Association between atherosclerotic cardiovascular disease score and skin carotenoid levels estimated via refraction spectroscopy in the Japanese population: a cross-sectional study.

Carotenoids play a role in preventing and impeding the progression of atherosclerotic cardiovascular diseases (ASCVDs) through their anti-oxidative effects. This study evaluated associations between ASCVD risk and skin carotenoid (SC) levels, reflecting dietary carotenoid intake. Participants' ASCVD risk was assessed using the Hisayama ASCVD risk prediction model, and SC levels were measured through a reflection spectroscope (Veggie Meter). The associations between high ASCVD risk and SC levels were analyzed using logistic regression analysis and a restricted cubic spline (RCS) model. A total of 1130 men and women (mean age: 56 years) from participants who underwent a health examination in Seirei Center for Health Promotion and Prevention Medicine in 2019 and 2022 were analyzed. Of these, 4.6% had moderate or high ASCVD risk. Mean SC values were 236, 315, 376, 447, and 606 in quintile Q1 to Q5, respectively. The adjusted odds ratios (95% confidence intervals) of SC quintile for moderate- or high-risk ASCVD was 0.24 (0.12-0.51) in Q5 (495 ≤), 0.42 (0.23-0.77) in Q4, 0.50 (0.29-0.88) in Q3, and 0.68 (0.41-1.12) in Q2 compared to Q1 (< 281). High SC values continuously showed non-linear inverse association with moderate- or high-risk for ASCVD in Japanese adults. Non-invasive SC measurements may be a good indicator for recommending carotenoids to prevent cardiovascular disease.

Deep learning-based correction of cataract-induced influence on macular pigment optical density measurement by autofluorescence spectroscopy.

PURPOSE: Measurements of macular pigment optical density (MPOD) using the autofluorescence spectroscopy yield underestimations of actual values in eyes with cataracts. Previously, we proposed a correction method for this error using deep learning (DL); however, the correction performance was validated through internal cross-validation. This cross-sectional study aimed to validate this approach using an external validation dataset. METHODS: MPODs at 0.25°, 0.5°, 1°, and 2° eccentricities and macular pigment optical volume (MPOV) within 9° eccentricity were measured using SPECTRALIS (Heidelberg Engineering, Heidelberg, Germany) in 197 (training dataset inherited from our previous study) and 157 eyes (validating dataset) before and after cataract surgery. A DL model was trained to predict the corrected value from the pre-operative value using the training dataset, and we measured the discrepancy between the corrected value and the actual postoperative value. Subsequently, the prediction performance was validated using a validation dataset. RESULTS: Using the validation dataset, the mean absolute values of errors for MPOD and MPOV corrected using DL ranged from 8.2 to 12.4%, which were lower than values with no correction (P < 0.001, linear mixed model with Tukey's test). The error depended on the autofluorescence image quality used to calculate MPOD. The mean errors in high and moderate quality images ranged from 6.0 to 11.4%, which were lower than those of poor quality images. CONCLUSION: The usefulness of the DL correction method was validated. Deep learning reduced the error for a relatively good autofluorescence image quality. Poor-quality images were not corrected.

Measuring macular pigment optical density using reflective images of confocal scanning laser system.

PURPOSE: To develop a method to measure the macular pigment optical density (MPOD) using scanning laser ophthalmoscopic images in young adults and children. STUDY DESIGN: Cross-sectional study. METHODS: Blue light reflectance fundus images of 32 healthy subjects were used. A profile of the linear reflectance changes across the center of the fovea on a grayscale fundus image was generated. The ratio of the macula-to-periphery reflection was designated as the peak value of the MPOD (MPOD[FR]) based on established fundamentals. In the MPOD profile, the basal width of the pixels at MPOD < 0 (wMP) and width at one-half value of the MPOD[FR] (wMP0.5) were determined. The MOPD at eccentricity of 0.5° was measured by heterochromatic flicker photometry (MPOD[HFP]), and the correlation between the MPOD[FR] and MPOD[HFP] was evaluated. RESULTS: The MPOD[FR] ranged from 0.17 to 0.73 with a mean of 0.40 ± 0.13. The wMP ranged from 88 to 173 pixels with a mean of 121.7 ± 24.2 pixels, and the wMP0.5 ranged from 38 to 83 pixels with a mean of 54.1 ± 10.3 pixels. A significant correlation was found between the MPOD[FR] and MPOD[HFP] (r = 0.41, P = 0.02). CONCLUSIONS: This simplified method can provide accurate and reliable values of the MPOD comparable to heterochromatic flicker photometry. Obtaining the fundus images in this fast and easy way should be suitable for children thus enabling clinicians to determine the MPODs for children.

Which is More Effective and Safer? Comparison of Propensity Score-Matched Microhook Ab Interno Trabeculotomy and iStent Inject.

INTRODUCTION: The purpose of this study was to compare the surgical outcomes between ab interno trabeculotomy (LOT) and iStent inject W implantation (iStent) both combined with cataract surgery, matching the background factors including age, intraocular pressure (IOP), medication score, central corneal thickness (CCT), and axial length. METHODS: A total of 100 eyes from 75/79 patients with primary open-angle glaucoma were included in the LOT/iStent groups. The background factors were matched between the two groups using the propensity score. RESULTS: There were no significant differences in age, IOP, medication score, CCT, and axial length, preoperatively. The postoperative medication scores were 1.3 ± 1.2 and 1.2 ± 1.2 in the LOT and iStent groups. The postoperative IOPs were 12.8 ± 2.8 and 13.1 ± 2.4 mmHg in the LOT and iStent groups, respectively. The changes in the medication score were - 0.64 ± 1.4 and - 0.44 ± 1.6 in the LOT and iStent groups, respectively. The changes in the IOP were - 2.1 ± 3.3 and - 1.5 ± 3.0 mmHg in the LOT and iStent groups, respectively. These values were not significantly different between the two groups. The postoperative IOP and changes in the IOP were significantly associated with preoperative IOP and CCT. There was no significant difference in the occurrence of postoperative complications (hyphema, 11.0% and 6.0%, and transient ocular hypertension, 8.0% and 5.0%, in the LOT and iStent groups, respectively). CONCLUSION: LOT and iStent have similar surgical outcomes with sufficient safety. Postoperative IOP was significantly associated with preoperative IOP and CCT in both groups.

Inter-device concordance of Veggie Meter-A reflection spectroscopy to measure skin carotenoids.

The Veggie Meter® (VM) is a refraction spectrometer that detects skin carotenoids. We tested the variability of the two modes (single-scan and averaging modes) of four VMs of three different versions (VM-1, 2, 3, 4) with 92 healthy volunteers. Both the modes exhibited a high intra-class correlation coefficient (ICC); however, the averaging mode had a significantly lower coefficient of variance than the single-scan mode. The Bland-Altman analysis showed a systematic error between VM-1 and other three VMs. The actual errors between the VM-1 and the other three VMs in the averaging mode were 7.4%, 10.4%, and 11.8% of the median of VM scores, but the errors could be reduced to 2.8%, 6.3%, and 7.0% by compensating VM scores using the regression equations. Averaging mode had higher accuracy than single-scan mode. The reliability of the VMs was validated by the small coefficient of variation and high ICC. The error was improved using linear regression compensation.

Accuracy of pattern deviation in estimating the glaucomatous damage in the central 10° visual field in eyes with glaucoma and cataract.

BACKGROUND/AIMS: The accuracy of pattern deviation (PD) in estimating the damage to the glaucomatous visual field (VF) in the central 10° in eyes with glaucoma and cataract is unclear. METHODS: This retrospective study includes 63 eyes of 52 glaucoma patients who successfully underwent cataract surgery or cataract surgery plus iStent implantation. Using the Humphrey Field Analyser 10-2 test, VF was measured within 6 months preoperatively and postoperatively (VFpre and VFpost, respectively). The mean total deviation values in VFpost (mTDpost) indicates glaucomatous damage without cataract and the difference between this value and mean PD values in VFpre (mPDpre) was evaluated (εmPD). The effect of cataract was then evaluated as the difference between mTDpost and mTDpre (ΔmTD), while the effects of mTDpost and ΔmTD on εmPD were also assessed. In addition, based on preoperative visual acuity (VApre) and VFpre, the optimal model for predicting mTDpost was identified. The error of this method (εOptimalModel) was estimated as the difference against mTDpost, which was compared with εmPD. RESULTS: Compared with mTDpre, there was a significant improvement in mTDpost (p=0.028). A significant difference was observed between mPDpre and mTDpost (p<0.001). Further, εmPD significantly increased with the increase of mTDpost or ΔmTD (p<0.001 and p=0.0444, respectively). The absolute εOptimalModel was significantly smaller than the absolute εmPD (p<0.001). CONCLUSIONS: This study warns clinicians that PD of the central 10° VF might underestimate the glaucomatous VF damage with the progression of glaucoma and overestimate it as a cataract progresses.

The Association Between Age and Systemic Variables and the Longitudinal Trend of Intraocular Pressure in a Large-Scale Health Examination Cohort.

Purpose: The detailed effects of age and systemic factors on intraocular pressure (IOP) have not been fully understood because of the lack of a large-scale longitudinal investigation. This study aimed to investigate the effect of various systemic factors on the longitudinal change of IOP. Methods: There were a total of 20,909 eyes of 10,471 subjects from a health checkup cohort that were followed up for systemic factors: (i) age at baseline, (ii) sex, (iii) time series body mass index (BMI), (iv) time series smoking habits, (v) time series systolic and diastolic blood pressures (SBP and DBP), and (vi) time series 19 blood examinations (all of the time series data was acquired at each annual visit), along with IOP annually for at least 8 years. Then the longitudinal effect of the systemic factors on the change of IOP was investigated. Results: IOP significantly decreased by -0.084 mm Hg/year. BMI, SBP, DBP, smoking habits, total triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and glycosylated hemoglobin A1c were not significantly associated with the change of IOP. Higher values of age, aspartate aminotransferase, hemoglobin, platelet, and calcium were suggested to be significantly associated with the decrease of IOP, whereas higher alanine aminotransferase, guanosine triphosphate, white blood cell count, red blood cell count, and female gender were significantly associated with the increase of IOP. Conclusions: Age, aspartate aminotransferase, hemoglobin, platelet, calcium, alanine aminotransferase, guanosine triphosphate, white blood cell count, red blood cell count, and gender were the systemic variables significantly associated with the change of IOP.

Improving Skin Carotenoid Levels in Young Students through Brief Dietary Education Using the Veggie Meter.

The antioxidant and anti-inflammatory effects of carotenoid have been determined to aid in the prevention of a wide range of oxidative disorders, arteriosclerosis, obesity, and various types of cancers. In order to keep high carotenoid levels in the body, much of the vegetable and fruit (V/F) intake is mandatory. However, the actual intake of V/F is not enough in many countries. The aim of this study was to assess whether brief dietary education using the Veggie Meter (VM) that could measure skin carotenoid (SC) levels could induce the increase in carotenoid levels via V/F intake. Two hundred and sixty-one elementary and junior high school students (ages 7−14 years old) received brief educational session and SC evaluation by VM, and the changes in SC levels were examined after 6 months. The baseline VM scores ranged from 131 to 825, and the average significantly increased from 400.0 ± 124.7 (standard deviation) to 447.4 ± 140.4 at Month 6 (p < 0.0001). The percentage of increase at month 6 was negatively correlated with the baseline values (r = −0.36, p < 0.0001). This finding implies that subjects who became aware of their inferiority tended to make a significant effort to change their behavior. The multivariate logistic regression analysis demonstrated that subjects taking much of green and yellow vegetables, drinking vegetable/tomato juice, and eating any fruit had higher VM scores than the average value. In conclusion, the educational approach using VM was supposed to be an effective method of raising awareness of the V/F shortage and increasing V/F intake that could indue the increase in SC levels.

Effects of water chestnut (Tarpa bispinosa Roxb.) extract/lutein on fingertip-measured advanced glycation endproduct/carotenoid levels.

This pilot study tested the effects of the supplements containing water chestnut extract and carotenoids on antiglycation and carotenoid levels. Twenty Japanese subjects (mean age, 67 ± 7 years; 13 men) ingested 200 mg of Tarpa bispinosa Roxb. extract (containing >50 mg of polyphenols), 20 mg of lutein, and 3 mg of zeaxanthin daily for 3 months. Advanced glycation end product (AGEs) levels were estimated by fingertip skin autofluorescence using the AGEs Sensor; carotenoid levels were estimated by pressure-mediated reflection spectroscopy of the fingertips using the Veggie Meter. Compared to baseline, the mean AGEs score decreased significantly (0.55 ± 0.04 arbitrary units (AU) vs. 0.52 ± 0.07 AU, p = 0.03); the mean carotenoid score increased significantly (256 ± 68 optical density (OD) vs. 302 ± 109 OD, p = 0.02) at 3 months. Blood pressure, body weight, visual acuity, refractive error, and intraocular pressure were equivalent between baseline and 3 months. Compared to baseline, 13 (65%) patients had decreased AGEs scores, and 14 (70%) had increased carotenoid scores at 3 months; 9 (45%) subjects had both decreased AGEs scores and increased carotenoid scores, and two (10%) subjects had an inverse response. Co-administration of water chestnut extract and lutein for 3 months decreased the AGEs and increased the carotenoids estimated in the fingertip skin of humans.

Lutein and Zeaxanthin Distribution in the Healthy Macula and Its Association with Various Demographic Factors Examined in Pseudophakic Eyes.

The macular pigment consisting of lutein (L) and zeaxanthin (Z) protects photoreceptors via its antioxidative and barrier activities. This study aimed to determine L and Z distribution in the healthy macula and their association with various demographic factors. Macular pigment optical density (MPOD) was measured using fundus autofluorescence spectroscopy in 352 pseudophakic eyes with no fundus diseases. Pseudophakia was chosen to avoid the influence of cataract in the measurement of fundus autofluorescence. The mean patient age was 72.3 ± 8.6 years. MPOD was analyzed separately in three zones, i.e., A: a central area within a radius of 0.5°, mainly containing Z; B: a ring area with radii from 0.5° to 1.3°, containing Z and L; C: a ring area with radii from 1.3° to 9°, containing L. Multivariate analyses were performed with MPOD as the dependent variable and sex, supplement intake, smoking habits, glaucoma, diabetes, age, body mass index (BMI), skin carotenoid levels, retinal thickness, retinal volume, axial length as the independent variables. The mean total MPOD volume within 9° eccentricity was 20,121 ± 6293. Age was positively associated with MPOD in all zones. Supplement and BMI were positively and negatively associated with MPOD in zones B and C. Smoking was negatively associated with MPOD in zone A. This study revealed the standard MP values of aged Japanese, which resulted to be higher than the previously reported values in other races. Age was found to have a positive association with MP values. L in the outer foveola was affected by BMI and supplements, but Z in the foveola was not. The amount of Z in the Müller cell cone may not be changed easily by factors such as hunger and satiety in the context of preservation of homeostasis in the human body, but tobacco had a negative effect on Z.

Identification of susceptibility loci for light-induced visual impairment in rats.

Bright light exposure in animals results in the selective degeneration of the outer retina, known as "retinal photic injury" (RPI). The susceptibility to RPI differs among rat strains. WKY rats display susceptibility to RPI with extensive retinal degeneration observed in the sagittal eye specimen, whereas LEW strain rats are resistant to it, showing only slight or no degeneration. In the present study, we first established an ethological screening method using the Morris water maze to discern differential susceptibility among the living rats. WKY and LEW were crossed to produce the first filial generation (F1) offspring. Maze-trained individuals were exposed to bright, white light. The screening test results demonstrated that the susceptibility to light-induced visual impairment in rats is a dominant Mendelian susceptibility trait, as F1 rats were susceptible to visual impairment like WKY rats. Therefore, F1 rats were backcrossed with recessive LEW to produce the first backcross offspring (BC1). Subsequent recurrent backcrossing while selecting for the susceptibility, indicated a segregation ratio of ca. 24% in BC1 and BC2 generations, indicating the involvement of two or more genes in the susceptibility. Further, microsatellite analysis of BC1-to-BC4 individuals using microsatellite markers mapped two susceptibility loci on chromosome segments 5q36 and 19q11-q12, named RPI susceptibility (Rpi)1 and Rpi2, respectively. This study provides an insight into mechanisms underlying differential susceptibility, which could help decipher the mechanism underlying the onset/progression of human age-related macular degeneration.

Correction for the Influence of Cataract on Macular Pigment Measurement by Autofluorescence Technique Using Deep Learning.

Purpose: Measurements of macular pigment optical density (MPOD) by the autofluorescence technique yield underestimations of actual values in eyes with cataract. We applied deep learning (DL) to correct this error. Subjects and Methods: MPOD was measured by SPECTRALIS (Heidelberg Engineering, Heidelberg, Germany) in 197 eyes before and after cataract surgery. The nominal MPOD values (= preoperative value) were corrected by three methods: the regression equation (RE) method, subjective classification (SC) method (described in our previous study), and DL method. The errors between the corrected and true values (= postoperative value) were calculated for local MPODs at 0.25°, 0.5°, 1°, and 2° eccentricities and macular pigment optical volume (MPOV) within 9° eccentricity. Results: The mean error for MPODs at four eccentricities was 32% without any correction, 15% with correction by RE, 16% with correction by SC, and 14% with correction by DL. The mean error for MPOV was 21% without correction and 14%, 10%, and 10%, respectively, with correction by the same methods. The errors with any correction were significantly lower than those without correction (P < 0.001, linear mixed model with Tukey's test). The errors with DL correction were significantly lower than those with RE correction in MPOD at 1° eccentricity and MPOV (P < 0.001) and were equivalent to those with SC correction. Conclusions: The objective method using DL was useful to correct MPOD values measured in aged people. Translational Relevance: MPOD can be obtained with small errors in eyes with cataract using DL.

Macular pigment changes after cataract surgery with yellow-tinted intraocular lens implantation.

PURPOSE: We previously reported that macular pigment optical density (MPOD) levels decreased during a long follow-up period after clear intraocular lens (IOL) implant surgery presumably due to excessive light exposure. We examined changes in MPOD levels in the eyes that received yellow-tinted IOL implant surgery. SUBJECTS AND METHODS: This was a prospective, observational study. Fifty-five eyes of 35 patients were studied. MPOD levels were measured with a dual-wavelength autofluorescence technique on day 4; months 1, 3, and 6; and years 1 and 2 postoperatively. The average optical densities at 0°- 2° eccentricities (local MPODs) and total volumes of MPOD (MPOVs) in the area within 1.5° and 9° eccentricities were analyzed. RESULTS: The mean local MPOD at baseline (on day 4) was 0.79 at 0°, 0.71 at 0.5°, 0.68 at 0.9°, and 0.32 at 2°. The mean MPOV within 1.5° and 9° at baseline was 2950 and 18,897, respectively. Local MPOD at 0.9° and 2° and MPOVs were slightly decreased at month 1 and increased after that. The increase reached statistical significance in local MPOD at 0.5° and 2° and MPOVs (Tukey-Kramer test). The changes in MPOV within 9° at year 2 [(MPOV on year 2 - MPOV on day 4) / MPOV on day 4] were from -0.21 to 1.18 (mean and standard deviation: 1.14 ± 0.28). The MPOV of 15 eyes increased more than 10% from the initial value, was maintained within 10% in 21 eyes, and deteriorated more than 10% in only 3 eyes. CONCLUSIONS: Local MPOD and MPOV tended to slightly decrease month 1 postoperatively and gradually increased after that, but the rates of increases in MPOD levels were small. Yellow-tinted IOLs that have a lower transmittance of blue light might be preferable for preserving MPOD levels after surgery.

Experience using mTOR inhibitors for subependymal giant cell astrocytoma in tuberous sclerosis complex at a single facility.

BACKGROUND: Subependymal giant cell astrocytoma (SEGA) is occasionally seen in tuberous sclerosis complex (TSC). Two main options are currently available for treating SEGA: surgical resection or pharmacotherapy using mammalian target of rapamycin inhibitors (mTORi). We hypothesized that opportunities for surgical resection of SEGA would have reduced with the advent of mTORi. METHODS: We retrospectively reviewed the charts of patients treated between August 1979 and July 2020, divided into a pre-mTORi era group (Pre-group) of patients treated before November 2012, and a post-mTORi era group (Post-group) comprising patients treated from November 2012, when mTORi became available in Japan for SEGA. We compared groups in terms of treatment with surgery or mTORi. We also reviewed SEGA size, rate of acute hydrocephalus, recurrence of SEGA, malignant transformation and adverse effects of mTORi. RESULTS: In total, 120 patients with TSC visited our facility, including 24 patients with SEGA. Surgical resection was significantly more frequent in the Pre-group (6 of 7 patients, 86 %) than in the Post-group (2 of 17 patients, 12 %; p = 0.001). Acute hydrocephalus was seen in 1 patient (4 %), and no patients showed malignant transformation of SEGA. The group treated using mTORi showed significantly smaller SEGA compared with the group treated under a wait-and-see policy (p = 0.012). Adverse effects of pharmacotherapy were identified in seven (64 %; 6 oral ulcers, 1 irregular menstruation) of the 11 patients receiving mTORi. CONCLUSIONS: The Post-group underwent surgery significantly less often than the Pre-group. Since the treatment option to use mTORi in the treatment of SEGA in TSC became available, opportunities for surgical resection have decreased in our facility.

Predicting intraocular pressure using systemic variables or fundus photography with deep learning in a health examination cohort.

The purpose of the current study was to predict intraocular pressure (IOP) using color fundus photography with a deep learning (DL) model, or, systemic variables with a multivariate linear regression model (MLM), along with least absolute shrinkage and selection operator regression (LASSO), support vector machine (SVM), and Random Forest: (RF). Training dataset included 3883 examinations from 3883 eyes of 1945 subjects and testing dataset 289 examinations from 289 eyes from 146 subjects. With the training dataset, MLM was constructed to predict IOP using 35 systemic variables and 25 blood measurements. A DL model was developed to predict IOP from color fundus photographs. The prediction accuracy of each model was evaluated through the absolute error and the marginal R-squared (mR2), using the testing dataset. The mean absolute error with MLM was 2.29 mmHg, which was significantly smaller than that with DL (2.70 dB). The mR2 with MLM was 0.15, whereas that with DL was 0.0066. The mean absolute error (between 2.24 and 2.30 mmHg) and mR2 (between 0.11 and 0.15) with LASSO, SVM and RF were similar to or poorer than MLM. A DL model to predict IOP using color fundus photography proved far less accurate than MLM using systemic variables.

Relationships between Skin Carotenoid Levels and Metabolic Syndrome.

Carotenoids have potential antioxidant and anti-inflammatory effects; their protective roles are of particular interest in the pathogenesis of metabolic syndrome (MetS). The reflection spectroscopy method has been recently developed to noninvasively measure skin carotenoid (SC) levels, which highly correlates with serum concentration of carotenoids. The relationship between SC levels and metabolic syndrome has been investigated. We aimed to identify the differences in patient characteristics and SC levels between participants with and without MetS in a large health examination population. In addition, the relationships between SC levels and various clinical parameters related to MetS were investigated. SC levels were measured using a reflection spectroscopy. A total of 1812 Japanese participants (859 male, 953 female; mean age ± standard deviation (SD), 57.8 ± 11.0 years) comprised the study population, i.e., participants with MetS (n = 151) and those without MetS (n = 1661). Multivariate logistic regression analysis was performed to identify variables associated with MetS. Compared to controls (377.3 ± 122.8), SC indices were significantly lower in patients with MetS (340.7 ± 112.5, p = 0.0004). Multivariate models also suggested that lower SC was significantly associated with MetS after adjustment for age, sex, smoking habit, and other potential risk factors for MetS. Furthermore, male gender (p < 0.0001), smoking habit (p < 0.0001) and worse lipid profiles (i.e., serum triglyceride (r = -0.1039, p < 0.0001), high-density lipoprotein (r = 0.1259, p < 0.0001), and usage of hypolipidemic agents (p = 0.0340)) were significantly associated with lower SC levels. The current study indicated that lower SC levels were significantly associated with MetS. This study highlights the antioxidant capacity of carotenoids in patients with MetS and the clinical utility of non-invasive and cost-effective SC measurement to detect participants who are at risk of developing MetS in a large population.

Evaluation of Relevance between Advanced Glycation End Products and Diabetic Retinopathy Stages Using Skin Autofluorescence.

Advanced glycation end products (AGEs) are thought to play important roles in the pathogenesis of diabetic microangiopathy, particularly in the progression of diabetic retinopathy (DR). We assessed the levels of skin autofluorescence (sAF) to assess the association between AGEs and DR stages. A total of 394 eyes of 394 Japanese subjects (172 men, 222 women; mean age ± standard deviation [SD], 68.4 ± 13.7 years) comprised the study population, i.e., subjects with diabetes mellitus (DM) (n = 229) and non-diabetic controls (n = 165). The patients with DM were divided into those without DR (NDR, n = 101) and DR (n = 128). DR included simple (SDR, n = 36), pre-proliferative (PPDR, n = 25), and PDR (n = 67). Compared to controls (0.52 ± 0.12), the AGE scores were significantly higher in patients with DM (0.59 ± 0.17, p < 0.0001), NDR (0.58 ± 0.16, p = 0.0012), and DR (0.60 ± 0.18, p < 0.0001). The proportion of patients with PDR was significantly higher in the highest quartile of AGE scores than the other quartiles (p < 0.0001). Compared to those without PDR (SDR and PPDR), those with PDR were younger (p = 0.0006), more were pseudophakic (p < 0.0001), had worse visual acuity (VA) (p < 0.0001), had higher intraocular pressure (IOP) (p < 0.0001), and had higher AGE scores (p = 0.0016). Multivariate models also suggested that younger age, male gender, pseudophakia, worse VA, higher IOP, and higher AGE scores were risk factors for PDR. The results suggested that AGE scores were higher in patients with DM and were independently associated with progression of DR. In addition, more PDR was seen in the highest quartile of AGE scores. This study highlights the clinical use of the AGE score as a non-invasive, reliable marker to identity patients at risk of sight-threatening DR.

Macular Pigment in Eyes With Macular Hole Formation and Its Change After Surgery.

Purpose: To observe the macular pigment (MP) appearances in eyes with macular hole (MH) and clarify the origin of the appearances. The mechanisms underlying the development of MH are discussed based on the observation of MP. Methods: This observational case series included 33 eyes of 31 patients with MH who underwent vitrectomy. The MP optical density was measured using the two-wavelength fundus autofluorescence technique. The exact localization of MP was evaluated by comparing MP distribution images and optical coherent tomography B-scan images. Results: MP was missing at the MH. The area of the MP defect corresponded with the area of the defect of outer plexiform layer. MP was present in the retinal flap in stage 2 MH that included glia (Müller cells) and plexiform layers and in the operculum in stage 3 MH, which mainly comprised Müller cells. Cystic spaces in the outer plexiform layer surrounding stage 3 and 4 MHs showed a honeycomb appearance on MP images. MP reappeared to form an irregularly shaped pigment plane after surgical closure of MH. The MP optical volume did not change before and after surgery. Fellow eyes with a central dip in MP distribution subsequently developed MH. Conclusions: The characteristic appearances of MP at the MH were attributed to MP in the plexiform layers and Müller cell cones. A central dip of MP distribution might be a sign of Müller cell cone damage that proceeds with MH formation. Translational Relevance: Observation of MP was useful for understanding the mechanisms of MH formation.

Advanced Glycation End Product Accumulation in Subjects with Open-Angle Glaucoma with and without Exfoliation.

Advanced glycation end products (AGEs), which are the products of a non-enzymatic reaction between reducing sugars and other macromolecules, are critical in aging, as well as metabolic and degenerative diseases. To assess the involvement of AGEs in glaucoma, skin autofluorescence (sAF) level, which is a measurement of AGEs' accumulation, was compared among Japanese patients with glaucoma (316 with primary open-angle glaucoma (PG) and 127 exfoliation syndrome and glaucoma (EG)) and controls (133 nonglaucomatous controls) (mean age 71.6 ± 12.8 years, 254 men and 322 women). The sAF values were estimated from the middle fingertip using a 365 nm light-emitting diode for excitation and detection at 440 nm emission light. The estimated AGE values (arbitrary unit) were 0.56 ± 0.15, 0.56 ± 0.11, and 0.61 ± 0.11 in the control, PG, and EG groups, respectively (p < 0.0001, analysis of variance); and were significantly higher in the EG group than the control (p = 0.0007) and PG (p < 0.0001) groups. After adjustment for various demographic parameters by multivariate analyses, male sex (standard ß = 0.23), EG (0.19), and diabetes (0.09) were associated with higher AGE levels; PG (-0.18) and smoking (-0.19) were associated with lower AGE levels. Age, visual acuity, intraocular pressure, glaucoma medications, lens status, and systemic hypertension were not associated with AGEs. The high AGE level in EG suggested that specific oxidation and glycation mechanisms underlie the glaucoma pathogenesis associated with pseudoexfoliation syndrome.

Potential roles of MNREAD acuity charts and contrast/glare sensitivity in Ranibizumab treatment of branch retinal vein occlusion.

BACKGROUND/OBJECTIVES: To investigate the potential utility of MNREAD acuity charts and contrast/glare sensitivity (CGS) assessment for evaluating the efficacy of an initial treatment with ranibizumab (Lucentis®) for branch retinal vein occlusion (BRVO). METHODS: Intravitreal injections of ranibizumab were administered in 43 eyes of 43 treatment-naïve patients with BRVO. Efficacy was assessed 1 month later. Best-corrected far/near visual acuity (BCFVA/BCNVA), MNREAD parameters (reading acuity [RA], maximum reading speed [MRS], critical print size [CPS]), CGS (CS/GS), and central macular thickness (CMT) in optical coherence tomography (OCT) before and after treatment were evaluated. The area (superior/inferior) affected by BRVO was determined by fluorescein angiography. RESULTS: All parameters improved significantly following treatment (p < 0.05), and all MNREAD and CGS parameters were significantly correlated with BCVA in the treated eye before and after treatment (p < 0.01). The changes in BCFVA, BCNVA, MRS, and CS were significantly correlated with the amount of change in CMT (p < 0.007; r = 0.415, 0.528, -0.465, and -0.508, respectively). MRS exhibited a percentage change that was significantly correlated with that in CMT (p < 0.007; r = -0.511). Additionally, MRS exhibited the lowest threshold CMT (397 µm) at which the most significant change in improvement was observed. CMT was less likely to improve if BRVO occurred at a superior site than if it occurred at an inferior site (0.05 < p = 0.07 < 0.1). CONCLUSIONS: MNREAD and CGS testing were useful for evaluating BRVO treatment efficacy. MRS might be a valuable index for evaluating treatment success and making treatment decisions.