Reduction of inner retinal thickness in patients with autosomal dominant optic atrophy associated with OPA1 mutations

PURPOSE: To determine the morphologic changes in the retina in the macula and around the optic disc in patients with autosomal dominant optic atrophy (ADOA) associated with a mutation in the OPA1 gene. METHODS: Cross-sectional images of the macular area of the retina were obtained by optical coherence tomography (OCT) in patients with ADOA who had a heterozygous mutation in the OPA1 gene. There were 15 eyes of eight patients from five families: four men and four women. The average age of the patients was 48.1 years. In the OCT images, the cross sections of the sensory retina were divided manually into four areas. The thickness of the overall sensory retina and the divided areas were measured at 1 and 2 mm on the temporal, nasal, superior, and inferior sides of the fovea as well as at the fovea. The thickness of the retinal nerve fiber layer (RNFL) around the optic discs was measured by taking circular scans (3.4 mm in diameter) centered on the optic disc. The results in the patients with ADOA were compared with those from 11 normal control subjects. RESULTS: The overall thickness of the sensory retina in the macular area was significantly thinner in the patients with ADOA than in the control subjects at all points except the fovea (P < 0.0001). The RNFL in the macular area in the patients with ADOA was significantly thinner than that in control subjects at all points (P < 0.0001), especially at 1 mm from the fovea. The circumpapillary RNFL was significantly thinner at the temporal, superior, and inferior areas in patients with ADOA but not in the nasal area. The total cross-sectional area of the circumpapillary RNFL was significantly correlated with visual acuity. The thickness of the combined ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer in the macular area was significantly thinner in the patients (P < 0.0056). The thickness of the outer nuclear layer and the photoreceptor inner segments and the thickness of the photoreceptor outer segments were not significantly different between the patients with ADOA and normal control subjects. CONCLUSIONS: The RNFL and the layer including the ganglion cell layer are significantly thinner in patients with ADOA associated with an OPA1 gene mutation, whereas the photoreceptor layers are not affected morphologically. The inner retina is the main area of the retina altered in ADOA.     

眼部缺血综合征患者视网膜电图明视负向反应和震荡电位的变化特点

目的观察眼部缺血综合征(ocular ischemic syndrome,OIS)患者视网膜电图(electroretinogram,ERG)明视负向反应(PhNR)和震荡电位(oscillatory potentials,OPs)的变化特点。方法选取2009年6月至2010年2月在我院就诊的OIS患者12例15眼行常规闪光ERG检查,同时选取正常对照眼15人15眼,视网膜中央静脉阻塞(central retinal vein occlusion,CRVO)患者15例15眼行闪光ERG检查。比较OIS患眼与正常对照眼、CRVO患眼的PhNR和OPs,及其余各项ERG指标的振幅变化差异。采用Stata11统计学软件分析受试者工作曲线下面积(AUC),并进行数据分析,比较OPs及PhNR区分正常眼及OIS眼的敏感度及特异性。结果 PhNR振幅在OIS组为(49.36±12.20)μV、CRVO组为(25.62±6.72)μV、正常组为(59.79±11.83)μV。三组之间两两比较,差异有显著统计学意义(F=41.287,P<0.01)。OPs振幅在OIS组为(128.44±23.86)μV、CRVO组为(102.69±10.55)μV、正常组为(154.01±15.08)μV。三组之间两两比较,差异也有显著统计学意义(F=78.098,P<0.01)。PhNR指标的AUC为0.7240±0.0945,95%的可信区间为(0.53871,0.90925),其敏感度为73.3%,特异性为86.7%。OPs指标的AUC为0.8170±0.0810,95%的可信区间为(0.65814,0.97579),其敏感度为86.7%,特异性为80.0%。结论 OIS患者PhNR、OPs振幅较正常对照组明显降低,但较CRVO患者降低程度轻,表明OIS患者视网膜组织存在缺血的现象,但其缺血程度较CRVO患者轻。OPs在评估OIS患者内层视网膜的血液循环功能方面比PhNR更好。     

非动脉炎性前部缺血性视神经病变患者的明适应负向波变化特点分析

目的　探讨非动脉炎性前部缺血性视神经病变（non-arterial anterior ischemic optic neuropathy,NAION）患者随病程变化的明适应负向波（photopic negative response,PhNR）变化特点。方法　选取2018年6月至12月就诊于我院的NAION患者18例作为NAION组,另选取正常16人作为正常对照组。根据NAION患者不同视盘水肿状态盘周视网膜神经纤维层（retinal nerve fiber layer,RNFL）厚度的差别,将NAION组进一步分为视盘水肿时的盘周RNFL厚度增加组（以下简称“增加组”）和视盘水肿消退后的盘周RNFL厚度正常及减少组（以下简称“正常及减少组”）。所有受检者均进行PhNR和光学相干断层扫描（optical coherence tomography,OCT）的盘周RNFL厚度检查。结果　NAION组与正常对照组相比,PhNR幅值［分别为（28.23±14.62）μV、（46.24±16.04）μV］显著降低,差异有统计学意义（P=0.00）。增加组、正常及减少组与正常对照组相比,PhNR幅值［（28.77±11.87）μV、（27.96±16.32）μV、（46.24±16.04）μV］均显著降低,差异均有统计学意义（P=0.03、0.00）,但增加组和正常及减少组相比,PhNR幅值差异无统计学意义（P=0.92）。增加组PhNR幅值与RNFL厚度呈负相关性（r=-0.86,P=0.03）,正常及减少组PhNR幅值与RNFL厚度呈正相关性（r=0.96,P=0.00）。结论　NAION患者发病初期PhNR幅值即显著降低,随着病程进展,PhNR幅值未发生显著变化。NAION视盘水肿时盘周RNFL厚度越大,PhNR幅值越低;视盘水肿消退后盘周RNFL厚度越小,PhNR幅值越低。     

Correlation between visual acuity and OCT-measured retinal nerve fiber layer thickness in a family with ADOA and an OPA1 mutation

Purpose: To assess the association between retinal nerve fiber layer (RNFL) thickness and visual acuity in a family from Siracusa (Sicily) with autosomal dominant optic atrophy (ADOA) due to a heterozygous c.869G>A OPA1 mutation.

Methods: Affected family members underwent complete neuro-ophthalmological evaluation, including visual acuity testing, colour vision testing, tonometry, visual field testing, colour fundus photography, pattern visual-evoked potential (PVEP) testing, and pattern electroretinography (PERG). Patients and age-matched control subjects were scanned by spectral-domain optical coherence tomography (SD-OCT) to assess circumpapillary RNFL thickness.

Results: All patients showed the characteristic optic disc pallor and central scotomas in the visual field. PVEP testing and PERG also showed alterations consistent with ADOA. The average circumpapillary RNFL thickness was thinner in ADOA patients than in control subjects (60.87?±?6.58µm and 108.13?±?6.53µm, respectively; p = 0.0001). The visual acuity in patients with ADOA correlated significantly with the circumpapillary average RNFL thickness (r = ?0.845, p = 0.008).

Conclusions: OCT-measured peripapillary RNFL thickness is reduced in ADOA patients compared with healthy subjects and correlates significantly with visual acuity in patients with ADOA. The photoreceptor layers are morphologically unaffected.     

Correlation between photopic negative response and retinal nerve fiber layer thickness and optic disc topography in glaucomatous eyes

PURPOSE: To investigate whether there is a significant correlation between the photopic negative response (PhNR) of the electroretinogram (ERG) and retinal nerve fiber layer thickness and optic disc topography in glaucomatous eyes. METHODS: Ninety-nine eyes of 53 patients with open-angle glaucoma (OAG) and 30 eyes of 28 normal volunteers were studied. Photopic ERGs were elicited by red stimuli (644 nm, 1600 cd/m(2)) on a blue background (470 nm, 40 cd/m(2)). The mean deviation (MD) of the visual field was obtained by static visual field analyses. The topography of the optic nerve head was determined by confocal scanning laser ophthalmoscopy. The retinal nerve fiber layer thickness (RNFLT) around the optic nerve head was measured with a scanning laser polarimeter. RESULTS: The amplitude of the PhNR and the PhNR/b-wave ratio decreased with an increase in visual field defects. The logarithmic values of the PhNR amplitude and PhNR/b-wave amplitude ratio were significantly correlated with the MD better than the linear values. The PhNR amplitude and PhNR/b-wave amplitude ratio were significantly correlated with the RNFLT and the rim area of the optic disc and with the cup/disc area ratio. These correlations were higher when expressed linearly than when stated logarithmically. The sensitivity and specificity were 77% and 90% for the PhNR amplitude and 70% and 87% for the PhNR/b-wave amplitude ratio when the optimal cutoff values were used. Although the a-wave amplitude correlated with the MD, the a-wave amplitudes of most of the patients fell within the normal range. The correlation between the b-wave amplitude and MD was not significant. CONCLUSIONS: The PhNR amplitudes correlate with the decrease in function and morphology of retinal neurons in eyes with OAG. The linear relationship between the PhNR and the structural parameters indicates that inner retinal function declines proportionately with neural loss in eyes with glaucoma.     

The photopic negative response of the flash electroretinogram in retinal vein occlusion

The photopic negative response (PhNR) has recently been shown to be severely affected in central retinal artery occlusion (CRAO), despite relative preservation of the cone b-wave compared to that in the healthy unaffected fellow eye. The aim of this study was to test how the PhNR of the flash electroretinogram (ERG) is affected in human retinal vein occlusion. PhNR was elicited with red stimuli (1 cd s/m², 5 cd s/m², and 7 cd s/m² with 4 ms duration) and blue background (10 cd/m²). Standard Ganzfeld flash ERG was produced according to the ISCEV standard for the clinical electroretinogram (2004). Sixteen patients with central retinal vein occlusion (CRVO), 14 patients with branch retinal vein occlusion (BRVO), and 16 controls were analyzed. The amplitude of the PhNRs was significantly smaller in the CRVO and BRVO eyes than those in the unaffected fellow or control eyes (p = 0.000). There was a significantly greater reduction of PhNR amplitudes than that of other waves including the OPs, rod b-wave, combined a-wave and b-wave, cone a-wave and b-wave, and 30 Hz flicker ERG. Thus, PhNR amplitude in retinal vein occlusion is severely affected. There is a potential role for PhNR in assessing inner retinal damage and evaluating the effect of treatment.     

Comparisons of cone electroretinograms after indocyanine green-, brilliant blue G-, or triamcinolone acetonide-assisted macular hole surgery

Purpose

To compare the function of retinal ganglion cells (RGCs) using the photopic negative response (PhNR) in patients who had undergone indocyaine green (ICG)-assisted, brilliant blue G (BBG)-assisted, or triamcinolone acetonide (TA)-assisted internal limiting membrane (ILM) peeling during macular hole (MH) surgery.

Methods

Forty-eight eyes of 48 patients with a macular hole were randomly divided into those undergoing ICG-assisted, BBG-assisted, or TA-assisted vitrectomy (n?=?16 for each group). Full-field cone ERGs were recorded before and 1, 3, 6, 9, and 12 months postoperatively. The amplitudes and implicit times of the a-waves and b-waves and the amplitudes of the oscillatory potentials (OPs) and PhNRs were measured. The mean deviations (MDs) of standard automated perimetry and the best-corrected visual acuity (BCVA) were measured. The circumferential retinal nerve fiber layer (RNFL) thickness was evaluated by SD-OCT.

Results

All macular holes were closed with a significant improvement of the BCVA and MD without differences among the groups. There was no significant difference between the preoperative and postoperative RNFL thickness. The implicit times of the a-waves and b-waves were significantly prolonged, and the ΣOPs amplitude was significantly decreased postoperatively in all groups. These ERG changes were not significantly different among the groups. The postoperative PhNR amplitudes were significantly lower in the ICG group than in the BBG or TA group.

Conclusions

The results indicate that the PhNR may detect subclinical impairments of RGCs caused by the possible toxic effect of ICG. This finding adds to the data that BBG and TA may be safer than ICG for use during MH surgery.     

Changes in retinal thickness are correlated with alterations of electroretinogram in eyes with central retinal artery occlusion

BACKGROUND: We investigated the relationship between the retinal thickness and electroretinogram (ERG) components in patients with central retinal artery occlusion (CRAO). METHODS: The optical coherence tomographic (OCT) images and ERGs of the nine patients (six men and three women; mean age, 61.8 years) were retrospectively analyzed. The thickness of the inner and outer retinal layers at 1 and 2 mm nasal and temporal to the fovea was measured in the horizontally scanned OCT images. The ratio of the inner layer thickness/sensory retinal thickness (IT/ST ratio) was calculated. The amplitudes of the a- and b-waves of the mixed rod-cone ERGs and the photopic negative response (PhNR) of the photopic ERGs were analyzed. The ratio of the amplitude of each component in the affected eye to that of the healthy fellow eye (a/f ratio) was calculated. RESULTS: In the chronic phase (1 to 8 months after onset, eight eyes), the inner layer was significantly thinner than that in the acute phase (P = 0.0147, 0.0076, 0.002, and 0.0003 for 2 mm nasal, 1 mm nasal, 1 mm temporal, and 2 mm temporal respectively, within 5 days of onset, six eyes), while the thickness of outer layer was not significantly changed. The ERGs were recorded 6.4 +/- 1.5 days after the onset of CRAO. The median of the a/f ratio was 0.84 in the a-wave, 0.56 in the b-wave, and 0.27 in the PhNR. The IT/ST in the chronic phase was positively correlated with the a/f ratio of the amplitude of the PhNR. CONCLUSIONS: Measurement of retinal thickness by OCT can be useful for monitoring the changes following CRAO. The correlation between the retinal thickness, especially inner layer thickness, and the ERG components was determined, suggesting that the PhNR in the acute phase might be a good indicator for predicting the thinning of the damaged retina in the chronic phase.     

Structural and Functional Measures of Inner Retinal Integrity Following Visual Acuity Improvement in a Patient with Hereditary Motor and Sensory Neuropathy Type VI

Purpose: To report measures of inner retinal integrity following improvement in visual acuity and visual fields in a patient with hereditary motor and sensory neuropathy type VI (HMSN VI).

Case Report: The patient is a Caucasian male with HMSN VI (type 2A Charcot-Marie-Tooth disease and associated optic atrophy) and a c.1090C→T (p.R364W) mutation in the mitofusin 2 (MFN2) gene. The patient’s best-corrected visual acuity improved from 20/200 (OD) and 20/400 (OS) at the initial visit to 20/25 in each eye when tested 7 years later. The visual field defects in both eyes that were present at the initial visit were absent at the follow-up visit. The structural integrity of the inner retina was assessed by an evaluation of retinal nerve fiber layer thickness (RNFLT) using optical coherence tomography (OCT), and the functional integrity was assessed by the amplitude of the photopic negative response (PhNR) of the electroretinogram (ERG). At the follow-up visit, the patient’s RNFLT was less than the 5th percentile for control subjects in the superior and inferior quadrants OD and in one sector of the temporal quadrant OS, but was within normal limits elsewhere. The PhNR amplitude of each eye was below the lower limit of the normal range.

Conclusion: The abnormally low PhNR amplitudes and abnormally thin RNFL in certain quadrants of the retina following improvement of visual acuity and visual fields to near-normal values illustrates the potential usefulness of assessing the structure and function of the inner retina in HMSN VI patients.     

Focal macular photopic negative response in patients with optic neuritis

Purpose

To investigate, by focal macular electroretinography (ERG), the change of photopic negative response (PhNR) in the recovery of visual function in patients with optic neuritis.

Methods

Focal macular ERG was recorded from nine patients with acute optic neuritis (38.6±10.2 years). The photostimulator device projected 15° visual angle spotlight onto the macula. Focal macular ERG recording was performed at the onset and at 1 month and 6 months after the onset of optic neuritis. The results were compared between each recording for seven of the patients.

Results

All patients decreased in the vision below 20/100 and had central scotoma. Vision improved more than 20/20 within 1 month and full-visual field recovered within 6 months after the onset in all patients. The amplitude of the a-wave, b-wave, and PhNR of focal macular ERG at the onset was significantly attenuated in eyes with optic neuritis (66.8±15.5, 65.8±17.7, and 65.2±14.4% of normal control, respectively). The amplitude of the a-wave and b-wave increased gradually after steroid pulse therapy. The increase in a-wave amplitude was significant at 6 months (P=0.046), whereas the PhNR amplitude did not show any significant change over 6 months after the onset of optic neuritis.

Conclusions

Our results suggest that inflammation at the onset of optic neuritis leads to functional deficits that extend to at least the inner nuclear layers of the retina, and that all but the ganglion cell layers of retina recover.     

Clinical Application of Photopic Negative Response of the Flash Electroretinogram in Primary Open-angle Glaucoma

 PURPOSE: To evaluate the diagnostic performance of the photopic negative response (PhNR) for the detection of primary open-angle glaucoma (POAG). METHODS: Fifty-two normal subjects (52 eyes) and 173 POAG patients (173 eyes) were studied. The PhNR was elicited using a white stimuli on a white background. The mean deviation (MD) and pattern standard deviation (PSD) of the visual field were measured using standard automated perimetry (SAP). Spectral domain optical coherence tomography (SD-OCT) was used to measure the mean thickness of the retinal nerve fiber layer (RNFL). RESULTS: In the glaucoma group, as compared to the normal group, the amplitudes of a-waves, b-waves and PhNR were significantly smaller (P<0.001), and the PhNR implicit time was significantly longer (P=0.004). The MD, PSD and mean thickness of the RNFL were significantly correlated with the amplitude of the PhNR (P<0.001). The area under the receiver operating characteristic curve (AUCs) for the amplitudes of a-waves, b-waves and PhNR were 0.853, 0.830 and 0.918, respectively. When the specificity was ≥95%, the sensitivities were 60.4%, 54.2% and 85.4% respectively. CONCLUSION：The PhNR amplitude was reduced even when the loss in visual field sensitivity was mild, which suggests that PhNR might be a useful indicator of early glaucoma disease.       

视网膜电图PhNR和OPs在非增生型DR中的变化特点

目的观察非增生型糖尿病视网膜病变（DR）中视网膜电图PhNR和OPs的变化特点,比较OPs、PhNR指标在早期诊断及评估视网膜功能的敏感性和特异性。方法选取经间接检眼镜、荧光素眼底血管造影（FFA）确诊的DR患者30例（30眼）,同时选取与其性别、年龄相匹配的正常对照25例（25眼）作为对照组。2组均进行视力、闪光视网膜电图（F-ERG）、FFA检查。比较2组PhNR振幅、OPs振幅及ERG其他参数指标,并探讨不同DR分级与PhNR振幅、OPs振幅的变化关系。结果在OPs指标中,DRⅠ~Ⅳ级OPs振幅与正常值比较差异均有统计学意义（P〈0.05）,PhNR指标显示,DRⅠ级PhNR振幅与正常值比较,差异无统计学意义（P〉0.05）,DRⅡ~Ⅳ级与正常组比较,差异均有统计学意义（P〈0.05）。在比较各参数ROC下面积（AUC）中,OPs指标的AUC最高,为0.866;其次是PhNR指标,AUC为0.754。OPs诊断NPDR的敏感性和特异性分别为63.6%和80%,而PhNR的敏感性和特异性分别为54.5%和73.3%。结论DR在病变初期即出现血液循环性改变、神经细胞功能障碍,表现为PhNR振幅和OPs振幅均明显降低。OPs指标在DR的早期诊断及评估视网膜功能方面敏感性和特异性更高。     

Specific deficits in visual electrophysiology in a mouse model of dominant optic atrophy

Autosomal dominant optic atrophy (ADOA) is a slowly progressive optic neuropathy caused by mutations in the OPA1 gene. OPA1 is ubiquitously expressed and plays a key role in mitochondrial fusion. Heterozygous Opa1 mutant mice (B6; C3-Opa1^Q285STOP), have previously been reported to develop visual defects and optic nerve changes. In this study, in vivo visual electrophysiological testing (ERGs and VEPs) was performed on 11–13 month old B6; C3-Opa1^Q285STOP mice (n = 5) and age/sex matched wildtype littermate controls. Full intensity series were recorded in response to brief (4 ms) single flash stimuli delivered in a Ganzfeld dome under dark- and light-adapted conditions. The major ERG components (a-wave and b-wave) showed no detectable difference from wildtype in the amplitude or implicit time of dark-adapted ERGs across the full intensity range tested. This was also true for the components of the dark-adapted VEP. However, the light-adapted ERG responses revealed a significant reduction in the photopic negative response (PhNR) amplitude in Opa1^+/− animals relative to wildtypes at the brighter intensities tested. Elements of the light-adapted VEP were also abnormal in mutant mice. Overall Opa1^+/− mice display functional deficits in electrophysiology that are consistent with ganglion cell dysfunction. These deficits may correlate with a reduction in the dendritic arborisation of retinal ganglion cells, which has been previously reported to occur at a similar age in the same mutant mouse line (Williams et al., 2010). The functional phenotype we have described in this mouse model may be useful in the robust and accurate assessment of potential treatments for ADOA.     

Idiopathic bilateral optic atrophy in the rhesus macaque

PURPOSE: To document the existence of idiopathic bilateral optic atrophy (BOA) in rhesus macaque monkeys and to characterize the structural and functional consequences of this condition. METHODS: In vivo assessment of retinal and optic nerve structure included fundus biomicroscopy and stereophotography. Functional analyses included transient pattern-reversal electroretinography (PERG) and full-field flash ERG, with both white flashes while dark adapted and red flashes on a blue background used to assess the photopic negative response (PhNR). Also measured were visual evoked cortical potentials (VEPs) and multifocal (mf)ERGs, with both a standard fast and slowed (7F) stimulation sequence. Post mortem histologic evaluation was performed on a subset of five animals with BOA and compared with data from 22 healthy normal animals. Blood tests, including vitamin E, B(12), folate, lead, and complete blood cell count with differential were obtained on the four animals that remained alive. RESULTS: Animals with BOA showed temporal pallor of the optic nerve head and thinning of the retinal nerve fiber layer (RNFL) between the temporal vascular arcades (i.e., of the papillomacular bundle). Severity of optic atrophy and RNFL loss varied between animals from mild to severe, but was similar in the two eyes of each animal. Functional changes included greater loss of the PERG N95, compared with the P50 component and substantial reduction of mfERG high-frequency components. The mfERG low-frequency components were slightly larger than normal. None of the full-field flash ERG amplitudes (a-wave, b-wave, oscillatory potentials, or PhNR) was significantly different from normal. There were no consistent abnormalities found in the results of any blood test. Histologic findings included axonal loss and gliosis limited to the temporal optic nerve, reduction of nuclei within the retinal ganglion cell layer, and thinning of the temporal retinal RNFL. CONCLUSIONS: The existence of BOA in nonhuman primates warrants caution on the part of investigators who use these animals in experimental models of ophthalmic disease.     

Photopic ERGs in patients with optic neuropathies: comparison with primate ERGs after pharmacologic blockade of inner retina

PURPOSE: To determine whether anterior ischemic optic neuropathy and compressive optic neuropathy in humans alter the photopic flash ERG and to investigate the cellular origins of the waves that are affected by pharmacologic agents in primates. METHODS: Photopic flash ERGs were recorded differentially, with DTL electrodes, between the two eyes of 22 patients with diagnosed optic neuropathy (n = 17, anterior ischemic optic neuropathy [AION]; n = 5, compressive optic neuropathy) and 25 age-matched control subjects and in 17 eyes of 13 monkeys (Macaca mulatta). The stimulus consisted of brief (<5 ms) red (lambda(max) = 660 nm) Ganzfeld flashes (energy range, 0.5-2.0 log td-s) delivered on a rod-saturating blue background of 3.7 log sc td (lambda(max) = 460 nm). An eye of the patient with ischemic changes at the disc was classified as symptomatic if it showed visual field defects with a mean deviation (MD) of P < 2%. Recordings in macaque monkeys were made before and after inner retinal blockade with tetrodotoxin (TTX) (1.2-2.1 microM; n = 7), TTX+N-methyl-d-aspartate (NMDA; 1.4-6.4 mM; n = 7), and cis-2, 3 piperidine dicarboxylic acid (PDA; 3.3-3.8 mM; n = 3). RESULTS: The PhNR amplitude was significantly reduced in both symptomatic (P = 3.4 x 10(-8)) and asymptomatic (P = 0.036) eyes of patients with AION or compressive optic neuropathy (P = 0.0054) compared with control subjects. The PhNR amplitude in the symptomatic eye showed a moderate correlation with field defects (P < 0.05) similar to previous findings in open-angle glaucoma. The a-wave also was reduced significantly in the symptomatic eye (P = 0.0002) of patients with AION. The i-wave, a positive wave on the trailing edge of the b-wave peaking around 50 ms, became more prominent in eyes in which the PhNR was significantly reduced. In monkeys, the PhNR was eliminated by TTX. The a-wave at the peak and later times was reduced by TTX, further reduced by NMDA, and eliminated after PDA in response to the red stimuli. PDA also eliminated the i-wave. CONCLUSIONS: PhNR amplitude is significantly reduced in eyes with open-angle glaucoma, AION, and compressive optic neuropathy. Experiments in primates indicate that this reduction reflects loss of a spike-driven contribution to the photopic ERG. There also are small spike-driven contributions to the a-wave elicited by full-field red stimuli. The i-wave, which becomes more prominent when the PhNR is reduced, has origins in the off-pathway distal to the ganglion cells.     

Photopic negative response of the human ERG: losses associated with glaucomatous damage

PURPOSE: To evaluate in glaucomatous eyes the photopic electroretinogram (ERG) negative response (PhNR), a component that follows the b-wave peak and is thought to be correlated with inner retinal activity. METHODS: Eleven patients with open-angle glaucoma (OAG) and moderate field loss (Humphrey 30-2 [Humphrey Instruments, San Leandro, CA] mean deviation < or = -6 dB), eight with ocular hypertension (OHT), and eight age-matched normal subjects were tested. Optic discs of patients and control subjects were evaluated by confocal scanning laser ophthalmoscopy. ERGs were recorded to long-duration stimuli (250 msec) of photopic luminance (78 candelas [cd] /m2), presented in the macular region (12 degrees x 12 degrees field size) on a steady, adapting background. Amplitudes of the a-wave and b-wave and the PhNR were measured. Pattern reversal ERGs to 30-minute checkerboards were also recorded from patients and control subjects. RESULTS: Compared with control subjects, patients with OAG showed reduced PhNR (average reduction: 62%, P < 0.01), but normal a- and b-wave amplitudes. In patients with OHT, PhNR and a- and b-wave amplitudes did not differ from control values. In individual patients with OAG, PhNR amplitudes were correlated positively with pattern ERG amplitudes (r = 0.80; P < 0.01) and central (12 degrees) perimetric mean deviations (r = 0.68; P < 0.05) and negatively with cup-to-disc area ratios (r = -0.79; P < 0.01) and cup shape measures (r = -0.78; P < 0.01). CONCLUSIONS: Similar to that found in monkeys with experimentally induced glaucoma, the PhNR is selectively altered in human glaucoma. The correlation between PhNR losses and clinical parameter abnormalities suggests that this component depends on inner retina integrity and may be of clinical value for detecting glaucomatous damage.     

正常成年SD大鼠明视闪光视网膜电图特征

目的:探讨正常成年SD大鼠的明视视网膜电图(Electroretinogram,ERG)特征.方法:选取正常9～12周SD大鼠60只,使用罗兰视觉电生理仪记录大鼠右眼的明视闪光ERG.使用SPSS统计分析a波、b波和明视负波反应(Photopic negative response,PhNR)的隐含期和振幅.比较雄性和雌性SD大鼠明视ERG特征.结果:每只SD大鼠均能记录到稳定的a波、b波和PhNR,其中a波的隐含期和PhNR的隐含期及振幅均符合正态分布,而其余指标均不符合正态分布.PhNR的隐含期为124.6±8.5ms,其变异系数最小(0.07).PhNR的振幅为(11.3±4.2)μV,变异系数为0.37.雄性和雌性SD大鼠明视ERG的各反应波之间无显著差异.结论:在正常成年SD大鼠,明视闪光ERG是一项客观评价大鼠明视状态下视网膜功能的手段,PhNR可以作为一项稳定的评价内层视网膜功能的指标.     

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

Purpose

To investigate the clinical significance of the oscillatory potentials (OPs) and photopic negative response (PhNR) of the electroretinogram (ERG) in patients with early diabetic retinopathy.

Methods

One 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.

Results

The 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.

Conclusions

The 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 © Japanese Ophthalmological Society 2006     

Attenuation of the retinal nerve fibre layer and reduced retinal function assessed by optical coherence tomography and full‐field electroretinography in patients exposed to vigabatrin medication

Purpose: To investigate the clinical value of assessment of peripapillary retinal nerve fibre layer (RNFL) thickness with OCT in addition to the evaluation of retinal function measured by full‐field electroretinography (ff‐ERG) in patients with suspected vigabatrin (VGB)‐attributed visual field defects. Methods: Visual fields from adult patients in our clinical follow‐up program for VGB medication were analysed. Twelve patients with suspected VGB‐attributed visual field defects were selected for the study. They were re‐examined with computerized kinetic perimetry, ff‐ERG and OCT (2D circle scan). Results: Constricted visual fields were found in all patients. Comparative analysis of ff‐ERG parameters showed reduced b‐wave amplitudes for the isolated and the combined rod and cone responses (p < 0.0001). The a‐wave, reflecting photoreceptor activity, was reduced (p = 0.001), as well as the summed amplitude of oscillatory potentials (p = 0.029), corresponding to inner retinal function. OCT measurements demonstrated attenuation of the RNFL in nine of 12 patients, most frequently superiorly and/or inferiorly. No temporal attenuation was found. Significant positive correlations were found between the total averaged RNFL thickness, superior and inferior RNFL thickness and reduced ff‐ERG parameters. Positive correlations were also found between RNFL thickness and isopter areas. Conclusion: OCT measurements can detect attenuation of the RNFL in patients exposed to VGB medication. RNFL thickness correlates with reduced ff‐ERG parameters and isopter areas of constricted visual fields, indicating that VGB is retino‐toxic on several levels, from photoreceptors to ganglion cells. The study also supports previous studies, suggesting that OCT measurement of the RNFL thickness may be of clinical value in monitoring patients on vigabatrin therapy.     

The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma

PURPOSE: To investigate the photopic flash electroretinograms (ERGs) of macaque monkeys in which visual field defects developed as a consequence of experimental glaucoma. METHODS: Unilateral experimental glaucoma was induced in 10 monkeys by argon laser treatment of the trabecular meshwork. Visual field sensitivity was assessed behaviorally by static perimetry. Photopic ERGs were recorded to brief- (< or = 5 msec) and long-duration (200 msec) red ganzfeld flashes on a rod-suppressing blue-adapting background. Electroretinograms were recorded in four other monkeys, after intravitreal injection of tetrodotoxin (TTX; 3.8-8 p.M) to suppress action potentials of retinal ganglion and amacrine cells, and in six normal adult human subjects. RESULTS: Experimental glaucoma removed a cornea-negative response, the photopic-negative response (PhNR), from the ERG. The PhNR in control eyes was maximal approximately 60 msec after a brief flash, 100 msec after onset, and 115 msec after offset of the long-duration stimulus. The PhNR in experimental eyes was greatly reduced when the mean deviation of the visual field sensitivity was as little as -6 dB. As visual sensitivity declined further, the PhNR was reduced only slightly more. The a- and b-waves were unchanged, even when sensitivity decreased by more than 16 dB. Tetrodotoxin also selectively reduced the PhNR. The PhNR was observed in normal human ERGs. CONCLUSIONS: The cornea-negative PhNR of the photopic ERG depends on spiking activity and is reduced in experimental glaucoma when visual sensitivity losses are still mild. The PhNR most likely arises from retinal ganglion cells and their axons, but its slow timing raises the possibility that it could be mediated by glia. Regardless of the mechanism of its generation, the PhNR holds promise as an indicator of retinal function in early glaucomatous optic neuropathy.