Assessment of myopic rebound effect after discontinuation of treatment with 0.01% atropine eye drops in Japanese school-age children.

PURPOSE: Having previously demonstrated the efficacy of 0.01% atropine eye drops for inhibiting progression of childhood myopia, we conducted additional analyses to assess post-treatment changes in myopia progression. STUDY DESIGN: Analysis of follow-up data from a previously reported randomized controlled trial METHODS: A mixed-effects model was used to compare intergroup changes in spherical equivalent (SE) and axial length (AL) at 1 month and 12 months after discontinuation of 2-year treatment with atropine or placebo in 167 school-age children. RESULTS: Follow-up measurements were available for 149 participants at 1 month after discontinuation of treatment and for 51 participants at 12 months after discontinuation. At 1 month post-treatment, differences between the atropine and placebo groups in least squares (LS) mean changes in SE and AL, respectively, from 24 months were -0.06 diopters (D) (95% CI: -0.21, 0.08; P = .39) and 0.02 mm (95% CI: -0.05, 0.08; P = .60). At 12 months post-treatment, intergroup differences (atropine vs placebo) in LS mean changes in SE and AL, respectively, were -0.13 D (95% CI: -0.35, 0.10; P = .26) and -0.02 mm (95% CI: -0.12, 0.09; P = .75). LS mean changes in SE and AL from treatment discontinuation did not differ between the groups at 1 or 12 months post-treatment. CONCLUSION: Axial elongation was significantly less in the atropine group than in the placebo group. The suppression effect obtained at 2 years was maintained after 12 months. The absence of intergroup differences in myopia progression since treatment cessation suggests that myopic rebound did not occur.

NOTCH2NLC mutation-positive neuronal intranuclear inclusion disease with retinal dystrophy: A case report and literature review.

INTRODUCTION: Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder that produces a broad spectrum of clinical conditions such as dementia, upper motor neuron involvement, extrapyramidal symptoms, and neuropathy. Some studies have reported ophthalmological conditions associated with the disease; however, the details of these conditions remain unclear. PATIENT CONCERNS: We report a 63-year-old Japanese female with cognitive decline, blurred vision, photophobia, and color blindness at 52 years of age who was diagnosed with cone dystrophy. She also had anxiety, insomnia, depression, delusions, hallucinations, a wide-based gait with short steps, and urinary incontinence. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Magnetic resonance imaging revealed diffuse cerebral white matter changes and subcortical hyperintensity on diffusion-weighted imaging. Skin biopsy showed p62-positive intranuclear inclusions in sweat glands. NOTCH2NLC gene analysis revealed abnormal GGC expansion; therefore, NIID was diagnosed. CONCLUSION: NOTCH2NLC mutation-positive NIID may be associated with retinal dystrophy. Brain magnetic resonance imaging and skin biopsy are helpful diagnostic clues, and gene analysis is crucial for accurate diagnosis and appropriate management.

Glaucoma Diagnostic Performance of Retinal Blood Flow Measurement With Doppler Optical Coherence Tomography.

Purpose: The purpose of this study was to evaluate the diagnostic performance of retinal blood flow (RBF) measured with the Doppler optical coherence tomography (OCT) segmental scanning method to distinguish between healthy and glaucoma eyes. Methods: Fifty-eight patients with normal tension glaucoma (NTG) who had a single-hemifield visual field defect and 44 age-matched healthy subjects were enrolled. Retinal nerve fiber layer thickness (RNFLT) was measured with swept-source OCT. Superior and inferior temporal arteries (TAs) and temporal veins (TVs) RBF were measured with Doppler OCT. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to compare the diagnostic performances in the damaged and normal hemispheres. Results: Multivariate regression analysis showed TA RBF and TV RBF were significantly reduced in the damaged and normal hemispheres. The ROC analysis showed that the AUC for quadrant RNFLT, TA RBF, and TV RBF were 0.973, 0.909, and 0.872 in the damaged hemisphere, respectively. The AUC values in the normal hemisphere were 0.783, 0.744, and 0.697, respectively. The combination of quadrant RNFLT and TA/TV RBF had a greater AUC than quadrant RNFLT alone in both damaged (AUC = 0.987) and normal (AUC = 0.825) hemispheres. Conclusions: In NTG eyes with single-hemifield damage, the RBF was found to be significantly reduced in the damaged and normal hemispheres independent from structural changes. The combination of RNFLT and RBF could improve diagnostic performances for glaucoma. Translational Relevance: Combining morphological and blood flow measurements with Doppler OCT may be useful in glaucoma diagnosis.

Retinal Blood Velocity Waveform Characteristics With Aging and Arterial Stiffening in Hypertensive and Normotensive Subjects.

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.

Impact of the Pressure-Free Yutori Education Program on Myopia in Japan.

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 < 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.

Identification of risk factors for retinal vascular events in a population-based cross-sectional study in Rumoi, Japan.

We conducted a population-based, cross-sectional study in Japan to identify risk factors for retinal vascular events separately by gender. Forty years or older participants were recruited. Fundus photographs were taken, and lifestyle and health characteristics were determined through a questionnaire and physical examinations. We compared the group of those who had retinal vascular events and those who did not. A total of 1689 participants (964 men) were deemed eligible for the study and retinal vascular events were seen in 59 subjects (3.7% of the men, 3.2% of the women). Self-reported diabetes mellitus was significantly associated with the vascular events in each gender [odds ratio (OR) = 6.97, 6.19 (men, women); 95% confidence interval (CI) 3.02-15.9, 2.25-17.0; p < 0.001]. Higher systolic blood pressure (OR = 1.03; 95% CI 1.01-1.04; p = 0.006) and lower frequency of meat consumption (OR = 0.73; 95% CI 0.54-0.99; p = 0.04) were independently associated with the vascular events in men. In women, while vascular events were associated with self-reported hypertension (OR = 2.64; 95% CI 1.03-6.74; p = 0.04), no association was seen with systolic blood pressure. Women with hypertension may need extra care, not only for blood pressure.

Efficacy and safety of 0.01% atropine for prevention of childhood myopia in a 2-year randomized placebo-controlled study.

PURPOSE: 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. STUDY DESIGN: Multicenter (7 university hospitals), randomized, double-masked, placebo-controlled trial. METHODS: 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. RESULTS: 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 < 0.001) for SE and - 0.14 mm (-0.20, -0.08; P < 0.001) for AL. Three patients experienced mild allergic conjunctivitis side effects, with no inter-group difference in incidence (atropine: 2.4%; 2/84 patients; placebo: 1.4%; 1/84 patients). CONCLUSION: With good compliance, 0.01% atropine is effective and safe for preventing the progression of childhood myopia.

Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Retinal blood flow reduction in normal-tension glaucoma with single-hemifield damage by Doppler optical coherence tomography.

AIMS: To 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. METHODS: The 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. RESULTS: Forty-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, p<0.001; 5.61 (2.51) vs 6.94 (2.83) µL/min, p=0.010; 69.0 (19.7) vs 99.7 (22.8) µm, p<0.001). Those values in the normal hemisphere of NTG eyes also decreased compared with the healthy hemisphere of the healthy eyes (8.40 (3.36) µL/min, p<0.001; 9.28 (4.47) µL/min, p<0.002; 122.8 (20.2) µm, p<0.001). Multivariate model showed that normal and damaged hemispheres and RNFLT were associated with RBF reduction. In addition, the RBF in the normal hemisphere was lower than that in the healthy hemisphere even after adjusting for RNFLT. CONCLUSION: In 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.

Population-Based Prevalence and 5-Year Change of Soft Drusen, Pseudodrusen, and Pachydrusen in a Japanese Population.

Purpose: To elucidate the prevalence of soft drusen, pseudodrusen, and pachydrusen and their 5-year changes in a Japanese population. Design: Longitudinal population-based cohort study conducted from 2013 through 2017. Participants: Residents 40 years of age or older. Methods: Nonmydriatic color fundus photographs were used to grade drusen subtypes and retinal pigment epithelium (RPE) abnormalities according to the Three Continent Age-Related Macular Degeneration Consortium. The 5-year changes of each drusen were investigated. Main Outcome Measures: The prevalence of each drusen subtype and the 5-year changes of each drusen. Results: Among 1731 participants, 1660 participants had gradable photographs that were assessed. The age-adjusted prevalence of soft drusen, pachydrusen, and pseudodrusen was 4.3% (95% confidence interval [CI], 3.2%-5.8%), 7.7% (95% CI, 6.2%-9.7%), and 2.8% (95% CI, 1.7%-4.2%), respectively. Pachydrusen accounted for 82.0% (n = 50) of the extramacular drusen (n = 61). Pigment abnormalities were seen in 28.3% and 8.3% of eyes with soft drusen and pachydrusen, respectively (P < 0.0001). Longitudinal changes were investigated in 1444 participants with follow-up examinations, which showed an increase in size in 8.3% and 3.7% and regression in 1.7% and 5.5% for eyes with soft drusen and pachydrusen, respectively. No participants demonstrated RPE atrophy after pachydrusen regression. Conclusions: The prevalence of pachydrusen was higher than that of soft drusen and pseudodrusen combined. Pachydrusen may regress over time and typically is not associated with RPE atrophy as detected using color fundus photographs.

Effect of Background Brightness on Preferred Retinal Loci in Patients With Macular Disease.

Purpose: To evaluate the effect of background brightness on the preferred retinal locus (PRL) in patients with macular disease. Methods: The study included 27 eyes (27 patients) with macular disease. Microperimetry (MP) was performed to evaluate the PRL and retinal sensitivity (RS) at 10 cd/m2. A prototypical device was used to evaluate the PRL at 650 cd/m2. Patients were divided into two groups: central fixation (CF) and eccentric fixation (EF). Results: The PRLs under different brightness levels differed significantly (P < 0.001) in 15 of 27 eyes (two of 13 eyes in the CF group and 13 of 14 eyes in the EF group). The best-corrected visual acuities (BCVAs) in eyes with different PRLs were significantly worse (P = 0.019) than in eyes with one PRL, although the foveal RS did not differ significantly. In patients with BCVAs over 0.1, the PRLs differed in four of 13 eyes in the CF group and in three of four eyes in the EF group (P > 0.05); in patients with BCVAs of 0.1 or lower, the PRLs differed in one of four eyes and 10 of 10 eyes, respectively (P = 0.011). Conclusions: In patients with macular disease, PRLs can change depending on the surrounding brightness. It may be beneficial to evaluate PRLs under brighter background conditions (e.g., in ambient light) when performing visual rehabilitation for these patients. Translational Relevance: This study provides important information for visual rehabilitation of patients with macular disease.

Effect of illumination on reading performance in Japanese patients with age-related macular degeneration.

PURPOSE: Several studies of Western patients with age-related macular degeneration (AMD) have investigated reading performance that improved at high levels of illumination; however, the relation between reading performance and macular function has not been evaluated in detail in Japan. The goals of this study were to evaluate the effect of different levels of illumination on reading performance in Japanese patients with AMD and determine the factors, such as macular function, that affect these results. STUDY DESIGN: Cross-sectional study. METHODS: We prospectively included 39 patients with bilateral AMD or maculopathy. We evaluated reading performance; reading acuity (RA), critical print size (CPS), and maximal reading speed (MRS) using charts with Japanese sentences based on the MNREAD-J in 500-7500 lx. Patients were classified into two groups based on the presence of a central scotoma (CS) or no CS (NCS) diagnosed by microperimetry. RESULTS: The RA improved significantly in 500-7500 lx in both groups (NCS, p = 0.001; CS, p = 0.046). The RA improvement differed significantly (2000 lx, p = 0.021; 5,000 lx; p = 0.021; 7500 lx, p = 0.047) between 500 lx and other illumination levels only in the NCS group and then plateaued over 2000 lx. The CPS and MRS did not improve significantly at any illumination level. CONCLUSIONS: These results suggest that the difference in macular function was related to improvement in the RA with increased illumination in Japanese patients with AMD.

Circumpapillary collateral vessel development in iatrogenic central retinal artery occlusion observed using OCT angiography.

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.

Association Between Alterations of the Choriocapillaris Microcirculation and Visual Function and Cone Photoreceptors in Patients With Diabetes.

Purpose: The purpose of this study was to investigate the association between the choriocapillaris microcirculation and the visual function and cone photoreceptor structure in patients with diabetes. Methods: Thirteen control subjects and 26 patients with type 2 diabetes were recruited. The patients with diabetes were divided into three groups based on the grade of diabetic retinopathy (DR). The retinal sensitivity (RS) was evaluated using microperimetry. Cone photoreceptor mosaics were imaged using an adaptive optics retinal camera, and the cone heterogeneity packing index (HPi) was calculated. Optical coherence tomography angiography (OCTA) images of the choriocapillaris were obtained using spectral-domain OCTA, and the area of flow deficit (FD) was evaluated. All parameters were evaluated in the foveal and parafoveal areas. Results: The study included four patients with diabetes without retinopathy, 12 patients with nonproliferative diabetic retinopathy (NPDR), and 10 patients with proliferative diabetic retinopathy (PDR). The foveal and parafoveal FDs were correlated significantly (fovea, r = -0.58; P = 0.046 and r = -0.82; P = 0.003; parafovea, r = -0.59; P = 0.044 and r = -0.72; and P = 0.019, respectively) with the RS in patients with NPDR and PDR, but not in control and no diabetic retinopathy (NDR) groups. There were no differences in the foveal HPi among the groups. Conclusions: Impaired choriocapillaris microcirculation is associated with impaired visual function but not cone photoreceptor integrity in eyes with DR.

Deterioration of Retinal Blood Flow Parameters in Branch Retinal Vein Occlusion Measured by Doppler Optical Coherence Tomography Flowmeter.

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 ± 24.7 µm) was smaller than that of the non-occluded vein (127.9 ± 23.7 µm) and that of the healthy veins (116.4 ± 13.9 µm). The RBF was lower in the occluded veins (4.7 ± 3.7 µL/min) than that in the non-occluded veins (10.3 ± 5.1 µL/min; p < 0.01) and in the fellow eyes (8.6 ± 4.0 µL/min; 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 (ρ = 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.

A Proposed Classification of Intraretinal Microvascular Abnormalities in Diabetic Retinopathy Following Panretinal Photocoagulation.

Purpose: To investigate the characteristics of intraretinal microvascular abnormalities (IRMAs) before and after panretinal photocoagulation (PRP) for diabetic retinopathy (DR) by using optical coherence tomography angiography (OCTA). Methods: Forty-six eyes of 29 patients with DR were included (26 eyes with severe nonproliferative diabetic retinopathy [SNPDR] and 20 eyes with proliferative diabetic retinopathy [PDR]). En face OCTA images of IRMAs in a 6 × 6-mm area were acquired by using Cirrus 5000 with AngioPlex. The morphological changes in IRMAs were evaluated before and after PRP. The changes in the IRMAs were divided into five subtypes: unchanged; tuft regression; reperfusion; mixed (combined tuft regression/reperfusion); and worsening (new appearance of tuft). Results: Unchanged IRMAs were identified in 15 SNPDR eyes and 2 PDR eyes; all neovascularization (NV) had regressed after PRP. Tufts were more frequently observed in the PDR eyes (15/20, 75%) than in the SNPDR eyes (8/26, 31%) (P = 0.003), and two tufts tended to exceed the inner limiting membrane, which showed progression to NV before PRP. The reperfusion phenomenon was observed in 7/26 SNPDR eyes and 4/20 PDR eyes, including the mixed type, and showed two vascular patterns: abnormal (dilated, tortuous, and twisted) and normal vessels. The worsening type was observed in 1/26 SNPDR eye and 2/20 PDR eyes. Conclusions: OCTA enabled classification of IRMA into more detailed types. The unchanged and reperfusion types suggested that IRMAs had aspects of remodeling. However, IRMAs with tufts were observed in 75% of the PDR eyes, and the tufts had aspects of NV.

Longitudinal Changes in Retinal Blood Flow in a Feline Retinal Vein Occlusion Model as Measured by Doppler Optical Coherence Tomography and Optical Coherence Tomography Angiography.

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.

A Case of Progressive Diabetic Retinopathy Related to Pregnancy Followed on Optical Coherence Tomography Angiography.

A 27-year-old woman with type 2 diabetes mellitus had mild diabetic retinopathy (DR) during the early gestation period. Optical coherence tomography angiography (OCTA) showed microaneurysms and small capillary nonperfusion with little change until before delivery. The patient later developed pregnancy-induced hypertension, which continued after delivery, and the DR worsened markedly. OCTA showed onset and recovery of paracentral acute middle maculopathy. Macular edema (ME) also developed, and OCTA showed irregular dilation in the radial peripapillary capillaries. After starting antihypertensive therapy, the capillary dilation and ME decreased. OCTA enables close follow-up of DR related to pregnancy during the perinatal period. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:393-397.].

Effect of ripasudil on diabetic macular edema.

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 < 0.008). There was no significant difference in the VA changes between groups. Our results suggested that ripasudil may have positive effects on both IOP and DME.

A low meat diet increases the risk of open-angle glaucoma in women-The results of population-based, cross-sectional study in Japan.

BACKGROUND: Studies identifying modifiable lifestyle risk factors related to open-angle glaucoma (OAG) are limited, especially from Asian countries. This study aimed to identify lifestyle risk factors for OAG in a Japanese population. METHODS AND FINDINGS: This population-based, cross-sectional study recruited Japanese participants aged 40 years or older from January 2013 to March 2015. We took fundus photographs for OAG screening, determined lifestyle and health characteristics through a questionnaire and performed physical examinations. The participants who had suspect findings in the fundus photographs were sent for a detailed ophthalmic examination to diagnose OAG. Lifestyle and heath characteristics were statistically compared between the OAG and non-OAG participants. A total of 1583 participants were included in the study, of which 42 had OAG and 1541 did not have OAG. The number of days per week that the female participants consumed meat (mean±SD; OAG: 1.7±1.2 days, non-OAG: 2.7±1.5 days) was negatively associated with OAG (OR = 0.61; 95% CI: 0.43-0.88; p = 0.007). Higher intraocular pressure was positively associated with OAG in men (OR = 1.20; 95% CI: 1.05-1.38, p = 0.009). No significant difference between participants with and without OAG was observed for a range of other lifestyle factors and health criteria including self-report of diabetes, number of family living together, body mass index, blood pressure, pulse rate, coffee drinking, tea drinking, alcohol drinking, number of fruits consumed per day and days of fish consumption per week. CONCLUSIONS: A higher weekly consumption of meat appears to be negatively associated with OAG in Japanese women. Increasing the dietary intake of meat can contribute to reducing the risk of developing OAG.