Tetsu Asami

Restoration of Cone Interdigitation Zone Associated With Improvement of Focal Macular ERG After Fovea-Off Rhegmatogenous Retinal Reattachment

PURPOSE To determine whether a correlation exists between the parameters of the focal macular ERGs (FMERGs) and the microstructural changes of the photoreceptors after successful surgery for fovea-off rhegmatogenous retinal detachment (RRD). METHODS Twenty eyes of 20 patients who had undergone successful surgery to reattach the retina in eyes with fovea-off RRD were studied. Focal macular ERGs and spectral-domain OCT (SD-OCT) were recorded at 1 and 6 months after the surgery. Changes of the components of the FMERGs, as well as changes of the SD-OCT parameters including the length of the external limiting membrane (ELM), ellipsoid zone (EZ), cone interdigitation zone (CIZ), and size of the outer photoreceptor area (between ELM and RPE), were determined. RESULTS During the postoperative period, the mean amplitudes of the a-waves increased by 1.4 times and the b-waves by 1.7 times. Spectral-domain OCT showed that the mean length of the EZ and CIZ and the size of the outer photoreceptor area had increased significantly at 6 months. The degree of the increase in the CIZ and outer photoreceptor area was significantly correlated with the increase in the amplitudes of the b-waves of the FMERGs (r = 0.56, P = 0.042, r = 0.57, P = 0.040, respectively; Spearman rank correlation test). However, the length of the EZ was not significantly correlated with the increase of the b-waves. CONCLUSIONS A restoration of the EZ alone might not be enough to improve the FMERGs, and a restoration of the EZ accompanied by that of the CIZ was essential for the recovery of the FMERGs after fovea-off RRD.

Influence of Preoperative Intravitreal Bevacizumab on Visual Function in Eyes with Proliferative Diabetic Retinopathy

Purpose: Although bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), is effective in treating ocular neovascularization, there are some concerns about whether blocking VEGF might be harmful to retinal neurons. The purpose of this study was to evaluate the effects of preoperative intravitreal bevacizumab (IVB) on the visual function of eyes with proliferative diabetic retinopathy (PDR). Methods: Thirty eyes of 23 patients (13 men and 10 women) with PDR who were treated at the Nagoya University Hospital from November 2006 to October 2009 were studied. All of the eyes were treated with 1.25 mg/0.05 ml of IVB 2–8 days before the vitrectomy. The protocol was approved by the Institutional Review Board of Nagoya University, and a written informed consent was obtained from each patient. All of the eyes had an active proliferative membrane with vitreous hemorrhage, but the fundus was visible. The mean age of the patients was 41.6 ± 10 years (range, 27–59), and the mean follow-up period was 9.7 ± 8.9 months (range, 1–24) after the vitrectomy. The visual acuity (VA) was measured, the visual fields were determined by Goldmann perimetery, and full-field electroretinograms (ERGs) were recorded before IVB, and before and after the vitrectomy. Fluorescein angiography was also performed before and after IVB. The area of the visual field was measured using a computer software (Scion Image). Results: All eyes showed a regression of the new vessels and a reduction of fluorescent leakage from the new vessels after IVB. In addition, there was less bleeding during the removal of the proliferative membrane. The average VA was improved postoperatively from 20/250 to 20/70. However, there was no significant change in the amplitudes of the a- (from 261.4 to 259.2 µV) and b-waves (from 256.9 to 253.3 µV) of the ERGs, and there was no significant change in the visual field area after the surgery (from 8,322.5 to 7,496.3 degrees2). No significant ocular or systemic adverse events were observed. Conclusion: IVB-assisted vitrectomy led to an improvement of the VA in eyes with PDR without significant adverse events. There was no change in the visual fields and ERGs. Although only a small number of patients were studied, we conclude that IVB is most likely not harmful to retinal neurons if bevacizumab is washed out in less than 1 week. In addition, preoperative IVB made the surgery much easier by decreasing the activity of new vessels.

Triamcinolone-Assisted Removal of Internal Limiting Membrane Enhances the Effect of Vitrectomy for Diabetic Macular Edema

Purpose: To evaluate the efficacy of internal limiting membrane (ILM) peeling during vitrectomy to treat diabetic macular edema (DME). Methods: In this nonrandomized study, we retrospectively analyzed the medical charts of 107 eyes that had undergone three-port vitrectomy to treat DME. The ILM was peeled in 65 eyes and not peeled in 42 eyes (ILM ON group). Indocyanine green (ICG) was used on 36 eyes (ICG group) and triamcinolone acetonide (TA) on 29 eyes (TA group) to make the ILM more visible. Results: In all groups, the mean foveal thickness was significantly decreased after surgery. Visual acuity (VA) improved gradually after the surgery and was significantly better than the preoperative VA at 6 months in the ICG group and at 3 months in the TA group. Compared with the ILM ON group eyes, the eyes in the TA group had significantly better improvement of VA. Conclusion: TA-assisted ILM peeling may improve the VA outcome to treat DME.

Vitreoretinal traction maculopathy caused by retinal diseases.

PURPOSE To study the morphological findings of vitreoretinal traction maculopathy caused by retinal vascular diseases and their changes after vitrectomy. METHODS Optical coherence tomographic images of 13 eyes of 12 cases were evaluated before and after vitrectomy. RESULTS The tractional force appeared to be mainly tangential with a possible anterior vector in 11 eyes, and mainly in the anterior direction in 2 eyes. After surgery, the increased foveal thickness decreased markedly in all eyes, and visual acuity improved in 8 eyes. CONCLUSION Preoperative optical coherence tomographic examination can reveal the fine structure of vitreoretinal separations and adherences caused by retinal vascular diseases. These observations permitted better surgical planning and results.

Development of a Fiber-Optic Optical Coherence Tomography Probe for Intraocular Use.

PURPOSE To evaluate the performance of a newly developed 23-G optical coherence tomography (OCT) probe in animal and human eyes. METHODS The probe is a side-imaging OCT device with a scanning beam set 43° to the optical axis and a working distance of 1.5 to 2.0 mm. The performance of the OCT probe was tested during vitrectomy in porcine cadaver eyes and rabbit eyes in situ. Optical coherence tomography images of a normal retina, retinal break, optic disc, pars plicata of the ciliary body, and intraoperative surgical manipulations were recorded. The probe was also tested in a pilot study of clinical cases; intraoperative real-time OCT imaging was performed in three patients, including a 56-year-old woman with an epiretinal membrane. RESULTS The OCT probe was able to delineate intraocular tissues, including the posterior retina, and even the most peripheral pars plicata in animal eyes. The OCT probe also successfully delineated intraoperative surgical maneuvers such as membrane peeling and the minute structures of the vortex veins, ora serrata, and vitreous incarceration in the scleral incision from the trocar with sufficient resolution in the patients. There were no complications resulting from its use. CONCLUSIONS The ability of this new 23-G OCT probe to obtain images of intraoperative manipulations from the most peripheral tissues in animal and patient eyes suggests that it could enable surgeons to make better decisions during the course of intraocular surgery.

Comparison of Macular Hole Surgery without Internal Limiting Membrane Peeling to Eyes with Internal Limiting Membrane Peeling with and without Indocyanine Green Staining

Background: To compare the long-term anatomical closure rates and visual acuity after vitrectomy for macular hole (MH) surgery with and without internal limiting membrane (ILM) peeling and with and without indocyanine green (ICG) staining. Methods: A total of 75 eyes of 71 patients with MH that had undergone vitrectomy were retrospectively studied. Group A consisted of 21 eyes that had vitrectomy without ILM peeling, Group B consisted of 38 eyes that had vitrectomy with ILM peeling without the ICG staining, and Group C consisted of 16 eyes that had vitrectomy with ILM peeling with ICG staining. The main outcome measures were the anatomical closure rates and visual acuities at 1, 2, and 3 years after surgery. Results: MH were closed in all 75 eyes after the initial surgery. The visual acuity improved significantly (p < 0.0005) at 1 year after surgery and did not change significantly at 2 and 3 years after surgery in the 3 groups. Differences in the mean visual acuity in the 3 groups were not significant at 1, 2, and 3 years after surgery. Conclusions: These results suggest that ILM peeling or the use of ICG dye do not significantly affect the MH closure rates and the long-term visual acuities.

Role of Caveolin-1 for Blocking the Epithelial-Mesenchymal Transition in Proliferative Vitreoretinopathy.

Purpose Proliferative vitreoretinopathy (PVR) is one of the most severe ocular diseases. Fibrotic changes in retinal cells are considered to be involved in the pathogenesis of PVR. Epithelial-mesenchymal transition (EMT) of RPE cells is one of the main concepts in the pathogenesis of fibrovascular membranes (FVMs) in PVR. In this study, we examined the expression of Caveolin-1 in human FVMs from patients with PVR. We also examined the role of Caveolin-1 in the pathogenesis of PVR. Methods Western blotting, real-time PCR, and immunohistochemistry were performed with human FVMs and mouse eyes with PVR. Cell migration assays were performed to evaluate the involvement of Caveolin-1 in EMT using primary human and mouse RPE cells. Results Caveolin-1 was expressed in human FVMs and upregulated in the mouse eyes with PVR. The alpha-smooth muscle actin (αSMA) expression and migration ability were increased in RPE cells with knockout or knockdown of Caveolin-1, whereas zonula occludens-1 (ZO-1) immunohistochemistry showed reduced morphology and expression of ZO-1. In addition, migration assays showed that Caveolin-1 reduction increased RPE cell migration abilities. Conclusions These results indicated that Caveolin-1 in RPE cells prevents PVR by blocking EMT.

Increased Ocular Levels of MicroRNA-148a in Cases of Retinal Detachment Promote Epithelial–Mesenchymal Transition

PURPOSE The purpose of this study was to determine microRNA expression in vitreous and subretinal fluid (SRF) samples from patients with retinal detachment (RD). The pathological importance of the identified microRNA transcript levels was analyzed in vitro. METHODS Vitreous fluid was collected from 10 patients with macular hole (MH), vitreomacular traction syndrome (VMTS), or foveoschisis and from 11 patients with RD. Subretinal fluid was collected from 7 patients with RD. Of these, blood serum was collected in 4 patients. MicroRNA microarray profiling was performed to identify microRNA transcripts that were present in vitreous fluid, and more redundantly detected in SRF, of patients with RD, but not detected in control eyes. Western blotting and scratch assays were performed in ARPE-19 cells and primary human RPE cell lines transfected with microRNA to elucidate the effect of identified microRNA transcripts on epithelial-mesenchymal transition (EMT). RESULTS MicroRNA microarray profiling revealed that hsa-miR-148a-3p was the most redundantly detected transcript in SRF and vitreous fluid from patients with RD, but not those with the other diseases. Expression levels of hsa-miR-148a-3p were higher in SRF samples than in blood serum samples in 3 out of 4 patients. Following hsa-miR-148a-3p mimic transfection, ARPE-19 and human RPE cells demonstrated increased expression of α-smooth muscle actin by Western blotting and increased migration ability during scratch assays. CONCLUSIONS The results of the present study indicate that hsa-miR-148a-3p was specifically detected in RD and promotes EMT in RPE.

Multicenter observational study comparing sedation/analgesia protocols for laser photocoagulation treatment of retinopathy of prematurity.

Objective:The aim of this study was to identify the best sedation/analgesia protocol for laser photocoagulation (PC) of retinopathy of prematurity (ROP).Study Design:This multicenter observational study included five hospitals, each using a specific sedation/analgesia protocol: local anesthesia with oxybuprocaine hydrochloride (Group L); intravenous pentazocine (Group P); intravenous fentanyl (Group F); air, oxygen and sevoflurane (AOS) inhalation (Group I). The groups were compared for pain responses, vital signs and adverse events.Results:Heart rates and systemic blood pressures were elevated by PC in Groups L and P and Groups L, P and F, respectively. Moreover, poor analgesic efficacy was recognized in Groups L, P and F. In contrast, Group I experienced hypothermia, enteral feeding intolerance and apnea more frequently.Conclusion:From the viewpoint of sedation/pain relief, AOS anesthesia should be the best protocol. However, considering all the various factors together, the most reasonable one can be varied based on the patient’s condition and hospital.

An Endovascular Cannulation Needle with an Internal Wire for the Fragmentation of Thrombi in Retinal Vein Occlusion.

Purpose We report a newly developed device to fragment thrombi in retinal vein occlusion. Methods The new instrument consists of a 23-gauge (G) pipe and a 37-G needle with an internal wire. A total of 40 porcine eyes were used; 20 eyes for experiments in the branch retinal vein (BRV group) and 20 eyes for experiments in the central retinal vein (CRV group). We placed 25-G 3-port trocars, and core vitrectomy was performed. Another 23-G scleral incision was performed for insertion of the needle. The needle pierced the retinal vein at a distance of three- to four- or one-disc diameters from the optic disc (BRV or CRV group, respectively), and the internal wire was advanced toward the disc. The success rates of needle piercing and cannulation of the internal wire were recorded in each group. In the CRV group, the cannulation was deemed successful when the tip reached inside the optic disc. Real-time optical coherence tomography imaging also was performed using the Zeiss Rescan 700 device in porcine eyes. Histologic examination of the retinal vessel inserted with the internal wire was performed. Results The success rates of needle piercing into the BRV and CRV were 85% and 95%, respectively. The success rates of cannulation of the internal wire into the BRV and CRV were 85% and 0%, respectively. The process of cannulation was recorded successfully with the Rescan 700. Histologic examination showed no damages to the endothelial cell layer. Conclusions The needle and internal wire intended to be used for recanalization of BRV occlusion were successfully pierced and cannulated into the BRV. Translational Relevance This newly developed device could become a treatment modality for retinal vein occlusion to fragment thrombi that present treatment methods cannot reach and remove directly.