography (OCT). We first determined the prevalence of ICCs and sinkholes and their locations. Next, we selected one eye from each patient and compared the clinical characteristics of eyes with and without ICCs. Finally, in eyes with ICCs, we compared the clinical characteristics of eyes with and without sinkholes. Blood flow (BF), represented by laser speckle flowgraphy-measured tissue-area mean blur rate (MBR), was measured in the temporal optic nerve head (ONH), temporal peripapillary chorioretinal atrophy (PPA) zone, and in the ICC zone. ICC area and angle were analyzed in OCT en-face images. Mean deviation and total deviation in the central area (TD-central) were measured with Humphrey visual-field testing. RESULTS: A total of 86 eyes (3.1%) had ICCs and 52 eyes (1.9%) had sinkholes. ICC eyes had a lower spherical equivalent and longer axial length (AL) than non-ICC eyes (P < 0.05). Patients with eyes with sinkholes were more elderly and had worse best-corrected visual acuity, worse TD-central, a larger ICC, and lower tissue-area MBR in the temporal ONH, temporal PPA zone, and ICC zone (P < 0.05). CONCLUSION: In eyes with glaucoma, AL elongation might be linked to ICC formation. Sinkhole formation might be associated with ICC enlargement, impaired ocular BF, and impaired retinal structure and function involving the central area.

The association between intraocular pressure dynamics during dark-room prone testing and intraocular pressure over a relatively long-term follow-up period in primary open-glaucoma patients.

PURPOSE: To investigate the relationship between the dynamics of intraocular pressure (IOP) during dark-room prone testing (DRPT) and IOP over a relatively long-term follow-up period. METHODS: This retrospective study enrolled 84 eyes of 51 primary open-angle glaucoma patients who underwent DRPT for whom at least three IOP measurements made using Goldmann applanation tonometry were available over a maximum follow-up period of two years. We excluded eyes with a history of intraocular surgery or laser treatment and those with changes in topical anti-glaucoma medication during the follow-up period. In DRPT, IOP was measured in the sitting position, and after 60 min in the prone position in a dark room, IOP was measured again. In this study, IOP fluctuation refers to the standard deviation (SD) of IOP, and IOP max indicates the maximum value of IOP during the follow-up. The relationship between these parameters was analyzed with a linear mixed-effects model, adjusting for clinical parameters including age, gender, and axial length. RESULTS: IOP increased after DRPT with a mean of 6.13 ± 3.55 mmHg. IOP max was significantly associated with IOP after DRPT (ß = 0.38; p < 0.001). IOP fluctuation was significantly associated with IOP change in DRPT (ß = 0.29; p = 0.007). CONCLUSION: Our findings suggest that short-term and relatively long-term IOP dynamics are associated. Long-term IOP dynamics can be predicted by DRPT to some extent.