Psychophysical and electrophysiological testing of retinal function. Macular recovery time and oscillatory potentials in normal subjects

We evaluated different aspects of 1) psychophysical and 2) electrophysiological testing procedures of retinal function, represented by macular recovery time (nyctometry) and oscillatory potentials (electroretinography), respectively. Ninety healthy males, aged 18-28 years, were used in the study. We registered two different phases of macular recovery time, IRT: initial recovery time (less than 40 sec) and AUC: area under the curve (less than 120 sec) and both individual and summed nodes of oscillatory potentials (OPs). A significant effect of training was observed in monocular registration of IRT and AUC (P less than 0.01), and the superiority of binocular recovery was numerically compared to monocular recovery (P less than 0.01). The inter-variability (coefficient of variation) of IRT was high (40%) in both monocular and binocular registrations, while AUC had a smaller variability binocularily than monocularily (33% vs 21%). The inter-variability of OPs was low (16%). Intra-variability, between first and second eye tested, showed highly correlated values in IRT, AUC and OPs (r = 0.51-0.82; P less than 0.004), while IRT/AUC was not correlated to amplitudes of OPs. The results emphasize that selecting one eye, mean of two eyes or both eyes are critical for accuracy and validity in psychophysical testing of visual performance.     

The effect of short-term near-normal blood glucose control on oscillatory potential and macular recovery time in insulin-dependent diabetic patients with long-standing metabolic dysregulation

Seven insulin-dependent diabetic patients (mean age 36 years and mean duration of diabetes 19 years) underwent intensified treatment with continuous subcutaneous insulin infusion (CSII) for one week. The patients were selected for the study due to long-standing hypergycemia in an endeavour to determine possible influence on retinal neurosensory function by even short-term near-normalization of blood glucose concentrations. During CSII treatment, near-normalization of the blood glucose levels was obtained (mean blood glucose concentration before treatment; 13.7 +/- 1.6 mmol/l-during treatment; 6.3 +/- 0.4 mmol/l. Recording of the oscillatory potentials by electroretinography and the macular recovery by nyctometry remained about the same in the course of this short-term treatment. Our study suggests that short-term strict metabolic control does not reverse the retinal neural abnormalities in long-standing insulin-dependent diabetes. Consequently; this regimen does not enable prediction of possible beneficial effect of sustained near-normoglycemic treatment.     

Macular recovery function (nyctometry) in diabetics without and with early retinopathy.

Nyctometry was used to assess macular recovery function in 234 diabetic patients; their retinopathy ranged from no retinopathy (99) to early background retinopathy (135). None had visual symptoms or macular oedema. Abnormal (reduced) nyctometry findings were significantly and directly related to the deterioration of diabetic retinopathy. There was no significant association between reduced or normal nyctometry findings and glycaemia at the time of the examination. The value of nyctometry in screening and follow-up is discussed.     

Macular recovery time, diabetic retinopathy, and clinical variables after 7 years of improved glycemic control.

Effects of long-term improved glucose control on neurosensory retinal function are investigated. Changes in macular recovery of nyctometry (photostress) are assessed in 45 insulin-dependent diabetic patients between study start and after 7 years prospective follow-up (the Oslo Study). Intensified insulin treatment improved glycosylated hemoglobin (HbA1) from 11.7 +/- 2.2% at start to a 7-year cumulative mean of 9.5 +/- 1.5% (p less than 0.0001). Improved macular recovery performance was observed in patients with 7-year mean HbA1 below 10%, compared to a worsening in those above 10% (p less than 0.001-0.02), and non-proliferative retinopathy progressed less in those with HbA1 below 10%, than in those above (p less than 0.01). Macular recovery at study start did not predict progression or outcome of retinopathy 7 years later. Intraocular pressure fell during the 7 years (p less than 0.001) and was cross-sectionally negatively correlated to macular recovery at the 7-year end-point (p less than 0.001-0.002). Macular recovery was not related to age, duration of diabetes, systemic blood pressure, or urinary albumin excretion level. The study indicates that severity of retinopathy, glycemic control and intraocular pressure are interesting covariants to neurosensory dysfunction in diabetes. Furthermore, the study suggests a critical level of long-term blood glucose or retinopathy, or both, above which neurosensory function of macular recovery is significantly reduced.     

Diabetic retinopathy after 3 years' treatment with continuous subcutaneous insulin infusion (CSII)

Twenty-four insulin-dependent juvenile diabetics with no or minimal background retinopathy were randomly allocated to conventional insulin therapy (CIT) or continuous sc insulin infusion (CSII) administrated by a portable pump. At the present 3 year follow-up, there was one drop-out in the CSII group. Although the metabolic control was significantly better in the CSII patients, both groups improved significantly in metabolic control during the observation period. After 3 years, the HbA lc level was 7.4% +/- 1.2 (+/- SD) in the CSII patients and 8.6% +/- 1.6 in the CIT patients (P less than 0.01). As compared to the status at the beginning of the study, a progression of diabetic retinopathy (criteria: development of more than 2 microaneurysms) was observed in 4 of 11 in the CSII group and in 5 of 12 in the CIT group (P greater than 0.05). None of the patients were seen to develop soft exudates or neovascularisations. This study confirms the impression gained from a previous one-year follow-up of similar progression of retinopathy in patients on CSII and CIT.     

Macular recovery during onset and development of diabetic retinopathy in childhood and adolescence

The relationship between the macular recovery recorded by nyctometry and the retinal findings was examined in 60 initially pre-pubescent children with insulin-dependent diabetes mellitus during a 6-year period with special reference to the clinical applicability of nyctometry in selecting children and adolescents at risk of developing proliferative diabetic retinopathy. At the end of the study period the mean age of the patients was 21.9 years (range 18-23 years) and the mean diabetes duration 13.2 years (range 8.1-21.2 years). At the initial recording of macular recovery, only 7% of the children showed retinopathy, and this only in the form of a few microaneurysms or dot haemorrhages. During the study period, however, nearly all (93%) developed retinopathy, and in 9 (14%) the disease progressed into proliferative retinopathy. The initially recorded macular recovery time (MRI) of those children developing proliferative retinopathy was significantly lower (616 +/- 95; X +/- SEM) compared to the initial MRT performances (900 +/- 47) of the rest of the children. However, due to a high coefficient of variation in the material; predictive sensitivity showed low (56%) at a specificity level of 90%, suggesting that nyctometry is less suitable for selecting risk patients in children than in adults.     

Local macular electroretinographic responses in idiopathic central serous chorioretinopathy

Using focal stimuli to human macular regions, we recorded electroretinograms in 24 patients with central serous chorioretinopathy of recent onset (mean visual acuity, 20/20). The stimulus spot was 10 degrees in diameter. Intact fellow eyes served as controls. The local macular electroretinograms of the affected eyes were significantly reduced and the implicit time in each component was significantly prolonged. The mean (+/- S.D.) amplitudes, expressed as percentages of mean amplitudes recorded in fellow eyes, were 64.6% +/- 22.7% (a-wave), 49.6% +/- 21.0% (b-wave), and 15.0% +/- 21.6% (oscillatory potentials). Two to five months after the macular detachment resolved, recordings in 18 patients showed remarkable recovery of a- and b-waves and shortened implicit times. However, the oscillatory potentials showed significantly small recovery in amplitude. Since oscillatory potentials and b-waves were significantly more deteriorated than a-waves in the presence of macular detachment, and oscillatory potentials showed selective delay of recovery in the convalescent stage, central serous chorioretinopathy may involve functional disturbances in the inner retinal layer as well as the photoreceptors.     

Effects of intensified insulin treatment on retinal vessels in diabetic patients.

Forty-five diabetic patients were randomly assigned to treatment with continuous subcutaneous insulin infusion (CSII), multiple injections (MI), and conventional insulin treatment (CIT). They were prospectively followed up for one year. A computerised scanning microdensitometer was applied on fundus photographs of retinal vessels, and we studied changes in calibres of the blood column (W0) and in width (Wr/W0) and intensity (Ir) of the central 'light reflex'. After six months of improved metabolic control the Ir was reduced in both MI and CSII cases compared with CIT cases (p less than 0.01), indicating haemorrheological changes in the retinas. Within these six months cotton-wool spots appeared in half the patients (n = 15) on CSII and MI, but not in CIT patients. Subjects who developed cotton-wool spots, compared with those who did not, had greater intensities of reflection and larger calibres of vessels at the start of the study (p less than 0.01). On intensifying the treatment they were characterised by a larger fall in hemoglobin A1 (p less than 0.01) and by a larger decrease in Ir on arteries (p less than 0.05) and veins (p less than 0.01). The behaviour of the retinal circulation is different in patients developing transient ischaemic lesions on intensified insulin treatment from its behaviour in those who do not.     

Methodologic dependence of electroretinogram oscillatory potential amplitudes

The International Society for Clinical Electrophysiology of Vision (ISCEV) protocol for eliciting oscillatory potentials uses a considerably lower flash intensity and a different preconditioning stimulus than the only oscillatory potential protocol used to predict progression of diabetic retinopathy. To determine if the ISCEV protocol will be useful in predicting progression of diabetic retinopathy, summed oscillatory potential amplitudes were measured by both protocols in a population of diabetics. Summed oscillatory potential amplitudes measured by the ISCEV protocol, although smaller, are highly correlated with the summed oscillatory potential amplitudes measured with the higher-intensity flash. Thus, summed oscillatory potential amplitudes measured with the ISCEV protocol should be useful in predicting outcome in diabetic retinopathy. Different signal processing filters used to extract oscillatory potentials from the electroretinogram waveform have a small, but significant, effect on summed oscillatory potential amplitude. Use of the caliper-square method or the summed peak-to-trough method for measuring oscillatory potential heights had an insignificant effect on measured oscillatory potential amplitude.Abbreviation FIR finite impulse response     

Asymmetry of focal ERG in human macular region

Electroretinograms (ERGs) were elicited by hemicircular (half-disc) stimuli to the upper, lower, temporal and nasal maculas of 26 normal subjects, and the amplitudes and implicit times of the ERGs from opposing macular regions were compared. The amplitudes of a-wave, b-wave and oscillatory potentials (OPs) were significantly larger in the upper macular region than in the lower macular region (P less than 0.05). The amplitudes of a- and b-waves did not differ significantly between temporal and nasal macular regions, but OPs showed enormous asymmetry, with significantly larger amplitudes in the temporal retina than in the nasal retina (P less than 0.001). The implicit times of a-waves, b-waves and OPs did not differ significantly between upper and lower retina, or between temporal and nasal retina. These findings aided analysis of the ERG of a patient with a retinal defect.     

Electroretinographic oscillatory potentials in diabetic retinopathy

The oscillatory potentials of the electroretinogram in dark and light adaptation were evaluated by Fourier transform in 87 diabetics and 74 age-matched controls. The study consisted of four groups: normal control, no observable diabetic retinopathy, background diabetic retinopathy and proliferative diabetic retinopathy. A reduction in the amplitude of each oscillatory potential, the summed amplitudes, the area and the total power of the oscillatory potentials as well as delayed implicit time of each oscillatory potential peak in dark and light adaptation could be found in patients with background diabetic retinopathy and proliferative diabetic retinopathy. The amplitude of oscillatory potential 4 in dark adaptation and the total power of the oscillatory potentials in light adaptation seemed to be affected in patients with no observable diabetic retinopathy. The implicit time of oscillatory potential 2 in dark adaptation was valuable to distinguish between patients with no observable diabetic retinopathy and background diabetic retinopathy.Abbreviations NC normal control - NDR no observable diabetic retinopathy - BDR background diabetic retinopathy - PDR proliferative diabetic retinopathy     

Abnormal focal macular electroretinograms in eyes with idiopathic epimacular membrane.

PURPOSE: To study the functional state of the retina beneath an epimacular membrane by means of focal macular electroretinography. METHODS: Focal macular electroretinograms of 30 consecutive patients (age 25 to 75 years) with unilateral idiopathic epimacular membrane were recorded prospectively. The amplitudes and implicit times of the a and b waves and the oscillatory potentials (O1, O2, O3) recorded from the eye with idiopathic epimacular membrane were compared with those of the normal fellow eye. RESULTS: There was a statistically significant reduction in the amplitude of the a wave (P < .001), the b wave (P < .001), and the oscillatory potentials (O1 + O2 + O3; P < .001) of the affected eyes. The reduction of the b-wave amplitude was significantly greater than that of the a wave, resulting in a lower b/a wave ratio (P = .003) in the affected eyes. The reduction in the amplitude of the oscillatory potentials was significantly greater than that of the other two components (P < .001). The implicit times were significantly prolonged for the a wave (P < .001), the b wave (P = .004), and 03 (P < .001). There was a significant correlation between relative b-wave amplitude (affected/normal fellow eye) and the visual acuity (r = -0.50, P = .007). These findings were similar to those we reported for eyes with aphakic cystoid macular edema. CONCLUSIONS: The focal macular electroretinograms in eyes with epimacular membrane disclosed abnormalities that were similar to those of eyes with cystoid macular edema. This suggests that the epimacular membrane probably induced damage to the neurons in the inner retinal layers. Dysfunction of these neurons is one possible cause of visual impairment in this disease.     

年龄相关性萎缩型黄斑变性OCT和电生理检查的关系

目的将年龄相关性萎缩型黄斑变性患者黄斑区的OCT形态学检查及视觉电生理视功能检查相结合,探讨该病变黄斑部形态学改变与视功能改变之间的相互关系。方法选取初次诊断为年龄相关性萎缩型黄斑变性患者35例（40眼）以及同年龄段正常对照20例（40眼）,分别设为萎缩组和正常组。对两组分别进行黄斑中心凹的OCT检查及眼电生理检查,眼电生理检查包括视网膜电图（electroretinogram,ERG）和图形视觉诱发电位（pattern visual evoked potential,P-VEP）。采用独立样本t检验分析检查结果。结果①黄斑中心凹水平及垂直神经上皮层厚度：萎缩组与正常组差异无统计学意义（P〉0.05）。②暗适应ERG：萎缩组较正常组有b波潜伏期的延长（P〈0.05）和a、b波振幅的下降（P〈0.05）;萎缩组a波潜伏期与正常组相比,差异无统计学意义（P〉0.05）。③Ops振荡电位：萎缩组幅值较正常对照组显著下降（P〈0.05）。④P-VEP：萎缩组较正常组（空间频率34′）潜伏期显著延长（P〈0.05）,振幅显著下降（P〈0.05）。结论对于萎缩型黄斑变性患眼,眼电生理的变化早于OCT变化。这说明,年龄相关性萎缩型黄斑变性患者视功能改变早于视网膜神经上皮层的厚度改变,对于早期患者可优先选择电生理检查。     

糖尿病视网膜病变临床前期的视功能变化分析

目的:观察糖尿病视网膜病变临床前期患者的图形视觉诱发电位、视网膜振荡电位以及视神经纤维层厚度的变化,评估糖尿病视网膜病变临床前期视功能的变化.方法:收集糖尿病视网膜病变临床前期的2型糖尿病患者89例,以及健康志愿者80例.均采用罗兰电生理检查系统检测图形诱发电位(P-VEP)的P100潜伏期和振幅、视网膜振荡电位(Ops)总振幅和各子波振幅,以及RTVueOCT检测视神经纤维层厚度(RNFL),对检测结果进行比较分析.结果:糖尿病组患者的P100潜伏期比正常对照组的P100潜伏期明显延长,差异有统计学意义(t=-10.633,P=0.000).糖尿病组患者的P100振幅比正常对照组的P100振幅明显降低,差异具有统计学意义(t=3.610,P=0.000).糖尿病组患者OPS总振幅及各子波振幅均比正常对照组OPS总振幅及各子波振幅明显降低,差异具有统计学意义(t=17.320,P=0.000;t=3.239,P=0.000;t=4.144,P=0.000;t=7.666,P=0.000;t=5.319,P=0.000).与正常对照组相比,糖尿病组患者的平均RNFL厚度及鼻侧、下方及颞侧RNFL厚度均无明显改变,差异无统计学意义(t=1.730,P=0.085;t=0.664,P=0.547;t=1.923,P=0.063;t=1.814,P=0.072).而上方RNFL厚度明显变薄,与正常对照组相比差异显著(t=7.989,P=0.000).结论:在糖尿病视网膜病变临床前期的患者,视乳头及黄斑区均出现了视功能改变.     

Oscillatory potentials in electroretinographic evaluation of retinal function in insulin-dependent diabetics without retinopathy

PURPOSE: Can oscillatory potentials be a useful method for detection of retinal dysfunction in insulin-dependent diabetics without retinopathy? MATERIAL AND METHODS: In this study scotopic oscillatory potentials (OPs) were obtained in 35 subjects (70 eyes) with insulin-dependent diabetes without retinopathy (mean disease duration--5 years) and in 15 healthy subjects (30 eyes). This examination was performed according to the recommendations of the International Society of Clinical Electrophysiology of Vision (ISCEV). The oscillatory potentials were extracted from the maximal combined response by high-pass filtering. We analysed amplitude and peak-latencies of the first three electroretinographic oscillatory potentials O1, O2, O3, index of wavelets [sum of amplitudes (O1 + O2 + O3)] and compared with the results of the control group. RESULTS: In group of patients with insulin-dependent diabetes without retinopathy, we received statistically significant reduction of amplitude O1 (p < 0.003) and index of wavelets (p < 0.04). Reduced amplitude O1 was obtained in 10%, index of wavelets in 31.4% of analysed eyes. We didn't observe statistically significant changes in amplitudes O2, O3 and latencies O1, O2, O3. CONCLUSIONS: Our results suggest that retinal dysfunction is present in insulin-dependent diabetics without retinopathy 5 years after onset of the disease. The sum of amplitudes (O1 + O2 + O3) was the most sensitive parameter of retinal abnormalities. It seems reasonable to have more frequent ophthalmological examination of the diabetics with abnormal oscillatory potentials.     

Weber''s law for position is incidental rather than fundamental

Purpose: To compare the visual functions of a group of young patients with insulin dependent diabetes mellitus (IDDM) to a control group, and identify those with retinopathy and assess the influence of metabolic control.
Methods: A group of IDDMs (aged 10–21 years), were examined for two years at the UHW ( n = 123). Fundus photography and ophthalmoscopy were performed under mydriasis. Visual acuity, colour vision (desaturated D15), contrast sensitivity (Vistech VCTS 6500) and metabolic control were assessed. In a subgroup ( n = 7), accommodation, macular threshold, central visual fields and dark adaptation were measured.
Results: IDDMs made significantly more errors with the desaturated D15 than the control group, and had higher macular thresholds and lower amplitudes of accommodation ( P < 0.05). IDDMs with retinopathy had significantly poorer metabolic control (HbA1) than those without.
Conclusion: Colour vision differed significantly between IDDMs and the control group. Fifty-two IDDMs exhibited diabetic retinopathy. The need for good metabolic control is demonstrated.     

Development of the electroretinographic oscillatory potentials in normal and ROP rats

PURPOSE: To study the development of the electroretinographic (ERG) oscillatory potentials (OPs) in rats and to compare normal OPs with those in a rat model of retinopathy of prematurity (ROP). METHODS: Following a longitudinal design, ERG responses to a greater than 5 log unit range of full-field stimuli were recorded in dark-adapted rats at postnatal day (P) 18, P31, P47, and P67. The ERG records were digitally filtered (60-235 Hz), and the trough-to-peak amplitudes and implicit times of OP2, OP3, OP4, and OP5 were measured. Additionally, rats with oxygen-induced retinopathy, a model of ROP, were studied at P31. RESULTS: Generally, OP amplitude increased and implicit time decreased with increasing stimulus intensity. The shape of the stimulus-response functions changed with age. The amplitudes of OP2, OP3, and OP4 were largest at P31. OP5 was largest at P47. All OPs were significantly affected in ROP rats; OP5 was least affected by ROP. CONCLUSIONS: A prolonged normal course of OP development, which featured waxing and waning of amplitudes, was observed and might have been consequent to maturation and then to final refinements of inner retinal circuitry. In ROP rats, marked attenuation of early OPs was consistent with persistent dysfunction of photoreceptors, and significant attenuation of the late OP5 was evidence of compromised function of inner retinal circuitry.     

Function and morphology of macula before and after removal of idiopathic epiretinal membrane

PURPOSE: To study the function and morphology of the macula of the eye before and after the removal of unilateral idiopathic epiretinal membrane (ERM). METHODS: Focal macular electroretinograms (fmERGs) elicited by a 15 degrees stimulus were recorded in 37 eyes of 37 patients with a unilateral ERM. The amplitudes of the a- and b-waves and the oscillatory potentials (OPs) were compared with the corresponding waves in the normal fellow eyes before and after removal of the ERM. In 29 eyes followed up for more than 6 months after surgery, the fmERGs and foveal and parafoveal thicknesses, measured by optical coherence tomography (OCT), were evaluated. RESULTS: Before surgery, the mean amplitudes of all components of the fmERGs were significantly smaller than in the fellow eyes, with the decrease largest for the OPs, followed by the b-waves and then the a-waves. The eyes with less severely reduced a-wave amplitude (>70% of the fellow eyes) had significantly lower b-wave to a-wave (b/a) ratios. After surgery, the amplitudes of the b-wave and OPs were still significantly smaller in the affected eyes. The mean foveal and parafoveal thicknesses were significantly less after surgery; however, the thickness was still more in the affected eyes. The decrease of the OPs remained after surgery and correlated with increased parafoveal thickness (r = -0.460, P = 0.011). CONCLUSIONS: The decreased fmERGs indicate that macular function is impaired in eyes with ERM. The decrease of the b-wave and OPs in the 29 eyes examined after vitrectomy may be due to the still thickened macular retina.     

Reduced oscillatory potentials of the full-field electroretinogram of eyes with aphakic or pseudophakic cystoid macular edema

PURPOSE: To report reduced oscillatory potentials (OPs) in the full-field electroretinogram (ERG) of eyes with aphakic or pseudophakic cystoid macular edema (CME). DESIGN: Observational case series. METHODS: Bright white flash full-field ERGs were recorded from 19 eyes of 19 patients (ages, 53-84 years) with aphakic or pseudophakic CME. Seven of the cases had uncomplicated phacoemulsification (PE) with implantation of a posterior chamber intraocular lens (PC-IOL) and 6 had posterior capsular rupture during phacoemulsification and aspiration with implantation of a PC-IOL. Four additional patients had uncomplicated intracapsular cataract extraction (ICCE), and 2 had secondary anterior chamber intraocular lens after ICCE. Their fellow eyes without CME served as controls. Cystoid macular edema was diagnosed as clinically significant by slit-lamp examination and by fluorescein angiography. The grading for severity of CME was based on the fluorescein angiography. The visual acuity ranged from 20/200 to 20/16. RESULTS: There were no significant differences in the mean amplitudes and implicit times of the a-waves and b-waves between the affected eyes and the fellow eyes. The mean summed amplitude of the OPs was significantly reduced in the affected eyes (P =.0003, Wilcoxon signed rank test). This decrease was strongly correlated with visual acuity (r =.779, P <.0001). The mean implicit time of the first OP was significantly delayed in the affected eyes (P =.0089, Wilcoxon signed rank test). CONCLUSIONS: Because the peripheral retina contributes more significantly to full-field ERGs than the macula, the reduced OP amplitudes of the full-field ERGs in eyes with aphakic or pseudophakic CME suggest a functional impairment not only in the macula but also throughout the retina.     

Reversal of diabetic retinopathy by continuous subcutaneous insulin infusion: a case report.

We report the case history of a 20-year-old diabetic girl with long-standing poorly controlled disease who presented with severe retinopathic features and who was treated with continuous subcutaneous insulin infusion (CSII). When first seen she had macular oedema and a visual acuity of 6/18 in her only eye, together with multiple blot haemorrhages and intraretinal microvascular abnormalities. Marked reversal of the retinal lesions occurred within 65 days of initiating SCII and after only 36 days of constant normoglycaemia. Subsequent good blood glucose control on conventional subcutaneous insulin injections has been achieved, and the retinopathy remains quiescent with a visual acuity of 6/5. We suggest that CSII may be a potentially useful method of arresting and reversing early diabetic retinopathy.