Hisashi Matsubara

Time-Dependent Course of Electroretinograms in the Spontaneous Diabetic Goto-Kakizaki Rat

PurposeThis study evaluates the relevance to human retinopathy of electroretinograms (ERGs) from the spontaneously diabetic Goto-Kakizaki (GK) rat.MethodsStarting from 4 weeks of age, we obtained ERGs every 4 weeks from six GK rats and seven Wistar (control) rats, and from two GK and two Wistar rats at 14 days of age. The a-wave, b-wave, and oscillatory potentials (OPs) were recorded after stimulation with a single bright flash. We compared the amplitudes and implicit times and measured a-wave latencies to evaluate photoreceptor function.ResultsThe amplitudes of the a-wave, b-wave, and OPs (O1 and O2) of the GK rats were reduced between 4 and 48 weeks of age. The time-dependent courses of change in a-wave, b-wave, and O2 amplitude did not differ between the two groups. The a-wave latencies in GK rats were significantly prolonged, but not the implicit times of OPs. At 14 days of age, the a-wave amplitudes were significantly smaller in GK than in Wistar rats.ConclusionFunctional abnormalities of photoreceptors might be induced by inheritable degeneration at an early age in the GK rat. Although hyperglycemia would cause retinal hypoxia, it would not be severe enough to disturb the generation of OPs. Jpn J Ophthalmol 2006;50:211–216

10-year follow-up of visual functions in patients who underwent scleral buckling.

Purpose: To study long-term visual functions in eyes that underwent scleral buckling for treatment of rhegmatogenous retinal detachment. Methods: We retrospectively studied a nonconsecutive case series of 205 eyes with retinal detachment that underwent scleral buckling and were followed up for 10 years after surgery. Preoperatively, postoperatively, and 10 years after surgery, best-corrected visual acuities and visual fields were recorded. Results: During the first postoperative year and during the next 9 years, there were significant increases in visual acuity (P < 0.0001 and P < 0.0001, respectively). Between the operation and 1 month postoperatively, there was a significant increase in the area size of visual field measured by Goldmann perimetry (V-4 isopter, P = 0.0001; I-4 isopter, P = 0.0001). Between 1 month and 10 years after surgery, there was no significant change of the area size of each isopter (V-4, P = 0.786; I-4, P = 0.211). Conclusion: Improvement in visual acuity after scleral buckling is possible over a long period. There may be a limit to long-term improvement of visual field after scleral buckling.

Extraction Method of Retinal Border Lines in Optical Coherence Tomography Image by Using Dynamic Contour Model

In the field of ophthalmology, the needs of retina diagnosis using optical coherence tomography (OCT) images have been growing, and the automatic measurement of a retina thickness and its quantitative evaluation are desired for the diagnosis of retinal diseases. Previously, the automatic measurement methods of the retinal thickness have been reported for retinal OCT images. These previous methods can extract the retinal border lines (ILM and RPE) appropriately in most cases of normal OCT image. However these methods caused the tracking error to some OCT images with large noises. In this paper, we propose a new automatic measurement method of a retinal thickness in OCT image. The method employs ODAN (One Directional Active Net) to extract ILM and RPE. ODAN employs a new energy function to extract the retinal border lines exactly and all nodes of ODAN moves only to one direction to minimize the total energy repeatedly. The energy function consists of (1) the conformity characteristics energy of image and (2) the internal strain energy. We confirmed the usefulness of the ODAN by the experimental results for ten OCT images with large noises. We compared the positions of retinal border lines by the proposed method with the positions in a manual trace by ophthalmology specialist. In the comparative result, the proposed method is useful as the basic method for the detection of retinal diseases.

Effect of topical rebamipide on conjunctival goblet cell recovery after vitrectomy.

In vitro and in vivo experiments have shown that topical rebamipide will increase the number of goblet cells in the bulbar conjunctiva. The purpose of this study was to determine whether topical rebamipide will enhance the recovery of conjunctival goblet cells that were damaged during vitrectomy. Forty patients who underwent vitrectomy surgery were studied. The 40 patients consisted of 20 with diabetes mellitus (DM) and 20 patients without DM. They were randomized in a 1:1 ratio into groups that were treated or not treated with topical 2% rebamipide after the surgery. Impression cytology was performed at the end of surgery and at 14 days after the surgery. The mean goblet cell density of each specimen was determined by averaging the total number of goblet cells obtained from three consecutive high magnification microscopic images. In patients without DM, the mean goblet cell density at 14 days after the vitrectomy was significantly higher in eyes with topical rebemipide than in eyes without rebemipide (P < 0.01). In patients with DM, a similar tendency was observed but the difference was not significant (P = 0.09). These results suggest that topical rebamipide can be helpful in patients with globlet cell damage that occur during and after vitrectomy.

Changes in Outer Retinal Microstructures during Six Month Period in Eyes with Acute Zonal Occult Outer Retinopathy-Complex

Purpose To study the changes in the outer retinal microstructures during a six month period after the onset of acute zonal occult outer retinopathy (AZOOR)-complex by spectral-domain optical coherence tomography (SD-OCT). Methods Seventeen eyes of 17 patients with the AZOOR-complex were studied. The integrity of the external limiting membrane (ELM), ellipsoid zone (EZ; also called the inner/outer segment junction), and interdigitation zone (IDZ; also called the cone outer segment tips) were evaluated in the SD-OCT images obtained at the initial visit and at six months. The three highly reflective bands were divided into three types; continuous, discontinuous, and absent. The integrity of the outer nuclear layer (ONL) was also assessed. Results Among the three highly reflective bands, the IDZ was most altered at the initial visit and least recovered at six months. Fifteen of 17 eyes (88%) had a recovery of at least one of the three bands at six months in the retinal area where the ONL was intact, and these areas showed an improvement of visual field. Three eyes (18%) had retinal areas where the ONL was absent at the initial visit, and there was no recovery in both the retinal structures and visual fields in these areas. Conclusions Our results indicate that more than 85% eyes with AZOOR-complex show some recovery in the microstructures of the outer retina during a six month period if the ONL is intact. We conclude that SD-OCT is a useful method to monitor the changes of the outer retinal microstructure in eyes with the AZOOR-complex.

A Retinal Layer Structure Analysis to Measure the Size of Disease Using Layer Boundaries Detection for Optical Coherence Tomography Images

In the field of ophthalmology, optical coherence tomography (OCT) is rapidly becoming popular in clinical applications to diagnose retinal disease. In this paper, we proposed a new profile analysis to evaluate the size of the retinal disease using the number of layer boundaries. The number is established by a new analysis method of a gray level profile scanned in longitudinal direction for an OCT image. We employed the proposed method for 50 OCT images of normal retina and 50 OCT images of abnormal retina. The experiment result showed that a significant difference was obtained in the significance level at 1%, when we employed Mann-Whitney U method on the standard deviation of the number of layer boundaries for normal and abnormal retinal images group. Therefore, we confirmed that the proposed method becomes one of the indexes to evaluate the size of the retinal disease. In addition, we confirmed that our system can measure the size of abnormal part in horizontal direction using the number of layer boundaries.

Inducible nitric oxide synthase mediates retinal DNA damage in Goto-Kakizaki rat retina

PurposeTo examine the nitrosative and oxidative DNA damage induced by 8-nitroguanine and 8-hydroxy-2-deoxy guanosine (8-OHdG), and to determine the role played by inducible nitric oxide synthase (iNOS) in damage to DNA in the retina of the Goto-Kakizaki (GK) rat.MethodsExperiments were performed on GK rats, an animal model of spontaneous type 2 diabetes without obesity or visible diabetic vascular lesions. Immunohistochemistry was used to determine the retinal distribution of 8-nitroguanine, 8-OHdG, and iNOS in GK rats and control rats. The change in the expression of 8-nitroguanine and 8-OHdG in GK rats was also determined following an intravitreal injection of 1400W, an inhibitor of iNOS activity.ResultsImmunohistochemical analysis showed that 8-nitroguanine and 8-OHdG were expressed strongly in the inner nuclear layer of GK retinas but only weakly in control retinas. This expression was correlated with an increase in the expression of iNOS in GK retinas, which was confirmed by the inhibition of iNOS activity by 1400W.ConclusionThese findings demonstrate that iNOS plays a crucial role in nitrosative and oxidative DNA damage in GK rats, suggesting a retinal neurotoxic role of nitric oxide and superoxide in diabetic retinas.

Incidence of retinal detachment associated with atopic dermatitis in Japan: review of cases from 1992 to 2011

Purpose The present study aims to investigate the number and characteristics of retinal detachment with atopic dermatitis (AD) in these 20 years, and the number of the first visit AD outpatients in almost the same period. Methods A retrospective review of 101 consecutive surgically treated retinal detachments with AD patients from 1992 to 2011 was conducted. Retinal detachments were divided into two groups: eyes operated on from 1992 to 2001 (former AD group, n=63) and eyes operated on from 2002 to 2011 (recent AD group, n=38). We also reviewed the records of the first visit AD outpatients from 1993 to 2011 except 1998. Results The percentage of bilateral detachment was significantly higher in the former AD group (14/63) than that in the recent AD group (0/38) (P=0.0002). In addition, patients in the recent AD group were significantly older than those in the former AD group (P=0.0084). The annual cases with non-AD retinal detachment remained invariant for 20 years. The ratio of the retinal detachment with AD for the total retinal detachment was significantly lower in the recent (38/847) AD group than that in the former (63/796) AD group (P=0.0038). The number of the first visit AD outpatients linearly decreased in these 19 years (153 cases in 1993 and 65 cases in 2011). Conclusion Our study indicates an apparent decrease in retinal detachment with AD in the recent 10 years, and might suggest the importance of dermatitis control for prevention of retinal detachment with AD.

A Case of Sustained Intraocular Pressure Elevation after Multiple Intravitreal Injection of Ranibizumab and Aflibercept for Neovascular Age-Related Macular Degeneration.

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are widely used to treat neovascular age-related macular degeneration (nAMD). Although these treatments are effective, multiple injections have recently been recommended to ensure that there is a good long-term prognosis. However, sustained intraocular pressure (IOP) elevations have been reported to develop after multiple injections of anti-VEGF agents. We present our findings of a case of uncontrolled and persistent IOP elevation after switching from intravitreal ranibizumab injections to intravitreal aflibercept injections. A 74-year-old Japanese man without a history of glaucoma underwent 22 ranibizumab injections for nAMD and suddenly developed an elevated IOP after the 22nd injection. Although the subsequent medical treatment led to normalization of his IOP, the subretinal fluid under the central fovea remained even after the 25th injection of ranibizumab. Thus, ranibizumab treatment was switched to bimonthly intravitreal aflibercept injections in conjunction with glaucoma medications. His IOP recovered to within the normal range; however, after the 11th aflibercept injection, there was a sudden elevation of his IOP in spite of the continued glaucoma medications. Due to this sustained IOP elevation, his aflibercept injections were suspended for 16 weeks. Because his IOP could not be normalized by a full glaucoma medication regimen, the patient underwent trabeculotomy, which resulted in a lowering of the IOP to normal levels. We conclude that patients who receive serial intravitreal injections of anti-VEGF agents need to be closely monitored because severe and sustained ocular hypertension can develop.

Ultra-WideField fluorescein angiography by oral administration of fluorescein.

Dear Editor, U tilization of pars plana vitrectomy (PPV) for rhegmatogenous retinaldetachment (RRD)hasexpanded in the past decade mostly due to refinements in surgical techniquesandmodern equipment. Several reports have highlighted the benefits of smaller gauge intraocular instruments and higher cutting speeds. Surgeons can choose machine variables and generally seem to use their preferred system for PPV, relying on a vitrector equipped with either Venturi or peristaltic pumps. There is no detailed evidence comparing peristaltic and Venturi pump systems concerning anatomic success rates. To compare the anatomic results when different vitrectomy machine parameters (gauge, pump and cutting speed) are applied in RRD repair, the European VitreoRetinal Society (EVRS) analysed the data gathered during the EVRS RD Study. The Study includes outcome of 7678 cases of RRD operated on by 176 surgeons from 48 countries with at least 3-month follow-up. In this manuscript, we included cases that RD was treated by primary PPV and excluded cases that previous investigation had shown other independent factors influencing outcome (such as hypotony and choroidal detachment). From the collected data on 4976 cases of PPV, we evaluated preoperative clinical findings, vitrector gauge, aspiration pump type and cutting rate. Detailed methodology is available in the EVRS RD Study Reports Numbers 1 and 2 (Adelman et al. 2013a,b). Twenty-four per cent of vitrectomies were performed using a flow control machine and 76% using a vacuum control machine. The initial distribution of PVR grades between groups was similar. The primary outcome measure was the final anatomical failure rate. Operations were considered successful when the retina remained attached throughout the study period. ‘Level 1’ failure was determined as cases where the retina remained detached by the conclusion of the study. ‘Level 2’ failure was the percentage of eyes with remaining silicone oil. ‘Level 3’ failure was the percentage of cases with recurrence of retinal detachment. Three vitrectomymachine parameters were associated with higher failure rate: First, in univariate analysis, the ‘Level 1’ failure rate of procedures carried out with 20 Gauge instrumentation was higher than that of 23 Gauge (p = 0.009). After adjusting for the level of PVR, there was no statistically significant difference in the failure rates between 20G or 23G vitrectomy. This may be because surgeons performed 20 Gauge PPV in more complex cases where advanced PVR was present. Thus 20 Gauge was not an independent risk factor for failure. Second, Venturi pump vitrectomy equipment was associated with a significantly (odds ratio = 2.9) higher Level 1 failure rate compared with peristaltic pump vitrectomy (p = 0.006) Third, when used with Venturi pump systems, high-speed vitrectomy cutters resulted in a lower failure rate than low-speed cutters (p = 0.014; OR = 0.5). High-speed cutting is employed to decrease the risk of cutting the retina, but complete removal of adherent vitreous may be difficult. These are statistical correlations and we would like to point out that overall, anatomical results with both systems are very satisfactory and the attachment rate is high.