To assess and compare choroidal thickness changes related to aging, we determined whether changes are due to thinning of the choriocapillaris plus Sattler's (CS) layer and/or the large vessel layer ...in healthy eyes using swept-source optical coherence tomography (SS-OCT) at a wavelength of 1,050-nm.
We studied 115 normal eyes of 115 healthy volunteers, all with refractive errors of less than -6 diopters. All 115 eyes underwent analysis of choroidal thickness at the fovea, the CS layer and the large choroidal vessel layer. In 68 of the 115 eyes, choroidal thickness was determined at five sites (the fovea, and superior, inferior, nasal, and temporal sites) using SS-OCT with an Early Treatment of Diabetic Retinopathy grid scan.
Total choroidal thicknesses at each of the five sites were related to subject age (P<0.0001). The choroid was thinnest at the nasal site, followed by the temporal, inferior, superior and finally the subfoveal site itself. The total choroidal thickness at the nasal site was significantly less than those at the other four sites (p<0.05). The CS layer showed thinning which correlated with age (P<0.0001). The thickness of the choroidal large vessel layer also decreased with age (p = 0.02). Subfoveal choroidal thickness was calculated as follows: 443.89-2.98×age (μm) (P<0.0001).
Subfoveal choroidal thickness decreases by 2.98 μm each year. Total choroidal thickness diminishes with age. The CS and large vessel layers of the choroid at the subfovea showed significant decreases, though only the former correlated strongly with age.
To determine the size of the foveal avascular zone (FAZ) by optical coherence tomography angiography before and after idiopathic epiretinal membrane surgery.
Thirteen consecutive patients (13 eyes) ...with unilateral epiretinal membrane were studied retrospectively. Optical coherence tomography angiography was used to measure the FAZ area within 3 mm × 3 mm scans of the superficial (superficial FAZ) and deep plexus layers (deep FAZ) before and 6 months after vitrectomy. The unaffected fellow eyes were used as controls.
The mean superficial and deep FAZ areas at 6 months after vitrectomy (0.080 ± 0.038 and 0.113 ± 0.045 mm, respectively) were significantly (P < 0.0001, P = 0.0035) larger than the corresponding mean preoperative FAZ areas (0.056 ± 0.030 and 0.082 ± 0.035 mm). However, the areas of FAZ expansion were small (0.024 ± 0.013 and 0.031 ± 0.031 mm). The mean postoperative superficial and deep FAZ areas were significantly (P < 0.0001, P < 0.0001) smaller than those of fellow eyes (0.295 ± 0.108 and 0.410 ± 0.142 mm). Multiple regression analysis showed that preoperative FAZ area had the highest correlation with postoperative FAZ area (P < 0.05).
This study showed horizontal contraction of the FAZ area in eyes with epiretinal membrane. Because preoperative FAZ area correlates with postoperative FAZ area, FAZ area may be a useful parameter for determining timing of surgery for epiretinal membrane.
Pathological neovascularization in the eye is a leading cause of blindness in all age groups from retinopathy of prematurity (ROP) in children to age-related macular degeneration (AMD) in the ...elderly. Inhibiting neovascularization via antivascular endothelial growth factor (VEGF) drugs has been used for the effective treatment. However, anti-VEGF therapies may cause development of chorioretinal atrophy as they affect a physiological amount of VEGF essential for retinal homeostasis. Furthermore, anti-VEGF therapies are still ineffective in some cases, especially in patients with AMD. Hypoxia-inducible factor (HIF) is a strong regulator of VEGF induction under hypoxic and other stress conditions. Our previous reports have indicated that HIF is associated with pathological retinal neovascularization in murine models of ROP and AMD, and HIF inhibition suppresses neovascularization by reducing an abnormal increase in VEGF expression. Along with this, we attempted to find novel effective HIF inhibitors from natural foods of our daily lives. Food ingredients were screened for prospective HIF inhibitors in ocular cell lines of 661W and ARPE-19, and a murine AMD model was utilized for examining suppressive effects of the ingredients on retinal neovascularization. As a result, rice bran and its component, vitamin B6 showed inhibitory effects on HIF activation and suppressed
mRNA induction under a CoCl
-induced pseudo-hypoxic condition. Dietary supplement of these significantly suppressed retinal neovascularization in the AMD model. These data suggest that rice bran could have promising therapeutic values in the management of pathological ocular neovascularization.
Purpose
Optical coherence tomography angiography (OCTA) was performed on patients with juvenile-onset type 1 diabetes (T1DM) but with no diabetic retinopathy to measure the foveal avascular zone ...(FAZ) area.
Study Design
Retrospective single-facility study
Methods
Twenty-nine patients (58 eyes) with juvenile-onset T1DM were studied. Images (3 mm x 3 mm cube centered on the fovea) were acquired using an OCTA device. Age at examination was 16.1 ± 8.7 years; onset age was 6.4 ± 3.5 years; duration of diabetes was 9.7 ± 8.3 years. Twenty-four age-matched healthy individuals were studied as controls.
Results
FAZ area was significantly larger in T1DM patients than in controls (0.29 ± 0.09 vs. 0.25 ± 0.08 mm
2
,
P
= 0.0234). Parafoveal vessel density was not significantly different between patients and controls (50.43 ± 4.24 vs. 50.07 ± 4.64, P = 0.8842). By generalized linear model analysis, annual HbA1c (
P
= 0.0190), number of serious hypoglycemic attacks (
P
= 0.0210), and onset age (
P
= 0.0447) were identified as variables significantly associated with FAZ area. Age, gender, duration of disease, total cholesterol, high or low-density lipoprotein, triglycerides, and body mass index were not significantly associated with FAZ area.
Conclusion
Patients with juvenile-onset T1DM and no diabetic retinopathy had increased FAZ, but no significant difference in parafoveal vessel density compared to healthy controls. Larger FAZ area was associated with higher annual HbA1c, more episodes of severe hypoglycemic attacks, and older onset age.
To assess risk factors for serous retinal detachment (SRD) in the fellow eye of patients with central serous chorioretinopathy (CSC) based on clinical data and multimodal imaging findings, including ...baseline late-phase indocyanine green angiography (ICGA).
Consecutive patients with unilateral CSC were retrospectively assessed. Inclusion criteria were the availability of late-phase ICGA and a spectral-domain optical coherence tomography (OCT) macular cube for both eyes at baseline and over 3 months. Subsequent OCT of fellow eyes was reviewed to detect the development of SRD during the follow-up. Baseline medical data and multimodal imaging findings were analysed using Kaplan-Meier survival curves (log-rank test).
Sixty-eight patients with unilateral CSC were included. An SRD was detected in 19% of fellow eyes during a mean follow-up of 25.8±18.7 months. Hyperfluorescent plaques on midphase ICGA, hypofluorescent foci on late-phase ICGA, retinal pigment epithelium changes on fundus autofluorescence and fluorescein angiography abnormalities were associated with the occurrence of SRD (log-rank test; p<0.001, p=0.02, p=0.002 and p=0.001, respectively).
These results suggest that the fellow eyes with specific findings on multimodal imaging in patients with unilateral CSC should be carefully followed up for possible incidence of CSC.
Retinal ischemia/reperfusion (I/R) injury can cause severe vision impairment. Retinal I/R injury is associated with pathological increases in reactive oxygen species and inflammation, resulting in ...retinal neuronal cell death. To date, effective therapies have not been developed. Nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD+) intermediate, has been shown to exert neuroprotection for retinal diseases. However, it remains unclear whether NMN can prevent retinal I/R injury. Thus, we aimed to determine whether NMN therapy is useful for retinal I/R injury-induced retinal degeneration. One day after NMN intraperitoneal (IP) injection, adult mice were subjected to retinal I/R injury. Then, the mice were injected with NMN once every day for three days. Electroretinography and immunohistochemistry were used to measure retinal functional alterations and retinal inflammation, respectively. The protective effect of NMN administration was further examined using a retinal cell line, 661W, under CoCl2-induced oxidative stress conditions. NMN IP injection significantly suppressed retinal functional damage, as well as inflammation. NMN treatment showed protective effects against oxidative stress-induced cell death. The antioxidant pathway (Nrf2 and Hmox-1) was activated by NMN treatment. In conclusion, NMN could be a promising preventive neuroprotective drug for ischemic retinopathy.
Drusen are one of the most characteristic pathologies of precursor lesion of age-related macular degeneration (AMD). Drusen comprise a yellowish white substance that accumulates typically under the ...retinal pigment epithelium (RPE), and their constituents are lipids, complement, amyloid, crystallin, and others. In the past, many researchers have focused on drusen and tried to elucidate the pathophysiology of AMD because they believed that disease progression from early AMD to advanced AMD might be based on drusen or drusen might cause AMD. In fact, it is well established that drusen are the hallmark of precursor lesion of AMD and a major risk factor for AMD progression mainly based on their size and number. However, the existence of advanced AMD without drusen has long been recognized. For example, polypoidal choroidal vasculopathy (PCV), which comprises the majority of AMD cases in Asians, often lacks drusen. Thus, there is the possibility that drusen might be no more than a biomarker of AMD and not a cause of AMD. Now is the time to reconsider the relationship between AMD and drusen. In this review, we focus on early AMD pathogenesis based on basic research from the perspective of cholesterol metabolism and hypoxic response in the retina, and we discuss the role of drusen.
We evaluated subfoveal choroidal thickness measured with two different forms of optical coherence tomography (OCT), enhanced-depth imaging (EDI) and swept-source (SS) OCT, in central serous ...chorioretinopathy (CSC).
Fifty-six eyes of 48 patients diagnosed with acute or chronic CSC, were studied prospectively. Subfoveal choroidal thickness was measured as the distance between the outer border of the retinal pigment epithelium-Bruch's membrane complex, and the chorioscleral border under the fovea. Subfoveal choroidal thickness was measured using EDI-OCT and SS-OCT. We also measured serous retinal detachment (SRD) only with SS-OCT. The Pearson correlation coefficient was used to assess the correlation between subfoveal choroidal thickness values determined by the two different OCT modalities.
The mean patient age was 52 ± 13 years (range, 32-82 years). Among the 56 eyes, 21 had acute CSC and 35 had chronic CSC. Subfoveal choroidal thickness measured with EDI-OCT was 336.6 ± 91.6 μm in acute and 388.0 ± 103.4 μm in chronic CSC. With SS-OCT, the thickness in acute CSC was 332.0 ± 96.7 μm and that in chronic CSC was 392.6 ± 101.3 μm. Acute CSC (p <0.001, correlation coefficient; r = 0.99) and chronic CSC (p <0.001, correlation coefficient; r = 0.97) values obtained with the two different OCT modalities correlated significantly. Among the 56 eyes, 43 (19 eyes with acute and 24 with chronic CSC) were evaluable for SRD height by SS-OCT. The mean SRD height was 128.9 ± 83.6 μm in acute cases and 96.3 ± 62.0 μm in chronic cases.
Subfoveal choroidal thickness obtained with two different OCT modalities correlated significantly.
Key points
During long‐duration spaceflights, some astronauts develop structural ocular changes including optic disc oedema that resemble signs of intracranial hypertension.
In the present study, ...intracranial pressure was estimated non‐invasively (nICP) using a model‐based analysis of cerebral blood velocity and arterial blood pressure waveforms in 11 astronauts before and after long‐duration spaceflights.
Our results show that group‐averaged estimates of nICP decreased significantly in nine astronauts without optic disc oedema, suggesting that the cephalad fluid shift during long‐duration spaceflight rarely increased postflight intracranial pressure.
The results of the two astronauts with optic disc oedema suggest that both increases and decreases in nICP are observed post‐flight in astronauts with ocular alterations, arguing against a primary causal relationship between elevated ICP and spaceflight associated optical changes.
Cerebral blood velocity increased independently of nICP and spaceflight‐associated ocular alterations. This increase may be caused by the reduced haemoglobin concentration after long‐duration spaceflight.
Persistently elevated intracranial pressure (ICP) above upright values is a suspected cause of optic disc oedema in astronauts. However, no systematic studies have evaluated changes in ICP from preflight. Therefore, ICP was estimated non‐invasively before and after spaceflight to test whether ICP would increase after long‐duration spaceflight. Cerebral blood velocity in the middle cerebral artery (MCAv) was obtained by transcranial Doppler sonography and arterial pressure in the radial artery was obtained by tonometry, in the supine and sitting positions before and after 4−12 months of spaceflight in 11 astronauts (10 males and 1 female, 46 ± 7 years old at launch). Non‐invasive ICP (nICP) was computed using a validated model‐based estimation method. Mean MCAv increased significantly after spaceflight (ANOVA, P = 0.007). Haemoglobin decreased significantly after spaceflight (14.6 ± 0.8 to 13.3 ± 0.7 g/dL, P < 0.001). A repeated measures correlation analysis indicated a negative correlation between haemoglobin and mean MCAv (r = −0.589, regression coefficient = −4.68). The nICP did not change significantly after spaceflight in the 11 astronauts. However, nICP decreased significantly by 15% in nine astronauts without optic disc oedema (P < 0.005). Only one astronaut increased nICP to relatively high levels after spaceflight. Contrary to our hypothesis, nICP did not increase after long‐duration spaceflight in the vast majority (>90%) of astronauts, suggesting that the cephalad fluid shift during spaceflight does not systematically or consistently elevate postflight ICP in astronauts. Independently of nICP and ocular alterations, the present results of mean MCAv suggest that long‐duration spaceflight may increase cerebral blood flow, possibly due to reduced haemoglobin concentration.
Key points
During long‐duration spaceflights, some astronauts develop structural ocular changes including optic disc oedema that resemble signs of intracranial hypertension.
In the present study, intracranial pressure was estimated non‐invasively (nICP) using a model‐based analysis of cerebral blood velocity and arterial blood pressure waveforms in 11 astronauts before and after long‐duration spaceflights.
Our results show that group‐averaged estimates of nICP decreased significantly in nine astronauts without optic disc oedema, suggesting that the cephalad fluid shift during long‐duration spaceflight rarely increased postflight intracranial pressure.
The results of the two astronauts with optic disc oedema suggest that both increases and decreases in nICP are observed post‐flight in astronauts with ocular alterations, arguing against a primary causal relationship between elevated ICP and spaceflight associated optical changes.
Cerebral blood velocity increased independently of nICP and spaceflight‐associated ocular alterations. This increase may be caused by the reduced haemoglobin concentration after long‐duration spaceflight.
Retinal ischemic stresses are associated with the pathogenesis of various retinal vascular diseases. To investigate pathological mechanisms of retinal ischemia, reproducible, robust and clinically ...significant experimental rodent models are highly needed. Previously, we established a stable murine model of chronic hypoperfusion retinal injuries by permanent unilateral common carotid artery occlusion (UCCAO) and demonstrated chronic pathological processes in the ischemic retina after the occlusion; however, retinal functional deficits and other acute retinal ischemic injuries by UCCAO still remain obscure. In this study, we attempted to examine retinal functional changes as well as acute retinal ischemic alterations such as retinal thinning, gliosis and cell death after UCCAO.
Adult mice (male C57BL/6, 6-8 weeks old) were subjected to UCCAO in the right side, and retinal function was primarily measured using electroretinography for 14 days after the surgery. Furthermore, retinal thinning, gliosis and cell death were investigated using optical coherence tomography, immunohistochemistry and TUNEL assay, respectively.
Functional deficits in the unilateral right retina started to be seen 7 days after the occlusion. Specifically, the amplitude of b-wave dramatically decreased while that of a-wave was slightly affected. 14 days after the occlusion, the amplitudes of both waves and oscillatory potentials were significantly detected decreased in the unilateral right retina. Even though a change in retinal thickness was not dramatically observed among all the eyes, retinal gliosis and cell death in the unilateral right retina were substantially observed after UCCAO.
Along with previous retinal ischemic results in this model, UCCAO can stimulate retinal ischemia leading to functional, morphological and molecular changes in the retina. This model can be useful for the investigation of pathological mechanisms for human ischemic retinopathies and furthermore can be utilized to test new drugs for various ischemic ocular diseases.
PDF
