Association of SDF-1 and its receptor CXCR4 polymorphisms on the susceptibility of diabetic retinopathy in the Taiwanese population.

Stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine 4 (CXCR4) have been demonstrated to play critical roles in diabetic retinopathy (DR). This study investigated whether single-nucleotide polymorphisms (SNPs) of SDF-1 and its receptor CXCR4 are correlated with diabetic retinopathy (DR). Three SDF-1 SNPs, namely, rs1801157 (G/A), rs2297630 (G/A), and rs266085 (T/C), and two CXCR4 SNPs, namely, rs2228014 (C/T) and rs6430612 (C/T), were chosen and genotyped via the TaqMan allelic discrimination for 454 non-DR subjects and 276 DR individuals. Our results revealed that subjects carrying SDF-1 SNP rs2297630 GA (AOR: 2.962, 95% CI: 1.279-6.861, p = 0.011) and SDF-1 SNP rs2297630 GA + AA (AOR: 3.095, 95% CI: 1.394-6.872, p = 0.006) had significantly higher risk in the non-proliferative diabetic retinopathy (NPDR) groups than in the non-DR group. Further analyses using the datasets from the Genotype-Tissue Expression (GTEx) Portal revealed that SDF-1 SNP rs2297630 GA and AA genotypic variants have higher SDF-1 expression than the GG wild-type alleles (p = 0.000016). In conclusion, our findings revealed that SDF-1 SNP rs2297630 was associated with NPDR.

The Utilization of Glucagon-like Peptide 1 Agonists and Risk of Following External Eye Diseases in Type 2 Diabetes Mellitus Individuals: A Population-Based Study.

The glucagon-like peptide 1 (GLP-1) agonist showed anti-hyperglycemic and anti-inflammatory effects, which may retard the risk of external eye disease. The protective effect of GLP-1 agonist and dry eye disease (DED) was found, while the relationship between GLP-1 agonist and other corneal diseases was not clear. Herein, we aim to evaluate the association between the usage of GLP-1 agonists and the development of the following external eye disease in type 2 diabetes mellitus (T2DM) patients. A retrospective cohort study using the National Health Insurance Research Database (NHIRD) of Taiwan was conducted. The T2DM patients were divided into those with GLP-1 treatment and those without GLP-1 treatment and matched with a 1:2 ratio. The main outcomes were the development of dry eye disease (DED), superficial keratitis, and infectious keratitis. The Cox proportional hazard regression was adopted to produce the adjusted hazard ratio (aHR) with a 95% confidence interval (CI) of external eye diseases between groups. There were 115, 54, and 11 episodes of DED, superficial keratitis, and infectious keratitis in the GLP-1 group. Another 280, 168, and 31 events of DED, superficial keratitis, and infectious keratitis were recorded in the control group. The GLP-1 group demonstrated a significantly lower incidence of DED (aHR: 0.853, 95% CI: 0.668-0.989, p = 0.0356) and superficial keratitis (aHR: 0.670, 95% CI: 0.475-0.945, p = 0.0107) compared to the control group. In the subgroup analyses, the correlation of GLP-1 agonist and DED development was more prominent in patients younger than 60 years old (p = 0.0018). In conclusion, the GLP-1 agonist treatments are significantly associated with a lower incidence of subsequent DED and superficial keratitis, while the relationship was not significant between GLP-1 agonist usage and infectious keratitis.

Association of Long Non-Coding RNA Growth Arrest-Specific 5 Genetic Variants with Diabetic Retinopathy.

The aim of this work was to appraise the potential associations of single nucleotide polymorphisms (SNPs) of long non-coding RNA growth arrest-specific 5 (GAS5) with diabetic retinopathy (DR) in a diabetes mellitus (DM) population. Two loci of the GAS5 SNPs (rs55829688 and rs145204276) were genotyped via TaqMan allelic discrimination in 449 non-DR patients and 273 DR subjects. The SNP rs145204276 Del/Del showed a significantly higher distribution in the DR group compared to the non-DR group (AOR: 2.487, 95% CI: 1.424-4.344, p = 0.001). During subgroup analyses, the non-proliferative diabetic retinopathy (NPDR) subgroup demonstrated a significantly higher ratio of the SNP rs145204276 Del/Del (AOR: 2.917, 95% CI: 1.574-5.406, p = 0.001) and Ins/Del + Del/Del (AOR: 1.242, 95% CI: 1.016-1.519, p = 0.034) compared to the non-DR population, while the proliferative diabetic retinopathy (PDR) subgroup did not reveal significant differences in either SNP rs145204276 or rs55829688 distributions compared to the non-DR group. Furthermore, patients with a GAS5 SNP rs145204276 Del/Del showed a significantly shorter DM duration than the wild type (Ins/Ins) (p = 0.021). In conclusion, our findings demonstrate that the GAS5 SNP rs145204276 Del/Del variant is associated with an increased susceptibility to DR in DM patients, particularly in those patients with NPDR.

Investigation of Possible Correlation Between Retinal Neurovascular Biomarkers and Early Cognitive Impairment in Patients With Chronic Kidney Disease.

Purpose: To investigate the association between retinal neurovascular biomarkers and early cognitive impairment among patients with chronic kidney disease (CKD). Methods: Patients with CKD stage ≥3 were evaluated using the standardized Mini-Mental State Examination (MMSE). Patients were classified as having a low (<24), middle (24 to 27), and high (>27) MMSE level. Retinal nerve fiber layer thickness, ganglion cell complex (GCC) thickness, GCC global loss volume, and GCC focal loss volume were measured using optical coherence tomography (OCT). Superficial vascular plexus vessel density, deep vascular plexus vessel density (DVP-VD), and size of the foveal avascular zone were obtained by OCT angiography. Results: The study enrolled 177 patients with a mean ± SD age of 64.7 ± 6.6 years. The mean ± SD MMSE score was 27.25 ± 2.30. Thirteen, 65, and 99 patients were classified as having a low, middle, and high MMSE level, respectively. The patients with a high MMSE level were younger, had more years of education, had less severe CKD, and had higher DVP-VD than patients with a low MMSE level. The multivariable regression revealed that age (coefficient, 0.294; 95% confidence interval [CI], 0.195-0.393; P = 0.041), years of education (coefficient, 0.294; 95% CI, 0.195-0.393; P < 0.001), estimated glomerular filtration rate (coefficient, 0.019; 95% CI, 0.004-0.035; P = 0.016), and DVP-VD (coefficient, 0.109; 95% CI, 0.007-0.212; P = 0.037) were independent factors associated with MMSE score. Conclusions: Retinal DVP-VD was associated with early cognitive impairment among patients with CKD. Translational Relevance: DVP-VD measured by OCT angiography may facilitate early detection of cognitive impairment.

A Multimodal Imaging-Based Deep Learning Model for Detecting Treatment-Requiring Retinal Vascular Diseases: Model Development and Validation Study.

BACKGROUND: Retinal vascular diseases, including diabetic macular edema (DME), neovascular age-related macular degeneration (nAMD), myopic choroidal neovascularization (mCNV), and branch and central retinal vein occlusion (BRVO/CRVO), are considered vision-threatening eye diseases. However, accurate diagnosis depends on multimodal imaging and the expertise of retinal ophthalmologists. OBJECTIVE: The aim of this study was to develop a deep learning model to detect treatment-requiring retinal vascular diseases using multimodal imaging. METHODS: This retrospective study enrolled participants with multimodal ophthalmic imaging data from 3 hospitals in Taiwan from 2013 to 2019. Eye-related images were used, including those obtained through retinal fundus photography, optical coherence tomography (OCT), and fluorescein angiography with or without indocyanine green angiography (FA/ICGA). A deep learning model was constructed for detecting DME, nAMD, mCNV, BRVO, and CRVO and identifying treatment-requiring diseases. Model performance was evaluated and is presented as the area under the curve (AUC) for each receiver operating characteristic curve. RESULTS: A total of 2992 eyes of 2185 patients were studied, with 239, 1209, 1008, 211, 189, and 136 eyes in the control, DME, nAMD, mCNV, BRVO, and CRVO groups, respectively. Among them, 1898 eyes required treatment. The eyes were divided into training, validation, and testing groups in a 5:1:1 ratio. In total, 5117 retinal fundus photos, 9316 OCT images, and 20,922 FA/ICGA images were used. The AUCs for detecting mCNV, DME, nAMD, BRVO, and CRVO were 0.996, 0.995, 0.990, 0.959, and 0.988, respectively. The AUC for detecting treatment-requiring diseases was 0.969. From the heat maps, we observed that the model could identify retinal vascular diseases. CONCLUSIONS: Our study developed a deep learning model to detect retinal diseases using multimodal ophthalmic imaging. Furthermore, the model demonstrated good performance in detecting treatment-requiring retinal diseases.

Impact of blood pressure control on retinal microvasculature in patients with chronic kidney disease.

Chronic kidney disease (CKD) is an emerging disease worldwide. We investigated the relationship between blood pressure (BP) control and parafoveal retinal microvascular changes in patients with CKD. This case-control study enrolled 256 patients with CKD (stage 3-5) and 70 age-matched healthy controls. Optical coherence tomography angiography showed lower superficial vascular plexus (SVP) vessel density, lower deep vascular plexus (DVP) vessel density, and larger SVP flow void area in the CKD group. The BP parameters at enrollment and during the year before enrollment were collected in patients with CKD. Partial correlation was used to determine the relationship between BP parameters and microvascular parameters after controlling for age, sex, diabetes mellitus, axial length, and intraocular pressure. The maximum systolic blood pressure (SBP) (p = 0.003) and within-patient standard deviation (SD) of SBP (p = 0.006) in 1 year were negatively correlated with SVP vessel density. The average SBP (p = 0.040), maximum SBP (p = 0.001), within-patient SD of SBP (p < 0.001) and proportion of high BP measurement (p = 0.011) in 1 year were positively correlated with the SVP flow void area. We concluded that long-term SBP was correlated with SVP microvascular injury in patients with CKD. Superficial retinal microvascular changes may be a potential biomarker for prior long-term BP control in these patients.

Correlation of corneal pigmented arc with wide epithelial thickness map in orthokeratology-treated children using optical coherence tomography measurements.

PURPOSE: To determine the intensity of corneal pigmented arc in orthokeratology (ortho-k)-treated children and its correlation with wide epithelial thickness map (ETM) obtained through anterior segment optical coherent tomography (AS-OCT). METHODS: This retrospective case series reviews medical records of children who received ortho-k treatment for myopia control. Intensity of ortho-k-associated pigmented arc after wearing ortho-k lens more than 12 months and its correlation with each sector/zone of wide ETM obtained by AS-OCT was explored. Pigmented arcs were further divided into apparent and unapparent groups, and the clinical differences between groups were determined. RESULTS: This study included 57 eyes of 29 children (mean age, 11.4 years, range 9-15); after initiating ortho-k treatment, the incidence of the corneal pigmented arc was 91.2% with mean lens wear duration of 26.1 months. Intensity of pigmented arc was significantly correlated with lens wear duration, target power, baseline degree of myopia, C zone and sectors I2, I3 and IT3 on wide ETM. Comparison between apparent and unapparent groups showed the same significant results except for C zone. After adjusting for lens wear duration and target power, sector I2 has the highest association with pigmented arc severity. CONCLUSION: Children treated with ortho-k are likely to develop ortho-k-associated pigmented arcs. The new wide ETM of AS-OCT can provide important information regarding the intensity of pigmented arc in these children. This can support customized pigmented arc-free ortho-k treatment for children in the future.

Correlation between pigmented arc and epithelial thickness (COPE) study in orthokeratology-treated patients using OCT measurements.

PURPOSE: To determine the intensity of corneal pigmented arc in orthokeratology (ortho-k)-treated children, and its correlation with key epithelial thickness measurements obtained by anterior segment optical coherence tomography (AS-OCT). METHODS: This study is a retrospective case series. Medical records of children who received ortho-k treatment for myopia control in our hospital were reviewed. Intensity of ortho-k-associated pigmented arc and its correlation with key epithelial thickness parameters in the central 7-mm-diameter zone obtained by AS-OCT was examined. The subjects were further divided into apparent and unapparent pigmented arc groups for severity comparison. RESULTS: The mean age of children was 11.4 years, and the incidence of corneal pigmented arc was 92.2% after lens wear for a mean duration of 21.2 months. Intensity of pigmented arc was found to be significantly correlated with key epithelial thickness parameters, including maximum and minimum epithelial thickness (Spearman's rank correlation coefficient (rs) = 0.404, P = 0.003; rs = - 0.426, P = 0.002, respectively), the difference between them (Min-Max) (rs = -0.624, P < 0.001) and standard deviation (rs = 0.659, P < 0.001). Significant correlation between intensity of pigmented arc and ortho-k target power (rs = 0.454, P = 0.001) was found. Comparison between the two groups showed significant difference in the same key epithelial thickness parameters. CONCLUSIONS: Children receiving ortho-k treatment tended to develop pigmented arcs. Significant correlation between intensity of pigmented arc and key epithelial thickness parameters was observed. AS-OCT can be a useful tool for predicting intensity of pigmented arc in ortho-k-treated children.

Intraocular lens power calculation after radial keratotomy and LASIK - A case report.

PURPOSE: To report a challenging intraocular lens (IOL) power calculation case who received both radial keratotomy (RK) and laser-assisted in situ keratomileusis (LASIK). OBSERVATIONS: A 51-year-old man had received refractive surgery with RK and later enhanced by LASIK more than 20 years ago. He developed severe cataract in left eye with best-corrected visual acuity of 20/100. The IOL power calculation was made using several methods available at the American Society of Cataract and Refractive Surgery (ASCRS) online calculator, including IOL calculation formulas for post-LASIK condition (Shammas, Haigis-L, Barrett True K no history, and Potvin-Hill Pentacam) and formulas for post-RK condition (Double K-modified Holladay 1 based on Oculus Pentacam and IOL Master, and Barrett True K). Haigis-L, Shammas and Barrett true K no history were found to be most accurate in predicting IOL power. CONCLUSIONS: Haigis-L, Shammas and Barrett true K no history are reliable formulas for IOL power calculation in patients who received both RK and LASIK.

Real-World Experience with Half-Time Versus Half-Dose Photodynamic Therapy in Chronic Central Serous Chorioretinopathy.

PURPOSE: To evaluate the real-world experience with half-time photodynamic therapy (PDT) versus half-dose PDT for chronic central serous chorioretinopathy (CSC). METHODS: This multicenter retrospective study enrolled patients who received half-time PDT (with irradiation time shortened to 42 s) or half-dose PDT (with the dosage of verteporfin reduced to 3 mg/m2) for chronic CSC and who were followed up for ≧12 months. The success rate, central subfield retinal thickness (CST), and best-corrected visual acuity (BCVA) were documented in each group of patients. RESULTS: A total of 53 eyes from 49 patients were enrolled in this study. Seventeen eyes (15 patients) received half-time PDT and 36 eyes (34 patients) received half-dose PDT. The success rates in both groups were similar at 12 months (94.1% vs. 94.4%; P = 0.543). The mean CST at 1, 6, 12 months decreased significantly when compared with the baseline in both groups (all P < 0.001). The BCVA significantly improved at 6 and 12 months in both groups (all P < 0.05). There were no significant differences in changes of BCVA and changes of CST between the 2 groups at any time point. CONCLUSIONS: Half-time PDT is a feasible treatment for chronic CSC. It has success rates similar to half-dose PDT at 12 months. There were no significant differences in changes of BCVA and changes of CST between the 2 groups at 1, 6, and 12 months after treatment.