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Purpose To describe the distribution and determinants of choroidal thickness (CT) in participants in a population study based on spectral-domain (SD)-OCT measurements. Design Population-based, cross-sectional study. Participants Ethnic Chinese, Indian, and Malay adults aged more than 50 years without any retinal diseases (e.g., diabetic retinopathy, macular edema, age-related macular degeneration, central serous chorioretinopathy) that might affect the CT were recruited from the Singapore Epidemiology of Eye Diseases Study. Methods Choroidal imaging was performed by SD-OCT (Spectralis, Heidelberg Engineering, Heidelberg, Germany) in enhanced depth imaging (EDI) mode. Subfoveal choroidal thickness (SFCT) was measured on the foveal line scan by 2 retinal experts independently (YS and KT), and the average was used in the analyses. In Chinese and Indian cohorts in whom macular raster scans were captured, the manufacturer-supplied research software (Heyex SP-X version 6.4.8.116; Heidelberg Engineering) was used to obtain automated segmentation yielding mean choroidal thickness in each of the 9 ETDRS grid sectors. Main Outcome Measures Subfoveal choroidal thickness and regional CT in the 9 ETDRS grid sectors. Results For the SFCT analysis, 2794 eyes of 1619 participants (Chinese, Indian, and Malay ) were included. The mean age was 60.9 years (standard deviation, 7.7), and 797 (49.2%) were male. Mean SFCT was 255.2 μm (standard deviation, 102.6). The normal range of SFCT was 106 to 447 μm (corresponding to 5th and 95th percentile limits of SFCT, respectively). In multivariable models, thinner SFCT was associated with older age, female gender, longer axial length, and Malay (vs. Chinese) ethnicity. In the subset of Chinese and Indian eyes (n = 1842) in whom regional variation was evaluated, the choroid was thickest at the superior and temporal sectors and thinner at the inferior and nasal sectors. Conclusions Subfoveal choroidal thickness is influenced by age, gender, and ethnicity along with regional differences even within individual eyes. Subfoveal choroidal thickness also shows a wide range in physiologic limits. These data may be used as a reference in future studies.

Atropine eye drops prevent the progression of myopia, but their use has not been tested in the Japanese schoolchildren population. Here, we evaluate the efficacy and safety of 0.01% atropine eye drops for myopia control in Japanese children. Multicenter (7 university hospitals), randomized, double-masked, placebo-controlled trial. Participants were 171 Japanese schoolchildren aged 6 to 12 years, with progressive myopia, spherical equivalence (SE) of −1.00 to −6.00 diopters (D), and astigmatism of ≤1.5 D. They were randomized to receive either 0.01% atropine (n=85) or placebo (n=86) eye drops once nightly OU for 24 months. Primary and secondary efficacy endpoints were changes in SE and axial length (AL), respectively, from baseline to month 24. Data from 168 subjects were analyzed. At month 24, compliance was similar in both groups (atropine: 83.3%; placebo: 85.7%). The least squares mean change in SE and AL from baseline were, respectively, −1.26 D (95% confidence interval [CI]: −1.35, −1.17) and 0.63 mm (0.59, 0.67) for atropine and −1.48 D (− 1.57, −1.39) and 0.77 mm (0.73, 0.81) for placebo. Inter-group differences were 0.22 D (95% CI: 0.09, 0.35; P

Purpose We aimed to explore the velocity waveform characteristics of the retinal artery associated with age and the cardio-ankle vascular index (CAVI) as a conventional arterial stiffness marker by applying the Doppler optical coherence tomography (DOCT) flowmeter. Methods In this cross-sectional study, DOCT flowmeter imaging was performed in 66 participants aged 21 to 83 years (17 men, 49 women) with no history of eye diseases and no systemic diseases, except for hypertension. Retinal blood velocity waveform was analyzed where several parameters in time (upstroke time, T1, T2, T3, and T4) and area under the waveform (area elevation, area declination, A1, A2, A3, and A4) were extracted. Systolic blood pressure-adjusted Pearson's coefficients were calculated to determine the correlations of each parameter with age or CAVI. Results Corrected upstroke time (UTc) was the waveform parameter most positively correlated with age (r = 0.497, P < 0.001). Area declination was the waveform parameter most negatively correlated with age (r = -0.682, P < 0.001) and CAVI (r = -0.601, P < 0.001). Conclusions We extracted the waveform parameters associated with the risks of arterial stiffening. The velocity waveform analysis of the retinal artery with DOCT flowmeter potentially could become a new method for arterial stiffness identification. Translational Relevance DOCT flowmeter could evaluate arterial stiffening in a different way from the conventional method of measuring arterial stiffening using pressure waveform. Because the DOCT flowmeter can easily, quickly, and noninvasively provide a retinal blood velocity waveform, this system could be useful as a routine medical examination for arterial stiffening.

To evaluate choroidal volume and thickness changes after photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC). Chronic CSC eyes with a history of PDT were selected. Average choroidal volume, average choroidal thickness, the maximum and minimum choroidal thickness of the macula irradiated area and peripheral non-irradiated areas before and after one and three months of treatment were examined. A total of 14 patients with chronic CSC and 9 controls without any eye pathology were enrolled. The mean choroidal volume in CSC before and, and after one and three months of treatment were 2.36 (standard deviation: 0.70), 1.90 (0.69), 1.86 (0.66) mm3 for the central area, 1.25 (0.38), 1.14 (0.35), 1.13 (0.34) mm3 for superior nasal area, 1.47 (0.41), 1.28 (0.43), 1.26 (0.43) mm3 for superior temporal area, 1.07 (0.49), 0.95 (0.38), 0.93 (0.35) mm3 for inferior nasal area, 1.17 (0.38), 1.04 (0.32), 1.03 (0.33) mm3 for inferior temporal area. This study revealed the choroidal volume changes in a short period after PDT and a decrease in unirradiated choroidal volume was also shown after the treatment. The algorithm provided on the ARI Network enables to evaluate the choroidal changes quantitatively and qualitatively.

This study aimed to investigate the influence of educational pressure on myopia. A less-intense school curriculum was introduced nationally in Japan beginning in 2012 based on a pressure-free education policy. In this retrospective observational study, a total of 1025 Japanese medical students of Asahikawa Medical University underwent measurements of the cycloplegic refractive error and axial length (AL), from 2011 to 2020. The spherical equivalent (SE) and AL were correlated significantly with the fiscal year of births (p = 0.004 and p = 0.034, respectively) only during enforcement of the system of high-pressure education. The SE and AL regression rates during the two educational approaches differed significantly (p = 0.004 and p = 0.037, respectively). The prevalence of high myopia was correlated significantly (p &lt, 0.001) only during the system of high-pressure education. The regression of the prevalence rate of high myopia during the two education approaches differed significantly (p = 0.010). The progression rates of myopia and increased prevalence of high myopia were observed only during high-pressure education, suggesting that not only ophthalmologists but also educators and the government should work on together to control the progression of myopia.

Purpose It has been reported that peripapillary loops develop after central retinal artery occlusion (CRAO). Although cilioretinal anastomoses have been shown by fluorescein angiography (FA) and indocyanine green angiography, these examinations cannot confirm the structural continuity between the retinal arteries and the posterior ciliary arteries. In the current report, we followed a patient with iatrogenic CRAO in which circumpapillary collaterals formed and assessed the connection between these two vascular systems using optical coherence tomography angiography (OCTA). Observation Iatrogenic CRAO developed in the left eye of a 30-year-old woman during preoperative embolization of a convexity meningioma. FA and OCTA showed complete impairment of the retinal circulation. Two weeks after this event, OCTA images showed flow in the retinal vessels and the beginning of collateral vessel development on the optic disc margin. Six months later, OCTA images showed that these circumpapillary collaterals connected branches of the retinal arteries with the vessels supplying the optic disc, which originate from the posterior ciliary arteries. Conclusion and importance OCTA aided our understanding of the three-dimensional configuration of the circumpapillary collaterals that developed after iatrogenic CRAO, which included anastomosis of the retinal and posterior ciliary artery systems. OCTA is useful for noninvasively monitoring the status of retinal circulatory dynamics after iatrogenic CRAO.

The current study aimed to address whether ripasudil, a Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor developed to treat glaucoma and ocular hypertension (OH), improves diabetic macular edema (DME) since it is known that ROCK upregulates vascular endothelial growth factor. We retrospectively investigated the foveal thickness (FT) measured by spectral-domain optical coherence tomography, visual acuity (VA), and intraocular pressure (IOP) in 12 eyes with DME that received ripasudil treatment for primary open-angle glaucoma or OH and compared them with 14 eyes that received no treatment. One month after ripasudil therapy, the mean FT decreased significantly from 439 ± 72 µm to 395 ± 62 µm (P = 0.003); this change was significantly different from that in the controls, in which the mean FT increased by 1 ± 39 µm (P = 0.01). Ripasudil also caused a significant decrease in IOP from 17.3 ± 5.2 mmHg to 14.6 ± 4.0 mmHg (P = 0.02); this change was significantly greater than that in the controls, in which IOP changed by 0.0 ± 1.6 mmHg (P

Background: Doppler optical coherence tomography (DOCT) flowmeter can be used to measure retinal blood flow (RBF) parameters, including vessel diameter, blood velocity, and the absolute value of RBF within 2.0 s. We investigated the RBF parameters in eyes with branch retinal vein occlusion (BRVO) using a DOCT flowmeter. Methods: Seventeen patients with unilateral BRVO were enrolled. All subjects underwent comprehensive ophthalmologic examinations. The RBF parameters were assessed from three veins, i.e., (1) an occluded vein, (2) a non-occluded vein in the BRVO eyes, and (3) an equivalent (superior or inferior) vein in the fellow eye (non-affected vein), using prototype DOCT flowmeter (Topcon, Tokyo, Japan). Moreover, the correlation between RBF parameters and the best corrected visual acuity (BCVA) was examined. We investigated the correlation between (1) the RBF parameters and the time from the initial visit, (2) the RBF parameters and the time from the last injection, and (3) the RBF parameters and the number of anti-vascular endothelial growth factor injections (VEGF). Results: The diameter of the occluded vein (95.9 &plusmn, 24.7 &micro, m) was smaller than that of the non-occluded vein (127.9 &plusmn, 23.7 &micro, m) and that of the healthy veins (116.4 &plusmn, 13.9 &micro, m). The RBF was lower in the occluded veins (4.7 &plusmn, 3.7 &micro, L/min) than that in the non-occluded veins (10.3 &plusmn, 5.1 &micro, L/min, p &lt, 0.01) and in the fellow eyes (8.6 &plusmn, 4.0 &micro, p = 0.013). In contrast, the blood velocity was not significantly different among the three types of veins. BCVA was correlated with the diameter of the occluded vein (&rho, = 0.711, p = 0.001) but not with the RBF and blood velocity. The time from the initial visit, the time from the last injection, and the total number of anti-VEGF injections were not associated with any RBF parameters on the occluded vein. Conclusions: The RBF was significantly lower in the occluded veins than that in the other veins, and the diameter of the occluded vein was significantly smaller than that of the other veins in patients with BRVO. However, neither the time from the initial visit, nor the time from the last injection, nor the number of anti-VEGF injections were correlated with the RBF parameters on the occluded vein.

Purpose We aimed to observe longitudinal changes in retinal blood flow (RBF) and structural transformations in capillaries using Doppler optical coherence tomography (DOCT) and optical coherence tomography angiography (OCTA) in a feline retinal blood occlusion (RVO) model. Methods RVO was induced by argon green laser photocoagulation (PC) in six eyes of six cats. RBF was measured at a first-order retinal artery and vein by a DOCT flowmeter, and structural changes in the capillaries around the occluded vessels (12 × 12 and 3 × 3 mm) were assessed by OCTA before (at baseline); immediately after PC; and on days 1, 4, 7, and 14 thereafter. Systemic and ocular parameters were monitored during the observation period. Results There were no significant differences in any systemic or ocular parameters before and after PC. Arterial RBF increased significantly on day 1 (160.6 ± 8.6% vs. baseline, P < 0.001) and decreased below baseline after day 1 through 14. Venous RBF decreased immediately after PC (17.4 ± 9.6% vs. baseline, P = 0.001) and then gradually increased afterwards, but did not return to baseline. OCTA showed dilatation of retinal venules immediately after PC to day 1. Collateral vessels began to form on day 4, had matured by day 7, and were pruned on day 14, which formed as mature as normal retinal venule diameters. Conclusions With increasing arterial RBF within 1 day after inducing RVO, venules gradually expanded to form collateral vessels, suggesting that collateral vessels originate from existing capillary networks, not neovascularization.

AimsTo evaluate the associations between retinal blood flow (RBF) and optical coherence tomography (OCT) structural measurements in normal-tension glaucoma (NTG) eyes with single-hemifield visual field (VF) damage by the Doppler OCT.MethodsThe Doppler OCT was used to measure temporal artery (TA) RBF and temporal vein (TV) RBF. Retinal nerve fibre layer thickness (RNFLT) was measured by spectral-domain OCT.ResultsForty-three consecutive eyes of 43 patients with NTG with VF defect confined to a single hemifield and 24 eyes of 24 age-matched healthy subjects were studied. TA and TV RBF and RNFLT were reduced in the damaged hemisphere compared with the normal hemisphere (mean (SD), 3.61 (1.68) vs 5.86 (2.59) µL/min, pConclusionIn NTG eyes with single-hemifield damage, the RBF was significantly reduced in the damaged hemisphere compared with the normal one. The RBF decreased in the normal and damaged hemispheres of NTG eyes compared with the healthy hemisphere independent from RNFLT.

PurposeTo investigate the changes in extracellular matrix (ECM) gene and protein expressions in human trabecular meshwork (HTM) cells in response to mechanical fluid flow stimulation.MethodsHTM cells were cultured on a glass plate and exposed to shear stress (0, 0.2, and 1.0 dyne/cm2) for 12 hours. Changes in gene expressions were evaluated using microarray analysis. The representative genes related to ECM metabolism underwent real-time reverse-transcriptase polymerase chain reaction. Fibronectin (FN) and collagen (COL) IV levels in the supernatant were evaluated using immunoassays. Rho-associated coiled-coil-containing protein kinase (ROCK) activity also was investigated.ResultsAfter stimulation, transforming growth factor β2 mRNA levels were significantly (p < 0.01) lower than that of the static control (0 dyne/cm2 for 12 hours). Matrix metalloproteinase 2 mRNA levels were significantly (p < 0.05) higher than the static control. COL type 1 alpha 2 mRNA, COL type 4 alpha 2 mRNA, and COL type 6 alpha 1 mRNA levels were significantly (p < 0.05, < 0.01, and < 0.05, respectively) higher than the static control. The mean ± standard deviation FN levels (ng/mL) in the supernatant after stimulation (0, 0.2, 1.0 dyne/cm2) were 193.7 ± 7.6, 51.5 ± 21.8, and 34.9 ± 23.6, respectively (p < 0.01). The FN and COL IV levels and ROCK activity were significantly (p < 0.01 and < 0.05, respectively) lower than the static control.ConclusionsChanges in gene and protein expressions related to ECM metabolism occurred in HTM cells after stimulation. Specifically, the suppression of FN and COL IV production might explain the importance of mechanical fluid flow stimulation on maintenance of the normal aqueous humor outflow.

A 64-year-old man first developed ligneous conjunctivitis at the age of 58 years after right pulmonary resection because of suspected cancer; otherwise, he had been healthy. Since then, he began to suffer from various forms of chronic pseudomembranous mucositis. Laboratory tests demonstrated that he had 7.8 % of plasminogen activity and 5.9 % of the normal antigen level. Thus, he was diagnosed as having severe type I plasminogen deficiency, making him the third case in Japan. DNA sequencing and PCR-restriction fragment length polymorphism analyses revealed that this patient was a compound heterozygote of a G-to-A missense mutation (G266E) in exon VIII and a g-to-a mutation at the obligatory splicing acceptor site in intron 12 (IVS12-1g>a). These two mutations were confirmed to be novel. Molecular modeling and splice site strength calculation predicted conformational disorder(s) for the Glu266 mutant and a drastic decrease in splicing efficiency for intron 12, respectively. Western blot analysis demonstrated that the patient contained a small amount of the normal-sized plasminogen protein. Mass spectrometric analysis of the patient's plasminogen revealed a peptide containing the wild-type Gly266 residue and no peptides with mutations at Glu266. However, he had never suffered from thrombosis. Low levels of fibrinogen/fibrin degradation products (FDP), D-dimer, and plasmin-α2-plasmin inhibitor complex clearly indicated a hypo-fibrinolytic condition. However, his plasma concentration of elastase-digested crosslinked FDPs was 4.8 U/mL, suggesting the presence of an on-going plasmin(ogen)-independent "alternative" fibrinolytic system, which may protect the patient from thrombosis. The patient has been free from recurrence of ligneous conjunctivitis for approximately 2.5 years.

Purpose To evaluate the repeatability and reproducibility of the measurement of retinal arteriole pulse waveforms using a novel fully-automated Doppler optical coherence tomography (DOCT) flowmeter in healthy subjects. Methods Twenty eyes of 20 healthy subjects were included to test the intrasession repeatability of pulse waveform analysis. DOCT measurements were performed based on a newly developed instantaneous Doppler angle measurement method. Upstroke time (UT), which is the time from the minimum to the maximum retinal blood velocity, and the resistance index (RI) of the retinal arteriole pulse waveform were measured. Coefficients of variation (CVs) and intraclass correlation coefficients (ICCs) were calculated. Interdevice reproducibility between two instruments was assessed in five eyes of five subjects. Results The mean UT was 130.3 ms (range, 110.1-152.1 ms), and the mean RI was 0.66 (range, 0.51-0.82). The respective ICCs of UT and the RI for the intrasession repeatability of assessment were 0.87 and 0.78. The respective CVs of UT and the RI were 6.6 ± 3.3% and 4.7 ± 2.1%. Regarding interdevice reproducibility, there were no significant differences between the measurements derived from the instruments (P > 0.05). Conclusions Pulse waveform measurement in retinal arterioles using a fully-automated DOCT flowmeter exhibited good repeatability and interdevice reproducibility. Translational relevance The above-described improved DOCT flowmeter system provides reasonably repeatable measurements of retinal arteriole pulse waveforms, potentially facilitating systemic-circulation abnormality monitoring. The examination of the circulation with the novel device can be potentially useful for evaluating systemic circulation.

PURPOSE: To evaluate the ability of OCT optic nerve head (ONH) and macular parameters to detect disease progression in eyes with advanced structural glaucomatous damage of the circumpapillary retinal nerve fiber layer (cRNFL). DESIGN: Longitudinal study. PARTICIPANTS: Forty-four eyes from 37 subjects with advanced average cRNFL damage (≤60 μm) followed for an average period of 4.0 years. METHODS: All subjects were examined with spectral-domain optical coherence tomography (SD-OCT) and visual field (VF) during at least 4 visits. MAIN OUTCOME MEASUREMENTS: Visual field (VF) mean deviation (MD) and visual field index (VFI). OCT cRNFL (average, superior and inferior quadrants), ganglion cell/inner plexiform layer (GCIPL) (average, superior and inferior), rim area, cup volume, average cup-to-disc (C/D) ratio, vertical C/D ratio. RESULTS: At baseline, subjects had a median VF mean deviation (MD) of −10.18 dB and mean cRNFL of 54.55±3.42 μm. The rate of change for MD and VFI were significant. No significant rate of change was noted for cRNFL, while significant (p

To use a Doppler optical coherence tomography (DOCT) flowmeter to investigate segmental retinal blood flow (RBF) and sum of the segmental RBFs (SRBF) changes after panretinal photocoagulation (PRP) was used to treat type 2 diabetes mellitus with severe diabetic retinopathy (DR). Data from five patients with proliferative DR (PDR) (mean age 51.9 ± 10.5 years) was analyzed. The vessel diameter (D), average velocity (V), and retinal blood flow (RBF) in veins were measured using a DOCT flowmeter before and four weeks after PRP. Segmental RBF from inferotemporal (IT), superotemporal (ST), inferonasal (IN), and superonasal (SN) veins were measured, and SRBF was defined as the sum of these measurements. All data were analyzed by Wilcoxson test. After PRP, there were statistically significant decreases in the every segmental D, V, RBF (P0.05). The DOCT flowmeter has the potential to be a clinically useful tool to noninvasively evaluate the changes in retinal circulation during PRP in patients with PDR.

PURPOSE: Previously we introduced a state based two-dimensional continuous time hidden Markov model (2D CT-HMM) to model the pattern of glaucoma detected changes using structural and functional information simultaneously. The purpose of this study was to evaluate the glaucoma detected change prediction performance of the model in a real clinical setting using a retrospective longitudinal dataset. DESIGN: A longitudinal retrospective study SUBJECTS: One hundred thirty-four eyes from 134 subjects diagnosed as glaucoma or glaucoma suspect (average follow-up period 4.4 ± 1.2 years, average number of visits 7.1 ± 1.8 visits). METHODS: A 2D CT-HMM model was trained using optical coherence tomography (OCT; Cirrus HD-OCT, Zeiss, Dublin, CA) average circumpapillary retinal nerve fiber layer (cRNFL) thickness and visual field index (VFI) or mean deviation (MD) (Humphrey Field Analyzer, Zeiss, Dublin, CA). The model was trained using a subset of the data (107 out of 134 eyes, 80%) including all visits except for the last visit, which was used to test the prediction performance (training set). Additionally, the remaining 27 eyes were used for secondary performance testing as an independent group (validation set). The 2D CT-HMM predicts one out of 4 possible detected state changes based on one input state. MAIN OUTCOME MEASURES: Prediction accuracy was assessed as the percentage of correct prediction against the actual patients’ recorded state. In addition, deviations of the predicted long-term detected change paths from the actual detected change paths were measured. RESULTS: Baseline age was 61.9 ± 11.4 years (mean ± standard deviation), VFI was 90.7 ± 17.4, MD was −3.50 ± 6.04 dB, and cRNFL thickness was 74.9 ± 12.2 µm. The accuracy of glaucoma detected change prediction using the training set was comparable to the validation set (57.0% and 68.0%, respectively). Prediction deviation from the actual detected change path showed stability throughout patient follow-up. CONCLUSIONS: The 2D CT-HMM demonstrated promising glaucoma detected change prediction performance in a simulated clinical setting using an independent cohort. The 2D CT-HMM allows information from just one visit to predict at least 5 subsequent visits with similar performance.

オープンアクセス誌, Trapdoor fractures, or blowout fractures, result from muscle entrapment after orbital floor fractures. The incarcerated muscles may become necrotic because of ischemia; immediate surgery is recommended for symptomatic persistent diplopia or clinical evidence of entrapment. We report a case of spontaneous resolution of diplopia in a patient with a high suspicion of a trapdoor fracture. A 15-year-old girl presented with diplopia after being hit in the eye while playing volleyball. Computed tomography did not show a fractured orbital bone, but the forced duction test was positive when the left eye was pulled forward toward the left. Magnetic resonance imaging was negative for edema and inflammation in the extraocular muscles. With observation only, the diplopia resolved 2 weeks after onset. A negative forced duction test confirmed the resolution. Observation only may be appropriate in cases with posttraumatic limited ocular movement, after imaging has excluded an emergent condition.

Purpose To characterize the morphology of neovascularization at the disc (NVD) and neovascularization elsewhere (NVE) in treatment-naive or previously treated proliferative diabetic retinopathy (PDR) patients using optical coherence tomography (OCT) angiography. Methods En face OCT angiograms of NVD/NVE in 40 eyes of 33 patients with PDR were acquired using RTVue XR Avanti OCT. The morphology of NVD/NVE on OCT angiograms was evaluated, and the activity was determined by biomicroscopy and fluorescein angiography (FA). In 12 eyes that were treated or treatment-naive, changes in the morphology and vessel area of NVD/NVE before and after panretinal photocoagulation (PRP) were investigated. Results Twenty eyes had treatment-naive PDR, whereas 20 eyes were previously treated with PRP. All treatment-naive NVD/NVE had remarkable (i.e., active) leakage in early-phase FA. Ninety-five percent of treatment-naive NVD/NVE observed by OCT angiography had exuberant vascular proliferation (EVP), identified as irregular proliferation of fine (smaller-caliber) new vessels; whereas, the presence of EVP in previously treated eyes (13/20) was significantly less than in treatment-naive eyes (65% vs. 95%, P = 0.043). The remaining seven treated eyes had pruned NVD/NVE without EVP, observed as fibrotic changes or faint (inactive) leakage in FA. The vessel areas of NVD/NVE significantly decreased following PRP (n = 12, P = 0.019), and NVD/NVE morphology showed pruning and decreased EVP. Conclusions Exuberant vascular proliferation on OCT angiograms should be considered as an active sign of neovascularization; therefore, morphologic evaluation of neovascularization using OCT angiography may be useful to estimate the activity of each neovascularization in eyes with PDR.

PURPOSE To study retinal blood flow (RBF) measurement reproducibility using segmental-scanning Doppler optical coherence tomography (DOCT) in vitro in glass capillaries and in vivo in anesthetized cats. METHODS As a preliminary study, the flow rates of human blood through glass capillaries were changed by using an infusion pump and measured at 13 preset velocities by DOCT. For in vivo measurement, the cats were anesthetized using sevoflurane. The flow in the parent vessel was compared with the sum of the flow values in the two daughter vessels. The RBF was measured using two different instruments: bidirectional laser Doppler velocimetry (LDV) and DOCT. The reproducibility of the measurements was assessed by calculating the coefficients of variation (CVs) for repeated measurements of RBF at the superior retinal arterioles and venules. RESULTS In vitro, the flow velocities measured by DOCT agreed well with the preset velocities. In vivo, the flow in the parent vessel agreed with the sum of the flow values in the two daughter vessels. In addition, there were no significant differences in the mean averaged CVs of the RBF in both the arterioles and venules between LDV and DOCT. CONCLUSIONS The newly developed segmental-scanning DOCT revealed the accuracy of the measurement in in vitro glass capillaries and reproducibility of the measurements of blood velocity in both the retinal arterioles and venules in anesthetized cats.

PURPOSE The visual outcome after vitrectomy for proliferative diabetic retinopathy (PDR) is often poor. Bilateral vitrectomy has been especially associated with a poor visual prognosis in patients with PDR. The authors investigated the systemic risk factors for PDR requiring bilateral vitrectomy compared with unilateral vitrectomy. METHODS The authors retrospectively reviewed 86 consecutive patients with Type 2 diabetes mellitus with PDR who underwent vitrectomy. These patients were divided into 2 groups: bilateral vitrectomy within 1 year (n = 25) and unilateral vitrectomy (n = 61). The authors compared the systemic risk factors: age, sex, duration of diabetes, hemoglobin A1c, body mass index, estimated glomerular filtration rate, uric albumin, hypertension, dyslipidemia, history of ischemic heart disease, arteriosclerosis obliterans, and smoking. RESULTS There were significantly more cases with severe renal dysfunction in the bilateral vitrectomy group compared with the unilateral one (estimated glomerular filtration rate

PURPOSE: To investigate how glial cells participate in retinal circulation during flicker stimulation in cats. METHODS: Using laser Doppler velocimetry, we measured the vessel diameter and blood velocity simultaneously and calculated the retinal blood flow (RBF) in feline first-order retinal arterioles. Twenty-four hours after intravitreal injections of L-2-aminoadipic acid (LAA), a gliotoxic compound, and the solvent of 0.01 N hydrochloric acid as a control, we examined the changes in RBF in response to 16-Hz flicker stimulation for 3 minutes. We also measured the changes in RBF 2 hours after intravitreal injection of Nω-propyl-L-arginine (L-NPA), a selective neuronal nitric oxide synthase inhibitor, in LAA-treated eyes. To evaluate the effects of LAA on retinal neuronal function, ERGs were monitored. Immunohistochemical examinations were performed. RESULTS: In LAA-treated eyes, histologic changes selectively occurred in retinal glial cells. There were no significant reductions in amplitude or elongation of implicit time in ERG after LAA injections compared with controls. In control eyes, the RBF gradually increased and reached the maximal level (53.5% ± 2.5% increase from baseline) after 2 to 3 minutes of flicker stimulation. In LAA-treated eyes, the increases in RBF during flicker stimulation were attenuated significantly compared with controls. In LAA-treated eyes 2 hours after injection of L-NPA, flicker-evoked increases in RBF decreased significantly compared with LAA-treated eyes. CONCLUSIONS: The current results suggested that increases in RBF in response to flicker stimulation were regulated partly by retinal glial cells.

Purpose To investigate how neuronal nitric oxide synthase (nNOS) contributes to regulation of the retinal circulation during rest and flicker stimulation in cats. Methods Using laser Doppler velocimetry, we measured the vessel diameter and blood velocity simultaneously and calculated the retinal blood flow (RBF) in feline first-order retinal arterioles. After intravitreal injections of Nω-Nitro-L-arginine methyl ester (L-NAME), a nonselective NOS inhibitor, and Nω-propyl-L-arginine (L-NPA), a selective nNOS inhibitor, we continuously monitored the retinal circulation without any perturbations for 2 hours. We then examined the changes in the RBF in response to 16-Hz flicker stimuli for 3 minutes at 2 hours after intravitreal injection of phosphate-buffered saline (PBS) as a control, L-NAME, L-NPA, and thromboxane A2 (TXA2) analogue U46619 as a basal tone-adjusted control. Results After intravitreal injection of L-NAME and L-NPA, the baseline RBF decreased gradually in a dose-dependent manner. In the PBS group, the RBF increased gradually and reached a maximal level after 2 to 3 minutes of flicker stimuli. After 3 minutes of 16-Hz flicker stimuli, the RBF increased by 53.5% ± 3.4% compared with baseline. In the L-NAME and L-NPA groups, the increases in RBF during flicker stimulation were attenuated significantly compared with the PBS group. In the TXA2 group, the reduction in the flicker-induced increase in RBF was comparable to that in the PBS group. Conclusions The current results suggested that increased RBF in response to flicker stimulation may be mediated by nitric oxide (NO) production via nNOS activation.

Purpose To evaluate the repeatability and reproducibility of retinal blood flow (RBF) measurements in humans by using new auto-alignment and measurement software in a commercially available Doppler optical coherence tomography (DOCT) system. Methods The DOCT flowmeter assessed the intrasession repeatability and the intersession and interobserver reproducibility of the RBF measurements. For intrasession repeatability, the coefficients of variation (CVs) of five repeated RBF measurements were calculated at the retinal arteries and veins in 20 normal eyes of 20 healthy volunteers. For intersession reproducibility, two sets of three measurements obtained by one observer on 2 different days were compared. For interobserver reproducibility, two sets of three measurements obtained by two observers on the same day were compared. Intraclass correlation coefficients (ICCs) also were used to evaluate the repeatability and reproducibility. The relevance of the DOCT flowmeter and laser Doppler velocimetry (LDV) also was assessed. Results Regarding intrasession repeatability, the ICC of the RBF exceeded 0.90 in arterioles and venules (ICC: 0.994 and 0.970, respectively). The CVs of the RBF in the arterioles and venules were 6.0% ± 3.4% and 8.8% ± 5.1%, respectively. The intersession and interobserver RBF values had high reproducibility in the arterioles (ICC: 0.980 and 0.993, respectively) and venules (ICC: 0.982 and 0.986, respectively). The RBF measured with the DOCT flowmeter was correlated strongly with LDV in the arterioles (r = 0.76; P < 0.001). Conclusions The DOCT flowmeter had good reproducibility in the arterioles and venules and precisely measured the RBF as compared to the LDV in the arterioles.

Ligneous conjunctivitis is a rare severe conjunctivitis characterised by fibrin-rich, ‘woody’, pseudomembranes on the tarsal conjunctiva complicated by congenital hypoplasminogenaemia. A previous report suggested that ligneous conjunctivitis may result from tranexamic acid (TA)-induced ‘secondary’ hypoplasminogenaemia. However, the serum plasminogen level has not been confirmed in that scenario. We report for the first time a case of TA-induced ligneous conjunctivitis with reversible hypoplasminogenaemia. A 70-year-old woman developed a gastric ulcer that was treated with oral TA. After 5 weeks of treatment, the patient presented with bilateral pale yellow pseudomembranes on the palpebral conjunctivae. Haematological analysis showed hypoplasminogenaemia. We diagnosed ligneous conjunctivitis. TA was discontinued after 14 weeks after the gastric ulcer symptoms resolved. Six weeks after discontinuation of therapy, the pseudomembranes regressed and the serum plasminogen level returned to the normal range. TA should be considered a possible aetiology in the setting of unresolving ligneous conjunctivitis.

We report a case of hypertensive choroidopathy with detailed retinal images obtained using spectral-domain optical coherence tomography (SD-OCT).A 19-year-old pregnant woman with no history of high blood pressure had an eclamptic seizure at the 39th week of pregnancy; the baby was delivered by emergency Caesarean section. Six days later, she presented with bilateral blurred vision (best-corrected visual acuity [VA], 0.5, right eye; 0.3, left eye). Bilateral extensive, punctate, pale-yellow Elschnig's spots were present in the posterior fundus. SD-OCT showed a serous retinal detachment (SRD) and retinal pigment epithelium detachment (PED) representing a waveform retinal pigment epithelium (RPE) layer in each eye. The reflective intensity decreased partly at the waveform RPE. A wavy structure suggestive of fibrin was present in both foveas between the photoreceptor ellipsoid zone and the RPE-outer segment line. Four weeks after delivery and oral antihypertensive treatment, the SRDs, PEDs and wavy structure resolved and the VA recovered.SD-OCT visualized SRDs, PEDs, wavy structures under the photoreceptor ellipsoid zone, and areas of low intensity RPE layer in hypertensive choroidopathy.

This work is licensed under a Creative Commons Attribution 4.0 International License., Purpose: To investigate the role of endothelin-1 (ET-1) in retinal glial cells in regulating retinal blood flow (RBF) during hyperoxia in cats. Methods: We measured the vessel diameter (D), blood velocity (V), and blood flow (F) simultaneously in first-order retinal arterioles using a laser Doppler velocimetry system. The animals were under general anesthesia during hyperoxia (100% oxygen) for 10 minutes 24 hours after intravitreal injection of L-2-aminoadipic acid (LAA), a gliotoxic compound, or diluted hydrochloric acid (0.01 N) used as the vehicle control. We also measured the changes in the RBF after intravitreal injection of BQ-123, a specific ET type A receptor antagonist, in LAA-treated eyes. To examine if endothelin-converting enzyme-1 (ECE-1), as an ET-1-generating enzyme located in retinal glial cells, immunohistochemical examinations with costaining of antiglial fibrillary acidic protein (GFAP) antibody and anti-ECE-1 antibody were performed in whole-mount retinas. Results: During hyperoxia, the decreases in D, V, and F in response to hyperoxia were attenuated significantly (P < 0.01 for all comparisons) in the LAA-treated eyes compared with the vehicle control (LAA, D, -8.5 ± 1.5%; V, -13.8 ± 1.5%; F, -27.8 ± 3.0% versus vehicle control, D, -16.8 ± 1.3%; V, -26.3 ± 2.0%; F, -48.9 ± 2.4%). In LAA-treated eyes, intravitreal injections of BQ-123 did not change the rate of hyperoxia-induced RBF compared to LAA-treated eyes. The anti-ECE-1 antibody was costained with anti-GFAP antibody in the whole-mount retinas. Conclusions: The current findings suggest that retinal glial ET-1 may play an important role in regulating RBF during hyperoxia in cats.

Blood banking has a broad public health impact influencing millions of lives daily. It could potentially benefit from emerging biopreservation technologies. However, although vitrification has shown advantages over traditional cryopreservation techniques, it has not been incorporated into transfusion medicine mainly due to throughput challenges. Here, we present a scalable method that can vitrify red blood cells in microdroplets. This approach enables the vitrification of large volumes of blood in a short amount of time, and makes it a viable and scalable biotechnology tool for blood cryopreservation., National Institutes of Health (U.S.) (NIH R21 EB007707), Wallace H. Coulter Foundation, United States. Army Medical Research and Materiel Command (Acquisition Activity Cooperative Agreement RO1 A1081534), Center for Integration of Medicine and Innovative Technology, United States. Army Medical Research and Materiel Command (Acquisition Activity Cooperative Agreement R21 AI087107), United States. Army. Telemedicine & Advanced Technology Research Center