Jiro Kogo

Photoreceptor Outer Segment Length: A Prognostic Factor for Idiopathic Epiretinal Membrane Surgery

PURPOSE To investigate prognostic factors for visual improvement in patients undergoing vitrectomy for epiretinal membrane (ERM) using spectral domain (SD) optical coherence tomography (OCT). DESIGN Prospective cohort study. PARTICIPANTS A total of 41 eyes of 38 patients. METHODS A total of 41 eyes of 38 patients with idiopathic ERM underwent ERM resection. Ophthalmic evaluations included best-corrected visual acuity (BCVA) and OCT parameters before and 1, 3, and 6 months after surgery. Correlations between OCT parameters and BCVA were assessed at each time point. Correlations between postoperative BCVA and preoperative factors were evaluated, including age, preoperative BCVA, photoreceptor outer segment (PROS) length, central foveal thickness (CFT), outer foveal thickness (OFT), and outer nuclear layer thickness (ONLT). The factors influencing postoperative BCVA were evaluated using multiple regression analysis. MAIN OUTCOME MEASURES The BCVA at 6 months postoperatively. RESULTS The PROS length had the most significant correlation with BCVA at each time point (baseline: P = 0.0098, r = -0.409; 1 month: P = 0.0002, r = -0.586; 3 months: P < 0.0001, r = -0.642; 6 months: P = 0.0002, r = -0.577). The PROS length 1 month postoperatively was significantly decreased compared with that preoperatively (P = 0.0325), and the PROS length at 3 months recovered to the baseline length. Preoperative BCVA and PROS length were significantly correlated with postoperative BCVA at 6 months (P = 0.0055, r = 0.439 and P = 0.0089, r = -0.414, respectively). Other parameters, including age, CFT, OFT, and ONLT, were not significantly correlated with postoperative BCVA. Multiple regression analysis showed that preoperative PROS length yielded the highest regression coefficient with postoperative BCVA (P = 0.0363, standard regression coefficient = -0.335, overall R(2) = 0.289). CONCLUSIONS Imaging of PROS length with SD-OCT was found to be a good indicator of BCVA at each time point after surgery and a predictor of postoperative BCVA in patients with idiopathic ERM. The PROS length changes after surgery may indicate surgical injury and restoration of the macular outer layer.

Contribution of mitogen-activated protein kinases to NMDA-induced neurotoxicity in the rat retina

We examined the contributions of the mitogen-activated protein kinases (MAPKs) family [extracellular signal-regulated kinase (ERK), p38 kinase (p38), and c-Jun N-terminal kinase (JNK)] to N-methyl-D-aspartate (NMDA)-induced neurotoxicity in the rat retina. Detection of apoptotic cell death in the retinal ganglion cell layer (RGCL) and the inner nuclear layer (INL) by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining began 6 h after intravitreal NMDA (100 nmol) injection and continued to increase thereafter. Western blot analysis showed that phosphorylated MAPKs (p-MAPKs) were expressed in the retina following a temporal manner: maximal expression of phosphorylated ERK (p-ERK) at 1 h, maximal expression of phosphorylated p38 (p-p38) at 6 h, and beginning of phosphorylated JNK (p-JNK) significant increase at 6 h after injection. An immunohistochemical/TUNEL co-localization study showed that p-JNK- and p-p38-positive cells in the RGCL were frequently TUNEL-positive, whereas few p-ERK-positive cells were TUNEL-positive. Moreover, co-injection of inhibitors for JNK (0.2 nmol SP600125) and/or p38 (2.0 nmol SB203580) with NMDA was effective in ameliorating NMDA-induced apoptotic cell loss in the RGCL 12 h after injection, as shown by TUNEL-positive cell counts. These inhibitors also protected the inner retina as shown by morphometric studies such as cell counts in the RGCL and measurement of the IPL thickness 7 days after injection. On the other hand, an ERK inhibitor (2.0 nmol U0126) did not suppress NMDA-induced cell death in the RGCL nor thinning of the IPL. These findings suggest that JNK and p38 are proapoptotic in NMDA-induced cell death in the RGCL, but not ERK.

Neuroprotective effect of atrial natriuretic peptide against NMDA-induced neurotoxicity in the rat retina

Atrial natriuretic peptide (ANP) can regulate aqueous humor production in the eye and has recently been suggested to play some functional roles in the retina. It has also been reported that ANP increases tyrosine hydroxylase (TH) mRNA levels and intracellular dopamine levels in PC12 cells. The effect of ANP on TH levels and the role of ANP in retinal excitotoxicity remain unknown. In this study, we investigated the effects of ANP on TH expression and dopamine levels in rat retina after intravitreal injection of NMDA. Immunohistochemistry localized natriuretic peptide receptor-A (NPRA) in the ganglion cell layer (GCL), the inner nuclear layer (INL) and the outer nuclear layer (ONL) in the rat retina. Quantitative real-time PCR and Western blot analysis showed a dramatic reduction in retinal TH levels 5 days after NMDA injection, while ANP, at a concentration of 10(-4) M, ameliorated this reduction in TH mRNA and TH protein levels. High-performance liquid chromatography (HPLC) analysis showed that NMDA reduced dopamine levels in the retina, and that ANP attenuated this reduction. Moreover, morphological analysis showed that ANP ameliorated NMDA-induced neurotoxicity through NPRA. The ameliorative effect of ANP was inhibited by a dopamine D(1) receptor antagonist. These results suggest that ANP may have a neuroprotective effect through possible involvement of dopamine induction.

Comparative study of 27-gauge vs 25-gauge vitrectomy for epiretinal membrane

PurposeThe purpose of this study was to compare 27-gauge (27G) with 25-gauge (25G) microincision vitrectomy in patients with epiretinal membrane (ERM).ParticipantsSeventy-four eyes of 66 patients undergoing 3-port pars plana vitrectomy using 27G or 25G instrumentation.MethodsSeventy-four eyes of 66 patients with ERM, who underwent 27G or 25G microincision vitrectomy were prospectively evaluated.ResultsThe mean operation time for vitrectomy was significantly longer in the 27G group than in the 25G group (9.9±3.5 vs 6.2±2.7 min, respectively, P<0.0001). No statistically significant difference was found between the two groups in terms of the mean operation time for ERM–inner limiting membrane peeling (27G vs 25G: 20.2±9.9 vs 16.1±9.3 min, P=0.14), although the time for vitreous cutting was longer in the 27G group (9.9±3.5 vs 6.2±2.7 min, respectively, P<0.0001). The flare value, intraocular pressure (IOP), and rate of hypotony 1 day after surgery did not differ between the 27G and 25G groups (flare value: 18.7 vs 17.2; IOP: 8.8 vs 9.7 mm Hg; rate of hypotony: 30 vs 35%, respectively). There was no significant difference in the surgically induced astigmatism between the two groups in the follow-up period. The mean time required for wound closure did not show a significant difference between the 27G and 25G groups (7.7 vs 8.6 weeks, respectively).ConclusionThe 27G system is as safe and useful for ERM vitrectomy as the 25G system. Based on its potential, further improvement of 27G instruments could result in greater efficiency.

Involvement of TNF-α in glutamate-induced apoptosis in a differentiated neuronal cell line

We examined the involvement of tumor necrosis factor (TNF)-alpha on glutamate-induced cytotoxicity in a differentiated neuronal cell line. In this study, we used nerve growth factor (NGF)-differentiated PC12h cells. Glutamate cytotoxicity was assessed using the MTS and TUNEL assays. To detect TNF-alpha levels in culture supernatants after glutamate exposure, we used ELISA methods. The involvement of caspase-8, which is downstream from TNF receptor 1 (TNF-R1) in glutamate-induced cytotoxicity, was determined by Western blot analysis. The MTS assay showed that the addition of glutamate resulted in dose-dependent cell death, while the TUNEL assay showed that glutamate induced apoptosis in differentiated PC12h cells in a dose-dependent manner. TNF-alpha levels in the supernatant of glutamate-exposed cells were significantly increased compared with those in unexposed cells. In addition, glutamate caused increases in the levels of caspase-8 protein. The increases in caspase-8 levels were ameliorated by pretreatment with soluble TNF-R1. Moreover, soluble TNF-R1 significantly ameliorated the cell death induced by glutamate. These results suggest that TNF-alpha released from neuronal cells may be associated with glutamate-induced neuronal cell death.

Inverted internal limiting membrane flap technique as a useful procedure for macular hole-associated retinal detachment in highly myopic eyes

PurposeTo determine whether the inverted internal limiting membrane (ILM) flap technique contributes to high reattachment and closure rates in patients with macular hole-associated retinal detachment (MHRD).Patients and methodsIn all, 15 eyes of 15 patients with MHRD undergoing 25-gauge pars plana vitrectomy with the inverted ILM flap technique or ILM peeling. The patients were divided into the inverted ILM flap technique group (6 eyes) and ILM peeling group (9 eyes). The logarithm of minimal angle of resolution best-corrected visual acuity (BCVA) and retinal attachment and macular hole closure rates were compared between the two groups before and after surgery.ResultsNo significant differences were found in the pre- and postoperative BCVA at 1 and 3 months after surgery in either group (inverted ILM flap technique group, preoperatively 1.04±0.55, 1 month 0.95±0.30, 3 months 0.83±0.22; ILM peeling group, preoperatively 1.00±0.44, 1 month 1.05±0.38, 3 months 1.06±0.49; P>0.05, respectively). The postoperative BCVA at 6 months after surgery was significantly better in the inverted ILM flap technique group than in the ILM peeling group (inverted ILM flap technique group, 0.62±0.35; ILM peeling group, 1.02±0.41, P=0.045). The improvement in BCVA was significantly better in the inverted ILM flap technique group than in the ILM peeling group (inverted ILM flap technique group, –0.41±0.29; ILM peeling group, 0.02±0.36; P=0.021). The primary macular hole closure rates were 100% in the inverted ILM flap technique group and 55.5% in the ILM peeling group. The primary reattachment rates were 100% in the inverted ILM flap technique group and 55.5% in the ILM peeling group. The primary macular hole closure and reattachment rates were not significantly different in both groups (P=0.056, respectively).ConclusionThe inverted ILM flap technique is a useful procedure for MHRD in highly myopic eyes.

Axonal Protection by Ripasudil, a Rho Kinase Inhibitor, via Modulating Autophagy in TNF-Induced Optic Nerve Degeneration

Purpose The Rho kinase inhibitor ripasudil decreases intraocular pressure, although its role in optic nerve axonal damage should be clarified. We therefore investigated whether ripasudil modulates TNF-induced axonal loss and affects autophagy machinery after the induction of optic nerve degeneration. Methods Rats were given intravitreal injection of TNF, concomitant injection of ripasudil hydrochloride hydrate and TNF, or ripasudil alone. Axon numbers were counted to evaluate the effects of ripasudil against axon loss. Immunoblot analysis was performed to examine p62 as well as LC3-II expression in optic nerves. Electron microscopy was used to determine autophagosome numbers in axons and glia. Immunogold labeling was performed to evaluate autophagosomes in axons. Results Ripasudil injected intravitreally resulted in significant neuroprotection against TNF-induced axon loss. Intravitreal TNF injection upregulated p62 in the optic nerve, but ripasudil completely inhibited this increment. The ripasudil alone injection diminished p62 and enhanced LC3-II protein levels significantly compared with baseline. Ripasudil-induced upregulation of LC3-II was seen after TNF injection, and immunohistochemical analysis revealed that LC3 colocalized in nerve fibers. Electron microscopic analysis revealed that autophagosomes were present in axons and glia, although autophagosome numbers increased significantly after ripasudil injection only in axons. Conclusions These results suggest that ripasudil-enhanced intra-axonal autophagy is at least partly involved in axonal protection.

Effects of indocyanine green staining on the recovery of visual acuity and macular morphology after macular hole surgery.

Purpose: To evaluate whether indocyanine green (ICG)-assisted internal limiting membrane peeling affects visual outcome and macular morphologic changes in spectral-domain optical coherence tomography images after macular hole (MH) surgery. Methods: A retrospective analysis was performed of 34 eyes in 34 patients who had undergone surgical treatment for MH. Best-corrected visual acuity (BCVA) and optical coherence tomography parameters including central foveal thickness, length of the external limiting membrane (ELM) defect, and length of the inner segment and outer segment (IS/OS) defect were analyzed pre- and postoperatively. Results: The eyes were divided into 2 groups based on ICG use (ICG+/-). The changes in BCVA did not differ significantly between the 2 groups at 6 months. However, the ICG+ group had poorer changes compared with the ICG- group at 1 and 3 months (p = 0.038, p = 0.012, respectively). Central foveal thickness and ELM defect did not differ between the 2 groups at each period. The IS/OS defect in the ICG+ group was significantly greater at 1 and 3 months than that in the ICG- group (p = 0.026, p = 0.048, respectively). Conclusions: ICG staining may affect the recovery process of macular morphology and visual acuity in the first several months after MH surgery.

Optical coherence tomography findings as a predictor of clinical course in patients with branch retinal vein occlusion treated with ranibizumab

Purpose To examine the relationship between optical coherence tomography (OCT) images and clinical course in eyes with branch retinal vein occlusion (BRVO) treated with intravitreal ranibizumab injection (IVR). Design Prospective cohort study. Participants Thirty eyes of 30 patients with BRVO treated with IVR. Methods All patients received 1 initial IVR followed by repeated injections in the pro re nata (PRN) regimen. Correlations between logarithm of minimum angle of resolution best-corrected visual acuity (logMAR BCVA) or number of IVRs after 12 months and OCT parameters including the external limiting membrane (ELM), ellipsoid zone (EZ), interdigitation zone (IZ), and photoreceptor outer segment (PROS) length at first resolution of macular edema (ME) were assessed. Resolution of ME was defined as central foveal thickness <300 μm and the absence of subretinal fluid. OCT parameters influencing BCVA and number of IVRs were evaluated using multivariate analysis. Correlations between nonperfusion areas (NPAs) and thinning areas and changes in retinal thickness of BRVO-affected areas were assessed. Results Of the 30 patients, 27 completed this study and were included in the statistical analyses. The mean logMAR BCVA at 3, 6, and 12 months was 0.16 ± 0.19, 0.09 ± 0.20, and 0.07 ± 0.20, respectively, which improved significantly from baseline at each visit (p < 0.0001, respectively), while the mean number of IVRs at 12 months was 3.9 ± 2.2. The mean number of IVRs for the first resolution of ME was 1.6 ± 0.8. Eyes with ELM and EZ defects at the points of first resolution of ME were correlated with a significantly lower BCVA at 12 months compared with eyes with preserved ELMs and EZs (p = 0.035, p = 0.002, respectively). However, eyes with IZ defects at the points of first resolution of ME were not correlated with a significantly lower BCVA at 12 months compared with eyes with preserved IZs (p = 0.160). Defects in the EZ at the points of first resolution of ME significantly affected the number of IVRs at 12 months (p = 0.042), although the ELM and IZ did not. PROS length at the points of first resolution of ME was significantly correlated with BCVA and number of IVRs at 12 months (p = 0.006, p = 0.0008, respectively). In multivariate analysis, PROS length at the points of first resolution of ME had the most significant effect on BCVA and number of IVRs (p = 0.013, p = 0.012, respectively). NPA size on fluorescein angiography and thinning area on OCT within the macular area showed a significant correlation (p = 0.003, r = 0.971). The retinal thickness of ischemic BRVO-affected areas was significantly less than that of control areas at 10, 11, and 12 months (p = 0.001, p = 0.005, p = 0.003, respectively). Conclusion We showed that the 1+PRN regimen may be a useful therapy for ME due to BRVO. In addition, PROS length at points of first resolution of ME appears to be a good indicator of BCVA and number of IVRs in BRVO patients.