Shigeki Machida

Changes of Oscillatory Potentials and Photopic Negative Response in Patients with Early Diabetic Retinopathy

PurposeTo investigate the clinical significance of the oscillatory potentials (OPs) and photopic negative response (PhNR) of the electroretinogram (ERG) in patients with early diabetic retinopathy.MethodsOne hundred two diabetic patients with diabetic retinopathy at different stages were examined. Thirty-two age-matched normal controls were also studied. Full-field maximal and photopic cone ERGs were recorded. The amplitudes and implicit times of the OPs, cone b wave, and PhNR were compared at the different stages of diabetic retinopathy.ResultsThe a and b wave amplitudes of the maximal scotopic ERGs remained unchanged despite advancing stages of retinopathy, but the OP amplitudes were significantly attenuated even at an early stage of diabetic retinopathy. The amplitudes of both the PhNR and cone b wave were reduced at an early stage of diabetic retinopathy. Analysis of the receiver operating characteristic curves demonstrated that the amplitudes and implicit times of the OPs were more sensitive and specific than those of the PhNR in detecting changes of retinal function in the early stages of diabetic retinopathy.ConclusionsThe amplitudes of the OPs and PhNR progressively decrease with the progression of diabetic retinopathy. The PhNR amplitudes were reduced along with the cone b wave, indicating that earlier change of the PhNR in diabetic patients reflects reduced input to the retinal ganglion cell from the distal retina. The amplitudes and implicit times of the OPs are better indicators than those of the PhNR in detecting functional decreases in patients with early diabetic retinopathy. Jpn J Ophthalmol 2006;50:367–373

Identification of Autoantibodies against TRPM1 in Patients with Paraneoplastic Retinopathy Associated with ON Bipolar Cell Dysfunction

Background Paraneoplastic retinopathy (PR), including cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), is a progressive retinal disease caused by antibodies generated against neoplasms not associated with the eye. While several autoantibodies against retinal antigens have been identified, there has been no known autoantibody reacting specifically against bipolar cell antigens in the sera of patients with PR. We previously reported that the transient receptor potential cation channel, subfamily M, member 1 (TRPM1) is specifically expressed in retinal ON bipolar cells and functions as a component of ON bipolar cell transduction channels. In addition, this and other groups have reported that human TRPM1 mutations are associated with the complete form of congenital stationary night blindness. The purpose of the current study is to investigate whether there are autoantibodies against TRPM1 in the sera of PR patients exhibiting ON bipolar cell dysfunction. Methodology/Principal Findings We performed Western blot analysis to identify an autoantibody against TRPM1 in the serum of a patient with lung CAR. The electroretinograms of this patient showed a severely reduced ON response with normal OFF response, indicating that the defect is in the signal transmission between photoreceptors and ON bipolar cells. We also investigated the sera of 26 patients with MAR for autoantibodies against TRPM1 because MAR patients are known to exhibit retinal ON bipolar cell dysfunction. Two of the patients were found to have autoantibodies against TRPM1 in their sera. Conclusion/Significance Our study reveals TRPM1 to be one of the autoantigens targeted by autoantibodies in at least some patients with CAR or MAR associated with retinal ON bipolar cell dysfunction.

Photopic Negative Response of Focal Electoretinograms in Glaucomatous Eyes

PURPOSE To determine the clinical importance of the photopic negative response (PhNR) of the focal electoretinogram (fERG) for diagnosing glaucoma. METHODS Fifty-nine eyes of 38 patients with open-angle glaucoma (OAG), 12 glaucoma suspects, and 32 eyes of 32 normal controls were studied. The fERGs were elicited by a 15 degrees stimulus spot on the macula region, the supero-temporal, and infero-temporal regions of the macula. The mean of the visual sensitivity was measured by standard automated perimetry (SAP). The optimal cutoff amplitudes of the focal PhNR and ratios of the focal PhNR/b-wave amplitudes that discriminated glaucomatous eyes from normal eyes were obtained from the receiver operating characteristic curves. RESULTS The amplitudes of the PhNR were significantly smaller in patients with OAG than in normal controls (P < 0.00001). A curvilinear relationship was found between the mean sensitivity (dB, on log scale) and the PhNR amplitude, and between the mean sensitivity and the PhNR/b-wave amplitude ratio. After converting the mean sensitivity from a logarithmic to a linear scale, the amplitude of the PhNR and PhNR/b-wave ratio were linearly correlated with the SAP-determined visual sensitivity in all retinal areas (r = .428-0.544, P < 0.0001). When the optimal cutoff values were used, the sensitivity and specificity of the PhNR/b-wave amplitude ratio were 98.3% and 90.1%, respectively. CONCLUSIONS The reduction of the focal PhNR amplitude was associated with a local decrease in the retinal sensitivity in OAG. The high sensitivity and specificity suggest that the focal PhNR can be used to detect functional loss in OAG.

Idiopathic choroidal neovascularization as an early manifestation of inflammatory chorioretinal diseases.

Purpose: We describe four patients with idiopathic choroidal neovascularization (ICNV) who developed inflammatory chorioretinal diseases in the ipsilateral or contralateral eye. Methods: The medical records of 58 eyes of 58 patients with an initial diagnosis of ICNV (age range, 19–49 years; mean, 34.9 years) were reviewed. Results: Of the 58 patients, 4 women (7.0%) with moderate to high myopia (age range, 17–39 years) developed inflammatory chorioretinal diseases. In Cases 1 and 2, white dots were transiently seen in the deep retina of the contralateral eye, consistent with the clinical features of multiple evanescent white dot syndrome (MEWDS). In Case 3, vitritis and multifocal white spots emerged in the ipsilateral eye. These white spots spread throughout the ocular fundus and progressed to punched-out chorioretinal scars, which led to a diagnosis of multifocal choroiditis (MFC). In Case 4, an enlarged blind spot and a few chorioretinal scars around the optic nerve head developed without vitritis in the ipsilateral eye, suggesting a diagnosis of punctate inner choroidopathy (PIC). Conclusions: These findings suggest that ICNV can be an early manifestation of inflammatory chorioretinal diseases, including MEWDS, MFC, and PIC.

Correlation of retinal function with retinal histopathology following ischemia-reperfusion in rat eyes

Purpose. To investigate the relationship between retinal function and histopathology following retinal ischemia-reperfusion in rats. Methods. Retinal ischemia was induced in 27 Sprague-Dawley rats by raising the intraocular pressure for 60- or 90-minutes. Two weeks after the retinal ischemia-reperfusion, ganzfeld stimuli of different luminances (maximum 0.51 log cd-s/m2) were used to elicit full-field ERGs from the right (experimental) and left (control) eyes. The amplitudes of the scotopic b-waves were measured, and intensity-response curves were plotted. The b-wave amplitudes at the initial peak (VbIP), the dip (Vbdip), and the maximum stimulus intensity (Vbmax) were measured. The animals were sacrificed after the ERG recordings to determine the surviving retinal cells in the inner nuclear layer (INL). Results. The log values of the VbIP, Vbdip and Vbmax were linearly correlated with the number of surviving cells in the INL (r = 0.928, 0.905, and 0.913 for VbIP, Vbdip and Vbmax, respectively; p < 0.0001 for each). The slope of the regression line for the Vbdip was significantly steeper than that for the VbIP and Vbmax (p < 0.005). The regression line for the Vbdip reached undetectable level of the b-wave (<1 µV) even though approximately 25% of the cells still remained in the INL. Conclusions. The amplitude of the scotopic b-wave is a sensitive index of the surviving INL cells. However, if one selects the stimulus intensity at the dip, the functional loss would be exaggerated in spite of the presence of cells in the INL.

Observation of the ocular fundus by an infrared-sensitive video camera after vitreoretinal surgery assisted by indocyanine green.

Purpose To investigate how long indocyanine green (ICG) dye remains in the ocular fundus and how the remaining dye interferes with ICG angiographic findings after vitreoretinal surgery assisted by ICG. Methods Eight eyes with macular hole, three with epiretinal membrane, and one with an intraocular foreign body were included. Those patients underwent vitrectomy facilitated by an intraocular administration of ICG. An infrared sensitive video camera was used to take fundus pictures pre- and postoperatively. In 2 of 12 cases, the authors performed ICG angiography at 2 weeks and at 3 months after the surgery. Results At 1 month after surgery, diffuse hyperfluorescence was observed throughout the posterior pole of the ocular fundus in all cases. The area where macular hole existed before the surgeries revealed hyperfluorescence in 6 of 8 eyes with macular hole (75%). These hyperfluorescent findings became less prominent with time postoperatively, while optic disk hyperfluorescence persisted for 12 months in all cases. In the early phase of ICG angiography at 2 weeks postoperatively, the retinal and choroidal circulation could be depicted. However, in the middle phase the choroidal veins were hardly visible. The angiographic pictures of the late phase mimicked those seen without intravascular administration of ICG. Even at 3 months after surgery, the optic nerve head revealed hyperfluorescence in the middle and late phases. Conclusions The residual ICG in the ocular fundus produced prolonged hyperfluorescence after surgery. This abnormal condition affected ICG angiographic findings in the middle and late phases.

Choroidal findings in idiopathic uveal effusion syndrome

Purpose We report choroidal findings by means of enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT) in a patient with idiopathic uveal effusion syndrome (IUES). Case report A 41-year-old man was referred to us with ciliochoroidal and non-rhegmatogenous retinal detachments. Sclerectomies and sclerostomies were performed at the equator in the lower quadrants, resulting in resolution of the ciliochoroidal and retinal detachments. EDI-OCT demonstrated low-reflective areas in the outer choroid. The subfoveal choroidal thickness measured vertically from the outer border of the RPE to the inner border of the sclera was 787 μm which was significantly thicker than the normal value (272 ± 90 μm, n = 131) obtained from age-matched normal controls. Conclusions The findings made by EDI-OCT have provided additional evidence that choroidal alterations play a role in the pathological process in IUES.

Protective effect of hepatocyte growth factor against degeneration of the retinal pigment epithelium and photoreceptor in sodium iodate-injected rats.

Purpose: To investigate the possible protective effect of hepatocyte growth factor (HGF) against degeneration of photoreceptors and retinal pigment epithelium (RPE) in vivo. Methods: Sprague-Dawley (SD) rats received an intravitreal injection of HGF in the right eye. The left eye was injected with vehicle as a control. Two days after the intravitreal injections, rats were administered 40 mg/kg of sodium iodate (NaIO3) intravenously. Scotopic ERGs were elicited by different stimulus intensities with a maximum luminance of 0.84 log cds/m2. To evaluate RPE function, the azide response was evoked by intravenous injection of 0.1 mg sodium azide. These electrophysiological measurements were conducted on days 4, 7, 14, and 28 after the NaIO3 injections. After recording ERGs or azide response, animals were sacrificed for quantification of the histological change and immunohistochemical analysis using antibodies against RPE 65. Results: The threshold for the scotopic b-wave was significantly lower in HGF-treated eyes than in untreated control eyes (p < 0.005), and maximum b-wave amplitudes (Vbmax) were significantly larger in HGF-treated eyes (p < 0.05) across all experimental time points after NaIO3 injection. Azide response amplitudes were significantly larger in the HGF-treated eyes than in the untreated eyes (p < 0.05). The structure of the outer retina was preserved to a greater degree in the HGF-treated eyes than in the untreated eyes (p < 0.05). Immunohistochemical analysis demonstrated that irregular alignment of the outer nuclear layer was confined to the retinal area that was not stained with RPE 65. Conclusions: Our results indicated that an intravitreal injection of HGF provided significant protection against degeneration of the photoreceptor and RPE induced by systemic administration of NaIO3. This suggests that HGF could be used as a therapeutic agent for degeneration of photoreceptors as well as RPE.

Sensitivity and Specificity of Photopic Negative Response of Focal Electoretinogram to Detect Glaucomatous Eyes

Aims To determine the sensitivity and specificity of the photopic negative response (PhNR) of the focal electroretinograms (ERG; focal PhNR) to detect glaucomatous eyes with different degrees of visual field defects. Methods One-hundred and fourteen eyes of 114 patients with open angle glaucoma and 42 eyes of 42 normal controls were studied. The focal ERGs were elicited by a 15° stimulus spot centred on the macula, and on the supero-temporal and on the infero-temporal areas of the macula. The receiver operating characteristic curves were determined to obtain optimal cut-off values. Eyes were classified as being glaucomatous when their focal PhNRs were less than the cut-off values in either retinal area (combined criterion). Results The focal PhNR amplitudes were significantly reduced with an advance in the stage of glaucoma. In early glaucoma, the sensitivities of the PhNR measured for each retinal area ranged from 58.1% to 80.7%. The sensitivities were significantly increased to 90.6% and 96.9% for the focal PhNR amplitude and the focal PhNR/b-wave amplitude ratio, respectively, when the combined criterion was employed. The specificity was >90%. Conclusions Focal PhNRs have diagnostic ability in detecting early glaucoma with high sensitivity and specificity, especially when the combined criterion is used.

Comparison of Photopic Negative Response of Full-Field and Focal Electroretinograms in Detecting Glaucomatous Eyes

Purpose. To compare the photopic negative response (PhNR) of the full-field electroretinogram (ERG) to the PhNR of the focal ERGs in detecting glaucoma. Methods. One hundred and three eyes with glaucoma and 42 normal eyes were studied. Full-field ERGs were elicited by red stimuli on a blue background. The focal ERGs were elicited by a 15° white stimulus spot centered on the macula, the superotemporal or the inferotemporal areas of the macula. Results. In early glaucoma, the areas under the receiver operating characteristic curves (AUCs) were significantly larger for the focal PhNR (0.863–0.924) than those for the full-field PhNR (0.666–0.748) (P < .05). The sensitivity was significantly higher for the focal PhNR than for the full-field PhNR in early (P < .01) and intermediate glaucoma (P < .05). In advanced glaucoma, there was no difference in the AUCs and sensitivities between the focal and full-field PhNRs. Conclusions. The focal ERG has the diagnostic ability with higher sensitivity in detecting early and intermediate glaucoma than the full-field ERG.