Tomoharu Nishimura

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.

Correlation between photopic negative response of focal electroretinograms and local loss of retinal neurons in glaucoma.

Purpose: To determine the relationship between the photopic negative response of the focal electroretinogram and the structural parameters of the inner retina and optic nerve head in glaucoma. Methods: Sixty-one eyes of 61 patients with open angle glaucoma, 13 eyes of 13 patients who were classified as glaucoma suspects, and 30 eyes of 30 normal subjects were studied. The focal electroretinograms were elicited by a 15° circular white stimulus on a white background centered on the fovea. The focal electroretinograms were also elicited by half of an annulus placed above or below the macula. The diameter of the inner border of the annulus was 15° and that of the outer border was 30°. The structure of the optic nerve head and retinal nerve fiber layer thickness were evaluated by scanning laser ophthalmoscopy and laser scanning polarimetry, respectively. Results: The amplitudes of the focal photopic negative responses and the ratio of the focal photopic negative response/b-wave amplitude were linearly correlated with the corresponding retinal nerve fiber layer thickness in the superior/temporal and inferior/temporal regions (r = 0.43 to 0.47; P < 0.0001) but not in the temporal region. The focal photopic negative response amplitude and focal photopic negative response/b-wave amplitude ratio were also linearly and significantly correlated with the corresponding rim areas and cup/disc area ratio (r = 0.38 to 0.50, P < 0.0001). Conclusions: These results strongly suggest that the anatomical losses of retinal neurons in local areas of the retina or optic nerve head are a cause of the reduction in the amplitude of the focal photopic negative response in open angle glaucoma.

Retinal ganglion cell function after repeated intravitreal injections of ranibizumab in patients with age-related macular degeneration.

Background The purpose of this study was to evaluate the safety of intravitreal ranibizumab injection in patients with age-related macular degeneration. Materials and methods We examined retinal ganglion cell function using the photopic negative response of the electroretinogram (ERG) in patients with age-related macular degeneration (AMD) treated with intravitreal injections of ranibizumab. We studied 32 eyes of 32 patients with AMD and aged 50–84 years with a mean of 71 years. An intravitreal ranibizumab injection was given three times at monthly intervals. Additional injections were given according to an optical coherence tomography-guided variable dosing regimen. ERG recordings were made before treatment (baseline) and at 3, 6, 9, and 12 months postoperatively. Full-field cone ERGs were elicited by red stimuli on a blue background. The focal macular ERGs were elicited by a 15 degree white stimulus spot centered on the macular region. We measured the amplitudes of the a and b waves, oscillatory potentials, and the photopic negative response of the full-field cone and focal macular ERGs. Results Visual acuity was significantly better than the baseline acuity, and macular thickness was significantly reduced after the intravitreal injections of ranibizumab. The amplitudes and implicit times of each wave of the full-field cone ERGs were not significantly changed after intravitreal ranibizumab injections. However, the amplitudes of each wave of the focal macular ERGs were increased after the injections. The implicit times of the a and b waves of the focal macular ERGs were significantly shortened after intravitreal injections of ranibizumab. The ratio of the full-field and focal photopic negative response/b-wave amplitude was not significantly changed after the injections. Conclusion The amplitudes of the focal macular ERGs, including the photopic negative response improved after repeated intravitreal ranibizumab injections, accompanied by a recovery of visual acuity and macular structure. The results of the full-field cone ERGs indicate that retinal ganglion cell function was not altered by repeated intravitreal ranibizumab injection.

Pharmacological dissection of multifocal electroretinograms of rabbits with Pro347Leu rhodopsin mutation

PurposeTo determine whether photoreceptor degeneration in transgenic (Tg) rabbits carrying the Pro347Leu rhodopsin mutation alters the neural activity of the middle and inner retinal neurons.MethodsMultifocal electroretinograms (mfERGs) were recorded from eight 12-week-old Tg rabbits both before and after intravitreal injection of the following: tetrodotoxin citrate (TTX), N-methyl-dl-aspartic acid (NMDA), 2-amino-4-phosphonobutyric acid (APB), and cis-2,3-piperidine-dicarboxylic acid (PDA). Digital subtraction of the mfERGs recorded after the drugs were administered from those recorded before was used to extract the components that were eliminated by these drugs. Eight agematched, wild-type (WT) rabbits were studied with the same protocol.ResultsThere was no reduction in the amplitude of the cone photoreceptor response of the mfERGs in Tg rabbits. Both the first positive and the first negative waves of the ON-bipolar cell responses were significantly larger in the Tg than in the WT rabbits. Late negative waves of the ON-bipolar cell response were recorded only in the WT rabbits. The first negative wave of the inner retinal responses was larger in the Tg than in the Wt rabbits. The late positive waves were seen mainly in the WT rabbits.ConclusionsThe ON-bipolar cell and inner retinal responses were altered at the early stage of photoreceptor degeneration in Tg rabbits despite the preservation of the cone photoreceptor responses.

Enhancement of ON-bipolar cell responses of cone electroretinograms in rabbits with the Pro347Leu rhodopsin mutation.

PURPOSE To determine how the different stages of retinal processing change after photoreceptor degeneration in rabbits carrying the Pro347Leu rhodopsin mutation (Tg rabbits). METHODS Cone electroretinograms (ERGs) were elicited by 150-ms duration stimuli from 13 Tg rabbits at 12 and 24 weeks of age. The ERG recordings were made before and after an intravitreal injection of tetrodotoxin citrate (TTX) plus N-methyl-dl-aspartic acid (NMDA), with the addition of 2-amino-4-phosphonobutyric acid (APB) and then cis-2,3-piperidine-dicarboxylic acid (PDA) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Digital subtraction of the ERG after the injection from the ERG before the injection was used to extract the components that were blocked by these drugs. Thirteen age-matched, wild-type (WT) rabbits were studied with the same protocol. RESULTS In Tg rabbits, the cone ERGs elicited by intermediate intensities had a depolarizing pattern. At 12 weeks of age, the photoreceptor and OFF-bipolar/horizontal cell responses reflected in the ERG in the Tg rabbits did not differ significantly from those in the WT rabbits. The ON-bipolar cells and the third-order neuronal responses recorded after pharmacologic blockade were significantly enhanced in the Tg rabbits compared with those recorded in the WT rabbits. At 24 weeks of age, the ERG waveforms representing the photoreceptors and OFF-bipolar/horizontal cell responses were significantly decreased, but those representing the ON-bipolar cell and third-order neuronal responses were still preserved in the Tg rabbits. CONCLUSIONS A depolarizing pattern of the cone ERG responses was seen in Pro347Leu Tg rabbits. The enhancement or preservation of the ON-bipolar cell response in the ERGs contributed to shaping the waveform in the Tg rabbits. In this model, the functional alterations in the ON-pathway took place before the deterioration of cone photoreceptor function.

Depolarizing focal macular electroretinogram pattern after photodynamic therapy in a patient with polypoidal choroidal vasculopathy

tissue with a shallow subretinal space (Fig. 1B). The vitrectomy was canceled, and his right BCVA improved to 0.6 after another month. Eighteen months after the initial visit, the patient noticed decreased vision in his left eye. BCVA was 0.7 OD and 0.4 OS. OCT in his left eye showed a full-thickness macular hole with perifoveal cysts and a separated posterior hyaloid membrane containing a pseudo-operculum (Fig. 2A). The right macula was normal. While waiting for vitrectomy, the patient returned for a two-month follow-up visit, during which we discovered the spontaneous closure of the macular hole in his left eye, with a similar OCT image as that observed in his right eye (Fig. 2B), although BCVA remained 0.4. Six months later, the left fovea recovered its normal confi guration, except for a split in the photoreceptor junction line between the inner and outer segments (IS/OS line) (Fig. 2C). At the follow-up 37 months after the initial visit, despite cataract formation OU, BCVA was 0.8 OD and 0.9 OS. Spectral-domain OCT (Cirrus OCT; Carl Zeiss Meditec) confi rmed the integrity of the IS/OS line OU (Figs. 1D and 2D).

Refractive changes after lens-sparing vitrectomy for macular hole and epiretinal membrane

Purpose Cataract progression after lens-sparing vitrectomy might differ according to original posterior segment diseases. Our objective was to analyze the refractive values after lens-sparing vitrectomy for macular hole (MH) and epiretinal membrane (ERM). Materials and methods We reviewed the medical records of 25 MH patients (25 eyes) and 23 ERM patients (23 eyes) who underwent lens-sparing vitrectomy. Refractive changes in both groups were compared. All patients underwent 20-gauge three-port pars plana vitrectomy. Fluid–air exchange was performed during vitrectomy only in the MH group. The results were analyzed using the unpaired t-test, chi-square test, or Fisher exact probability test, and multivariate analysis. Results There were no significant differences in the patient’s age (P=0.45). The myopia progression rate (D/month) was higher in the MH group after surgery than that in the ERM group (P=0.035). MH group had more females (P=0.043), longer surgical time (P<0.001), and higher frequencies of surgical adjuvants use (triamcinolone acetonide, P=0.019; brilliant blue G, P<0.001). The myopia progression rate in the MH group (R=0.568, P<0.001) correlated with female gender. However, no correlation was observed between longer surgical time and the use of surgical adjuvants. Conclusion The rate of myopia progression was higher in the MH group. Fluid–air exchange and gender may affect the rate of myopia progression.