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.

Prognostic value of modified coronary flow capacity by 13N-ammonia myocardial perfusion positron emission tomography in patients without obstructive coronary arteries.

BACKGROUND: Vasodilator capacity of coronary circulation is an important diagnostic and prognostic tool in patients with coronary artery disease (CAD). We aimed to clarify the incidence of coronary microvascular dysfunction (CMD), defined as impaired modified coronary flow capacity (mCFC) proposed by Johnson and Gould and measured by 13N-ammonia myocardial perfusion positron emission tomography (PET), in patients without obstructive CAD and to evaluate the risk of future cardiovascular events. METHODS: This retrospective study recruited 407 consecutive CAD-suspected patients who underwent both pharmacological stress/rest 13N-ammonia PET and coronary angiography. Of the 407 patients, 137 patients (median age, 70 years; 63 women) were eligible and followed up (median, 19.8 months). Endpoints were defined as cardiovascular death or major adverse cardiovascular events (MACEs), such as cardiovascular death, nonfatal myocardial infarction, unplanned hospitalization for any cardiac reasons, and unplanned coronary revascularization. The impaired mCFC group included patients with mildly to severely reduced regional CFC in, at least, one vascular territory (n=34), while the remaining patients (n=103) were categorized as having preserved mCFC. RESULTS: Overall, cardiovascular death and MACEs occurred in five (4%) patients. The Kaplan-Meier curve showed a significant reduction in event-free survival for cardiovascular death (p=0.004) and MACEs (p<0.0001) in the impaired mCFC group, compared to the preserved mCFC group. Impaired mCFC was independently associated with the incidence of both cardiovascular death and MACEs after propensity-score adjustments [hazard ratio (HR), 10.7; 95% confidence interval (CI), 1.0-106.0; p=0.04 and HR, 9.5; 95% CI, 2.5-36.2; p<0.001, respectively]. CONCLUSIONS: In CAD-suspected patients without obstructive coronary arteries, impaired mCFC was observed in approximately 25% and was associated with a higher risk of cardiovascular death and MACEs. The mCFC concept can help identify patients who would benefit from specific therapies or lifestyle modifications to prevent future MACEs and can clarify potential mechanisms of CMD.

Validating the usefulness of sectorwise regression of visual field in the central 10°.

AIM: To evaluate the usefulness of the application of the clustering method to the trend analysis (sectorwise regression) in comparison with the pointwise linear regression (PLR). METHODS: This study included 153 eyes of 101 patients with open-angle glaucoma. With PLR, the total deviation (TD) values of the 10th visual field (VF) were predicted using the shorter VF sequences (from first 3 to 9) by extrapolating TD values against time in a pointwise manner. Then, 68 test points were stratified into 29 sectors. In each sector, the mean of TD values was calculated and allocated to all test points belonging to the sector. Subsequently, the TD values of the 10th VF were predicted by extrapolating the allocated TD value against time in a pointwise manner. Similar analyses were conducted to predict the 11th-16th VFs using the first 10 VFs. RESULTS: When predicting the 10th VF using the shorter sequences, the mean absolute error (MAE) values were significantly smaller in the sectorwise regression than in PLR. When predicting from the 11th and 16th VFs using the first 10 VFs, the MAE values were significantly larger in the sectorwise regression than in PLR when predicting the 11th VF; however, no significant difference was observed with other VF predictions. CONCLUSION: Accurate prediction was achieved using the sectorwise regression, in particular when a small number of VFs were used in the prediction. The accuracy of the sectorwise regression was not hampered in longer follow-up compared with PLR.

Investigating the clinical usefulness of definitions of progression with 10-2 visual field.

BACKGROUND/AIM: To investigate the clinical validity of the Guided Progression Analysis definition (GPAD) and cluster-based definition (CBD) with the Humphrey Field Analyzer 10-2 test in diagnosing glaucomatous visual field (VF) progression, and to introduce a novel definition with optimised specificity by combining the 'any-location' and 'cluster-based' approaches (hybrid definition). METHODS: 64 400 stable glaucomatous VFs were simulated from 664 pairs of 10-2 tests (10 sets × 10 VF series × 664 eyes; data set 1). Using these simulated VFs, the specificity to detect progression and the effects of changing the parameters (number of test locations or consecutive VF tests, and percentile cut-off values) were investigated. The hybrid definition was designed as the combination where the specificity was closest to 95.0%. Subsequently, another 5000 actual glaucomatous 10-2 tests from 500 eyes (10 VFs each) were collected (data set 2), and their accuracy (sensitivity, specificity and false positive rate) and the time needed to detect VF progression were evaluated. RESULTS: The specificity values calculated using data set 1 with GPAD and CBD were 99.6% and 99.8%. Using data set 2, the hybrid definition had a higher sensitivity than GPAD and CBD, without detriment to the specificity or false positive rate. The hybrid definition also detected progression significantly earlier than GPAD and CBD (at 3.1 years vs 4.2 years and 4.1 years, respectively). CONCLUSIONS: GPAD and CBD had specificities of 99.6% and 99.8%, respectively. A novel hybrid definition (with a specificity of 95.5%) had higher sensitivity and enabled earlier detection of progression.