Relationship between fundus sex index obtained using color fundus parameters and body height or axial length in the Kumejima population.

PURPOSE: To investigate the relationship between the fundus sex index obtained from fundus photographs and body height or axial length in the Kumejima population. STUDY DESIGN: Prospective cross-sectional observational population study. METHODS: Using color fundus photographs obtained from the Kumejima population, 1,653 healthy right eyes with reliable fundus parameter measurements were included in this study. The tessellation fundus index was calculated as R/(R + G + B) using the mean value of the red-green-blue intensity in the eight locations around the optic disc and foveal region. The optic disc ovality ratio, papillomacular angle, and retinal vessel angle were quantified as previously described. The masculine or feminine fundus was quantified using machine learning (L2 regularized binominal logistic regression and leave one out cross validation), with the range of 0-1 as the predictive value, and defined as the fundus sex index. The relationship between the fundus sex index and body height or axial length was investigated using Spearman's correlation. RESULTS: The mean age of the 838 men and 815 women included in this study was 52.8 and 54.0 years, respectively. The correlation coefficient between fundus sex index and body height was - 0.40 (p < 0.001) in all, 0.01 (p = 0.89) in men, and - 0.04 (p = 0.30) in women, and that between fundus sex index and axial length was - 0.23 (p < 0.001) in all, - 0.12 (p < 0.001) in men, and - 0.13 (p < 0.001) in women. CONCLUSION: This study shows that a larger number of masculine fundi tend to have longer axial lengths in each sex group. However, sex index was not significantly related with body height either in men or in women.

Longitudinal changes of funduscopic optic disc size, color and cup-to-disc ratio in school children.

BACKGROUND: To investigate the relationship between changes in the optic disc size and color, cup-to-disc (C/D) ratio, and axial elongation in schoolchildren. METHODS: A prospective cohort study was performed in 75 right eyes of elementary school students for six years (from 8.5 to 14.5 years old). In the first and last year, all participants underwent optical axial length measurement and color fundus photography. The optic disc color was calculated by dividing the intensity of red by the sum of the intensity of red, green, and blue. The optic disc area was calculated by modifying the number of pixels according to Bennett's formula. The C/D ratio was calculated by dividing the vertical cup diameter by vertical optic disc diameter. Wilcoxon signed rank test was used to compare these optic disc parameters and axial length in the first and last year. RESULTS: Mean axial length in the last year (24.82 mm) was significantly longer than that in the first year (23.34 mm). Likewise, the mean optic disc size was significantly smaller in the last year (41,946 pixels) than that in the first year (46,144 pixels). The mean optic disc color in the last year (0.49) was significantly more reddish than that in the first year (0.46), while the mean C/D ratio in last year (0.50) was significantly smaller than that in first year (0.52). CONCLUSIONS: During the period from 8.5 years to 14.5 years of age, both the optic disc size and C/D ratio became smaller, while the color became more red.

Age prediction using fundus parameters of normal eyes from the Kumejima population study.

PURPOSE: Artificial intelligence can predict the age of an individual using color fundus photographs (CFPs). This study aimed to investigate the accuracy of age prediction in the Kumejima study using fundus parameters and to clarify age-related changes in the fundus. METHODS: We used nonmydriatic CFPs obtained from the Kumejima population study, including 1,646 right eyes of healthy participants with reliable fundus parameter measurements. The tessellation fundus index was calculated as R/(R + G + B) using the mean value of the red-green-blue intensity in eight locations around the optic disc and foveal region. The optic disc ovality ratio, papillomacular angle, and retinal vessel angle were quantified as previously described. Least absolute shrinkage and selection operator regression with leave-one-out cross-validation was used to predict age. The relationship between the actual and predicted ages was investigated using Pearson's correlation coefficient. RESULTS: The mean age of included participants (834 males and 812 females) was 53.4 ± 10.1 years. The mean predicted age based on fundus parameters was 53.4 ± 8.9 years, with a mean absolute error of 3.64 years, and the correlation coefficient between actual and predicted age was 0.88 (p < 0.001). Older patients had greater red and green intensities and weaker blue intensities in the peripapillary area (p < 0.001). CONCLUSIONS: Age could be predicted using the CFP parameters, and there were notable age-related changes in the peripapillary color intensity. The age-related changes in the fundus may aid the understanding of the mechanism of fundus diseases such as age-related macular degeneration.

Predicting central choroidal thickness from colour fundus photographs using deep learning.

The estimation of central choroidal thickness from colour fundus images can improve disease detection. We developed a deep learning method to estimate central choroidal thickness from colour fundus images at a single institution, using independent datasets from other institutions for validation. A total of 2,548 images from patients who underwent same-day optical coherence tomography examination and colour fundus imaging at the outpatient clinic of Jichi Medical University Hospital were retrospectively analysed. For validation, 393 images from three institutions were used. Patients with signs of subretinal haemorrhage, central serous detachment, retinal pigment epithelial detachment, and/or macular oedema were excluded. All other fundus photographs with a visible pigment epithelium were included. The main outcome measure was the standard deviation of 10-fold cross-validation. Validation was performed using the original algorithm and the algorithm after learning based on images from all institutions. The standard deviation of 10-fold cross-validation was 73 µm. The standard deviation for other institutions was reduced by re-learning. We describe the first application and validation of a deep learning approach for the estimation of central choroidal thickness from fundus images. This algorithm is expected to help graders judge choroidal thickening and thinning.

Quantification of peripapillary nerve fibre elevation and its association with axial length, optic disc tilt, and parapapillary atrophy area in young, healthy eyes.

BACKGROUND: Eyes with peripapillary nerve fibre elevation (pNFE) may have a gap between the optic nerve papillary margin on colour fundus photography and Bruch's membrane opening on cross-sectional optical coherence tomography (OCT). This study was conducted to evaluate the quantification of the height of pNFE in young healthy eyes and examine the relationship between pNFE height and axial length. METHODS: A prospective, observational, cross-sectional study was performed involving 117 right eyes. All participants (mean age 25.8 years) underwent comprehensive ophthalmologic examination involving axial length, fundus photography, and peripapillary and optic disc OCT. pNFE height was defined as the distance between the retinal surface plane and the upper edge of the pNFE in optic disc cross-sectional OCT images. Optic disc tilt was evaluated using a sine curve on retinal nerve fibre layer B-scan images. Parapapillary atrophy (PPA) area in colour fundus images was calculated using ImageJ and corrected using Bennett's formula. We evaluated relationships between pNFE height, axial length, optic disc papillary tilt, and PPA area using Spearman's correlation analysis. RESULTS: Sixty-five eyes had pNFE, with a mean pNFE height of 84.7 µm. pNFE height was significantly positively correlated with axial length (r = 0.32, p < 0.001), optic disc tilt (r = 0.25, p = 0.008), and PPA area (r = 0.27, p = 0.004). CONCLUSIONS: pNFE is not rare in young healthy eyes. Eyes with higher pNFE had a longer axial length and larger optic disc tilt and PPA area.

Three-year changes in sex judgment using color fundus parameters in elementary school students.

PURPOSE: In a previous cross-sectional study, we reported that the sexes can be distinguished using known factors obtained from color fundus photography (CFP). However, it is not clear how sex differences in fundus parameters appear across the human lifespan. Therefore, we conducted a cohort study to investigate sex determination based on fundus parameters in elementary school students. METHODS: This prospective observational longitudinal study investigated 109 right eyes of elementary school students over 4 years (age, 8.5 to 11.5 years). From each CFP, the tessellation fundus index was calculated as red/red + green + blue (R/[R+G+B]) using the mean value of red-green-blue intensity in eight locations around the optic disc and macular region. Optic disc area, ovality ratio, papillomacular angle, and retinal vessel angles and distances were quantified according to the data in our previous report. Using 54 fundus parameters, sex was predicted by L2 regularized binomial logistic regression for each grade. RESULTS: The right eyes of 53 boys and 56 girls were analyzed. The discrimination accuracy rate significantly increased with age: 56.3% at 8.5 years, 46.1% at 9.5 years, 65.5% at 10.5 years and 73.1% at 11.5 years. CONCLUSIONS: The accuracy of sex discrimination by fundus photography improved during a 3-year cohort study of elementary school students.

Effect of the macular shape on hole findings in idiopathic macular hole differs depending on the stage of the macular hole.

This study aimed to investigate the relationship between macular shape and idiopathic macular hole (MH) findings using an objective method. We present retrospective observational case series on patients with MH. The shape of the macular area was quantified using quadratic equations, and the ocular shape (OS) index was calculated. The correlation between the OS index and macular hole findings for each stage was evaluated. Pearson's correlation coefficient showed a significant correlation between the OS index and horizontal hole diameter (p = 0.044), bottom diameter (p = 0.006), and vertical bottom diameter (p = 0.024) in stage 2. For stage 4, there was a negative and significant correlation between the OS index and age (p = 0.037), and horizontal (p = 0.021) and vertical (p = 0.027) bottom diameter. Multiple regression analysis showed that the horizontal (p = 0.0070) and vertical (p = 0.031) bottom diameter and OS index were independently and positively correlated in stage 2. In stage 4, the OS index was independently and negatively correlated with the horizontal (p = 0.037) and vertical (p = 0.048) bottom diameter. The ocular shape of the macula affects MH findings, and its impact depends on its stage.

Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.

INTRODUCTION: This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. METHODS: A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. RESULTS: BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. CONCLUSION: As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. TRIAL REGISTRATION NUMBER: jRCTs051190125.

Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC­prostaglandin analogue combination therapy.

Interaction of impaired myocardial flow reserve and extent of myocardial ischemia assessed using 13N-ammonia positron emission tomography imaging on adverse cardiovascular outcomes.

BACKGROUND: Myocardial flow reserve (MFR) and the extent of myocardial ischemia identify patients at high risk of major adverse cardiovascular events (MACEs). Associations between positron emission tomography (PET)-assessed extent of ischemia, MFR, and MACEs is unclear. METHOD: Overall, 640 consecutive patients with suspected or known coronary artery disease undergoing 13N-ammonia myocardial perfusion PET were followed-up for MACEs. Patients were categorized into three groups based on myocardial ischemia severity: Group I (n = 335), minimal (myocardial ischemia < 5%); Group II (n = 150), mild (5-10%); and Group III (n = 155), moderate-to-severe (> 10%). RESULTS: Cardiovascular death and MACEs occurred in 17 (3%) and 93 (15%) patients, respectively. Following statistical adjustment for confounding factors, impaired MFR (global MFR < 2.0) was revealed as an independent predictor of MACEs in Groups I (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.48-5.64; P = 0.002) and II (HR, 3.40; 95% CI 1.37-8.41; P = 0.008) but was not significant in Group III (HR, 1.15; 95% CI 0.59-2.26; P = 0.67), with a significant interaction (P < 0.0001) between the extent of myocardial ischemia and MFR. CONCLUSION: Impaired MFR was significantly associated with increased risk of MACEs in patients with ≤ 10% myocardial ischemia but not with those having > 10% ischemia, allowing a clinically effective risk stratification.

Sex determination using color fundus parameters in older adults of Kumejima population study.

PURPOSE: Deep learning artificial intelligence can determine the sex using only fundus photographs. However, the factors used by deep learning to determine the sex are not visible. Therefore, the purpose of the study was to determine whether the sex of an older individual can be determined by regression analysis of their color fundus photographs (CFPs). METHODS: Forty-two parameters were analyzed by regression analysis using 1653 CFPs of normal subjects in the Kumajima study. The parameters included the mean values of red, green, and blue intensities; the tessellation fundus index; the optic disc ovality ratio; the papillomacular angle; and the retinal vessel angles. Finally, the L2 regularized binomial logistic regression was used to predict the sex using all the parameters, and the diagnostic ability was assessed through the leave-one-cross-validation. RESULTS: The mean age of the 838 men and 815 women were 52.8 and 54.0 years, respectively. The ovality ratio and retinal artery angles in women were significantly smaller than that in men. The green intensity at all locations for the women were significantly higher than that of men (P < 0.001). The discrimination accuracy rate assessed by the area-under-the-curve was 80.4%. CONCLUSIONS: Our methods can determine the sex from the CFPs of the adult with an accuracy of 80.4%. The ovality ratio, retinal vessel angles, tessellation, and the green intensities of the fundus are important factors to identify the sex in individuals over 40 years old.

Impact of COVID-19 pandemic on emergency medical system and management strategies in patients with acute coronary syndrome.

The global coronavirus disease-2019 (COVID-19) pandemic is associated with reduced rate of percutaneous coronary intervention (PCI). However, there were a few data showing how emergency medical system (EMS) and management strategies for acute coronary syndrome (ACS) changed during the pandemic. We sought to clarify changes on characteristics, treatments, and in-hospital mortality of patients with ACS transported via EMS between pre- and post-pandemic. We examined consecutive 656 patients with ACS admitted to Sapporo City ACS Network Hospitals between June 2018 and November 2021. The patients were divided into pre- and post-pandemic groups. The number of ACS hospitalizations declined significantly during the pandemic (proportional reduction 66%, coefficient -0.34, 95% CI -0.50 to -0.18, p < 0.001). The median time from an EMS call to hospital was significantly longer in post-pandemic group than in pre-pandemic group (32 [26-39] vs. 29 [25-36] min, p = 0.008). There were no significant differences in the proportion of patients with ACS receiving PCI, and in-hospital mortality between the groups. The COVID-19 pandemic had a significant impact on EMS and management in patients with ACS. Although a significant decline was observed in ACS hospitalizations, the proportion of patients with ACS receiving emergency PCI remained during the pandemic.

Success Rate of Swept-Source Optical Coherence Tomography Biometry of Eyes of Elementary School Students.

Purpose: To determine the success rate of swept-source optical coherence tomography (SS-OCT) biometry (OA-2000) in elementary school students. Methods: This was a prospective observational longitudinal study of 115 right eyes of elementary school students who were 8- to 9-years-old at the initial examination. Biometric measurements of the eyes were performed annually for three years, viz., during the third, fourth, and fifth grades. The success rates of obtaining data from optical biometric measurements of the axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), pupillary diameter (PD), corneal diameter (CD), and corneal curvature (CC) were determined. Results: The AL, CCT, and CC could be measured in all images at the three measurement times in all subjects. The success rate of the measurements of the ACD was 92.2% in the third grade and 100% in the fourth and fifth grade. The LT was successfully measured in 88.7% in the third grade, 99.1% in the fourth grade, and 100% in the fifth grade. The PD was successfully measured in 100% of the third grade, 96.0% of the fourth grade, and 100% in the fifth grade. The CD was successfully measured in 84.3% in the third grade, 66% in the fourth grade, and 100% in the fifth grade. Conclusion: SS-OCT can obtain accurate measures of all ocular parameters in the primary school students with high success rates. However, care should be taken especially in analyzing the ACD, LT, PD, and CD because errors can occur in some cases.

Quantification of Anterior Chamber Particles Using Anterior Segment Optical Coherence Tomography in Angle-Closure Glaucoma Patients after Laser Iridotomy.

Purpose: To determine whether the degree of particle density in the anterior chamber can be evaluated objectively and quantitatively by anterior segment optical coherence tomography (AS-OCT) in cases after laser iridotomy (LI). Methods: This was a retrospective observational study. All of the subjects who received LI for angle-closure glaucoma between January 2018 and May 2019 at Kagoshima University Hospital were studied. AS-OCT recordings were made before, immediately after, and one week after LI in 22 eyes of 14 consecutive patients. The anterior chamber particle (ACP) index was defined as the ratio of the number of particles in the anterior chamber to the total area of the anterior chamber. The ACP index was determined by binarization of the AS-OCT images and analysis with the ImageJ program. Results: The mean age of the participants was 75.4 ± 8.9 years, with a range of 61−91 years. The ACP index before the LI was 0.78 ± 0.68, and it was significantly increased to 7.72 ± 2.64 immediately after the LI (paired t-test, p < 0.01). The ACP index returned to the pre-LI density of 0.92 ± 0.48 one week after the LI. Conclusions: We successfully quantified the degree of anterior chamber particles accumulation by analyzing images obtained by AS-OCT. This simple and repeatable technique should be useful because the particles, including inflammatory cells, in the anterior chamber can be evaluated non-invasively and objectively.

OCULAR FACTORS RELATED TO PREOPERATIVE ENLARGEMENT OF IDIOPATHIC MACULAR HOLE DIAMETER.

PURPOSE: To determine the preoperative factors that are significantly correlated with an enlargement of an idiopathic macular hole (MH) during the one-month preoperative period. METHODS: This was a retrospective cross-sectional study of patients with MH who had undergone vitrectomy in the Kagoshima University Hospital. The stage of the MH was determined by using spectral domain optical coherence tomography. Patients who had optical coherence tomography images at two time points more than 14 days apart before the vitrectomy were studied. RESULTS: The MH participants were at Stage 2 in 44 eyes, at Stage 3 in 58 eyes, and at Stage 4 in 38 eyes. The rate of increase of the hole diameter was 26.0 ± 42.3% at Stage 2, 5.52 ± 15.5% at Stage 3, and 8.04 ± 18.7% at Stage 4. The rate of change at Stage 2 was significantly greater than that at Stage 3 and Stage 4 (both P < 0.01). In Stage 2, the MH diameter at the initial visit was significantly and negatively correlated with the rate of MH enlargement (r = -0.35, P = 0.021). CONCLUSION: Patients with Stage 2 MHs, especially eyes with small hole diameter, should be considered for early surgery.

Characteristics of pigmentary glaucoma in Japanese individuals.

PURPOSE: Myopia is a known risk factor of pigmentary glaucoma (PG), and the increased prevalence of myopia in Asian countries indicates that more cases of PG will likely develop soon. However, there are no diagnostic criteria for PG for Asians. Therefore, the purpose of this study is to determine the characteristics of PG in Japanese individuals and establish three diagnostic signs for PG. METHODS: This was a single-center, retrospective, case series study of glaucoma patients who visited the Kagoshima University Hospital between January 2015 and January 2020. The inclusion criteria were age <50 years at time of diagnosis and presence of pigmentation in the anterior chamber (AC) angle including a Sampaolesi line. Eyes with pigmentation of the AC angle caused by other types of glaucoma such as uveitis, trauma, exfoliation, or childhood glaucoma were excluded. We investigated the classic diagnostic triad of signs of PG; posterior corneal pigmentation, mid peripheral iris transillumination defect, and pigmentation of the trabecular meshwork. We also examined the Sampaolesi line, iris concavity, and midperipheral iris depigmentation in eyes with PG. RESULTS: Ten eyes of 5 Japanese men and 10 eyes of 5 Japanese women were studied. Their age ranged from 13 to 46 years at the time of diagnosis. One eye had posterior corneal pigmentation and 6 eyes had pigmentation of the trabecular meshwork. None had mid peripheral iris transillumination defect. The Sampaolesi line, iris concavity, and midperipheral iris depigmentation were found in all patients except one patient who lacked the mid peripheral depigmentation. Two eyes had the pigment reversal sign, none had lens pigmentation, and 2 eyes had peripheral retinal degeneration. CONCLUSION: The presence of the Sampaolesi line, iris concavity, and midperipheral iris depigmentation may be appropriate signs for the diagnosis of PG in Asians.