Abilities of circumpapillary retinal nerve fiber layer thickness and vascular density to discriminate stages in primary open-angle glaucoma.

PURPOSE: To clarify the abilities of circumpapillary retinal nerve fiber layer thickness (cpRNFLT) obtained by optical coherence tomography (OCT) and circumpapillary vessel density (cpVD) measured by OCT-angiography to distinguish different stages in primary open-angle glaucoma determined by 24-2 or 30-2 static visual field (VF) testing. METHODS: This retrospective study includes 25 healthy normal eyes of 25 subjects and 87 primary open-angle glaucoma eyes of 87 patients. Areas under the receiver operating characteristic curves (AUROC) were evaluated for determining glaucoma stages using cpRNFLT and cpVD. The absolute errors of the estimated mean total deviation (mTD) using optimal models with cpRNFLT and cpVD were also compared. RESULTS: The AUROCs for discriminating glaucomatous eyes from normal eyes was significantly higher for cpRNFLT than the respective AUROCs for cpVD (0.969 [95% CI 0.939 to 0.998] vs. 0.872 [95% CI 0.806 to 0.938], p = 0.006), whereas cpVD had significantly higher AUROC for discriminating severe glaucoma eyes from moderate glaucoma eyes than cpRNFLT (0.771 [95% CI 0.655 to 0.886] vs. 0.578 [95% CI 0.420 to 0.736], p = 0.022). The mean absolute error in estimating mTD using both cpRNFLT and cpVD was significantly less than the error using cpRNFLT alone (4.56 ± 3.76 dB vs. 5.39 ± 4.00 dB, p = 0.027). CONCLUSION: Our results suggest that cpVD is better for follow-ups after moderate stage. The combination of cpRNFLT and cpVD may improve VF estimation compared to cpRNFLT alone.

Changes in pulse waveforms in response to intraocular pressure elevation determined by laser speckle flowgraphy in healthy subjects.

BACKGROUND: The influences of intraocular pressure (IOP) elevations on the pulse waveform in the optic nerve head (ONH) were evaluated using laser speckle flowgraphy (LSFG) in normal subjects. METHODS: This prospective cross-sectional study was conducted at the Nagoya University Hospital. An ophthalmodynamometer was pressed on the sclera to increase the IOP by 20 mmHg or 30 mmHg for 1 min (experiment 1, 16 subjects) and by 30 mmHg for 10 min (experiment 2, 10 subjects). The mean blur rate (MBR) and the eight pulse waveform parameters determined using LSFG were measured before, immediately after and during an IOP elevation, and after the IOP returned to the baseline pressure. RESULTS: A significant elevation in the IOP and a significant reduction in the ocular perfusion pressure (OPP) were found after applying the ophthalmodynamometer (both, P < 0.001). The blowout score (BOS) reduced significantly (P < 0.001), and the flow acceleration index (FAI; P < 0.01) and resistivity index (RI; P < 0.001) increased significantly immediately after increasing the IOP by 20 or 30 mmHg (experiment 1). The BOS reduced significantly (P < 0.001), and the FAI (P < 0.01) and RI (P < 0.001) increased significantly after the IOP elevation by 30 mmHg in both experiment 2 and 1. However, the BOS and RI recovered significantly at time 10 compared to that in time 0 (immediately after IOP elevation) during the 10-min IOP elevation (P < 0.001 and P = 0.008, respectively). CONCLUSIONS: In conclusion, the BOS, FAI, and RI of the pulse waveforms changed significantly with an acute elevation in the IOP. The change should be related to the larger difference between the maximum and minimum MBRs during the IOP elevation.

RELATIONSHIP BETWEEN ABNORMALITIES OF PHOTORECEPTOR MICROSTRUCTURES AND MICROVASCULAR STRUCTURES DETERMINED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN EYES WITH BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To determine whether the size of the foveal avascular zone (FAZ) is significantly correlated with the best-corrected visual acuity (BCVA) and to examine the relationship between the size and microstructural changes of the photoreceptors in eyes with a branch retinal vein occlusion. METHODS: The medical records of 69 eyes of patients (mean age, 64.6 ± 11.7 years) with a branch retinal vein occlusion were reviewed after the resolution of macular edema. All the patients underwent optical coherence tomography angiography for measurement of the FAZ area and spectral domain optical coherence tomography for determination of microstructural changes of the photoreceptors at the fovea. RESULTS: The superficial and deep FAZ areas in eyes with a branch retinal vein occlusion were 0.39 ± 0.36 mm and 0.63 ± 0.18 mm, respectively, and both were significantly larger than those observed in the fellow eyes (both, P < 0.001). The superficial FAZ area correlated with the posttreatment BCVA (r = 0.285, P = 0.027) but not with any parameters regarding the microstructures of the photoreceptors. Multivariate linear regression analysis showed that the pretreatment BCVA (ß = 0.519, P < 0.001) and integrity of the external limiting membrane (ß = -0.373, P = 0.001) were independent factors that significantly correlated with the posttreatment BCVA. CONCLUSION: There was no significant correlation between the FAZ area and microstructural parameters. However, the integrity of the external limiting membrane was significantly correlated with the posttreatment BCVA in eyes with a branch retinal vein occlusion.

INNER MACULAR CHANGES AFTER VITRECTOMY WITH INTERNAL LIMITING MEMBRANE PEELING FOR RHEGMATOGENOUS RETINAL DETACHMENT: Similarity With Alport Syndrome.

PURPOSE: The internal limiting membrane (ILM), the innermost basement membrane of the retina, is peeled occasionally during vitreous surgery. This study aimed to investigate the effect of ILM loss on the retina. METHODS: We used optical coherence tomography to retrospectively evaluate retinal changes in 26 eyes (11 ILM-peeled and 15 ILM-unpeeled eyes) of 26 patients after vitrectomy for retinal detachment. In addition, we studied six eyes of three patients with Alport syndrome, in which ILM is genetically impaired. RESULTS: We observed significant inner retinal displacement of the foveal pit toward the optic disk with inner retinal thickening in the nasal area (fellow, 191.9 ± 24.3 µm vs. affected, 210.3 ± 31.4 µm; P = 0.048), inner retinal thinning in the temporal area (fellow, 174.3 ± 18.3 µm vs. affected, 142.2 ± 23.6 µm; P < 0.001), foveal thickening (ILM-unpeeled, 217.0 ± 39.4 µm vs. ILM-peeled, 302.0 ± 86.2 µm; P = 0.006), inner retinal dimples predominantly in the temporal area, and deviation between the foveal pit and foveal bulge. Eyes with Alport syndrome exhibited similar findings. CONCLUSION: Internal limiting membrane loss seems to cause characteristic inner retinal changes of the macula in both congenital and acquired conditions.

BETTER PROGNOSIS FOR EYES WITH PRESERVED FOVEAL DEPRESSION AFTER INTRAVITREAL RANIBIZUMAB INJECTION FOR MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: To determine the prognosis of eyes with central retinal vein occlusion that had a preserved foveal depression at the baseline and were treated by intravitreal ranibizumab injections (IRIs). METHODS: The authors reviewed the medical records of 23 eyes of 23 consecutive treatment-naive patients who received IRIs to treat the macular edema due to central retinal vein occlusion. Eyes were classified by the pre-IRI presence or absence of a foveal depression. A foveal depression was defined as a central foveal thickness that was <50 µm thinner than the average thickness at 200 µm temporal and nasal to the central fovea. The characteristics of the two groups were compared. RESULTS: Seven of 23 eyes had a preserved foveal depression before the IRI. The mean number of injections within 12 months after the initial IRI was significantly fewer (P < 0.001) in eyes with foveal depression (1.6 ± 0.5) than in eyes without foveal depression (4.3 ± 1.3). The mean best-corrected visual acuity at 12 months after the initial IRI was significantly better (P = 0.003) in eyes with foveal depression (0.10 ± 0.17 logarithm of the minimum angle of resolution [logMAR] units; 20/25 Snellen units) than in eyes without foveal depression (0.77 ± 0.54 logMAR units; 20/118 Snellen units). CONCLUSION: These results indicate that the prognosis is better for eyes with a foveal depression before the IRI treatment for a macular edema secondary to central retinal vein occlusion.

Increased Retinal Thinning after Combination of Internal Limiting Membrane Peeling and Silicone Oil Endotamponade in Proliferative Diabetic Retinopathy.

BACKGROUND: The aim of this study was to examine the change in retinal thickness after vitrectomy with internal limiting membrane (ILM) peeling and/or silicone oil (SO) endotamponade in proliferative diabetic retinopathy (PDR). METHODS: The actual amount and ratio of changes in the retinal thickness were calculated. RESULTS: Compared to control eyes in the ILM peeling (-)/SO (-) group, the central, superior inner, and temporal inner retina in the ILM peeling (+)/SO (-) group, the central and superior inner retina in the ILM peeling (-)/SO (+) group, and the central, inferior inner, temporal inner, and nasal inner retina in the ILM peeling (+)/SO (+) group showed a significant reduction of the retinal thickness. The central, superior inner, and temporal inner retina in the ILM peeling (+)/SO (-) group, the central and superior inner retina in the ILM peeling (-)/SO (+) group, and the central, superior inner, inferior inner, and temporal inner retina in the ILM peeling (+)/SO (+) group showed a significantly increased reduction rate of the retinal thickness compared to the control group. CONCLUSIONS: Macular retinal thinning in PDR was observed after ILM peeling and SO endotamponade, and it was increased by the combination of these 2 factors.

Surgical Videos with Synchronised Vertical 2-Split Screens Recording the Surgeons' Hand Movement.

PURPOSE: To improve the state-of-the-art teaching system by creating surgical videos with synchronised vertical 2-split screens. METHODS: An ultra-compact, wide-angle point-of-view camcorder (HX-A1, Panasonic) was mounted on the surgical microscope focusing mostly on the surgeons' hand movements. In combination with the regular surgical videos obtained from the CCD camera in the surgical microscope, synchronised vertical 2-split-screen surgical videos were generated with the video-editing software. RESULTS: Using synchronised vertical 2-split-screen videos, residents of the ophthalmology department could watch and learn how assistant surgeons controlled the eyeball, while the main surgeons performed scleral buckling surgery. In vitrectomy, the synchronised vertical 2-split-screen videos showed the surgeons' hands holding the instruments and moving roughly and boldly, in contrast to the very delicate movements of the vitrectomy instruments inside the eye. CONCLUSIONS: Synchronised vertical 2-split-screen surgical videos are beneficial for the education of young surgical trainees when learning surgical skills including the surgeons' hand movements.

Interleukin-18 has antipermeablity and antiangiogenic activities in the eye: reciprocal suppression with VEGF.

Interleukin-18 (IL-18) is increased along with IL-1ß by activation of the inflammasome and has been implicated in inflammatory and autoimmune diseases, but its role in the eye is uncertain. In patients with macular edema due to retinal vein occlusion, intraocular IL-18 levels increased significantly (P < 0.001) after treatment with ranibizumab particularly in patients with high baseline IL-18 which correlated with good visual outcome (P < 0.05). In mice with ischemic retinopathy, suppression of VEGF caused an increase in IL18 mRNA due to an increase in IL-18-positive myeloid cells. VEGF significantly and specifically inhibited IL-18 production by myeloid cells stimulated with lipopolysaccharide (P < 0.001). Intraocular injection of IL-18 reduced VEGF-induced leakage and neovascularization, and reversed VEGF-induced suppression of Claudin5 expression and Claudin 5 labeling of vascular tight junctions. Injection of IL-18 also increased expression of Thrombospondin 1 and reduced ischemia-induced retinal neovascularization relevant to diabetic retinopathy and subretinal neovascularization relevant to neovascular age-related macular degeneration. Thus, VEGF and IL-18 suppress each other's production and effects on the vasculature suggesting that IL-18 may provide benefit in multiple retinal/choroidal vascular diseases.

Antagonism of PDGF-BB suppresses subretinal neovascularization and enhances the effects of blocking VEGF-A.

Hypoxia-inducible factor-1 (HIF-1) plays an important role in retinal and subretinal neovascularization (NV). Increased levels of HIF-1 cause increased expression of vascular endothelial growth factor (VEGF-A) and current therapies for ocular NV focus on neutralizing VEGF-A, but there is mounting evidence that other HIF-1-responsive gene products may also participate. In this study, we tested the effect of a designed ankyrin repeat protein (DARPin) that selectively binds and antagonizes the hypoxia-regulated gene product PDGF-BB in three models of subretinal NV (relevant to neovascular age-related macular degeneration) and compared its effects to a DARPin that selectively antagonizes VEGF-A. Daily intraperitoneal injections of 10 mg/kg of the anti-PDGF-BB DARPin or 1 mg/kg of the anti-VEGF DARPin significantly suppressed subretinal NV from laser-induced rupture of Bruch's membrane. Injections of 1 mg/kg/day of the anti-PDGF-BB DARPin had no significant effect, but when combined with 1 mg/kg/day of the anti-VEGF-A DARPin there was greater suppression than injection of the anti-VEGF-A DARPin alone. In Vldlr (-/-) mice which spontaneously develop subretinal NV, intraocular injection of 1.85 µg of anti-PDGF-BB or anti-VEGF-A DARPin caused significant suppression of NV and when combined there was greater suppression than with either alone. The two DARPins also showed an additive effect in Tet/opsin/VEGF double transgenic mice, a particularly severe model of subretinal NV and exudative retinal detachment. In addition, intraocular injection of 1.85 µg of anti-PDGF-BB DARPin strongly suppressed ischemia-induced retinal NV, which is relevant to proliferative diabetic retinopathy and retinopathy of prematurity. These data demonstrate that PDGF-BB is another hypoxia-regulated gene product that along with VEGF-A contributes to ocular NV and suppression of both provides an additive effect.

Clear corneal vitrectomy combined with phacoemulsification and foldable intraocular lens implantation.

BACKGROUND: We have developed a technique for the treatment of cataract and epiretinal membrane using a 25-gauge vitrectomy system through corneal ports. DESIGN: Randomized, prospective study, Toyama Prefectural Central Hospital, Toyama, Japan. PARTICIPANTS: Twenty eyes of equal patients scheduled for cataract surgery combined with vitrectomy. METHODS: Twenty eyes with cataract and epiretinal membrane were received treatment with our newly developed system (clear corneal vitrectomy) or the standard 25-gauge pars plana vitrectomy with corneal incision cataract surgery. The newly developed system uses 0.5-mm wide corneal side ports located at the superonasal, superotemporal and inferotemporal positions. After phacoemulsification using corneal incision, an infusion cannula was inserted from the inferotemporal port. Then core 25-gauge vitrectomy was performed using the corneal three port. After the epiretinal membrane was removed using forceps, an intraocular lens was implanted into the capsular bag. Finally, all corneal incision wounds were hydrated. MAIN OUTCOME MEASUREMENT: Visual acuity, intraocular pressure, corneal thickness, corneal endothelial cell and ocular inflammation were examined. RESULTS: All procedures were uncomplicated in both groups. There was no leakage of aqueous humour from the corneal wounds in the developed system. There were no significant differences in visual acuity, corneal thickness and endothelial cell density loss. CONCLUSIONS: Clear corneal vitrectomy would be a good option for selected cases with cataract and vitreoretinal diseases.

Suppression of GLUT1; a new strategy to prevent diabetic complications.

High blood glucose results in high glucose levels in retina, because GLUT1, the sole glucose transporter between blood and retina, transports more glucose when blood glucose is high. This is the ultimate cause of diabetic retinopathy. Knockdown of GLUT1 by intraocular injections of a pool of siRNAs directed against SLC2A1 mRNA which codes for GLUT1 significantly reduced mean retinal glucose levels in diabetic mice. Systemic treatment of diabetic mice with forskolin or genistein, which bind GLUT1 and inhibit glucose transport, significantly reduced retinal glucose to the same levels seen in non-diabetics. 1,9-Dideoxyforskolin, which binds GLUT1 but does not stimulate adenylate cyclase had an equivalent effect to that of forskolin regarding lowering retinal glucose in diabetics indicating that cyclic AMP is noncontributory. GLUT1 inhibitors also reduced glucose and glycohemoglobin levels in red blood cells providing a peripheral biomarker for the effect. In contrast, brain glucose levels were not increased in diabetics and not reduced by forskolin. Treatment of diabetics with forskolin prevented early biomarkers of diabetic retinopathy, including elevation of superoxide radicals, increased expression of the chaperone protein ß2 crystallin, and increased expression of vascular endothelial growth factor (VEGF). These data identify GLUT1 as a promising therapeutic target for prevention of diabetic retinopathy.

Superconductors: unusual oxygen isotope effects in cuprates?

The possibility that a pairing boson might act as the 'glue' to bind electrons into a Cooper pair in superconductors with a high critical temperature (T(c)) is being actively pursued in condensed-matter physics. Gweon et al. claim that there is a large and unusual oxygen-isotope effect on the electronic structure, indicating that phonons have a special importance in high-temperature superconductors. However, we are unable to detect this unusual oxygen-isotope effect in new data collected under almost identical material and experimental conditions. Our findings point towards a more conventional influence of phonons in these materials.

Effect of prophylactic 360° laser treatment for prevention of retinal detachment after phacovitrectomy: (Prophylactic 360° laser treatment for prevention of retinal detachment).

BACKGROUND: To investigate the effect of intraoperative 360° laser retinopexy anterior to the equator for the prevention of retinal detachment after phacovitrectomy. METHODS: The patients were part of two consecutive case series cohorts in macular hole (MH) and rhegmatogenous retinal detachment (RRD), one which did not receive intraoperative prophylactic 360° laser, and one which received intraoperative prophylactic 360° laser. For the 360° laser treatment group, three rows of medium-white burns were positioned anterior to the equator. The baseline characteristics and the risk of retinal detachment over time were analyzed and compared between the groups. RESULTS: Prophylactic intraoperative 360° laser treatment was performed on 77 MH cases (67.3 years) and compared to a control group of 35 MH cases (65.8 years). Additionally, prophylactic intraoperative 360° laser treatment was performed on 108 RRD cases (64.0 years) and compared to 270 RRD cases (64.4 years). The 360° laser group showed a significant reduction (0%, 0/77 eyes) in the rate of the incidence of retinal detachment after vitrectomy at 12 months after surgery in MH cases, compared with the control group (5.7%, 2/35 eyes) (p = 0.034). Kaplan-Meier survival analysis demonstrated that the rate of retinal detachment in the control group was significantly higher than that in the 360° laser group (p = 0.035). There was no significant difference between the groups in RRD cases (p = 0.092). CONCLUSIONS: Intraoperative 360° laser retinopexy following phacovitrectomy resulted in a significant reduction in the rate of postoperative retinal detachment in MH cases.

Swept Source-Optical Coherence Tomography-Guided Facedown Posturing to Minimize Treatment Burden and Maximize Outcome after Macular Hole Surgery.

We evaluated the closure of full-thickness macular holes (MHs) the day after surgery in minimizing the burden and maximizing patient outcomes. Herein, 25-gauge pars plana vitrectomy, internal limiting membrane peeling, and fluid-gas (20% sulfur hexafluoride) were performed for the treatment. Patients were instructed to remain in the facedown position until the confirmation of MH closure, and the position was discontinued in cases where the closure was confirmed. In total, 43 eyes of 43 patients, whose average age was 69.7 ± 8.6 years, were enrolled in this study. We used swept source (SS)-optical coherence tomography (OCT) for the confirmation of MH closure for gas-filled eyes and used spectral domain (SD)-OCT for the reconfirmation of MH closure after the gas volume was reduced to less than half of the vitreous cavity. MH closure was confirmed in 40 eyes (93%, the closure group) on the next day after surgery. The time from surgery to SS-OCT imaging was 24.7 h. Although facedown positioning was terminated in cases where MH closure was confirmed, there were no cases in which the MH was re-opened afterward. The basal and minimum MH size was significantly larger in the non-closure group than that in the closure group (p = 0.027, p = 0.043, respectively). Therefore, checking with SS-OCT the day after surgery and terminating facedown positioning in cases where MH closure was confirmed would be a useful method, removing a great burden for the elderly without sacrificing the MH closure rate.

Relationship Between Retinal Microcirculation and Renal Function in Patients with Diabetes and Chronic Kidney Disease by Laser Speckle Flowgraphy.

This study investigated the effect of renal dysfunction categorized by the stage of chronic kidney disease (CKD) on the retinal microcirculation assessed by laser speckle flowgraphy (LSFG) and retinal artery caliber measured by adaptive optics imaging in diabetic patients particularly the early stage of retinopathy and nephropathy. We divided the patients with diabetes into three groups based on the CKD stage (non-CKD (n = 54); CKD stage 1 + 2 (n = 20); CKD stage 3 (n = 41)). The mean blur rate (MBR) of the stage 3 CKD group was significantly lower than that of the no-CKD group (p < 0.015). The total retinal flow index (TRFI) in the stage 3 CKD group was significantly lower than that of the no-CKD group (p < 0.002). Multiple regression analysis demonstrated that CKD stage was independently associated with MBR (ß = -0.257, p = 0.031) and TRFI (ß = -0.316, p = 0.015). No significant differences were observed in external diameter, lumen diameter, wall thickness, and wall to lumen ratio among the groups. These results indicated that the ONH MBR and TRFI as assessed by LSFG decreases in diabetic patients with stage 3 CKD, but the arterial diameter measured by adaptive optics imaging does not change, suggesting that impaired renal function may be associated with decreased retinal blood flow in early-stage diabetic retinopathy.

Narrowing Ratio of Retinal Veins at Arteriovenous Crossing in Patients With Branch Retinal Vein Occlusion Versus That in Healthy Individuals.

Purpose: This cross-sectional study aimed to clarify the differences in the retinal venous narrowing ratio (VNR) at retinal arteriovenous crossing by optical coherence tomography (OCT) among the eyes with branch retinal vein occlusion (BRVO), fellow eyes of patients with BRVO, and eyes of individuals without BRVO and to determine factors that influence the VNR. Methods: We studied 31 eyes of young participants, 54 eyes of an older control group, 56 fellow eyes of patients with BRVO, and 48 eyes with BRVO. Cross-sectional OCT images were used to determine the VNR at two arteriovenous crossings per eye. Results: Overall, 378 arteriovenous crossings were analyzed. The VNR of arterial overcrossings of fellow eyes (27.7% ± 11.1%) and BRVO eyes (27.3% ± 9.76%) were significantly higher than those in the young (16.0% ± 7.9%, all P < 0.001) and control (22.0% ± 8.81%, P < 0.001, P = 0.003, respectively) groups. The VNR of arterial overcrossings was significantly larger than that of venous overcrossings (24.0% ± 10.5% vs. 20.6% ± 13.0%, P = 0.021). A linear mixed-effects model showed that the VNR was significantly higher in arterial overcrossings, crossings with larger arterial internal diameters, smaller venous internal diameters, and participants with older age and a BRVO history. Conclusions: The VNR in arterial overcrossings was higher in BRVO eyes and even in the fellow eyes. Thus, a higher VNR in arterial overcrossings may contribute to BRVO development, and crossings with factors contributing to higher VNR might be associated with a risk of BRVO.