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Anti-oxidative intraocular irrigating solutions (IISs) based on reactive persulfides, such as oxidized glutathione disulfide (GSSG), are commonly used worldwide. However, even with GSSG-based IISs, it has been shown that oxidative stress can occur during surgery, posing a risk to intraocular tissues. This study compared two IISs: one containing GSSG and one containing an oxidized glutathione trisulfide (GSSSG). Experimental in vivo irrigation with the IISs in rabbits showed that there was less leakage into the anterior chamber of rabbit serum albumin during perfusion with a 300-μM GSSSG IIS than with a 300-μM GSSG IIS. Experimental in vivo cataract surgery in rabbits showed that aqueous flare was suppressed 3 days after surgery with a 600-μM GSSSG IIS, but not with a 300-μM GSSSG or 300-μM GSSG IIS. Furthermore, an in vitro experiment, without any live tissue, showed that reactive oxygen species were suppressed more strongly with a 600-μM GSSSG IIS than with a 300-μM GSSG IIS. Thus, this study found that novel IISs based on GSSSG had anti-inflammatory and anti-oxidative effects during and after intraocular surgery and may decrease the rate of complications after surgery.

Malignant hypertension, a form of hypertensive emergency, causes acute damage in vital organs such as the brain, eyes, and kidneys. We aimed to examine the concurrency of acute hypertensive damage across the target organs to elucidate the underlying analogous pathophysiology. This single-center retrospective study evaluated the characteristics of organ damage, short-term clinical course, and interorgan relationships in patients with malignant hypertension treated between 2008 and 2019. Baseline characteristics of 20 patients who met our inclusion criteria were mean age 48 ± 13 years and blood pressure 222 ± 18/142 ± 16 mmHg; the median estimated glomerular filtration rate and urinary protein level were 49 mL/min/1.73 m2 (interquartile range [IQR] 27–79) and 1.9 g/g creatinine (IQR 0.2–4.0), respectively. Posterior reversible encephalopathy syndrome (PRES) was found in 60% of patients with major involvement and a wide variety of distribution patterns in the brainstem. In the fundus, serous retinal detachment was found in 60% of patients. Patients with PRES and serous retinal detachment showed higher levels of urinary protein than those without symptoms (P = 0.007 and 0.02, respectively), and proteinuria >1 g/g creatinine highly complicated both PRES and serous retinal detachment (91%). Matrix analysis also showed that the three symptoms were highly associated with each other. These results demonstrate the close relationship and concurrency of hypertensive acute organ damage in the brain, eyes, and kidneys. A common analogous mechanism, such as hyperperfusion-induced capillary leakage in each organ, implies an underlying pathophysiology of PRES, serous retinal detachment, and proteinuria.

The success of surgical treatment for idiopathic epiretinal membrane (ERM) is measured by postoperative best-corrected visual acuity (BCVA), metamorphopsia, and foveal retinal sensitivity (RS).This study searched for predictive biomarkers of surgical success by determining the association between foveal RS and various aspects of vessel density (VD) in the fovea of patients with ERM. The study examined 25 eyes of 25 patients with ERM who underwent 27-gauge microincision vitrectomy surgery (MIVS). RS was measured with microperimetry (MP-3; NIDEK) at four central points in the fovea with an interpoint distance of 2°. VD was measured with SD-OCT (RS 3000; NIDEK) within the 1-mm2 square defined by the 4 RS points at various depths, including the superficial and deep retinal capillary plexus (SCP and DCP, respectively). Though VD did not change throughout the follow-up period, BCVA and RS significantly improved 1 and 3 months after surgery, respectively (both P

To screen for the 328 bp Alu insertion (c.4052_4053ins328, p.Tyr1352Alafs) in RP1 in a group of retinitis pigmentosa (RP) patients who had been previously identified with a heterozygous deleterious mutation in the gene. Prospective, clinical and experimental study. The Alu insertion in RP1 was screened with an optimized PCR-based method in 26 RP patients with a heterozygous deleterious mutation (nonsense or frameshift) in RP1 that had been identified in a preceding genetic study. The genetic location of the previously identified mutation and its inheritance pattern were assessed. Out of 26 RP patients with a heterozygous deleterious mutation in RP1, 5 (19.2%) were found to carry an additional heterozygous Alu insertion, presumably resulting in a compound heterozygous state. This included 3 patients who had been previously diagnosed as autosomal dominant RP based on genetic findings. They were re-diagnosed as having an autosomal recessive disease following our new findings. In all patients identified with the Alu insertion, the other mutations found in the preceding study were outside the defined region in exon 4 (encoding amino acids 677 to 917) in which truncation mutations have been suggested to exert a dominant negative effect. The founder Alu insertion in RP1 is an important cause of autosomal recessive RP in Japanese patients and can be missed in standard targeted resequencing. Screening optimized for this mutation is warranted, particularly in patients with a heterozygous deleterious mutation outside the defined region in exon 4 of RP1.

The genetic basis of Japanese autosomal recessive retinitis pigmentosa (ARRP) remains largely unknown. Herein, we applied a 2-step genome-wide association study (GWAS) in 640 Japanese patients. Meta-GWAS identified three independent peaks at P A, p.G843E) of unknown significance. mRNA harboring c.2528 G > A failed to restore rhodopsin mislocalization induced by morpholino-mediated knockdown of eys in zebrafish, consistent with the variant being pathogenic. c.2528 G > A solved an additional 7.0% of Japanese ARRP cases. The third peak was in linkage disequilibrium with a common non-synonymous variant (c.7666 A > T, p.S2556C), possibly representing an unreported disease-susceptibility signal. GWAS successfully unraveled genetic causes of a rare monogenic disorder and identified a high frequency variant potentially linked to development of local genome therapeutics., Koji Nishiguchi et al. identify three genetic variants within the EYS gene that are associated with retinitis pigmentosa using a genome-wide association study. They demonstrate that one of these variants (G843E) causes retinal dysfunction in zebrafish, suggesting a causal role for EYS in retinitis pigmentosa.

The purpose of this study was to investigate the relationship between laser speckle flowgraphy (LSFG) and optical coherence tomography angiography (OCTA) measurements of ocular microcirculation in normal and open-angle glaucoma (OAG) subjects. This study included 18 eyes of 18 OAG patients and ten eyes of ten age-matched healthy controls. LSFG was used to measure mean blur rate (MBR) in the optic nerve head (ONH) vessel area (MV) and tissue area (MT). OCTA was used to measure a new parameter, peripapillary relative intensity (PRI), in the superficial retina, superficial choroid, and deep choroid. Statistical associations were then determined. MV, MT, superficial-retinal PRI, and superficial-choroidal PRI were lower in the OAG subjects than the controls (P = 0.02, P

To report a case of endophthalmitis associated with Purpureocillium lilacinum (P. lilacinum) during infliximab treatment for surgically induced necrotizing scleritis, successfully treated with 27-gauge vitrectomy. A single case report. A 71-year-old man who had undergone immunosuppressive therapy, including infliximab, for surgically induced necrotizing scleritis (SINS) in his left eye complained of visual disturbance and eye pain in the eye. He had a past history of surgery for recurrent pterygium: pterygium excision, amnion transplantation with mitomycin C and limbal transplantation. Visual acuity in the left eye was counting fingers at 30 cm, and intraocular pressure was 3.0 mmHg. Slit-lamp examination revealed the presence of anterior chamber cells (3+), and a B-mode ultrasound scan showed a vitreous opacity. We made a diagnosis of endophthalmitis and performed 27-gauge microincision vitrectomy surgery (27GMIVS) with antibiotic perfusion of ceftazidime, vancomycin and voriconazole. Intraoperative findings included a fungus-like ball-shaped opacity in the vitreous, and a close-to-normal retinal appearance. A vitreous body culture identified the presence of P. lilacinum. After 2 months of antibacterial and antifungal therapy, inflammation decreased and visual acuity recovered to 20/100. This is the first report of a case of endophthalmitis associated with P. lilacinum during infliximab treatment for SINS. Scleral thinning due to necrotizing scleritis, especially during immunosuppressive therapy, is a risk factor for endophthalmitis. We found that 27GMIVS was a useful strategy for such a challenging clinical situation.

This study evaluated age-related changes in the superficial and deep retinal capillary plexus (SCP and DCP, respectively) and in the foveal avascular zone (FAZ). SCP and DCP perfusion density (PD) were measured in optical coherence tomography angiography (OCTA) macular scans of 145 eyes of 145 healthy Japanese subjects, and findings were compared with SCP FAZ and clinical data. We found that age was negatively correlated with SCP and DCP PD (r = −0.17, P = 0.04 and r = −0.20, P = 0.02, respectively) and positively correlated with FAZ area (r = 0.18, P = 0.03). SCP and DCP PD were correlated with each other (r = 0.67, P P = 0.03; r = −0.25, P P P = 0.01 and P < 0.001, respectively) in women than men. SCP and DCP PD were positively correlated with estimated glomerular filtration rate (r = 0.17, P = 0.03 and r = 0.24, P P = 0.02 and P P

To evaluate the association between ocular blood flow and biomarkers of systemic oxidative stress, as well as the potential of these biomarkers to assess normal-tension glaucoma (NTG). This study included 73 eyes of 73 patients with NTG. We assessed ocular blood flow by measuring mean blur rate (MBR) in the optic nerve head using laser speckle flowgraphy, both overall and separately in the vessel and tissue areas. We also measured urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) and skin autofluorescence (SAF), and lastly, determined correlations between these measurements and with other clinical parameters. SAF was correlated with age, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), mean deviation (MD), and overall MBR (P = 0.003, P = 0.013, P = 0.015 and P = 0.006, respectively). SAF and 8-OHdG were both correlated with tissue-area MBR (P = 0.006 and P = 0.010, respectively). Visual acuity, cpRNFLT, mean deviation and tissue-area MBR had a significant tendency to change with NTG severity (P = 0.014, P

To explore methods of automated visual field (VF) examination for the assessment of macular function.We used a VF examination (AP-7000 automatic perimeter, Kowa, Japan) to examine macular function in 53 eyes from 29 patients with open angle glaucoma. We measured the mean total deviation (c-MD) of 16 points in the central VF located in a 2-degree-interval 4 × 4 array with various stimulus sizes (Goldmann sizes III, II, and I). The retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC), and ganglion cell layer plus inner plexiform layer (GCL + IPL) were measured with the 3D OCT-2000 System (Topcon, Japan). The c-MDs of various stimulus sizes were compared with the OCT parameters using the Spearman rank correlation.The average examination time was 93.5 ± 23.5 s and the c-MD values were -11.8 ± 8.2 (stimulus size III), -11.9 ± 9.5 (stimulus size II), and -12.3 ± 9.6 dB (stimulus size I). The c-MD (stimulus size III) and averaged total deviations of the Humphrey Field Analysis 10-2 program were significantly correlated (ρ = 0.91). The C-MD values for stimulus size III were significantly correlated with the OCT parameters (RNFL: ρ = 0.59; GCC: ρ = 0.65; and GCL + IPL: ρ = 0.64). The correlation coefficient between the c-MD and the GCC was better for stimulus sizes II and I (ρ = 0.69) than for stimulus size III (ρ = 0.65).The C-MD values for the 16 measured central VF points were significantly correlated with macular structure, and the smaller stimulus sizes of the automated VF test had a higher correlation coefficient of within 8°.

To assess the visual outcome and complications of 25-G transconjunctival sutureless vitrectomy (25G-TSV) for rhegmatogenous retinal detachments. Retrospective, consecutive, interventional case series of 84 eyes of 84 consecutive patients with RRD who underwent 25G-TSV. All surgeries were performed by a single surgeon at a single centre. The initial and final reattachment rates were 95.2 and 100%, respectively. The mean visual acuity improved from 0.78 logarithm of the minimum angle of resolution (logMAR) units to 0.17 logMAR units at the final examination (P

Background Natural killer cell tumors can be broadly divided by origin into mature-cell and progenitor-cell types. The invasion of nasal-origin natural killer cells into the ophthalmologic field is sometimes observed in patients, but primary ocular natural killer cell tumors are a rare occurrence. Case presentation A 66 year-old woman without any systemic disease presented with blurred vision due to a severe vitreous opacity in the right eye. Flow cytometric analysis of the vitreous fluid suggested a natural killer cell tumor. Moreover, cytologic examination of vitreal and retinal specimens revealed the infiltration of a natural killer cell tumor, while PCR and immunocytochemistry revealed Epstein-Barr virus infection. The results of a gene rearrangement analysis were positive for IGH, while TCR beta chains were all negative. We examined the patient with whole-body magnetic resonance imaging and positron emission tomography, and performed a bone marrow examination. These examinations returned no abnormal results. Conclusion Thorough analysis of vitreal samples is essential when performing vitrectomies for vitreous opacities of unknown cause. Flow cytometric, cytologic, and PCR analysis of vitreal and retinal samples may reveal the presence and cause of severe illness.

To characterize the ophthalmological features and clinical course of an autosomal dominant cone–rod dystrophy (CORD2) in a Japanese family with an Arg41Trp mutation in the CRX gene. Mutation screening by direct sequencing was performed on 42 patients with cone–rod dystrophy. The clinical features of the patients were characterized by the visual acuity and by the findings of slit-lamp biomicroscopy, electroretinography, fluorescein angiography, and kinetic visual field testing. An Arg41Trp mutation in the CRX gene was identified in three members from three generations of one family with cone–rod dystrophy. Fundus examination demonstrated that the retinal dystrophy worsened with increasing age. A heterozygous Arg41Trp mutation in the CRX gene can produce cone–rod dystrophy in Japanese patients. Clinical examination of patients of different ages demonstrated that there was a rapid progressive worsening of the disease with increasing age.

Aqueous humor (AH) is one of the body fluids in the eye, which is known to be related with various ocular diseases, but the complete RNAs characteristic of the AH in patients is not yet known. The aim of this study was, with a microarray analysis, to reveal the disease-related extracellular miRNAs profiles in individual patients AH. 100 μl of AH was collected by anterior chamber paracentesis from 10 glaucoma, 5 cataract, and 5 epiretinal membrane patients. The extracted total RNAs were shorter than 200 nt, and their amount was 5.27 ± 0.41 ng in average. Among 530.5 ± 44.6 miRNA types detected in each sample with a microarray detectable 2019 types of matured miRNAs, 172 miRNAs were detected in all 10 glaucoma or control patients. From the glaucoma group, 11 significantly up-regulated and 18 significantly down-regulated miRNAs (P < 0.05 for both) were found to have areas under the curve better than 0.74 in a receiver operating characteristic analysis. They also formed a cluster composed only of glaucoma patients in a hierarchal cluster analysis. AH had a possibility of becoming a source of miRNA that can serve as a biomarker and a therapeutic target.

Abbreviations PDR proliferative diabetic retinopathy PEDF pigment epithelium-derived factor VEGF vascular endothelial growth factor To the Editor: Intraocular neovascularisation develops in many ischaemic retinal diseases, e.g. diabetic retinopathy, ischaemic retinal vein occlusion and retinopathy of prematurity. The new vessels are fragile and often rupture, leading to vitreous haemorrhage, tractional retinal detachment, neovascular glaucoma and subsequent vision decrease. The formation of new vessels is dependent on a local balance of stimulators and inhibitors of angiogenesis [1]. Among the stimulators, vascular endothelial growth factor (VEGF) has been shown to play a major role in mediating active neovascularisation in patients with diabetic retinopathy [2]. In addition, several studies have shown that the concentration of VEGF in the intraocular fluids was significantly elevated in eyes with proliferative diabetic retinopathy (PDR) [3–5]. On the other hand, pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis, and lower levels of PEDF have been found in the vitreous of eyes with active diabetic retinopathy [4]. It has also been shown that the vitreous level of endostatin, another inhibitor of angiogenesis, is correlated with the level of VEGF and that endostatin is produced in the fibrovascular membrane of eyes with PDR [5]. Vasohibin-1, a novel angiogenesis inhibitor, is mainly produced in endothelial cells and is induced by stimulation with VEGF or fibroblast growth factor 2. Vasohibin-1 selectively affects endothelial cells and inhibits angiogenesis [6]. We therefore hypothesised that vasohibin-1 is present in the vitreous of eyes with PDR and is associated with the vitreous level of VEGF. To examine this hypothesis, we measured the vitreous levels of vasohibin-1 and VEGF in 49 samples from 46 patients. This study was conducted in accordance with the tenets of the Declaration of Helsinki as revised in 2000 and was carried out with the approval of the Institutional Review Board of Tohoku University. Informed consent was obtained from all patients Diabetologia (2009) 52:359–361 DOI 10.1007/s00125-008-1229-z