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.     

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

Purpose

This study evaluates the relevance to human retinopathy of electroretinograms (ERGs) from the spontaneously diabetic Goto-Kakizaki (GK) rat.

Methods

Starting 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.

Results

The 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.

Conclusion

Functional 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 © Japanese Ophthalmological Society 2006     

Contribution of retinal ganglion cells to the mouse electroretinogram

Purpose

To quantify the direct contribution of retinal ganglion cells (RGCs) on individual components of the mouse electroretinogram (ERG).

Methods

Dark- and light-adapted ERGs from mice 8 to 12 weeks after optic nerve transection (ONTx, n = 14) were analyzed through stimulus response curves for a- and b-waves, oscillatory potentials (OPs), positive and negative scotopic threshold response (p/n STR), and the photopic negative response (PhNR) and compared with unoperated and sham-operated controls, as well as to eyes treated with 6-cyano-7-nitroquinoxaline-2,3-dion (CNQX).

Results

We confirmed in mice that CNQX intravitreal injection reduced the scotopic a-wave amplitude at high flash strength, confirming a post-receptoral contribution to the a-wave. We found that ONTx, which is more specific to RGCs, did not affect the a-wave amplitude and implicit time in either photopic or scotopic conditions while the b-wave was reduced. Both the pSTR and nSTR components were reduced in amplitude, with the balance between the two components resulting in a shortening of the nSTR peak implicit time. On the other hand, amplitude of the PhNR was increased while the OPs were minimally affected.

Conclusion

With an intact a-wave demonstrated following ONTx, we find that the most robust indicators of RGC function in the mouse full-field ERG were the STR components.     

Acute Visual Field Defect following Vitrectomy Determined to Originate from Optic Nerve by Electrophysiological Tests

Purpose

To present our findings on the cause of an acute visual field defect (VFD) that developed in a patient on the day after vitrectomy for proliferative diabetic retinopathy.

Case

A 50-year-old man complained of a blind area in the superior visual field that developed one day after vitrectomy. The patient had undergone uncomplicated vitrectomy for a long-duration vitreous hemorrhage associated with proliferative diabetic retinopathy. Residual vitreous hemorrhage hampered a clear view of the fundus. Goldmann perimetry showed a horizontal VFD in the superior field. The area corresponding to the VFD was examined by multifocal electroretinograms (mfERGs) and multifocal visual evoked potentials (mfVEPs). The amplitudes of the mfVEPs were reduced with prolonged implicit times especially when the superior hemifield was stimulated, while the amplitudes and implicit times were within the normal range when other parts of the visual field were stimulated. In addition, the full-field photopic ERGs and photopic negative responses were attenuated in the right eye. These findings suggested that the VFD did not originate from alterations in the retinal inner and middle layer but in the ganglion cells. The visual acuity improved to 1.2 but his optic disc became pale and the VFD remained unchanged more than 12 years after the surgery.

Conclusion

We suggest that vitrectomy can cause ischemic optic neuropathy by interfering with the circulation associated with diabetes mellitus. Evaluations by mfERGs, mfVEPs, and full-field photopic ERGs were helpful in making the diagnosis.Key words: Ischemic optic neuropathy, Proliferative diabetic retinopathy, Multifocal electroretinogram, Multifocal visual evoked potentials, Photopic negative response     

Contribution of N-methyl-dl-aspartic acid (NMDA)-sensitive neurons to generating oscillatory potentials in Royal College of Surgeons rats

Purpose

We investigated how the N-methyl-dl-aspartic acid (NMDA) receptor contributes to generating oscillatory potentials (OPs) of the electroretinogram (ERG) in the Royal College of Surgeons (RCS) rat.

Methods

Scotopic ERGs were recorded from dystrophic and wild-type congenic (WT) RCS rats (n = 20 of each) at 25, 30, 35, and 40 days of age. The stimulus intensity was increased from ?2.82 to 0.71 log cd-s/m² to obtain intensity-response function. NMDA was injected into the vitreous cavity of the right eyes. The left eyes were injected with saline as controls. The P3 obtained by a-wave fitting was digitally subtracted from the scotopic ERG to isolate the P2. For the OPs, the P2 was digitally filtered between 65 and 500 Hz. The amplitudes of OP1, OP2, OP3, and OP4 were then measured and summed and designated as ΣOPs. The implicit times of OP1, OP2, and OP3 were also measured. The frequency spectra of the OPs were analyzed using fast Fourier transform (FFT).

Results

The maximum ERG a- and b-waves as well as ΣOPs amplitudes reduced with age in dystrophic rats. Compared with intravitreal saline injection, administration of NMDA decreased ΣOPs amplitudes from 30 days of age in dystrophic rats, while it did not attenuate ΣOPs amplitudes in WT rats. The implicit times of the OPs of the maximum ERG were prolonged by NMDA injections in WT and dystrophic rats. NMDA/saline ratios of ΣOPs amplitudes area under the FFT curves were significantly lower in dystrophic rats from 30 days of age than that in WT rats.

Conclusion

In the early stage of photoreceptor degeneration, intravitreal NMDA injection attenuated OPs amplitudes in dystrophic rats. This indicates that NMDA receptors play a significant role in generating OPs amplitudes with advancing photoreceptor degeneration.     

Inter-ocular and inter-session reliability of the electroretinogram photopic negative response (PhNR) in non-human primates

PURPOSE: To assess the inter-ocular and inter-session reliability for a range of parameters derived from the photopic electroretinogram (ERG) in a group of normal non-human primates. METHODS: Inter-ocular differences for photopic ERGs were assessed in a group of normal anesthetized adult rhesus monkeys (Macaca mulatta, n=29); inter-session reliability was assessed for 23 eyes of 23 animals tested 3 months later. Signals were acquired using Burian-Allen contact lens electrodes, whereby the contralateral cornea served as a reference. Photopic ERGs were elicited using red Ganzfeld flashes (-0.5-0.67 log photopic cd.sm(-2)) on a rod suppressing blue-background (30 scotopic cdm(-2)). Measurement reliability was established for a-wave, b-wave, photopic negative response (PhNR) and oscillatory potential (OP) amplitudes, as well as for their implicit times, by calculation of the 95% limits-of-agreement (LOA) and the coefficient-of-variation (COV) for each parameter. RESULTS: OP and a-wave amplitudes increased with intensity up to 0.67 log photopic cd.sm(-2), following a typical saturating function, whereas b-wave and PhNR amplitudes both declined above 0.42 log photopic cd.sm(-2). Inter-session variability was greater than inter-ocular variability. The inter-session COVs for PhNR amplitude (10-20%) were similar to the other photopic ERG components (a-wave: 12-17%, b-wave: 12-17%, OPs: 13-19%). Inter-session LOAs were also similar across components, but on average, were smallest for responses to moderate intensities (0.0-0.42 log photopic cd.sm(-2)). CONCLUSION: In non-human primates, the 95% LOA for inter-session measurements of the photopic ERG a-wave, b-wave, OPs and PhNR are all similar. Inner-retinal damage may best be measured using the PhNR amplitude for moderately bright stimulus intensities. B-wave and PhNR amplitudes for brighter flashes are smaller and more variable. The ratio of PhNR:b-wave amplitudes manifests smaller variability and may therefore be useful for detection of selective PhNR loss.     

A comparison of photopic and scotopic electroretinographic changes in early diabetic retinopathy.

Previous studies of early diabetic retinopathy have shown that oscillatory potential (OP) amplitudes are reduced in many diabetic patients. OP amplitude is believed to be a more sensitive indicator of the development of future retinopathy than b-wave amplitude of the scotopic electroretinogram (ERG). Because OPs measured to a bright white flash reflect both rod and cone system activity, it is important to compare OP amplitudes to photopic ERG measures as well as scotopic measures in early diabetic retinopathy. In this study, OPs and ERG responses were measured under photopic and scotopic conditions in a group of diabetic patients. Although OPs were reduced in amplitude in the diabetic group, several other parameters of the scotopic and photopic b-waves were impaired. The results indicate that b-wave activity may indicate retinal changes in early diabetic retinopathy in the same manner as the OPs.     

New photic stimulating system with white light-emitting diodes to elicit electroretinograms from zebrafish larvae

Purpose

The zebrafish is an established animal model commonly used in biological, neuroscience, and genetic research. We have developed a new light stimulating system using white light-emitting diodes (LEDs) to elicit ERGs from zebrafish larvae. The purpose of this study was to record full-field ERGs and to evaluate the inter-trial reliability of the ERGs recorded with our system from zebrafish larvae.

Methods

The stimulating device used white LEDs that were attached to a stereomicroscope, and the location of the recording electrode on the cornea could be monitored while the eye was being stimulated. Full-field scotopic and photopic ERGs were recorded from larvae at the age of 5–7 days post-fertilization (dpf). Intensity–response curves were constructed from the ERGs. Inter-trial reliability of the ERGs recorded by our system was evaluated.

Results

This stimulating system could be used for efficient and reliable ERG recordings from 5–7 dpf larvae. The amplitudes, implicit times, and the waveforms of the scotopic and photopic ERGs were similar to those reported in earlier studies. Inter-trial reliability of the amplitudes of the photopic ERG b-waves was excellent with an intra-class correlation coefficient of 0.98.

Conclusion

We conclude that this new light stimulation system using white LEDs attached to a stereomicroscope will be helpful in recording reliable ERGs from zebrafish larvae.

     

Dark-adapted oscillatory potentials in preterm infants with and without retinopathy of prematurity

Purpose

To describe the appearance and maturation of dark-adapted oscillatory potentials (OPs) in electroretinograms (ERGs) recorded from preterm infants, and to determine any effect of retinopathy of prematurity (ROP).

Methods

Dark-adapted ERGs were recorded in conjunction with screening for ROP and at outpatient follow-up, using a flash luminance of 11.3 scot cd s m^?2 (4.06 phot cd s m^?2). Eligible infants were born before 31 weeks’ gestation and/or weighed ≤1,250 grams at birth.

Results

Presence or absence of OPs was established for 68 ERG recordings from 38 infants at maturities ranging from 30 weeks’ postmenstrual age (PMA) to 28 weeks’ post-term corrected age. 20 infants did not develop ROP, eight developed stage 1, one stage 2 and one stage 3 disease which regressed spontaneously. Eight infants received treatment for threshold ROP. OPs were present in 50 % of infants at 36 weeks’ PMA and in all by 50 weeks’ PMA. The earliest appearance of OPs was at 30+5 weeks’ PMA. Individual OP amplitudes increased and peak time of individual OPs decreased with increasing maturity. For infants with threshold ROP summed OP amplitudes tended to be smaller prior to treatment (6.5 vs 9.9μV, P = 0.09) and were significantly smaller by 50 weeks’ PMA (14 vs 30μV, P = 0.007). OP1 was less likely to be present in infants who developed stage 3 or worse ROP (P = 0.000).

Conclusions

Dark-adapted OPs are recordable in some preterm infants from 30 weeks’ PMA. Relative suppression of early OPs is a potential marker for developing ROP.     

Changes in Electroretinogram Oscillatory Potentials During Dark Adaptation

Purpose

To investigate changes in the oscillatory potentials (OPs) of electroretinograms (ERGs) during dark adaptation (DA).

Methods

ERGs were recorded from ten normal subjects. Following 15?min of light adaptation, ERGs were recorded every 30?s for 20?min to follow the changes in the OPs during the course of DA. A 20-ms, 560-nm rectangular pulse of light was presented at 3.3?Hz to elicit the ERGs.

Results

The latencies of OP1 and OP2 did not change significantly, but the amplitudes decreased slightly during DA. OP3 was not observed at 30?s, but appeared after 1?min of DA between OP2 and OP4. Similar results were obtained with stimulus durations of 10 to 100?ms in 10-ms steps. The amplitude of OP3 increased to 10?min of DA and then plateaued.

Conclusion

The characteristics of OP3, which increases during DA, indicate that it is probably related to rod activity. Jpn J Ophthalmol 2005;49:420–422 © Japanese Ophthalmological Society 2005     

Electroretinographic assessment of early changes in ocular siderosis

We examined a patient with an iron intraocular foreign body and recorded electroretinograms (ERGs) before and after the removal of the foreign body by vitrectomy. The amplitudes of the rod and cone ERGs and the oscillatory potentials (OPs) in the injured eye were reduced before the operation. In addition, the photopic on-responses (b wave) were more reduced than off-responses (d wave). One year after surgery, the amplitudes of the rod, cone and photopic on- and off-responses were markedly improved to within the low normal limit. However, the OP amplitudes remained unchanged with lower values. These findings suggest that iron retinotoxicity leads to a dysfunction of all layers but the changes may be reversible in the early period of the disease. The late period iron toxicity produces more severe damage to the inner retina than the outer retina.     

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。     

Visual prognostic value of photopic negative response and optical coherence tomography in central retinal vein occlusion after anti-VEGF treatment

Objective

To investigate the potential of optical coherence tomography (OCT) and photopic negative response (PhNR) for predicting visual outcome after intravitreal bevacizumab in patients with macular edema secondary to central retinal vein occlusion (CRVO).

Methods

Thirty-two consecutive patients with macular edema secondary to unilateral CRVO who were treated with three times of 6 weeks interval intravitreal bevacizumab were enrolled. LogMAR visual acuity (Va), OCT and PhNR were done before and 4 weeks after first and third injection. Stepwise multiple regression analysis was conducted between pre-treatment Va, central retinal thickness, b wave amplitude, PhNR amplitude, PhNR relative amplitude (affected eye/unaffected fellow eye,  % presentation) and post-treatment Va at 4 weeks after the third injection. The predictive values of pre-treatment parameters for good visual outcome (0.2 ≤ LogMAR Va) were assessed using receiver-operating characteristics (ROC) analysis.

Results

In multiple regression analysis, pre-treatment Va (β = 0.615, P = 0.001) and PhNR relative amplitude (β = ?0.352, P = 0.032) were correlated significantly with post-treatment Va. In ROC analysis, pre-treatment Va showed a 80 % sensitivity and 80 % specificity for predicting good visual outcome, at a cutoff value of 0.52 LogMAR. Pre-treatment PhNR relative amplitude demonstrated a 88 % sensitivity and 75 % specificity for predicting good visual outcome, at a cutoff value of 40.00 %.

Conclusions

The PhNR relative amplitude can be a useful prognostic factor for visual outcome after intravitreal bevacizumab therapy in patient with macular edema secondary to CRVO. Patients with larger pre-treatment PhNR relative amplitude with better pre-treatment Va showed a better post-treatment visual outcome.     

Human flicker electroretinography using different temporal modulations at mesopic and photopic luminance levels

Background

Electroretinographic measurement instruments allow the variation of several stimulation parameters enabling to study a wide range of retinal processes. The purpose of the present study was to measure human flicker electroretinograms (ERGs) varying temporal modulation, temporal frequency and mean luminance in the photopic and higher mesopic ranges where the change from cone to rod dominance occurs.

Methods

Fourteen healthy subjects (mean age = 31 ± 6) participated in this study. ERG recordings were performed with the RetiPort system (Roland Consult, Germany). The stimuli were ON and OFF sawtooth waves, square wave and sine wave. The temporal frequencies were 4 and 8 Hz. The mean luminance varied from 1 to 60 cd/m².

Results

The results confirmed the possibility to distinguish between rod- and cone-dominated retinal responses when using the flicker ERG at different temporal frequencies and luminances. We have also evaluated the responses at luminance levels at which the transition between rod- and cone-dominated responses occurs. This transition between rod- and cone-dominated flicker ERG responses is indicated by a significant change in the response characteristics between 4 and 8 cd/m² (between 200 and 400 phot Td).

Conclusions

The findings on the transition between rod- and cone-dominated ERGs along with the demonstration of ERG responses to different temporal flicker modulations might be informative for the electrophysiologists when setting up the stimulus at mesopic and photopic luminance levels.     

Early local functional changes in the human diabetic retina: a global flash multifocal electroretinogram study

Purpose

To investigate early functional changes of local retinal defects in type II diabetic patients using the global flash multifocal electroretinogram (MOFO mfERG).

Methods

Thirty-eight diabetic patients and 14 age-matched controls were recruited. Nine of the diabetics were free from diabetic retinopathy (DR), while the remainder had mild to moderate non-proliferative diabetic retinopathy. The MOFO mfERG was performed at high (98?%) and low (46?%) contrast levels. MfERG responses were grouped into 35 regions for comparison with DR classification at those locations. Z-scores of the regional mfERG responses were compared across different types of DR defects.

Results

The mfERG waveform consisted of the direct component (DC) and the induced component (IC). Local reduction in DC and IC amplitudes were found in diabetic patients with and without DR. With increasing severity of retinopathy, there was a further deterioration in amplitude of both components. Under MOFO mfERG paradigm, amplitude was a useful screening parameter.

Conclusion

The MOFO mfERG can help in detecting early functional anomalies before the appearance of visible signs, and may assist in monitoring further functional deterioration in diabetic patients.     

Establishing baseline rod electroretinogram values in achromatopsia and cone dystrophy

Purpose

To establish the normal range of values for rod-isolated b-wave amplitudes in achromatopsia and cone dystrophies.

Methods

We reviewed charts of 112 patients with various types of cone dystrophy, and compared their standardized electroretinographic rod b-wave amplitudes with age-matched normal controls. Twenty-six patients had known mutations in achromatopsia and cone dystrophy genes, while 53 were characterized by their inheritance pattern since they had yet to have their gene identified. Visual acuity information and scotomata were documented.

Results

We found that patients with achromatopsia and cone dystrophy had rod b-wave amplitudes that were significantly lower than age-matched controls, but found no evidence of rod amplitude progression nor loss of peripheral visual fields in the study group.

Conclusions

We found that cone dystrophy patients of all types had depressed rod-isolated ERGs across the board. If typical diagnostic criteria are used, these patients might be considered to have ??abnormal?? rod-isolated electroretinographic values, and might be called ??cone-rod dystrophy??, even though the waveforms are stable for years. Patients with cone-rod dysfunction patterns on ERG can be better understood by also performing kinetic (Goldmann) visual fields, which will help to distinguish cone dystrophies from progressive cone-rod dystrophies by central scotomata size and progression over time in many forms of cone-rod dystrophy.     

Rod and Cone a-Waves in Central Retinal Vein Occlusion

Purpose

To evaluate rod and cone a-waves in cases with unilateral central retinal vein occlusion (CRVO).

Methods

Scotopic and photopic flash electroretinograms (ERGs) were recorded in seven patients aged 54–84 with unilateral hemorrhagic CRVO. Rod and cone a-waves were analyzed using photoreceptor models, and Rm _p3 (maximum a-wave amplitude) and S (sensitivity) were calculated.

Results

Decreased rod log?S was found in all seven cases, and decreased cone log?S was found in five cases. In only one case, rod log?S in the fellow eye was decreased. The alterations in rod and cone log Rm _p3 were smaller than those in rod and cone log?S. Of three cases in which ERGs could be recorded again after a certain follow-up period, rod log?S and cone logS became larger in two cases and smaller in one case.

Conclusions

The change in the phototransduction cascade was confirmed not only in rods but also in cones in five of our seven cases of CRVO. The ERG findings might reflect the functional change in the photoreceptor layer after the onset of CRVO. Jpn J Ophthalmol 2005;49:402–410 © Japanese Ophthalmological Society 2005     

A comparison of oscillatory potential and pattern electroretinogram measures in diabetic retinopathy

Both basic and clinical electrophysiological investigations have established that the oscillatory potentials (OP) and pattern electroretinogram (PERG) appear to originate from retinal sites that are in proximity. The OPs, subcomponents of the flash ERG, have been shown to reflect disturbances in retinal circulation, and OP amplitude attenuation or loss may be a distinctive feature of diabetic retinopathy. The PERG has been shown to be abnormal in diseases of the optic nerve and ganglion cell body. Thus its relative sensitivity for detection of electroretinal abnormalities in diabetic retinopathy is in question. This study assessed the sensitivity of ERG and OP measures in their detection of abnormalities of electroretinal function in diabetic patients referred to our laboratory. Thirty-five adult Type I patients were studied: 21 with background retinopathy (BR group), 14 with no evidence of background retinopathy (No BR group), and 25 normal control subjects.Monocular OPs were recorded to full-field ganzfeld stimulation at four stimulus intensities. PERGs were obtained from checkerboard pattern reversal stimulation (checksize = 30 arc). Peak-to-peak amplitude and peak implicit time measures of PERGs and OPs were obtained. Subsequent multivariate analysis demonstrated significant differences between normals and diabetic patients, including diabetics with no clinical evidence of retinopathy. In addition, the OP and PERG implicit times appear to be unaffected while OP and PERG amplitudes were diminished in patients with background retinopathy. Only OP amplitudes were found to be significantly diminished in diabetic patients with no photographic evidence of background retinopathy. The PERGs were normal in these patients. Overall, the OP amplitude measures were more sensitive than PERG measures in detecting abnormalities in patients with no retinal photographic evidence of background retinopathy.     

Flicker cone function in normal and day blind sheep: a large animal model for human achromatopsia caused by CNGA3 mutation

Purpose

Recently we reported on day blindness in sheep caused by a mutation in the CNGA3 gene, thus making affected sheep a naturally occurring large animal model for therapeutic intervention in CNGA3 achromatopsia patients. The purpose of this study was to characterize flicker cone function in normal and day blind sheep, with the aim of generating a normative data base for ongoing gene therapy studies.

Methods

Electoretinographic (ERG) cone responses were evoked with full-field conditions in 10 normal, 6 heterozygous carriers and 36 day blind sheep. Following light adaptation (10 min, 30 cd/m²), responses were recorded at four increasing light intensities (1, 2.5, 5 and 10 cd s/m²). At each of these intensities, a single photopic flash response followed by 8 cone flicker responses (10–80 Hz) was recorded. Results were used to generate a normative data base for the three groups. Differences between day blind and normal control animals were tested in two age-matched groups (n = 10 per group).

Results

The normal sheep cone ERG wave is bipartite in nature, with critical flicker fusion frequency (CFF) >80 Hz. In all four flash intensities, the single photopic flash a-wave and b-wave amplitudes were significantly lower (p < 0.005), and implicit times significantly delayed (p < 0.0001), in day blind animals. In all four flash intensities, CFF values were significantly lower (p < 0.0001) in day blind sheep.

Conclusions

Cone function is severely depressed in day blind sheep. Our results will provide a normative data base for ongoing gene therapy studies.     

Photopic negative response of eyes with normal-tension glaucoma

PURPOSE: The purpose of this study was to investigate the behavior of the photopic negative response(PhNR) of cone-induced electroretinogram (cone ERG) in patients with normal-tension glaucoma (NTG). METHODS: Cone ERGs were recorded from 30 eyes of 30 patients with NTG according to the recording conditions of the International Society for Clinical Electrophysiology of Vision protocol which is now widely used in clinics. The amplitudes and implicit times of the PhNRs were measured and compared with normal controls. I further attempted to find a correlation between the PhNR amplitude loss and the cupping/disc ratio representing a loss of the nerve fiber layer and severity of visual field defbct. RESULTS: The PhNR amplitudes recorded from patients with NTG were significantly reduced compared with those from normal subjects (p < 0.05). However, the PhNR amplitude loss did not correlate with the cupping/disc ratio or the severity of visual field defect. CONCLUSIONS: The Results suggested that the PhNR amplitude qualitatively reflected ganglion cell loss in patients with NTG even under recording conditions which are widely used in the clinical field.