Yasuo Noda

Robot-Assisted Vitreoretinal Surgery Development of a Prototype and Feasibility Studies in an Animal Model

PURPOSE To develop a prototype robotic system designed to assist vitreoretinal surgery and to evaluate its accuracy and maneuverability. DESIGN Experimental study. PARTICIPANTS This study used harvested porcine eyes. METHODS After development of a prototype robotic system, pointing accuracy tests of the system were performed on graph paper and in harvested porcine eyes. The average maximal deviation from the aiming point to the actual position of the tip of the instrument was compared between manually conducted procedures and those conducted with robotic assistance. The feasibility of creating posterior vitreous detachment (PVD), retinal vessel sheathotomy (RVS), and retinal vessel microcannulation also were evaluated in porcine eye models, and the success rates of 4 consecutive attempts for each kind of procedure were evaluated. MAIN OUTCOME MEASURES The average maximum deviation in pointing accuracy tests both on graph paper and in animal eye models was a main outcome measure. The success rate of making PVD, RVS, and retinal vessel microcannulation was the other primary outcome measure. RESULTS The pointing accuracy was superior with robotic assistance both on graph paper (327.0 microm vs. 32.3 microm) and in animal eye models (140.8 microm vs. 33.5 microm). Creating PVD, RVS, and retinal vessel microcannulation was feasible in 4 of 4 attempts, 4 of 4 attempts, and 2 of 4 attempts, respectively. The 2 failures in microcannulation were considered to be the result of difficulty in visual differentiation between the retinal vessel and retina in harvested porcine eyes. CONCLUSIONS Improved accuracy and desirable feasibility of a prototype robotic system to assist vitreoretinal surgery were shown in this study. Research for wider implementation of robot-assisted surgery should be continued; there are some hurdles to overcome.

Systemic Vascular Safety of Ranibizumab for Age-Related Macular Degeneration: Systematic Review and Meta-analysis of Randomized Trials

BACKGROUND We conducted a meta-analysis of randomized trials of ranibizumab for age-related macular degeneration (AMD) to elucidate systemic vascular risk. CLINICAL RELEVANCE Although intravitreal vascular endothelial growth factor inhibitors are widely used to treat AMD, whether they produce systemic adverse effects remains uncertain. METHODS We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials through March 2014 to identify the randomized trials that compared systemic safety among different intensities of ranibizumab treatment for AMD. The outcome measures were the incidence of cerebrovascular accidents (CVAs), myocardial infarctions, nonocular hemorrhages, overall arterial thromboembolic events (ATEs), and all-cause mortality. We calculated the Peto odds ratio (OR) with 95% confidence interval for the comparisons between different intensities of regimens in terms of dose and retreatment frequency. RESULTS Eleven trials comprising 6596 patients with AMD were included in the meta-analysis. A significant increase was observed in the following comparisons: 0.5 versus 0.3/0.0 mg for CVA (OR, 1.86; 95% CI, 1.05-3.29; P = 0.03), monthly versus pro re nata (PRN)/0.0 mg for CVA (OR, 1.89; 95% CI, 1.06-3.38; P = 0.03), and 0.3/0.5 versus 0.0 mg for nonocular hemorrhage (OR, 1.57; 95% CI, 1.01-2.44; P = 0.04). A nonsignificant increase was observed in the following comparisons: 0.5 versus 0.0 mg for CVA (OR, 2.27; 95% CI, 0.90-5.69; P = 0.08), monthly versus PRN for CVA (OR, 2.04; 95% CI, 0.94-4.45; P = 0.07), 0.5 versus 0.0 mg for nonocular hemorrhage (OR, 1.68; 95% CI, 0.98-2.88; P = 0.06), 0.3 versus 0.0 mg for nonocular hemorrhage (OR, 1.68; 95% CI, 0.95-2.98; P = 0.07), monthly versus PRN/0.0 mg for nonocular hemorrhage (OR, 1.54; 95% CI, 0.98-2.42; P = 0.06), monthly versus PRN for ATE (OR, 1.58; 95% CI, 0.96-2.61; P = 0.07), and monthly versus PRN/0.0 mg for ATE (OR, 1.42; 95% CI, 0.99-2.05; P = 0.06). Among the other analyses, no protective or harmful effects of ranibizumab were observed. CONCLUSIONS In ranibizumab treatment for patients with AMD, a possible relationship of more intensive treatment to more systemic vascular adverse events was identified, but no relationship with mortality was identified.

Long-term increase in subfoveal choroidal thickness after surgery for senile cataracts.

PURPOSE To evaluate the impact of cataract surgery on subfoveal choroidal thickness and central retinal thickness in the elderly. DESIGN Prospective observational case series. METHODS This cohort study included 29 eyes of 29 patients with senile cataract, but no previous ocular surgery or other ocular abnormality. All 29 eyes received standard surgery by phacoemulsification and intraocular lens implantation. Subfoveal choroidal thickness and central retinal thickness were measured at baseline and 1, 3, and 6 months postoperatively by spectral-domain optical coherence tomography. Multiple regression analysis was conducted to identify predictors of larger changes in subfoveal choroidal thickness, including sex, age, baseline choroidal thickness, axial length, refractive status before surgery, and duration of surgery. RESULTS The 29 patients with senile cataract received cataract surgery without complication. Mean subfoveal choroidal thickness was 193.8, 208.9, 210.2, and 209.3 μm at baseline and at postoperative 1, 3, and 6 months, respectively, with a statistically significant increase after surgery (repeated-measures ANOVA; P < .0001). In 20 eyes (69.0%), subfoveal choroidal thickness remained high even 6 months after surgery. Multiple regression analysis revealed that male sex (P = .014) and thicker baseline choroid (P = .0048) predicted larger increases in subfoveal choroidal thickness. In contrast, the tendency of transient increase in central retinal thickness was not statistically significant. CONCLUSION Most elderly patients with senile cataracts are expected to maintain increased subfoveal choroidal thickness for at least 6 months after cataract surgery.

Polypoidal choroidal vasculopathy and history of central serous chorioretinopathy

PurposeTo evaluate the possible causative role of central serous chorioretinopathy (CSC) in the development of exudative age-related macular degeneration (AMD).MethodsIn a cross-sectional study at an institutional setting, 150 control subjects who had senile cataract or nasolacrimal duct stenosis and who were older than 50 years were enrolled. The background data for 89 patients with typical AMD (tAMD) and 138 patients with polypoidal choroidal vasculopathy (PCV) were used for comparison. Their medical records were taken for history of CSC, hypertension, systemic steroid use, and smoking. The fundus was also evaluated for signs of atrophic retinal pigment epithelial (RPE) tract and for focal photocoagulation scars in the macula.ResultsAfter adjusting for age, gender, and history of hypertension, systemic steroid use, and smoking, history of CSC was significantly more frequent (P<0.0001) in patients with PCV (15 patients, 10.9%) compared with patients with tAMD (2 patients, 2.2%) or control subjects (0 patients). On fundoscopy, an atrophic RPE tract (seven patients) or a focal photocoagulation scar (one patient) was observed only in patients with PCV (eight patients, 5.8%), and the frequency was statistically significant compared with that with tAMD (P=0.0143) or control subjects (P=0.0143). The laterality of CSC and AMD involved the same eye in 9 of 10 patients among those who had unilateral AMD and a reported unilateral CSC history.ConclusionA history of CSC may be a predisposing factor for the development of PCV in the Japanese population.

Impact of Robotic Assistance on Precision of Vitreoretinal Surgical Procedures

Purpose To elucidate the merits of robotic application for vitreoretinal maneuver in comparison to conventional manual performance using an in-vitro eye model constructed for the present study. Methods Capability to accurately approach the target on the fundus, to stabilize the manipulator tip just above the fundus, and to perceive the contact of the manipulator tip with the fundus were tested. The accuracies were compared between the robotic and manual control, as well as between ophthalmologists and engineering students. Results In case of manual control, ophthalmologists were superior to engineering students in all the 3 test procedures. Robotic assistance significantly improved accuracy of all the test procedures performed by engineering students. For the ophthalmologists including a specialist of vitreoretinal surgery, robotic assistance enhanced the accuracy in the stabilization of manipulator tip (from 90.9 µm to 14.9 µm, P = 0.0006) and the perception of contact with the fundus (from 20.0 mN to 7.84 mN, P = 0.046), while robotic assistance did not improve pointing accuracy. Conclusions It was confirmed that telerobotic assistance has a potential to significantly improve precision in vitreoretinal procedures in both experienced and inexperienced hands.

Quantitative assessment of manual and robotic microcannulation for eye surgery using new eye model

Microcannulation, a surgical procedure for the eye that requires drug injection into a 60–90 µm retinal vein, is difficult to perform manually. Robotic assistance has been proposed; however, its effectiveness in comparison to manual operation has not been quantified.

Protective Role of Glutathione Peroxidase 4 in Laser-Induced Choroidal Neovascularization in Mice

Purpose To evaluate the influence of glutathione peroxidase 4 (GPx4) expression in retinal pigment epithelium (RPE)/choroid tissue using a mouse model of laser-induced choroidal neovascularization (CNV). Methods In this study, GPx4+/−, GPx4+/+, and GPx4-overexpressing transgenic mice were created for comparison. The mRNA and protein expression of vascular endothelial growth factor (VEGF)-A in RPE/choroid tissue were evaluated before and after CNV induction by laser. Moreover, we investigated the changes in the VEGF-A mRNA level in RPE/choroid tissue in the CNV model that have not been clearly shown previously. Lipid peroxidation in RPE/choroid tissue was evaluated by immunohistochemistry using antibody against 4-hydroxy-2-nonenal. To investigate the protective role of GPx4, the size of laser-induced CNV was compared on day 7 among the mice expressing different levels of GPx4. Results In the laser-induced CNV mouse model, laser treatment reduced the VEGF-A mRNA level in RPE/choroid tissue, while it increased the VEGF-A protein level. Evaluation of VEGF-A expression in RPE/choroid tissue of the GPx4+/−, GPx4+/+, and GPx4 transgenic mice revealed that GPx4 increased the VEGF-A protein level under physiological conditions (i.e., without laser treatment), while GPx4 suppressed the increase in the VEGF-A protein level under pathological conditions (i.e., after CNV induction by laser). In addition, GPx4 reduced the CNV size in a dose-dependent manner in vivo. Conclusions GPx4 suppresses the increase in the VEGF-A protein level, which occurs during the development of pathological CNV, thus partly explaining the protective effect of GPx4 against CNV.

BRILLIANT BLUE G-ASSISTED INTERNAL LIMITING MEMBRANE PEELING FOR MACULAR HOLE: A Systematic Review of Literature and Meta-Analysis.

Purpose: To evaluate the effect of internal limiting membrane peeling with brilliant blue G (BBG) for the treatment of macular hole compared with peeling procedures with other dyes or without dye. Methods: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were systematically reviewed. Outcome measures were the primary closure rate and postoperative best-corrected visual acuity. Results: Nine studies that included 846 eyes were selected. There was no significant difference in preoperative best-corrected visual acuity between the BBG and no BBG (i.e., other dyes or no dye) groups (mean difference −0.02 logMAR [equivalent to 1 Early Treatment Diabetic Retinopathy Study (ETDRS) letter]; 95% confidence interval −0.09 to 0.04 [−2–4.5 ETDRS letters]; P = 0.45). The macular hole closure rate using BBG was not significantly different from that using indocyanine green (odds ratio 1.98; 95% confidence interval 0.71–5.48; P = 0.19). The postoperative best-corrected visual acuity was more favorable with BBG than with indocyanine green (mean difference −0.10 logMAR [5 ETDRS letters]; 95% confidence interval −0.16 to −0.03 [1.5–8 ETDRS letters]; P = 0.004) or with no BBG (mean difference −0.11 [5.5 ETDRS letters]; 95% confidence interval −0.18 to −0.04 [2–9 ETDRS letters]; P = 0.003). Conclusion: BBG could contribute to better visual acuity outcome than other dyes for internal limiting membrane peeling in patients with macular hole; however, it does not significantly influence the closure rate.

EFFECT OF INTERNAL LIMITING MEMBRANE PEELING DURING VITRECTOMY FOR DIABETIC MACULAR EDEMA: Systematic Review and Meta-analysis.

Purpose: To evaluate the effect of internal limiting membrane (ILM) peeling during vitrectomy for diabetic macular edema. Methods: MEDLINE, EMBASE, and CENTRAL were systematically reviewed. Eligible studies included randomized or nonrandomized studies that compared surgical outcomes of vitrectomy with or without ILM peeling for diabetic macular edema. The primary and secondary outcome measures were postoperative best-corrected visual acuity and central macular thickness. Meta-analysis on mean differences between vitrectomy with and without ILM peeling was performed using inverse variance method in random effects. Results: Five studies (7 articles) with 741 patients were eligible for analysis. Superiority (95% confidence interval) in postoperative best-corrected visual acuity in ILM peeling group compared with nonpeeling group was 0.04 (−0.05 to 0.13) logMAR (equivalent to 2.0 ETDRS letters, P = 0.37), and superiority in best-corrected visual acuity change in ILM peeling group was 0.04 (−0.02 to 0.09) logMAR (equivalent to 2.0 ETDRS letters, P = 0.16). There was no significant difference in postoperative central macular thickness and central macular thickness reduction between the two groups. Conclusion: The visual acuity outcomes using pars plana vitrectomy with ILM peeling versus no ILM peeling were not significantly different. A larger randomized prospective study would be necessary to adequately address the effectiveness of ILM peeling on visual acuity outcomes.

Changes in parafoveal retinal thickness and subfoveal choroidal thickness in a patient with dengue fever-associated maculopathy

BackgroundThe time courses of retinal and choroidal thickness changes in dengue fever-associated maculopathy are not known. We measured central macular thickness (CMT), parafoveal retinal thickness (PRT), and subfoveal choroidal thickness (SCT), in one case, employing optical coherence tomography.FindingsThe patient was a 43-year-old man diagnosed with dengue fever in Sri Lanka. He became aware of blurred vision bilaterally and visited our department 2 weeks after the onset. He showed reduced visual acuity. The Amsler test revealed a doughnut-shaped relative scotoma. Based on the course of this condition, dengue fever-associated maculopathy was diagnosed. One month later, 20 mg triamcinolone was injected into sub-Tenon space of the left eye. Both eyes showed subsequent improvement. PRT of both eyes increased 1 week after the first visit and decreased thereafter, reaching a plateau 1 month after the first visit. The change in CMT was minimal. SCT changed markedly, with the similar pattern in both eyes, though no particular tendency was noted during the observation period.ConclusionsDengue fever-associated maculopathy appears to be closely associated with thickening of the inner layer of the retina, but not with changes in choroidal thickness.