Diabetic choriocapillaris flow deficits affect the outer retina and are related to hemoglobin A1c and systolic blood pressure levels.

Patient systemic and ocular data based on optical coherence tomography (OCT) and OCT angiography images were analyzed (n = 45; control and diabetic eyes with or without diabetic retinopathy [DR]; mean age, 49.6 ± 8.1 years). All participants had best-corrected visual acuity < 0.05 in logMAR. The choriocapillaris flow area (CCFA) ratio was lower and the coefficient of variation (CV) of CCFA ratio was higher in diabetic eyes with or without DR than in control eyes. CCFA ratio of DR eyes was lower than that of diabetic eyes without DR. Superficial retinal vessel length density (VLD) was reduced only in DR eyes. CCFA ratio correlated with retinal VLD, photoreceptor outer segment (PROS) length, and retinal pigment epithelium (RPE) volume in the study population; mean PROS decreased in diabetic eyes with or without DR, and RPE volume increased in DR eyes. CCFA ratio < 65.9% and CV of CCFA ratio ≥ 0.140 were more frequently found in diabetic eyes (odds ratio [OR], 13.333; P = 0.001), and related to HbA1c ≥ 7.0% (OR, 4.992; 95% confidence interval [CI] 1.164-21.412; P = 0.030) or systolic blood pressure ≥ 135 mmHg (OR, 5.572; 95% CI 1.156-26.863; P = 0.032). These findings could help understand diabetic pathogenesis in the choriocapillaris and outer retina, and remind clinicians to manage both diabetes and hypertension.

Evaluating fine changes in visual function of diabetic eyes using spatial-sweep steady-state pattern electroretinography.

The visual function of diabetic eyes was assessed to evaluate spatial-sweep steady-state pattern electroretinography (swpPERG) as a potential high-sensitivity analysis method. Data from 24 control eyes, 28 diabetic eyes without diabetic retinopathy (DR), and 30 diabetic eyes with DR (all with best-corrected visual acuity [BCVA] better than logMAR 0.05; median age, 51) in response to spatial-patterned and contrast-reversed stimuli of sizes 1 (thickest) to 6 were converted into the frequency domain using a Fourier transform and expressed as signal-to-noise ratios (SNRs). SNRs of diabetic eyes, both with and without DR, were lower than those of controls (P < 0.05), and those of DR eyes were lower than those of diabetic eyes without DR (P < 0.05). The SNRs were correlated with ganglion cell layer volume measured using optical coherence tomography (OCT) and foveal vascular length density at the superficial retinal layer measured using OCT angiography (P < 0.05 or < 0.01, according to stimulus size). Therefore, swpPERG SNRs could detect fine reductions in visual function in diabetic eyes and were particularly low in DR eyes. Moreover, SNRs were correlated with inner retinal morphological changes in diabetic eyes, both with and without DR. swpPERG may therefore be useful for detecting fine fluctuations in visual function in diabetic eyes.

Retinal Pigment Epithelial Abnormality and Choroidal Large Vascular Flow Imbalance Are Associated with Choriocapillaris Flow Deficits in Age-Related Macular Degeneration in Fellow Eyes.

Choriocapillaris flow deficits detected on optical coherence tomography angiographs were retrospectively analyzed. In 38 age-related macular degeneration (AMD) fellow eyes, without fundus findings (26 men, 71.7 ± 1.9 years old), and 22 control eyes (11 men, 69.4 ± 1.8), the choriocapillaris flow area (CCFA) ratio and coefficient of variation (CV) of the CCFA ratio (which represented the heterogeneity of the ratio), negatively and positively correlated with age (all p < 0.01), respectively. Moreover, the respective mean values were lower (p = 0.0031) and greater (p = 0.002) in AMD fellow eyes than in the control eyes. The high-risk condition of AMD fellow eyes was defined by a CCFA ratio <58.5%, and the CV of the CCFA ratio ≥0.165 (odds ratio (OR), 5.408; 95% confidence interval (CI): 1.117-21.118, p = 0.035, after adjusting for age and sex) was related to the presence of fundus autofluorescence abnormality (OR, 16.440; 95% CI, 1.262-214.240; p = 0.033) and asymmetrically dilated choroidal large vasculature (OR, 4.176; 95% CI, 1.057-16.503; p = 0.042), after adjusting for age and sex. The presence of fundus autofluorescence abnormality indicated a retinal pigment epithelium (RPE) abnormality. The RPE volume was reduced in the latter eye group, particularly in the thinner choroidal vasculature. In addition to aging, RPE abnormality and choroidal large vascular flow imbalances were associated with exacerbated heterogeneous choriocapillaris flow deficits in AMD fellow eyes without macular neovascularization.

Retinal circulation time/arm-to-retina time ratio in the fluorescein angiography to evaluate retina-specific hemodynamics.

To evaluate dynamic circulatory flow in the retinal or choroidal circulatory disease, we retrospectively reviewed medical charts of 128 eyes of 128 patients who underwent video recorded fluorescein angiography (FA), at Department of Ophthalmology, St Luke's International Hospital, between April and September 2020. Mean age was 64.2 ± 14.0 (range 37-93) years, and 87 (67.9%) patients were men. Mean arm-to-retina (AR) time was 16.2 ± 4.1 s, and mean retinal circulation (RC) time was 10.9 ± 3.3 s. Mean RC time/AR time (RC/AR) ratio was 0.69 ± 0.22. AR time was correlated with age, whereas RC time was not. RC time was positively correlated with AR time (R = 0.360, P = 0.017). Moreover, mean RC time was significantly longer, and RC/AR ratio was greater, in the retinal-disease group after adjusting for age and sex. Patients who had an RC/AR ratio ≥ 0.8 more frequently presented with retinal diseases. RC time and RC/AR ratio were negatively correlated with systolic blood pressure only in the retinal-disease group. Given that AR time reflects systemic hemodynamics, RC time, which reflects local circulatory fluency, was influenced by the systemic circulatory condition. Moreover, RC/AR ratio revealed that circulatory changes peculiar to the retina may also be involved in retinal-disease pathogenesis. This study may help elucidate the mechanisms of retinal diseases and assist in diagnosis, although further studies are required.

Choriocapillaris Flow Imbalance in Fellow Eyes in Age-Related Macular Degeneration.

Purpose: The purpose of this study was to identify early changes in choriocapillaris flow in patients with age-related macular degeneration (AMD) with no history of macular neovascularization (MNV). Methods: Clinical records of fellow eyes of patients with unilateral neovascular AMD without fundus findings and control eyes of otherwise healthy individuals, except for mild cataract, diagnosed at St. Luke's International Hospital from April 2020 to March 2021, were retrospectively analyzed. Optical coherence tomography (OCT) angiography images of the choriocapillaris slab were binarized using the Phansalkar local thresholding methods to evaluate the choriocapillaris flow area (CCFA) and its coefficient of variation (CV). Results: The data of 24 AMD fellow eyes (17 for men, 71.7 ± 1.9 years old) and 21 control eyes (11 for men, 69.1 ± 2.0 years old) were analyzed. The mean CCFA ratio was lower in the AMD fellow eyes (58.6 ± 1.2%) than in the control eyes (62.4 ± 1.3%, P = 0.032), and the mean CV of CCFA ratio was greater in the AMD fellow eyes (0.174 ± 0.007) than in the control eyes (0.154 ± 0.007, P = 0.032). Eyes with CCFA ratio <60% and CV of CCFA ratio ≥0.154 had a 4.371-fold higher risk of being AMD fellow eyes (95% confidence interval = 1.029-18.56, P = 0.046). Differences in CV of CCFA ratio between AMD fellow eyes and control eyes were particularly clear in eyes with thick choroids (mean CV of CCFA in control versus AMD fellow eyes with central choroidal thickness ≥220 µm: 0.144 ± 0.005 vs. 0.173 ± 0.007, P = 0.009**). Conclusions: Neovascular AMD fellow eyes without MNV had reduced, heterogeneous, and imbalanced choriocapillaris flow, which may constitute early changes in neovascular AMD, although further studies are required.

Effects of intraocular treatments for Epstein-Barr virus (EBV) retinitis: A case report.

RATIONALE: Intraocular infection of Epstein-Barr virus (EBV) may cause severe visual loss. However, it is relatively rare, and there is no consensus on its treatment. PATIENT CONCERNS: A 44-year-old woman complained of a right-eye floater and exhibited a unilateral exudative change along the retinal veins at the Department of Ophthalmology, St. Luke's International Hospital. DIAGNOSIS: EBV retinitis was diagnosed based on EBV-positive (9.09 × 103 copies/µl) and cytomegalovirus-negative results in the aqueous humor. INTERVENTIONS: Oral prescription of valaciclovir hydrochloride, and an intravitreal injection of foscarnet sodium hydrate was administered. However, the retinal infiltration progressed, and vitreous opacity with cellular infiltration appeared. Intravitreal methotrexate (MTX) injection effectively suppressed retinal and vitreous infiltration. However, she developed optic-nerve papillitis, and central retinal vein occlusion related to the severe swelling of the optic-nerve, and began steroid pulse therapy. Considering the increase in intraocular EBV levels to 6.4 × 104 copies/ml, we restarted intravitreal foscarnet injections replacing MTX. This in turn rapidly reduced the EBV levels to 3.27 × 104 copies/ml, followed by papillitis alleviation. OUTCOMES: The intraocular MTX administration reduced the inflammatory vitreous and retinal infiltration, but not the EBV load, while foscarnet reduced the EBV load and papillitis, but not vitreous infiltration. LESSONS: The retinal infiltration may have involved EBV infection to the retinal neurons but also EBV-free reactive inflammatory cells. EBV infection to the neurons may have been, at least partially, treated by intravitreal foscarnet treatment, and the reactive inflammatory cells by intravitreal MTX. Further observations are warranted to reach a consensus on treating intraocular EBV infection.

Hyperreflective Material in Optical Coherence Tomography Images of Eyes with Myopic Choroidal Neovascularization May Affect the Visual Outcome.

The visual outcome of myopic choroidal neovascularization (CNV) after anti-vascular endothelial growth factor (anti-VEGF) therapy varies among individuals. We retrospectively analyzed the data of 24 eyes (24 patients) with treatment-naïve myopic CNV who underwent anti-VEGF monotherapy following a pro-re-nata regimen at the Division of Medical Retina Clinic, Department of Ophthalmology, Keio University Hospital between May 2014 and December 2017. The mean age was 70.6 ± 2.1 years, and 16 (66.7%) patients were female. Overall, the mean best-corrected visual acuity (BCVA) improved (p = 0.034), and the mean height of the hyperreflective material (HRM), involving the CNV lesion recorded by optical coherence tomography, decreased (p < 0.01) 12 months after the initial treatment. Fifteen eyes (62.5%) achieved a BCVA of better than 0.10 in LogMAR at 12 months; they had a better BCVA (p = 0.015) and lower HRM intensity (p = 0.033) at baseline than the others. Remarkably, the BCVA improved (p < 0.05) and the HRM height (p < 0.01) decreased only in eyes with a final BCVA better than 0.10 as early as 1 month after the initial treatment, which was still present at 12 months. The HRM height and intensity, not only the BCVA, would be valuable in evaluating the prognosis of myopic CNV after anti-VEGF therapy, although further study is required.

Desferrioxamine, an iron chelator, inhibits CXCL10 expression induced by polyinosinic-polycytidylic acid in U373MG human astrocytoma cells.

Although iron is essential in physiological processes, accumulation of iron in central nervous system is associated with various neurological diseases including Alzheimer's disease and Parkinson's disease. Innate immune reactions are involved in the pathogenesis of those diseases, but roles of iron in innate immunity are not known well. In the present study, pretreatment of U373MG human astrocytoma cells with an iron chelator desferrioxamine (DFX) inhibited the expression of CXCL10 induced by a Toll-like receptor 3 (TLR3) agonist polyinosinic-polycytidylic acid (poly IC). Induction of interferon-ß (IFN-ß) was not affected, but phosphorylation of signal transducer and transcription 1 (STAT1) was decreased by DFX. We have previously reported that various IFN-stimulated genes (ISGs) are involved in CXCL10 induction by poly IC. Pretreatment with DFX also decreased the expression of these ISGs. Pretreatment of cells with FeSO4 counteracted inhibitory effects of DFX on ISG56, retinoic acid-inducible gene-I (RIG-I), CXCL10 and phosphorylation of STAT1. These results suggest that iron may positively regulate STAT1 phosphorylation and following signaling to express ISG56, RIG-I and CXCL10 in U373MG cells treated with poly IC. Iron may contribute to innate immune and inflammatory reactions elicited by the TLR3 signaling in astrocytes, and may play an important role in neuroinflammatory diseases.