Mitigating Trunk Compensatory Movements in Post-Stroke Survivors through Visual Feedback during Robotic-Assisted Arm Reaching Exercises.

Trunk compensatory movements frequently manifest during robotic-assisted arm reaching exercises for upper limb rehabilitation following a stroke, potentially impeding functional recovery. These aberrant movements are prevalent among stroke survivors and can hinder their progress in rehabilitation, making it crucial to address this issue. This study evaluated the efficacy of visual feedback, facilitated by an RGB-D camera, in reducing trunk compensation. In total, 17 able-bodied individuals and 18 stroke survivors performed reaching tasks under unrestricted trunk conditions and visual feedback conditions. In the visual feedback modalities, the target position was synchronized with trunk movement at ratios where the target moved at the same speed, double, and triple the trunk's motion speed, providing real-time feedback to the participants. Notably, trunk compensatory movements were significantly diminished when the target moved at the same speed and double the trunk's motion speed. Furthermore, these conditions exhibited an increase in the task completion time and perceived exertion among stroke survivors. This outcome suggests that visual feedback effectively heightened the task difficulty, thereby discouraging unnecessary trunk motion. The findings underscore the pivotal role of customized visual feedback in correcting aberrant upper limb movements among stroke survivors, potentially contributing to the advancement of robotic-assisted rehabilitation strategies. These insights advocate for the integration of visual feedback into rehabilitation exercises, highlighting its potential to foster more effective recovery pathways for post-stroke individuals by minimizing undesired compensatory motions.

Sacral interface pressure can be alleviated by repositioning with a small-angle change using an automated bed in patients with spinal cord injury.

AIM OF THE STUDY: This study aimed to compare interface pressure and total contact area of the sacral region in different positions, including small-angle changes, in patients with spinal cord injury (SCI). Furthermore, we analyzed the clinical factors influencing pressure to identify the pressure injury (PI) high-risk group. MATERIALS AND METHODS: An intervention was conducted for patients with paraplegia (n = 30) with SCI. In the first and second trials, interface pressure and total contact area of the sacral region were recorded from large- and small-angled positions using the automatic repositioning bed, which can change the angle of the back, lateral tilt, and knee. RESULTS: Positions with back raised ≥45° showed significantly higher pressure on the sacrum than most other positions. The pressure and contact area differences were statistically insignificant for combinations of small-angled changes <30°. Additionally, the duration of injury (ß = 0.51, p = 0.010) and neurological level of injury (NLI) (ß = -0.47, p = 0.020) were significant independent predictors of average pressure. Similarly, the duration of injury (ß = 0.64, p = 0.001), the Korean version of the spinal cord independence measure-III (ß = -0.52, p = 0.017), and body mass index (BMI; ß = -0.34, p = 0.041) were significant independent predictors of peak pressure. CONCLUSIONS: For repositioning, combinations of small-angle changes <30° effectively reduce pressure on the sacral region in patients with SCI. Lower BMI, longer duration of injury, lower functioning score, and NLI ≥ T7 are predictors of high sacral pressures, which increase the risk for PI. Therefore, patients with these predictors require strict management.

Robot-Assisted Reach Training With an Active Assistant Protocol for Long-Term Upper Extremity Impairment Poststroke: A Randomized Controlled Trial.

OBJECTIVE: To assess whether robot-assisted reach training (RART) with an active assistant protocol can improve upper extremity function and kinematic performance in chronic stroke survivors. DESIGN: This study was conducted as a randomized controlled trial. SETTING: National rehabilitation center. PARTICIPANTS: Chronic stroke survivors (N=38) were randomized into 2 groups: a robot-assisted reach training with assist-as-needed (RT-AAN) group and a robot-assisted reach training with guidance force (RT-G) group. INTERVENTION: The RT-AAN group received robot-assisted reach training with an assist-as-needed mode for 40 minutes per day, 3 times per week over a 6-week period, and the RT-G group participated in the RART with a guidance mode for 40 minutes per day, 3 times per week over a 6-week period. MAIN OUTCOME MEASURES: Upper extremity functions were measured with Fugl-Meyer Assessment (FMA), Action Research Arm Test (ARAT), and Box and Block Test. In addition, movement velocities were measured as an index for upper extremity kinematic performances in 6 directions. RESULTS: Both groups showed significant improvements in FMA, ARAT, and kinematics (movement velocity) in all directions (targets 1-6, P<.05). However, the RT-AAN group showed significantly more improvement than the RT-G group in FMA and ARAT (P<.05). CONCLUSIONS: RART with an active assistant protocol showed improvements of upper extremity function and kinematic performance in chronic stroke survivors. In particular, assist-as-needed robot control was effective for upper extremity rehabilitation. Therefore robot-assisted training may be suggested as an effective intervention to improve upper extremity function in chronic stroke survivors.

Clinical and Genetic Characteristics Analysis of Korean Patients with Stargardt Disease Using Targeted Exome Sequencing.

PURPOSE: To investigate genetic mutations in Korean patients with Stargardt disease (STGD) using exome sequencing, and to analyze the correlations between genetic mutations and clinical phenotypes. METHODS: Peripheral venous blood was obtained from 24 clinically diagnosed Korean STGD patients, followed by extraction of genomic DNAs. Using exome sequencing we investigated gene mutations for the adenosine triphosphate-binding cassette, subfamily A, member 4 (ABCA4) elongation of very-long-chain fatty acids 4 (ELOVL4), and prominin 1 (PROM1), and confirmed gene mutations by the direct sequencing of polymerase chain reaction products. RESULTS: ABCA4 mutations were confirmed in 17 of 24 patients, and 12 novel mutations were identified. ELOVL4 and PROM1 gene mutations were not identified in this study. We also identified 16 previously reported mutations related to STGD1. In patients whose disease symptoms occurred before 20 years of age, visual acuity was poorer and atrophic flecks were more frequently found. In addition, more ABCA4 mutations were found in patients who had choroidal silence or atrophic flecks. CONCLUSIONS: Novel ABCA4 gene mutations were found in Korean patients with STGD1. This study will facilitate better understanding of the relationships between ABCA4 gene mutations and clinical symptoms in Korean patients.

Upper limb robotic rehabilitation for chronic stroke survivors: a single-group preliminary study.

[Purpose] This study aimed to assess whether robotic rehabilitation can improve upper limb function, activities of daily living performance, and kinematic performance of chronic stroke survivors. [Subjects and Methods] Participants were 21 chronic stroke survivors (19 men; 60.8 years; Mini-Mental State Examination score: 28; onset duration: 10.2 years). Training exercises were performed with a Whole Arm Manipulator and a 120-inch projective display to provide visual and auditory feedback. Once the training began, red and grey balls appeared on the projective display, and participants performed reaching movements, in the assist-as-needed mode, toward 6 directional targets in a 3-dimensional space. All participants received training for 40 minutes per day, thrice per week, for 6 weeks. Main outcome measures were upper limb function (Fugl-Meyer Assessment, Action Research Arm Test, and Box and Blocks Test scores), activities of daily living performance (Modified Barthel Index), and kinematic performance (movement velocity) in 6 directions. [Results] After 6 weeks, significant improvement was observed in upper limb function, activities of daily living performance, and kinematic performance. [Conclusion] This study demonstrated the positive effects of robotic rehabilitation on upper limb function, activities of daily living performance, and kinematic performance in chronic stroke survivors.

Feedback training using a non-motorized device for long-term upper extremity impairment after stroke: a single group study.

[Purpose] To investigate the effect of feedback training using a non-motorized device on the upper extremity kinematic performance of chronic stroke survivors. [Subjects] This study had a single group design. Thirteen chronic stroke survivors (onset duration: 11.5 years, 62.6 years, mini-mental state examination score: 26.0) were enrolled. [Methods] The feedback training system consisted of a non-motorized device that offered weight support, and a projective display device and loud speakers that provided suitable visual and auditory feedback to the user. Subjects participated in the feedback training for 40 min per day, two times a week for 4 weeks. Upper extremity kinematic performance (i.e., movement time) in three directions was confirmed twice (at baseline and post-intervention). [Results] After 4 weeks of the intervention, a significant improvement in upper extremity kinematic performance was observed in the three directions. [Conclusion] The present study demonstrated the positive effects of feedback training using a non-motorized device on the upper extremity kinematic performance of chronic stroke survivors. Therefore, the findings of this study may provide beneficial information for future studies on feedback training using a non-motorized device for chronic stroke survivors.

Rhythmic auditory stimulation using a portable smart device: short-term effects on gait in chronic hemiplegic stroke patients.

[Purpose] The effects of various rhythmic auditory stimulation tempos on stroke gait pattern changes when training patients with a smartphone-based rhythmic auditory stimulation application were investigated. [Subjects and Methods] Fifteen patients with chronic stroke were included. Cadence during comfortable walking was measured (baseline). After the baseline findings were recorded, rhythmic auditory stimulation with five different tempos (i.e., -10%, -5%, 0%, +5%, and +10% change from baseline) was randomly applied. Finally, comfortable walking without rhythmic auditory stimulation was initiated to evaluate gait pattern changes. [Results] As the tempo increased, the spatiotemporal gait parameters of the stroke patients changed significantly. Gait speed, cadence, and gait cycle duration showed the greatest improvement in the +10% rhythmic auditory stimulation condition compared to baseline. After gait training with rhythmic auditory stimulation, gait speed, cadence, stride length, gait cycle duration, and step length of the affected and unaffected sides improved significantly compared to baseline. [Conclusion] Significant changes in the gait pattern of stroke patients were noted for various tempos after training with rhythmic auditory stimulation. These findings could be used to customize rehabilitative gait training for patients who experience stroke with hemiplegia.

Robot-Assisted Reach Training for Improving Upper Extremity Function of Chronic Stroke.

Stroke, as a major risk factor for chronic impairment of upper limb function, can severely restrict the activities of daily living. Recently, robotic devices have been used to enhance the functional upper extremity movement of stroke patients. The purpose of the current study was to assess whether a robot-assisted reach training program using a whole arm manipulator (WAM) could improve upper extremity kinematic performance and functional movement for chronic stroke patients. Using a single-group design, this study followed 10 people with chronic stroke (6 men, 61.5 years; Mini-Mental State Examination score: 27.0; onset duration: 8.9 years). WAM with seven degrees of freedom for the shoulder, elbow, and wrist joints was used during robot-assisted reach exercises. Subjects participated in the training program for 40 minutes per day, 2 times a week, for 4 weeks. The main outcome measures were upper extremity kinematic performance (movement velocity) for three directions and functional movement (Action Research Arm Test). Upper extremity kinematic performance and functional movement measures were performed three times: at baseline, during intervention (at 2 weeks), and post intervention. Upper extremity kinematic performance and functional movement showed improvement after two weeks (P < 0.05) and four weeks (P < 0.05) of training compared to baseline. The findings of the current study demonstrated the positive effects of short-term robot-assisted reach training on upper extremity kinematic performance as well as functional movement in individuals with chronic stroke. In addition, the findings of the current study may provide valuable information for subsequent randomized controlled trials.

Usefulness of one-arm motorized gait device for chronic hemiplegic stroke survivors.

BACKGROUND: After stroke, gait training is a key component of rehabilitation, and most individuals use a variety of walking aids depending on their physical condition and environment. OBJECTIVE: This study aimed to investigate the potential effect of a one-arm motorized gait device for gait assist of chronic hemiplegic stroke survivors through comparison with traditional gait devices (parallel bar and hemi-walker). METHODS: This study was conducted on 14 chronic hemiplegic stroke survivors. The participants were asked to walk under three conditions using different gait devices, and their gait parameters during walking were collected and analyzed. The first condition involved walking on parallel bars; second condition, walking using hemi-walkers; and third condition, walking using one-arm motorized gait devices. With the use of a gait analysis system, the spatio-temporal gait parameters in each condition were collected, such as gait velocity, cadence, step length, stride length, single support time, and double support time. RESULTS: In the results by repeated-measures ANOVA or the Friedman test, a significant difference was found in the gait parameters among all three conditions (p< 0.05). The post-hoc test showed a significant change in the spatio-temporal gait parameters (especially, velocity, cadence and affected side single and double support time) when one-arm motorized gait device were used compared with parallel bars and hemi-walkers (p< 0.05). CONCLUSION: The results of this study suggest that one-arm motorized gait devices developed for hemiplegic stroke survivors may be more effective potentially than parallel bars and hemi-walkers in gait assistance of chronic hemiplegic stroke survivors.

Clinician-Driven Reanalysis of Exome Sequencing Data From Patients With Inherited Retinal Diseases.

Importance: Despite advances in next-generation sequencing (NGS), a significant proportion of patients with inherited retinal disease (IRD) remain undiagnosed after initial genetic testing. Exome sequencing (ES) reanalysis in the clinical setting has been suggested as one method for improving diagnosis of IRD. Objective: To investigate the association of clinician-led reanalysis of ES data, which incorporates updated clinical information and comprehensive bioinformatic analysis, with the diagnostic yield in a cohort of patients with IRDs in Korea. Design, Setting, and Participants: This was a multicenter prospective cohort study involving 264 unrelated patients with IRDs, conducted in Korea between March 2018 and February 2020. Comprehensive ophthalmologic examinations and ES analyses were performed, and ES data were reanalyzed by an IRD specialist for single nucleotide variants, copy number variants, mobile element insertions, and mitochondrial variants. Data were analyzed from March to July 2023. Main Outcomes and Measures: Diagnostic rate of conventional bioinformatic analysis and clinician-driven ES reanalysis. Results: A total of 264 participants (151 [57.2%] male; mean [SD] age at genetic testing, 33.6 [18.9] years) were enrolled, including 129 patients (48.9%) with retinitis pigmentosa and 26 patients (9.8%) with Stargardt disease or macular dystrophy. Initial bioinformatic analysis diagnosed 166 patients (62.9%). Clinician-driven reanalysis identified the molecular cause of diseases in an additional 22 patients, corresponding to an 8.3-percentage point increase in diagnostic rate. Key factors associated with new molecular diagnoses included clinical phenotype updates (4 patients) and detection of previously overlooked variation, such as structural variants (9 patients), mitochondrial variants (3 patients), filtered or not captured variants (4 patients), and noncanonical splicing variants (2 patients). Among the 22 patients, variants in 7 patients (31.8%) were observed in the initial analysis but not reported to patients, while those in the remaining 15 patients (68.2%) were newly detected by the ES reanalysis. Conclusions and Relevance: In this cohort study, clinician-centered reanalysis of ES data was associated with improved molecular diagnostic yields in patients with IRD. This approach is important for uncovering missed genetic causes of retinal disease.

Effectiveness of Visual Feedback in Reducing Trunk Compensation During Arm Reaching for Home-Based Stroke Rehabilitation.

This study investigates the effectiveness of visual feedback in reducing trunk compensation during one-arm reaching exercises using an end-effector robot. Results suggest that visual feedback is more effective than verbal feedback in suppressing trunk compensation, as evidenced by lower trunk movements. Synchronized target position with respect to trunk motion exhibited a suppressive effect on trunk motion, as observed by a reduction in trunk standard deviation, trunk root mean square, and trunk difference between the starting and ending positions. These findings have important implications for developing feedback techniques to address unnatural upper limb reach movements in stroke survivors during rehabilitation programs. However, the study's limitations, such as small sample size, should be considered. Future research should explore feedback techniques in different patient populations and exercise types and evaluate their long-term effects.

Care robot research and development plan for disability and aged care in Korea: A mixed-methods user participation study.

The population of Korea is aging rapidly, and this has led to a care burden for caregivers. Without adequate caregivers to address the increased burden, people with significant disabilities and older adults with disabilities who have greatly reduced mobility are at risk. The aim of this study was to determine suitable types of care robots for care applications in Korea and formulate a strategy for a future care robot R&D plan through a user participation study. We categorized nine types of care robots that are suitable for the care needs in Korea. By adopting a mixed research methodology involving user participation, we conducted discussions with caregivers, care receivers, and other stakeholders under a public-private-people partnership model. We also identified five primary strategies for care robot R&D: (1) intensive investment to match the needs of people with very severe disabilities to care robot technologies, particularly for transfer, repositioning, toileting, and feeding; (2) translational research and technology development; (3) realization of smart-care through fourth industrial revolution (i.e., digital) technologies; (4) user-centered research with stakeholders; and (5) building of a care robot ecosystem. The formulated plan would be shared with other developers and clinical experts to drive development of suitable care robots.

A Machine Learning-Based Initial Difficulty Level Adjustment Method for Balance Exercise on a Trunk Rehabilitation Robot.

Trunk rehabilitation exercises such as those for remediating core stability can help improve the seated balance of patients with weakness or loss of proprioception caused by diseases such as stroke, and aid the recovery of other functions such as gait. However, there has not yet been any reported method for automatically determining the parameters that define exercise difficulty on a trunk rehabilitation robot (TRR) based on data such as the patient's demographic information, balancing ability, and training sequence, etc. We have proposed a machine learning (ML)-based difficulty adjustment method to determine an appropriate virtual damping gain (Dvirtual) of the controller for the TRR's unstable training mode. Training data for the proposed system is obtained from 37 healthy young adults, and the trained ML model thus obtained is tested through experiments with a separate population of 25 healthy young adults. The leave-one-out cross validation results (37 subjects) from the training group for validation of the designed ML model showed 80.90% average accuracy (R2 score) for using the given information to predict the desired difficulty levels, which are represented by the level of balance performance quantified as Mean Velocity Displacement (MVD) of the center of pressure. Statistical analysis (Repeated measures analysis of variance) of subject performance also showed that ground truth difficulty levels from the training data and predicted difficulty levels did not differ significantly under any of the three exercise modes used in this study (Hard, Medium, and Easy), and the standard deviations were reduced by 16.39, 41.39, and 25.68%, respectively. Moreover, the Planar Deviation (PD) of the center of pressure, which was not the target parameter here, also showed results similar to the MVD, which indicates that the predicted Dvirtual affected the difficulty level of balance performance. Therefore, the proposed ML model-based difficulty adjustment method has potential for use with people who have varied balancing abilities.

Caregiver burden according to ageing and type of care activity in caregivers of individuals with spinal cord injury.

OBJECTIVE: To describe caregiver burden according to the caregivers' general characteristics, especially with ageing, and type of care activities provided by caregivers of individuals with spinal cord injury. DESIGN: A cross-sectional study was conducted utilizing a structured questionnaire that included general characteristics, health conditions, and caregiver burden. SETTING: A single center study in Seoul, Korea. SUBJECTS: Participants were recruited from 87 individuals with spinal cord injuries and 87 caregivers. METHODS: The Caregiver Burden Inventory was used to assess caregiver burden. RESULTS: Caregiver burden was significantly different by age (p = 0.001), relationship (p = 0.025), sleep hours (p = <0.001), underlying disease (p = 0.018), pain (p = <0.001), and daily activities of individuals with spinal cord injury (p = 0.001). Caregiver's age (B = 0.339, p = 0.049), sleep duration (B = -2.896, p = 0.012) and pain (B = 2.558, p < 0.001) predicted caregiver burden. Toileting assistance was the most challenging and time-consuming for caregivers, while patient transfer was associated with the greatest concerns for body injury. CONCLUSION: Caregiver education should be targeted according to caregiver's age and type of assistance. Social policies need to be developed to distribute devices and care-robots to reduce caregiver burden and thereby assist caregivers.

Upper-Limb Robot-Assisted Therapy Based on Visual Error Augmentation in Virtual Reality for Motor Recovery and Kinematics after Chronic Hemiparetic Stroke: A Feasibility Study.

The purpose of this study was to investigate the effect of upper-limb robot-assisted therapy based on visual error augmentation in virtual reality (UL-RAT-VEAVR) for motor recovery and kinematics after chronic hemiparetic stroke. This study applied a single-group pre- and post-intervention study design. A total of 27 stroke survivors (20 males and 7 females; mean age 54.51 years, mean onset duration 12.7 months) volunteered to participate in this study. UL-RAT-VEAVR was performed three times a week for four weeks, amounting to a total of twelve sessions, in which an end-effector-based robotic arm was used with a visual display environment in virtual reality. Each subject performed a total of 480 point-to-point movements toward 3 direction targets (medial, ipsilateral, and contralateral side) in the visual display environment system while holding the handle of the end-effector-based robotic arm. The visual error (distance to the targets on the monitor) in virtual reality was increased by 5% every week based on the subject's maximum point-to-point reaching trajectory. Upper-limb motor recovery was measured in all subjects using the Fugl−Meyer Assessment (FMA) upper-limb subscale, the Box and Block Test (BBT), and the Action Research Arm Test (ARAT), before and after training. In addition, a kinematic assessment was also performed before and after training and consisted of time, speed, distance, and curvilinear ratio for point-to-point movement. There were significant improvements in both upper-limb motor function and kinematics after 4 weeks of UL-RAT-VEAVR (p < 0.05). Our results showed that the UL-RAT-VEAVR may have the potential to be used as one of the upper-limb rehabilitation strategies in chronic stroke survivors. Future studies should investigate the clinical effects of the error-augmentation paradigm using an RCT design.

Development of a novel Korean reading chart.

CLINICAL RELEVANCE: Measuring reading ability is a crucial part of assessing patients who complain of reduced vision. Foreign language versions of such charts need to be developed and validated. BACKGROUND: It is difficult to measure or predict Korean reading ability due to a lack of a representative reading charts in Korean, and previous charts have limited capacity to detect deficits in reading ability among Korean patients with eye diseases. METHODS: Two printed versions of the reading chart were created. Thirty-four patients with no change in vision in the last three months and no expected change in vision in the next four weeks were included in this study. The results were validated by testing 13 normal-sighted adults (group 1), 14 patients with various macular diseases whose visual acuity was equal or better than 0.5 logarithm of the minimum angle of resolution (logMAR) (group 2), and seven patients with various macular diseases whose visual acuities were between 1.3 logMAR and 0.5 logMAR (group 3). Inter-chart and intra-subject repeatabilities were assessed for maximum reading speed (MRS) and critical print size (CPS). RESULTS: A total of 38 sentences were tested on 34 adults in three groups. Groups 1 and 2 did not differ significantly in terms of MRS and CPS. The MRS was lower in group 3, for each chart and between visits. The CPS was larger in group 3, for each chart and between visits, with the exception of chart 2 during visit one. With regard to test-retest reliability, the intraclass correlation co-efficients (ICCs) for chart 1 and chart 2 were more than 0.900. With regard to inter-chart reliability, the ICCs were more than 0.892, respectively. CONCLUSION: The reading chart developed in this study was reliable in producing consistent results among a normal Korean population and patients with various macular diseases.

Ocular ischemia with hypotony after injection of hyaluronic acid gel.

The authors experienced a case with ocular ischemia with hypotony following injection of a dermal filler for augmentation rhinoplasty. Immediately after injection, the patient demonstrated a permanent visual loss with typical fundus features of central retinal artery occlusion. Multiple crusted ulcerative patches around the nose and left periorbit developed, and the left eye became severely inflamed, ophthalmoplegic, and hypotonic. Signs of anterior and posterior segment ischemia were observed including severe cornea edema, iris atrophy, and chorioretinal swelling. The retrograde arterial embolization of hyaluronic acid gel from vascular branches of nasal tip to central retinal artery and long posterior ciliary artery was highly suspicious. After 6 months of follow up, skin lesions and eyeball movement became normalized, but progressive exudative and tractional retinal detachment was causing phthisis bulbi.

Effects of two different robot-assisted arm training on upper limb motor function and kinematics in chronic stroke survivors: A randomized controlled trial.

BACKGROUND: Comparative studies of different robotic types are warranted to tailor robot-assisted upper limb training to patient's functional level. OBJECTIVES: This study aimed to directly compare the effects of high inertia robot arm (whole arm manipulator, WAM) and low inertia robot arm (Proficio) on upper limb motor function in chronic stroke patients. METHODS: In this randomized controlled trial, 40 chronic stroke survivors were randomized into robot-assisted arm training with WAM (RAT-WAM) and robot-assisted arm training with Proficio (RAT-P) groups. The RAT-WAM and RAT-P groups participated in the robot-assisted arm training with WAM and robot-assisted arm training with Proficio, respectively, for 40 min daily, three times weekly over a four week. Upper limb motor function was measured before and after the intervention using the Fugl-Meyer assessment (FMA), action research arm test, and box and block test (BBT). Curvilinearity ratio (the length ratio of a straight line from the start to the target) was also measured as an index for upper limb kinematic performance. RESULTS: The RAT-WAM and RAT-P groups showed significant improvements in FMA-total and -proximal (shoulder/elbow units), BBT, and ARAT after the intervention (P < .05). Also, the RAT-P group showed significantly more improvement than the RAT-WAM group in FMA-distal (hand/wrist units) (P < .05). CONCLUSIONS: Improvements of upper limb motor function occurred during robot-assisted arm training with robotic systems. Low inertia robot arm was more effective in improving the motor function of the hand and wrist. The results may be useful for robot-assisted training for upper limb impairment.

Long-term safety and tolerability of subretinal transplantation of embryonic stem cell-derived retinal pigment epithelium in Asian Stargardt disease patients.

BACKGROUND: Although human embryonic stem cells (hESCs) have been considered a potential therapeutic option for regenerative medicine, there are some concerns regarding tumorigenicity, immunogenicity and ethical considerations. Stargardt macular dystrophy (SMD) is the most common form of juvenile macular degeneration that causes early onset blindness. Therapeutic options for SMD remain limited, although several treatment strategies are currently under investigation. Here, we report a 3-year assessment of a phase I clinical trial involving subretinal transplantation of hESC-retinal pigment epithelium (RPE) cells in patients with SMD. METHODS: This prospective, non-randomised clinical trial included three patients with SMD. All transplant recipients had central visual acuity no better than 20/400. Trans-pars plana vitrectomy was performed in the eye with poorer vision. RPE cells were reconstituted in balanced salt solution plus, then injected into the subretinal space using a semi-automated subretinal injection method. RESULTS: No serious adverse events occurred throughout the 3-year period following the injection of hESC-RPE cells. The functional and anatomical results were favourable, compared with the natural course of SMD reported in the ProgStar study. One patient showed best-corrected visual acuity improvement, while the other patients had stable best-corrected visual acuity during the 3-year follow-up period. CONCLUSION: These results suggest the long-term safety, tolerability, and feasibility of subretinal hESC-derived RPE cell transplantation in regenerative medicine. TRIAL REGISTRATION NUMBER: NCT01625559.

Clinicopathologic report of uveal melanoma with persistent exudative retinal detachment after gamma knife radiosurgery.

AIMS: Our purpose was to report the clinical and pathological findings from uveal melanoma patients with persistent exudative retinal detachment (RD) after Gamma Knife radiosurgery (GKR). METHODS: A retrospective review was performed. RESULTS: GKR was performed on 19 uveal melanoma patients from 2004 to 2006, and 5 of them developed persistent exudative RD. The mean initial largest basal tumor diameter in these 5 patients was 14.4 +/- 1.9 mm, and the mean tumor height was 9.2 +/- 1.0 mm. Marginal doses of 40-50 Gy radiation were administered. RD developed or had become aggravated an average of 3 (1-10) months after GKR. Two patients underwent enucleation, while the remaining 3 underwent tumor removal by endoresection with retinal reattachment surgery by vitrectomy and silicone oil tamponade. These procedures were undertaken an average of 6.3 (1.5-14) months after radiation and 3.3 (0.5-5) months after the onset or aggravation of RD. Histologically 4 tumors showed 50-100% necrosis without any mitotic activity. Thus local tumor control after GKR appeared sufficient regardless of RD. CONCLUSION: Aggravation or development of exudative RD after GKR does not necessarily entail treatment failure. Therefore, retinal reattachment surgery in persistent exudative RD may be an option to preserve the eye.