Method of Quantifying Size of Retinal Hemorrhages in Eyes with Branch Retinal Vein Occlusion Using 14-Square Grid: Interrater and Intrarater Reliability

Purpose. To describe a method of quantifying the size of the retinal hemorrhages in branch retinal vein occlusion (BRVO) and to determine the interrater and intrarater reliabilities of these measurements. Methods. Thirty-five fundus photographs from 35 consecutive eyes with BRVO were studied. The fundus images were analyzed with Power-Point® software, and a grid of 14 squares was laid over the fundus image. Raters were asked to judge the percentage of each of the 14 squares that was covered by the hemorrhages, and the average of the 14 squares was taken to be the relative size of the retinal hemorrhage. Results. Interrater reliability between three raters was higher when a grid with 14 squares was used (intraclass correlation coefficient (ICC), 0.96) than that when a box with no grid was used (ICC, 0.78). Intrarater reliability, which was calculated by the retinal hemorrhage area measured on two different days, was also higher (ICC, 0.97) than that with no grid (ICC, 0.86). Interrater reliability for five fundus pictures with poor image quality was also good when a grid with 14 squares was used (ICC, 0.88). Conclusions. Although our method is subjective, excellent interrater and intrarater reliabilities indicate that this method can be adapted for clinical use

Cetylpyridinium chloride at sublethal levels increases the susceptibility of rat thymic lymphocytes to oxidative stress

Cetylpyridinium chloride (CPC) is an antimicrobial agent used in many personal care products, with subsequent release into the environment. Since CPC is found at low concentrations in river and municipal wastewater, its influence on wildlife is of concern. Therefore, in this study, we used flow cytometry to examine the effects of sublethal concentrations of CPC on rat thymic lymphocytes in order to characterize the cellular actions of CPC at low concentrations in the presence and absence of H2O2-induced oxidative stress. CPC treatment increased the population of living cells with phosphatidylserine exposed on the outer surface of their plasma membranes (a marker of early stage apoptosis), elevated intracellular Zn2+ levels, and decreased the cellular content of nonprotein thiols. CPC also potentiated the cytotoxicity of H2O2. Our results suggest that, even at environmentally relevant sublethal concentrations, CPC exerts cytotoxic effects under oxidative stress conditions by increasing intracellular Zn2+ concentration and decreasing the cellular content of nonprotein thiols. These findings indicate that, under some in vitro conditions, CPC is bioactive at environmentally relevant concentrations. Therefore, CPC release from personal care products into the environment may need to be regulated to avoid its adverse effects on wildlife

Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells

Aging is enhanced by hypoxia and oxidative stress. As the lens is located in the hypoglycemic environment under hypoxia, aging lens with diabetes might aggravate these stresses. This study was designed to examine whether low glucose under hypoxic conditions induces the unfolded protein response (UPR), and also if the UPR then generates the reactive oxygen species (ROS) in lens epithelial cells (LECs). The UPR was activated within 1 h by culturing the human LECs (HLECs) and rat LECs in <1.5 mM glucose under hypoxic conditions. These conditions also induced the Nrf2-dependent antioxidant-protective UPR, production of ROS, and apoptosis. The rat LECs located in the anterior center region were the least susceptible to the UPR, whereas the proliferating LECs in the germinative zone were the most susceptible. Because the cortical lens fiber cells are differentiated from the LECs after the onset of diabetes, we suggest that these newly formed cortical fibers have lower levels of Nrf2, and are then oxidized resulting in cortical cataracts. Thus, low glucose and oxygen conditions induce the UPR, generation of ROS, and expressed the Nrf2 and Nrf2-dependent antioxidant enzymes at normal levels. But these cells eventually lose reduced glutathione (GSH) and induce apoptosis. The results indicate a new link between hypoglycemia under hypoxia and impairment of HLEC functions

Idiopathic Intracranial Hypertension in a Prepubertal Pediatric Japanese Patient Complicated by Severe Papilledema

Purpose: To report a rare case of idiopathic intracranial hypertension (IIH) in a prepubertal pediatric patient. Case Report: The patient was an 11-year-old Japanese boy. Initially, an ophthalmologist found severe papilledema, and the patient was diagnosed with IIH. He was unresponsive to conservative therapy, and a ventriculoperitoneal shunt was inserted in the Neurosurgery Department because the visual impairment was severe. Twelve months after the shunt, the improvement in vision was limited due to optic disc atrophy. Conclusion: Ophthalmologists need to be more aware of II, especially in cases with severe papilledema that can lead to permanent reduction of vision

Reliability of Binocular Esterman Visual Field Test in Patients with Glaucoma and Other Ocular Conditions

The binocular Esterman visual field test (EVFT) of 120 points was the first method to quantify the defects in the binocular visual field. It is used in many parts of the world as a standard test to determine whether an individual has the visual capabilities to drive safely. In Japan, it is required for the grading and issuance of visual disability certificates. The purpose of this study was to determine the reliability of the EVFT results. We studied 104 patients who had undergone the binocular EVFT at Mie University Hospital. Their mean age was 68.0 ± 11.4 years, and the best-corrected visual acuity of the better eye was 0.18 ± 0.38 logMAR units. The EVFT was performed twice on the same day, and the results of the first and second tests were compared. The mean Esterman scores for the first and second test were 89.3 ± 30.5 and 89.1 ± 30.2, respectively, and the test times were 338.9 ± 86.8 and 336.7 ± 76.4 s, respectively. The differences were not significant (p = 0.69 and p = 0.33). In the Bland–Altman analyses (second–first test) of the Esterman scores, the mean difference was 0.38 without significant fixed errors (p = 0.20) or proportional errors (p = 0.27). The limits of agreement within the 1.96 standard deviation were −8.96 to +9.45 points. The agreement rate for the most peripheral 24 test points was significantly lower than the agreement rate for the other 96 test points (p p < 0.01). The overall reliability rate of the EVFT is acceptable, but the peripheral and upper test points have relatively low reliability rates. These findings are important for interpretations of the EVFT results

A Case of Sustained Intraocular Pressure Elevation after Multiple Intravitreal Injection of Ranibizumab and Aflibercept for Neovascular Age-Related Macular Degeneration

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are widely used to treat neovascular age-related macular degeneration (nAMD). Although these treatments are effective, multiple injections have recently been recommended to ensure that there is a good long-term prognosis. However, sustained intraocular pressure (IOP) elevations have been reported to develop after multiple injections of anti-VEGF agents. We present our findings of a case of uncontrolled and persistent IOP elevation after switching from intravitreal ranibizumab injections to intravitreal aflibercept injections. A 74-year-old Japanese man without a history of glaucoma underwent 22 ranibizumab injections for nAMD and suddenly developed an elevated IOP after the 22nd injection. Although the subsequent medical treatment led to normalization of his IOP, the subretinal fluid under the central fovea remained even after the 25th injection of ranibizumab. Thus, ranibizumab treatment was switched to bimonthly intravitreal aflibercept injections in conjunction with glaucoma medications. His IOP recovered to within the normal range; however, after the 11th aflibercept injection, there was a sudden elevation of his IOP in spite of the continued glaucoma medications. Due to this sustained IOP elevation, his aflibercept injections were suspended for 16 weeks. Because his IOP could not be normalized by a full glaucoma medication regimen, the patient underwent trabeculotomy, which resulted in a lowering of the IOP to normal levels. We conclude that patients who receive serial intravitreal injections of anti-VEGF agents need to be closely monitored because severe and sustained ocular hypertension can develop

皮膚電極網膜電図装置を用いた網膜内層機能の評価とその汎用性の検討

application/pdf最近開発された新しい皮膚電極網膜電図装置レチバルによる網膜電図検査では、非常に短時間(5分程度)で検査を終えることができ、従来から知られている網膜外層・中層疾患のみでなく、緑内障などの患者数が大変多い、網膜内層疾患を対象としてもその検査の有用性を検証できた。例えば、緑内障であれば、中期から後期の病期であれば、レチバルを使用することにより、ほぼ前例で診断をすることが可能であった。Recently developed new skin electrode electroretinogram device RETeval can test the patient in a very short time (about 5 minutes9, and not only the cinventionally known outer and middle layer diseases of the retina, the usefulness of the test was verified even for the patients with a large number of patients such as glaucoma (inner retinal diseases).2017年度～2019年度科学研究費補助金(基盤研究(C))研究成果報告書17K1142

Optical coherence tomography angiography application to pigmented iris: Could a new index quantify blood flow?

Purpose: To assess the blood flow and vascular visibility of irises in relation to pigmentation and pupil size, using an anterior segment optical coherence tomography angiography (OCTA). Materials and methods: This is a cross-sectional study. OCTA images were acquired in the nasal and temporal quadrants from a cohort of 30 healthy subjects in photopic (miosis) and scotopic (mydriasis) conditions. Patients were divided according to iris color (less pigmented: group L vs more pigmented: group D). Vascular parameters (vessel density (VD), vessel length density (VLD), fractal dimension (FD)) were applied and compared among groups L and D, location and different pupil status. A novel vascular index called Luminance Index (LI) was developed and applied in order to quantify vascular flow and evaluate its variation in photopic and scotopic conditions. Multivariable analyses were performed to evaluate possible predictors of VD and LI. Results: No differences were found for all vascular measurements (VD, VDL, FD, LI) between nasal and temporal quadrants. All vascular measurements were higher in group L than in group D (p &lt; 0.05), except for LI and FD in photopic condition. In group L, all vascular parameters increased (p &lt; 0.001) after dark adaptation. In group D, only LI increased after dark adaptation (p &lt; 0.001). Pigmentation and iris thickness were significantly associated with VD in scotopic and photopic conditions, and with LI only in scotopic condition. Conclusions: Pigmentation still remains a major issue for vascular visibility. Quantitative and qualitative vascular changes follow pupil size variation. LI could be a new surrogate to quantify blood flow

完全型先天停在性夜盲のイヌモデルの確立と機能・遺伝子解析

application/pdf先天停在夜盲（CSNB）は非進行性の遺伝性網膜疾患であり、生来の夜盲を特徴とする。我々は自然発症の常染色体劣性のビーグル犬の家系を発見した。この犬は明所では正常な視覚を有するが、暗所では明らかな視機能低下がみられた。網膜電図（ERG）は陰性型を示し、長時間刺激錐体応答では、ON応答は低下しているがOFF応答は残存していた。いわゆるヒトのSchubert-Bornschein 型の完全型CSNBの犬モデルと考えられた。遺伝子検査では既知のCSNBの候補遺伝子は全てrule outされた。光学顕微鏡と電子顕微鏡では網膜形態は正常であった。我々の犬家系は世界で初めての完全型CSNBの犬モデルである。Congenital stationary night blindness (CSNB) is a non-progressive, clinically and genetically heterogeneous disease of impaired night vision. We report a naturally-occurring, stationary, autosomal recessive phenotype in beagle dogs with normal daylight vision but absent night vision. Affected dogs had normal retinas on clinical examination, but showed no detectable rod responses. They had "negative-type" mixed rod and cone responses in full-field ERGs. Their photopic long-flash ERGs had normal OFF-responses associated with severely reduced ON-responses. The phenotype is similar to the Schubert-Bornschein form of complete CSNB in humans. Genetic testing ruled out most known CSNB candidates. Retinal morphology showed normal cellular layers and structure, and electron microscopy revealed normal rod spherules and synaptic ribbons. Our results indicate involvement of a yet unknown gene in this canine model of complete CSNB.2014年度～2016年度科学研究費補助金(基盤研究(C))研究成果報告書2646268