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.

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 VEGF mRNA induction under a CoCl₂-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.

In recent years, the number of patients with age-related macular degeneration (AMD) is increasing worldwide along with increased life expectancy. Currently, the standard treatment for wet-AMD is intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. The upstream of VEGF is hypoxia-inducible factor (HIF), a master regulator of hypoxia-responsive genes responsive to acute and chronic hypoxia. HIF activation induces various pathological pro-angiogenic gene expressions including VEGF under retinal hypoxia, ultimately leading to the development of ocular ischemic neovascular diseases. In this regard, HIF is considered as a promising therapeutic target in ocular ischemic diseases. In clinical ophthalmology, abnormal hypofluorescent areas have been detected in the late-phase of indocyanine green angiography, which are thought to be lipid deposits at the level of Bruch’s membrane to choriocapillaris in vitreoretinal diseases. These deposits may interfere with the oxygen and nutrients that should be supplied to the retinal pigment epithelium, and that HIF/VEGF is highly suspected to be expressed in the hypoxic retinal pigment epithelium, leading to neovascularization. In this review, we comprehensively summarize pathophysiology of AMD-related ocular diseases with the HIF/VEGF pathway from basic and clinic researches with recent findings.

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.

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.

Cardiovascular abnormality-mediated retinal ischemia causes severe visual impairment. Retinal ischemia is involved in enormous pathological processes including oxidative stress, reactive gliosis, and retinal functional deficits. Thus, maintaining retinal function by modulating those pathological processes may prevent or protect against vision loss. Over the decades, nicotinamide mononucleotide (NMN), a crucial nicotinamide adenine dinucleotide (NAD⁺) intermediate, has been nominated as a promising therapeutic target in retinal diseases. Nonetheless, a protective effect of NMN has not been examined in cardiovascular diseases-induced retinal ischemia. In our study, we aimed to investigate its promising effect of NMN in the ischemic retina of a murine model of carotid artery occlusion. After surgical unilateral common carotid artery occlusion (UCCAO) in adult male C57BL/6 mice, NMN (500 mg/kg/day) was intraperitoneally injected to mice every day until the end of experiments. Electroretinography and biomolecular assays were utilized to measure ocular functional and further molecular alterations in the retina. We found that UCCAO-induced retinal dysfunction was suppressed, pathological gliosis was reduced, retinal NAD⁺ levels were preserved, and the expression of an antioxidant molecule (nuclear factor erythroid-2-related factor 2; Nrf2) was upregulated by consecutive administration of NMN. Our present outcomes first suggest a promising NMN therapy for the suppression of cardiovascular diseases-mediated retinal ischemic dysfunction.