Effect of Stride Management Assist Gait Training for Poststroke Hemiplegia: A Single Center, Open-Label, Randomized Controlled Trial.

BACKGROUND: Poststroke gait disorders negatively impact activities of daily living. Rehabilitation for stroke patients is aimed at improving their walking ability, balance, and quality of life. Robot-assisted gait training (RAGT) is associated with an increased number of task-specific exercises, which may benefit poststroke motor learning. We investigated the effects of RAGT using Stride Management Assist (SMA, which increases walk ratio by inducing hip-joint flexion and extension) in subacute stroke patients with hemiplegia. METHODS: We conducted a single center, open-label randomized controlled trial in hemiplegia patients who experienced a first ever stroke and were admitted to the convalescent rehabilitation ward. A total of 41 were divided into the control (20 patients) and experimental group (21 patients). A 10-day, conventional gait training program was carried out for the control group; and RAGT with SMA was used for the experimental group. The maximum walking speed and other gait parameters were compared preintervention and postintervention. The intergroup differences in the improvement ratio were compared using an intention-to-treat analysis. RESULTS: Ten-day intervention was completed by 36 patients. There was no difference between the 2 groups regarding gait parameters at intervention initiation. The improvement ratio of the maximum walking speed was significantly higher for the experimental group. Significant improvements were observed postintervention for maximum walking speed, paralysis-side step length, symmetry, and cadence in the experimental group. No adverse events attributable to the SMA were observed. CONCLUSIONS: Ten days of RAGT with the SMA was effective for improving gait disorders of subacute stroke patients.

Retinal morphologic changes and concentrations of cytokines in eyes with diabetic macular edema.

PURPOSE: To determine the relationship between the retinal morphologic changes and concentrations of intravitreal cytokines in eyes with diabetic macular edema. METHODS: A retrospective comparative study was performed. The preoperative optical coherence tomography images were evaluated to determine the presence of serous retinal detachments (SRDs), retinal cystic changes, and retinal swelling. The concentrations of vascular endothelial growth factor, interleukin (IL)-6, and IL-8 in vitreous samples collected during vitrectomy were determined. The correlations between optical coherence tomography parameters, other clinical factors, and the concentration of cytokines were calculated. RESULTS: Fifty-two eyes (52 patients) were investigated. An SRD was found in 19 of the 52 eyes (36.5%). Multivariate regression analysis showed that IL-6 was the only factor significantly associated with the presence of an SRD (P = 0.001; odds ratio, 1.268; 95% confidence interval, 1.105-1.452). The other morphologic changes, such as retinal cystic changes and retinal swellings, were not significantly associated with the concentrations of intravitreal cytokines. CONCLUSION: The significant association of SRD with intravitreal IL-6 indicates that inflammation may play an important role in the development of SRD in diabetic macular edema.

Early imaging of macular hole closure: a diagnostic technique and its quality for gas-filled eyes with spectral domain optical coherence tomography.

BACKGROUND/AIMS: This study was conducted to establish a reliable method to determine macular hole (MH) closure of gas-filled eyes. METHOD: 21 consecutive eyes with MH underwent vitrectomy with gas tamponade, and spectral domain optical coherence tomography (SD-OCT) was performed using our diagnostic technique. The quality of OCT images was rated as signal strength (SS) and evaluated by masked observers. RESULTS: The quality to determine MH closure (SS ≥4) was sufficient in all eyes. In addition, SD-OCT images (SS ≥6) obtained from 16/21 eyes showed detailed retinal structures including the inner segment/outer segment line. The next day after surgery, MH closure was confirmed in 12/21 eyes, and residual MH was observed in 9/21 eyes. Among these 9 eyes, 7 eyes were closed within 2 weeks. CONCLUSION: The present method provided clear SD-OCT images from gas-filled eyes, which is not only essential for the diagnosis of MH closure but also for establishing proper protocols and for studying the pathology of gas-filled eyes.

Comparative study of vitrectomy versus intravitreous triamcinolone for diabetic macular edema on randomized paired-eyes.

BACKGROUND: The present study was performed to compare the effects of pars plana vitrectomy (PPV) and single intravitreaous triamcinolone acetonide (IVTA) on diabetic macular edema (DME) in paired eyes. METHODS: Prospective comparative study on randomized paired-eyes was carried out at two hospitals. Forty eyes of 20 patients with bilateral DME were included. One randomly-selected eye was treated with PPV (PPV group), and the other eye was treated with IVTA (4 mg, IVTA group). The central macular thickness (CMT) measured by optical coherence tomography (OCT) and best-corrected visual acuity (BCVA) were monitored for 12 months after treatment. Changes from baseline and differences between groups were analyzed using a mixed model. RESULTS: At 1 and 3 months, CMT decreased significantly in the IVTA group compared to baseline (p < 0.0001 both), but CMT then increased gradually and no significant difference was found at 12 months (p = 0.90). In the PPV group, CMT decreased continuously and reached a significant level at 12 months (p < 0.0001). CMT of the IVTA group was significantly less than that of the PPV group at 1 month (p = 0.009); however, there was no significant difference at 3 months. Conversely, CMT was significantly less in the PPV group than in the IVTA group at 12 months (p = 0.0003). The changes of BCVA paralleled those of CMT, but no significant difference was detected between baseline BCVA and any time point. CONCLUSIONS: Despite the short-term improvement, DME recurred 6 months after IVTA, while it remained resolved after PPV. Although this study did not reveal a significant change of BCVA with either treatment, PPV resolved DME more effectively than IVTA at 1 year.

Early change of central macular thickness after intravitreous triamcinolone or bevacizumab in diabetic macular edema or retinal vein occlusion.

PURPOSE: To evaluate the immediate changes after intravitreous triamcinolone acetonide or intravitreous bevacizumab in diabetic macular edema (DME). METHODS: A nonrandomized interventional study. Type 2 diabetic patients were included. Intravitreous triamcinolone acetonide (4 mg) was injected for 22 eyes with DME and IVB (1.25 mg) for 18 eyes with DME. The early time-dependent changes of central macular thickness were evaluated by optical coherence tomography before and from 1 hour to 1 month after intervention. Intravitreous bevacizumab was also tested in patients with retinal vein occlusion as a control of non-DME. Visual acuity was also examined. RESULTS: Compared with the baseline, central macular thickness of eyes with DME decreased significantly 1 hour after intravitreous triamcinolone acetonide (P < 0.05, Wilcoxon signed rank test), while it did not significantly until 24 hours after IVB. The decrease in central macular thickness was observed significantly from 3 hours after IVB in retinal vein occlusion (P < 0.05, Wilcoxon signed rank test), and it was more evident in retinal vein occlusion than DME after IVB. Visual acuity improved significantly in DME with intravitreous triamcinolone acetonide or IVB at 1 month (P < 0.01 and P < 0.05, respectively, Wilcoxon signed rank test). CONCLUSION: Factors responsive to triamcinolone acetonide, other than vascular endothelial growth factor, might play an important role in pathogenesis of DME compared with retinal vein occlusion. Although no conclusion can be drawn, immediate decrease in central macular thickness after intravitreous triamcinolone acetonide might indicate the possible involvement of a nongenomic pathway of triamcinolone acetonide action.

Vitreous mediators after intravitreal bevacizumab or triamcinolone acetonide in eyes with proliferative diabetic retinopathy.

PURPOSE: To evaluate vitreous vascular endothelial growth factor (VEGF), stromal cell-derived factor 1alpha (SDF-1alpha), interleukins (ILs), and tumor necrosis factor-alpha (TNF-alpha) after intravitreal bevacizumab or triamcinolone acetonide (TA) in eyes with proliferative diabetic retinopathy (PDR). DESIGN: Interventional, consecutive, retrospective, comparative study with a historical control. PARTICIPANTS: Forty-seven eyes of 47 patients affected by active PDR were investigated. Bevacizumab (1.25 mg; 19 eyes; bevacizumab group) or TA (4 mg; 10 eyes; TA group) was injected into the vitreous cavity as preoperative adjunctive therapy 7 days before vitrectomy. Eighteen eyes without injection served as controls (control group). METHODS: The vitreous samples were obtained at vitrectomy and were analyzed for concentrations of total protein, VEGF, SDF-1alpha, IL-1beta, IL-6, IL-8, IL-10, IL-12p70, and TNF-alpha. MAIN OUTCOME MEASURES: Vitreous concentrations of VEGF, SDF-1alpha, ILs, and TNF-alpha were compared among bevacizumab, TA, and control groups. RESULTS: Vitreous concentrations of VEGF and SDF-1alpha were lower in bevacizumab and TA groups compared with the control group. The median VEGF level was 0 pg/ml (range, 0-79.2 pg/ml) in the bevacizumab group, 343.5 pg/ml (range, 0-1683.3 pg/ml) in the TA group, and 1202.5 pg/ml (range, 76-4213.9 pg/ml) in the control group. The median SDF-1alpha level was 149.2 pg/ml (range, 0-519.4 pg/ml) in the bevacizumab group, 87.5 pg/ml (range, 0-252.5 pg/ml) in the TA group, and 245.7 pg/ml (range, 0-856.8 pg/ml) in the control group. The differences in both vitreous VEGF and SDF-1alpha concentrations among 3 groups were statistically significant (P<0.001 and P = 0.010, respectively). The eyes with intravitreal bevacizumab demonstrated the lowest vitreous level of VEGF, and the level was statistically significant compared with the eyes with intravitreal TA and control eyes (P<0.001 and P<0.001, respectively). The control eyes had the highest vitreous level of SDF-1alpha, and the level was statistically significant compared with the eyes with intravitreal bevacizumab and TA (P = 0.015 and P = 0.009, respectively). There was no significant difference regarding ILs and TNF-alpha. CONCLUSIONS: Intravitreal injection of bevacizumab potentially diminishes not only VEGF but also SDF-1alpha. These findings suggest that intravitreal bevacizumab may influence intraocular mediators beyond VEGF. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment.

High-mobility group box 1 (HMGB1) protein is a multifunctional protein, which is mainly present in the nucleus and is released extracellularly by dying cells and/or activated immune cells. Although extracellular HMGB1 is thought to be a typical danger signal of tissue damage and is implicated in diverse diseases, its relevance to ocular diseases is mostly unknown. To determine whether HMGB1 contributes to the pathogenesis of retinal detachment (RD), which involves photoreceptor degeneration, we investigated the expression and release of HMGB1 both in a retinal cell death induced by excessive oxidative stress in vitro and in a rat model of RD-induced photoreceptor degeneration in vivo. In addition, we assessed the vitreous concentrations of HMGB1 and monocyte chemoattractant protein 1 (MCP-1) in human eyes with RD. We also explored the chemotactic activity of recombinant HMGB1 in a human retinal pigment epithelial (RPE) cell line. The results show that the nuclear HMGB1 in the retinal cell is augmented by death stress and upregulation appears to be required for cell survival, whereas extracellular release of HMGB1 is evident not only in retinal cell death in vitro but also in the rat model of RD in vivo. Furthermore, the vitreous level of HMGB1 is significantly increased and is correlated with that of MCP-1 in human eyes with RD. Recombinant HMGB1 induced RPE cell migration through an extracellular signal-regulated kinase-dependent mechanism in vitro. Our findings suggest that HMGB1 is a crucial nuclear protein and is released as a danger signal of retinal tissue damage. Extracellular HMGB1 might be an important mediator in RD, potentially acting as a chemotactic factor for RPE cell migration that would lead to an ocular pathological wound-healing response.

Posturing time after macular hole surgery modified by optical coherence tomography images: a pilot study.

PURPOSE: To see the early postoperative stage of macular hole (MH) surgery and to distinguish eyes needing prolonged posturing from those that do not use Fourier-domain optical coherence tomography (FD-OCT). DESIGN: Interventional case series. METHODS: Sixteen eyes of 15 patients with MH underwent the protocol at Kagoshima University Hospital. After the pars plana vitrectomy with 16% SF(6) gas tamponade followed by posturing, the eyes were examined by FD OCT from 3 hours to the day after surgery. After MH closure was confirmed, posturing was stopped. Follow-up was performed for 4 months or longer. The main outcome measures included time and OCT finding of MH closure after surgery. RESULTS: On the day after surgery, the macula could be examined by FD-OCT in 13 of 16 eyes; 10 eyes had a closed MH and 3 had an unclosed MH. At day 2, 2 of the 3 eyes with unclosed MHs on day 1 demonstrated a closed MH. Posturing continued for 8 days in 4 eyes whose MH closure was not confirmed. The MH was closed in all eyes within 1 month. FD-OCT showed bridge formation of the neural retina in 9 eyes and simple closure in 3 eyes within 7 days. At 1 month, 12 eyes showed simple closure and 4 eyes showed bridge formation. Among 9 eyes with bridge formation within 7 days, 6 eyes had changed to simple closure at 1 month. CONCLUSIONS: FD-OCT enabled confirmation of MH closure the day after surgery even in gas-filled eyes. This imaging method may be a good indicator to determine when to stop posturing for each patient.

Blockade of the OX40 ligand prolongs corneal allograft survival.

Although corneal transplantation is one of the most common tissue transplantations and is known to have a high graft acceptance rate, occasional corneal graft rejection remains a cause of blindness. OX40, a member of the TNF receptor superfamily, is expressed on activated T cells, and transmits a costimulatory signal by binding to OX40 ligand (OX40L) expressed on several cells with antigen-presenting functions. Using a blocking monoclonal antibody (mAb) against murine OX40L, we investigated the role of OX40 in a murine model of corneal transplantation. C3H/He mouse corneas were transplanted to BALB/c mice orthotopically. Administration of anti-OX40L mAb significantly reduced allograft rejection, and increased graft survival rate to 40% at 8 weeks after transplantation, while all corneas were rejected within 5 weeks in control IgG-treated mice. Similar reduced rejection was observed when wild-type donor corneas were transplanted to OX40L-deficient recipients. In vitro study revealed that the anti-OX40L mAb treatment reduced proliferative response and IFN-gamma production of draining lymph node cells in response to stimulation with donor alloantigen. These results demonstrate that OX40L blockade is effective for prolongation of corneal allograft survival by inhibiting recipient T cell activation.

Reduced incidence of intraoperative complications in a multicenter controlled clinical trial of triamcinolone in vitrectomy.

PURPOSE: To evaluate the benefits and potential complications of using triamcinolone acetonide (TA) in pars plana vitrectomy (PPV). DESIGN: Multicenter, prospective, controlled clinical trial. PARTICIPANTS: In total, 774 patients from 8 Japanese hospitals were enrolled, with 391 patients undergoing TA-assisted PPV and 383 control patients undergoing conventional PPV. INTERVENTION: Intraoperative use of TA to aid visualization of the vitreous. MAIN OUTCOME MEASURES: The incidence of intraoperative complications, including retinal breaks, was evaluated. Early postoperative complications, intraocular pressure (IOP), and adverse events occurring within 3 months of the operation were also monitored. RESULTS: The incidence of both retinal breaks and intraoperative retinal detachment was significantly lower in TA-assisted PPV than in conventional PPV. Retinal breaks were seen in 34 eyes (8.7%) undergoing TA-assisted PPV compared with 54 eyes (14.1%) undergoing conventional PPV (odds ratio [OR], 0.603; 95% confidence interval [CI], 0.381-0.955; P = 0.031). Retinal detachment was seen in only 3 eyes (0.8%) in which TA was used compared with 14 eyes (3.7%) in which TA was not used (OR, 0.204; 95% CI, 0.057-0.727; P = 0.014). In total, 388 eyes in the TA-assisted PPV group (99.2%) and 374 eyes in the conventional PPV group (97.6%) were followed up for 3 months after the operation. Although the mean postoperative IOPs were comparable in both groups, antiglaucoma eye drops were used more frequently by patients in the TA-assisted group than by those in the conventional PPV group (OR, 1.673; 95% CI, 1.126-2.484; P = 0.011). No serious adverse events, such as endophthalmitis or retinal degeneration, were observed in either group. CONCLUSIONS: Intraoperative use of TA reduced the incidence of retinal breaks and retinal detachments in eyes undergoing PPV. There were no serious adverse events related to the intraoperative use of TA. Although antiglaucoma eye drops were required more frequently after TA-assisted PPV than after conventional PPV, IOP was well-controlled in both groups.

Endoscopy-guided subretinal fluid drainage in vitrectomy for retinal detachment.

PURPOSE: To study the usefulness of endoscopy-guided subretinal fluid drainage in pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). PARTICIPANTS/METHODS: A prospective non-comparative study of a small number of RRD cases. The study involved examining 10 eyes of 10 patients with RRD that received PPV. Two eyes had hazy corneas, which hindered the observation by surgical microscopy. Fluid-gas exchange was performed and then subretinal fluid was drained through a primary retinal break guided by an endoscope. No drainage retinotomy was made. Each clinical feature was studied and the surgical outcome and complications were evaluated. RESULTS: All eyes had retinal reattachment by a single operation. No serious complication related to surgery was experienced. CONCLUSIONS: Endoscopy-guided subretinal fluid drainage is the safe and effective procedure in PPV for RRD.

Intravitreal triamcinolone acetonide for exudative age-related macular degeneration among Japanese patients.

AIM: To study the results of intravitreal triamcinolone acetonide (TA) for exudative age-related macular degeneration (AMD) among Japanese patients. METHODS: 13 eyes of 12 Japanese patients (9 males and 3 females) with subfoveal choroidal neovascularization (CNV) of exudative AMD received intravitreal TA (8 mg). Visual acuity, size of CNV and serous retinal detachment, and complications related to treatment were evaluated for 6 months or longer. RESULTS: Postoperative maximum visual acuity significantly improved (p < 0.05). Postoperative eyes had a greater probability of a reduced size of CNV and/or retinal detachment compared to preoperative eyes. Seven eyes showed increased intraocular pressure (21 mm Hg or over), which was controlled well by medication. Cataract development and advancement were observed in 90% of phakic eyes. No other serious complications were found. CONCLUSIONS: Intravitreal TA might be an effective treatment for subfoveal CNV of exudative AMD among Japanese as well as Caucasian patients for a comparatively short period.