mfERG Amplitudes Research Articles

Microperimetry and mfERG as functional measurements in diabetic macular oedema undergoing intravitreal ranibizumab treatment.

To evaluate Microperimetry (MP) and multifocal electroretinogram (mfERG) as whole-macula functional markers of treatment response in naive diabetic macular oedema (DMO) patients undergoing ranibizumab treatment. An exploratory sub-analysis of a prospective study (NCT01947881-CHARTRES). Patients received three monthly ranibizumab injections (loading dose) followed by pro re nata (PRN) regimen during 1 year. At baseline, during and after treatment (Months 0, 3, 6 and 12), subjects were tested using BCVA, OCT, MP and mfERG. MP was performed in the central 12°, and retinal sensitivity was measured overall (mean sensitivity (MS)), and in three concentric rings (R1-R3). mfERG P1 amplitude and implicit time were measured over six concentric rings (R1-R6). Thirty-two eyes were included. MP mean and rings sensitivity were significantly lower in DMO (p < 0.001). After loading dose, a significant improvement in retina sensitivity was observed, particularly in good BCVA responders (MS = +2.28 dB; R1 = +2.33 dB, R2 = +2.20 dB, R3 = +2.25 dB; p = 0.049). Overall retinal sensitivity was significantly correlated with BCVA improvement (r = 0.54; p = 0.026) and inversely correlated with OCT central subfield thickness improvement (r = -0.39; p = 0.026). mfERG amplitude and implicit time were also lower in DMO (p < 0.011). An improvement of mfERG P1 amplitude and implicit time in R1 was noted in good responders after ranibizumab loading dose (+16.49 nV/deg2; p = 0.013 and -0.005 ms; p = 0.048, respectively). When changing to PRN treatment regimen, BCVA was maintained during the 12 months of follow-up but worsening of the visual function was detected by MP and mfERG. Microperimetry and mfERG were able to demonstrate DMO functional improvement after treatment loading dose, as well as early visual changes when treatment regimen was switched to PRN.

Role of multifocal electroretinogram in assessment of early retinal dysfunction in hypertensive patients.

To investigate localized retinal dysfunction in hypertensive patients using multifocal electroretinogram (mfERG) and to assess its sensitivity as an early predictor for the development of retinopathy in hypertensive patients. Ninety-eight eyes were included in this case-control study. Twenty-eight eyes of healthy subjects served as a control group (group I). Seventy eyes belonged to patients with systemic hypertension assigned into two groups; group II including 39 eyes of hypertensive patients with normal fundus and group III including 31 eyes of patients with signs of hypertensive retinopathy. All participants were subjected to complete ophthalmic and electrophysiological examination using mfERG. N1 and P1 wave amplitudes and implicit times from the central hexagon and four concentric rings across the visual field were analyzed. mfERG amplitudes were significantly reduced in hypertensive group with retinopathy than in controls. N1 amplitude was significantly reduced in the most eccentric ring in eyes of hypertensive patients with normal fundus. mfERG is a sensitive objective tool for assessment of retinal dysfunction in hypertensive patients. mfERG amplitude is a promising predictor for early development of retinopathy in systemic hypertension.

Cone Dystrophies: An Optical Coherence Tomography Angiography Study

Background: This study investigates the relationship between retinal vascularization and macular function in patients with cone dystrophies (CDs). Methods: Twenty CD patients (40 eyes) and 20 healthy controls (20 eyes) were enrolled in this prospective case-control study. Patients underwent full ophthalmological examination, microperimetry, full-field, pattern and multifocal electroretinogram (ERG, PERG, mfERG) and optical coherence tomography angiography (OCTA). Main outcome measures were as follows: foveal and parafoveal inner and outer retinal thickness; microperimetry sensitivity in the central 4° and 8°, ERG b wave amplitudes and peak times, PERG P50 and N95 amplitudes and latencies, and mfERG N1 to P1 amplitudes; and superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillary (CC) plexus vessel densities, divided into foveal and parafoveal region. Results: Retinal thickness, SCP and DCP densities were significantly related to PERG. A significant relationship was found between foveal and parafoveal retinal thicknesses and foveal SCP density (p < 0.001 and p = 0.018, respectively) and between parafoveal retinal thickness and parafoveal SCP density (p = 0.002). Foveal and parafoveal retinal thicknesses were significantly related to parafoveal DCP density (p = 0.007 and p < 0.001). Foveal and parafoveal retinal thicknesses, foveal SCP and parafoveal DPC densities were significantly reduced in CD patients compared to controls (p < 0.001; p = 0.010 and p = 0.008, respectively). PERG and mfERG amplitudes were significantly reduced in CD patients compared to controls (p < 0.01). Conclusions: CD eyes showed reduced retinal thickness significantly related to reduced vessel density, possibly caused by a decreased metabolic demand. In addition, vessel density significantly correlated with loss of function.

Subretinal surgery: functional and histological consequences of entry into the subretinal space.

Gene-therapy, stem-cell transplantation and surgical robots hold the potential for treatment of currently untreatable retinal degenerative diseases. All of the techniques require entry into the subretinal space, which is a potential space located between the retina and the retinal pigment epithelium (RPE). Knowledge about obstacles and critical steps in relation to subretinal procedures is therefore needed. This thesis explores the functional and histological consequences of separation of the retina from the RPE, extensive RPE damage, a large cut in the retina (retinotomy) and RPE phagocytosis in a porcine model. Experiments were performed in 106 female domestic pigs of Danish landrace distributed over five studies. Under general anesthesia, different procedures for expansion of the subretinal space were conducted. Outcomes were visual function measured electrophysiologically with multifocal electroretinogram (mfERG) and retinal morphology examined histologically. Study I: The effect of anesthesia on mfERG was examined by repeated recordings for 3hr in isoflurane or propofol anesthesia. Outcome was mfERG amplitude. Study II: Consequences of a large separation of the photoreceptors from the RPE were examined by injecting a perfluorocarbon-liquid (decalin) into the subretinal space. Two weeks after, in a second surgery, decalin was withdrawn. Outcomes were mfERG and histology 4weeks after decalin injection. Study III: Extensive RPE damage was examined by expanding the subretinal space with saline and removing large sheets of RPE-cells through a retinotomy. Outcomes were mfERG and histology 2, 4 and 6weeks after the procedure. Study IV: Consequences of a large retinotomy were examined by similar procedures as in Study III, but in study IV only a few RPE cells were removed. Outcomes were mfERG and histology 2 and 6weeks after surgery. Study V: Clearance of the subretinal space was examined by injecting fluorescent latex beads of various sizes into the subretinal space. Outcome was histologic location of the beads at different time intervals after the procedure. Study I: MfERG amplitudes decreased linearly as a function of time in propofol or isoflurane anesthesia. Duration of mfERG recording could be decreased without compromising quality, and thereby could time in anesthesia be reduced. Study II: MfERG and histology remained normal after reattachment of a large and 2-week long separation of the photoreceptors and RPE. Repeated entry into the subretinal space was well tolerated. Fluid injection into the subretinal space constitutes a risk of RPE-damage. Study III: Removal of large sheets of retinal pigment epithelial cells triggered a widespread rhegmatogenous-like retinal detachment resulting in visual loss. Study IV: A large retinotomy with limited damage of the RPE was well tolerated, and visual function was preserved. Study V: Subretinal latex beads up to 4μm were phagocytosed by the RPE and passed into the sub-RPE space. Beads up to 2μm travelled further through the Bruch's membrane and were found in the choroid, sclera and inside blood vessels. A large expansion of the subretinal space, repeated entry, a large retinotomy and limited RPE damage is well tolerated and retinal function is preserved. Subretinal injection of fluid can damage the RPE and extensive RPE damage can induce a rhegmatogenous-like retinal detachment with loss of visual function. Foreign substances exit the subretinal space and can reach the systemic circulation.

Central mfERG amplitude ratio as a predictor for visual outcome of macular hole surgery

To investigate whether visual acuity improvement achieved after surgical treatment for macular hole (MH) can be predicted by preoperative multifocal ERG (mfERG) central/peripheral amplitude ratio. Thirty patients with unilateral MH were included. Evaluations with comprehensive ophthalmological examination including best-corrected visual acuity (BCVA) were performed at baseline and 1, 3, 8, 24 and 48weeks after surgery, while mfERG (Diagnosys LLC; 61 hexagons-30°) and spectral-domain optic coherence tomography (sOCT-Heidelberg Engineering) were performed at baseline and 2months after surgery. mfERG results are shown by means of the ratio between the amplitudes' average from rings 1 and 2 (central) and rings 4 and 5 (peripheral): the P1 ratio. mfERG data from 20 normally sighted age-matched subjects was used for comparison. A macular hole index (MH index) was defined as the quotient between hole height and base measured on OCT. Twenty-six patients finished the 48-week follow-up. Mean ± SE (logMAR) preoperative BCVA was 0.93 ± 0.22 and improved in 0.25 ± 0.07 at 48weeks. mfERG P1 ratio was reduced at baseline and increased significantly after surgery. A significant correlation was observed between preoperative P1 ratio and BCVA gain at week 8 (r = -0.42; P = 0.033). There was no significant correlation between preoperative MH index and postoperative BCVA (P > 0.05). Retinal function assessed using the ratio between central and peripheral mfERG responses might be used as predictor of visual acuity outcome after macular surgery for MH.

Loss of retinal tension and permanent decrease in retinal function: a new porcine model of rhegmatogenous retinal detachment.

PurposePermanent loss of visual function after rhegmatogenous retinal detachment can occur despite successful surgical reattachment in humans. New treatment modalities could be explored in a detachment model with loss of retinal function. In previous porcine models, retinal function has returned after reattachment, regardless of height and duration of detachment. Difference in retinal tension between the models and the disease might explain these different outcomes. This study investigates, for the first time in an in vivo porcine model, another characteristic of rhegmatogenous retinal detachment – the loss of retinal tension.MethodsLeft eyes (n = 12) of 3‐month‐old domestic pigs were included. Baseline multifocal electroretinogram (mfERG) and a fundus photograph were obtained following anaesthesia (isoflurane). The pigs were vitrectomized, saline was injected subretinally, and the RPE was removed. The eyes were evaluated at 2, 4 and 6 weeks after surgery. Four eyes were enucleated at each evaluation for histologic examinations.ResultsA retinal detachment structurally resembling rhegmatogenous retinal detachment was induced in 11 out of 12 pigs. MfERG amplitudes were significantly decreased despite partial reattachment four and 6 weeks after detachment. The retinal thickness decreased with 27%, the inner nuclear layer degenerated, Müller cells hypertrophied, and outer segments were lost. In the ganglion cell layer, cellularity increased and there was cytoplasmic staining with Cyclin D1. Vimentin and GFAP staining for glial cells increased. After 2 weeks of detachment, the ganglion cells had lost their nucleus and nucleolus.ConclusionsLoss of retinal tension in the detached retina seems to induce permanent damage with loss of retinal function. Death of ganglion cells, observed as soon as 2 weeks after detachment, explains the permanent loss of retinal function. The new model enables investigations of time‐relationship between retinal detachment and lasting damage in addition to exploration of novel treatment modalities.

Correlation between electroretinography, foveal anatomy and visual acuity in albinism.

Albinism patients have poor visual acuity in addition to hypopigmentation. Their foveal anatomy is abnormal, but correlation with function is incompletely understood. This study correlates retinal electrophysiology, visual acuity and optical coherence tomography (OCT) anatomy in albinism patients and compares with age-similar controls. Institutional Review Board approval was obtained (IRB# 201408782). Patients were recruited from clinical practice. Inclusion criteria were at least three clinical features of albinism including iris transillumination, nystagmus, fundus hypopigmentation, or foveal hypoplasia on OCT and/or molecular genetic confirmation. Diagnosys (Lowell, Mass) full-field ERG (ffERG) and VERIS multifocal ERG (mfERG; Electro-Diagnostic Imaging, Milpitas, California) were obtained using standard International Society for Clinical Electrophysiology of Vision protocols. The mfERG protocol was a 4-min 103-hexagon protocol covering approximately 40° in diameter of central retina. Control subjects without albinism were recruited by in-hospital notices and invitations in clinic. OCT central thickness was recorded, and an OCT foveal score was calculated. Nonparametric permutation testing was utilized to determine the statistical significance. A total of 16 albinism patients and 19 age-similar controls were recruited. Four of 16 albinism patients had no nystagmus. Seventeen non-albinism controls had no ocular disorder other than refractive error. Two controls had infantile nystagmus with normal maculas on OCT. There was no statistically significant difference in mfERG amplitude or latency between albinism patients with or without nystagmus (lowest p = 0.68; 0.54, respectively). mfERG: 12 of 16 (75%) albinism patients had average ring 1 amplitudes within one standard deviation of controls despite having abnormal foveal anatomy on OCT. Patients averaged shorter latencies in rings 1 and 2 than controls (p = 0.005, p = 0.02). Patients averaged higher amplitudes than controls in rings 4, 5 and 6 (p = 0.03, p = 0.006, p = 0.004). There was no significant correlation between visual acuity and mfERG amplitudes in any ring (smallest p = 0.15). ffERG: Patients averaged higher amplitudes on 30Hz flicker (p = 0.008). In all conditions, albinism patients had higher amplitude a-waves (p ≤ 0.03). B-waves were higher amplitude than controls in light-adapted 3.0 (p = 0.03). There was no statistical correlation between ffERG amplitudes and visual acuity (smallest p = 0.45). OCT: In albinism patients, thicker central macula on OCT correlated with lower mfERG amplitudes in all rings except for ring 1 (p < 0.05) and lower ffERG a-wave amplitudes on dark-adapted 0.01 (p = 0.003). Macular thickness on OCT did not correlate with visual acuity (p = 0.51); OCT foveal score did (p = 0.0004). Amplitude of mfERG does not correlate with visual acuity in any ring in patients with albinism. The slope of the change in amplitude from central to peripheral rings on the mferg is significantly different in albinism patients versus controls whether or not nystagmus is present. The decreased slope of change in amplitudes from center to periphery of the macula in albinism patients indicates changes in macular topography that are more important to visual deficits than the foveal depression.

Multifocal Electroretinography in Assessment of Macular Function after Internal Limiting Membrane Peeling in Macular Hole Surgery.

Purpose Internal limiting membrane (ILM) peeling is important for macular hole (MH) surgery but may have secondary effects visible on spectral domain optical coherence tomography (OCT) and multifocal electroretinography (mfERG). We relate integrity of inner and outer macular layers with functional results with mfERG. Methods Nonrandomized prospective study of 33 consecutive eyes of 33 patients with macular hole who underwent vitrectomy with ILM peeling. Best-corrected visual acuity was assessed, and integrity of external layers was measured using OCT. Each component of mfERG, N1 and P1 amplitude and latency, was also measured. Results All eyes showed macular hole closure. Visual acuity improved from 20/400 to 20/40 in the Snellen visual acuity chart (P < 0.001), and OCT external lines were intact in 19 eyes and disrupted in 14 eyes. Postoperatively, N1 and P1 amplitudes in ring 1 increased compared to preoperative values (P < 0.001 for both). Latency remained delayed for both N1 and P1 wave. In the group of 19 eyes with integrity of outer retinal layers, N1 amplitude in ring 1 was superior to the group of 14 patients with disrupted outer retinal layers (P=0.042). Conclusions In macular hole surgery, structure analysis in OCT is one of the important outcomes for the retinal surgeon. Functional results are parallel with anatomic results, but visual gain is limited. The limited recovery in mfERG suggests an alteration of retinal physiology that could explain limited vision recover.

Neurodegenerative changes of the retina in patients with diabetes

To investigate the morphological and functional state of the outer and inner layers of the retina in patients with diabetes mellitus (DM) and nonproliferative diabetic retinopathy (NPDR), to determine the presence and nature of the relationships between structural and functional changes. The study included 50 patients with subcompensated diabetes and NPDR and 40 people from the control group (healthy). All patients underwent OCT of the retina and optic nerve using RTVue-100 apparatus (Optovue, USA), as well as multifocal electroretinography (mfERG) and pattern electroretinography (PERG) on EP-1000 Multifocal device ('Tomey GmbH', Germany). When analyzing the results of OCT in patients with NPDR, a decrease in the total thickness of the retina and the thickness of its inner layers in the fovea and parafovea regions was found in comparison with the control group (p<0.001), thinning of the retinal ganglion cell (GCS) complex with increased focal losses (FLV) of up to 1.4% (Mann-Whitney test, p=0.001). In the group of patients with diabetes, there was a statistically significant decrease in the density and amplitude of P1 mfERG in all five 'rings' (Mann-Whitney test, p<0.001), increase in implicit time in the first 3 rings, decrease in P50 and N95 amplitude, increase in implicit time of N95 PERG (p=0.001) compared to the control group. The study revealed changes in the structure and functioning of the outer and inner layers of the retina in patients with NPDR, and established a reliable correlation between the morphological parameters (according to the OCT) and electrophysiological parameters (according to the mfERG and PERG data).

Morphological and Functional Inner and Outer Retinal Layer Abnormalities in Eyes with Permanent Temporal Hemianopia from Chiasmal Compression.

The aims of this study are to compare optical coherence tomography (OCT)-measured macular retinal layers in eyes with permanent temporal hemianopia from chiasmal compression and control eyes; to compare regular and slow-flash multifocal electroretinography (mfERG) in patients and controls; and to assess the correlation between OCT, mfERG, and central visual field (SAP) data. Forty-three eyes of 30 patients with permanent temporal hemianopia due to pituitary tumors who were previously submitted to chiasm decompression and 37 healthy eyes of 19 controls were submitted to macular spectral domain OCT, mfERG, and 10-2 SAP testing. After segmentation, the thickness of the macular retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer, and photoreceptor layer (PRL) was measured. Amplitudes and oscillatory potentials (OPs) were measured on regular and slow-flash mfERG, respectively, and expressed as the mean values per quadrant and hemifield. RNFL, GCL, and IPL thickness measurements were significantly reduced in all quadrants, whereas INL, OPL, and PRL thicknesses were significantly increased in the nasal quadrants in patients compared to those in controls. Significant correlations between OCT and 10-2 SAP measurements were positive for the RNFL, GCL, and IPL and negative for the INL, OPL, and PRL. OPs and mfERG N1 amplitudes were significantly reduced in the nasal hemiretina of patients. Significant correlations were found between OP and mfERG amplitudes for inner and outer nasal hemiretina OCT measurements, respectively. Patients with permanent temporal hemianopia from previously treated chiasmal compression demonstrated significant thinning of the RNFL, GCL, IPL, and thickening of the INL, OPL, and PRL associated with reduced OP and mfERG N1 amplitudes, suggesting that axonal injury to the inner retina leads to secondary damage to the outer retina in this condition.

Effect of axial length on full‐field and multifocal electroretinograms

PurposeThe aim was to investigate the effect of axial length on full‐field electroretinogram (ffERG) and multifocal electroretinogram (mfERG) in young Indian subjects.MethodsOne hundred subjects (44 male) with refractive errors from +0.50 to −18.00 DS and no myopic retinopathy underwent axial length measurement. ffERG was measured, which included scotopic and photopic responses according to International Society for Clinical Electrophysiology of Vision (ISCEV) guidelines. The mfERG was recorded after correcting for refractive error according to ISCEV standards. The dark‐adapted and light‐adapted parameters of ffERG and N1, P1 parameters of six rings in mfERG were analysed with axial length, controlled for refractive error. The subjects were divided into seven groups based on axial length. The b/a ratio of dark‐adapted and light‐adapted 3.0 ffERG and P1/N1 ratio of mfERG amplitudes were analysed for seven groups of axial length.ResultsThe axial length ranged from 21.79 to 30.55-mm. Significant negative correlations were noted for ffERG and mfERG amplitudes, whereas implicit times showed minimal delay with increase in axial length. In ffERG, the scotopic responses were more decreased compared to photopic responses. In mfERG, P1 and N1 amplitudes were significantly decreased in all the rings in all groups and more reduction was noted in the central ring compared to peripheral rings. The P1 amplitudes were more affected as compared to N1 amplitudes. The light‐adapted and dark‐adapted 3.0 ERG b/a ratio and P1/N1 ratio for seven axial length groups did not show statistically significant difference. The ERG parameters were not significant with refractive error.ConclusionThis study quantifies the relationship of axial length with ffERG and mfERG parameters in a young Indian population. Although the amplitudes were reduced significantly, the implicit times were not significantly affected. The ERG parameters were more related to axial length than refractive error. Hence, interpretation of ffERG and mfERG parameters needs careful consideration in subjects with increasing axial length.

Structural and functional assessment after intravitreal injection of ranibizumab in diabetic macular edema.

To evaluate structure and function improvement in central retina by optical coherence tomography (OCT) and multifocal electroretinography (mf-ERG) in diabetic macular edema (DME) patients after intravitreal injection of ranibizumab (IVR) treatment. Twenty-seven eyes in 27 patients with DME received three consecutive monthly injections of IVR (0.05ml, 10mg/ml) and as needed thereafter. The clinical parameters of best-corrected visual acuity (BCVA), central foveal thickness (CFT) and mf-ERG were monitored for 6months before and after IVR. The findings at baseline, 1, 3 and 6months were analyzed. Correlation and regression analyses were performed on BCVA, CFT, mf-ERG amplitude and implicit time of the N1 and P1 waves. IVR significantly improved visual acuity from the beginning of the treatment (P<0.05). There were significant decreases in the CFT compared with the baseline after IVR (P<0.05). The mean amplitude of P1 and N1 in the central ring at all examinations increased significantly compared with the baseline (P<0.05). The mean P1 and N1 implicit times in the central ring were shortened, but not significantly (P>0.05). There were significant correlations of BCVA with CFT, P1 and N1 amplitudes in the central retina (P<0.05). In addition to the improvement in BCVA and the reduction in CFT, IVR improved macular retinal function, as assessed by mf-ERG, in diabetic eyes. The combination of OCT and mf-ERG for macular evaluation may better assess DME.

Multifocal ERG Responses in Subjects With a History of Preterm Birth.

PurposeThe purpose of this study is to assess cone-mediated central retinal function in children with a history of preterm birth, including subjects with and without retinopathy of prematurity (ROP). The multifocal electroretinogram (mfERG) records activity of the postreceptor retinal circuitry.MethodsmfERG responses were recorded to an array of 103 hexagonal elements that subtended 43° around a central fixation target. The amplitude and latency of the first negative (N1) and first positive (P1) response were evaluated in six concentric rings centered on the fovea. Responses were recorded from 40 subjects with a history of preterm birth (severe ROP, mild ROP, no ROP) and 19 term-born control subjects.ResultsThe amplitude of N1 and P1 varied significantly with eccentricity and ROP severity. For all four groups, these amplitudes were largest in the center and decreased with eccentricity. At all eccentricities, N1 amplitude was significantly smaller in severe ROP and did not differ significantly among the other three groups (mild ROP, no ROP, term-born controls). P1 amplitude in all preterm groups was significantly smaller than in controls; P1 amplitude was similar in no ROP and mild ROP and significantly smaller in severe ROP.ConclusionsThese results provide evidence that premature birth alone affects cone-mediated central retinal function and that the magnitude of the effect varies with severity of the antecedent ROP. The lack of difference in mfERG amplitude between the mild and no ROP groups is evidence that the effect of ROP on the neurosensory retina may not depend solely on appearance of abnormal retinal vasculature.

Time-Dependent Decline in Multifocal Electroretinogram Requires Faster Recording Procedures in Anesthetized Pigs.

PurposeThe time-dependent effect of anesthetics on the retinal function is debated. We hypothesize that in anesthetized animals there is a time-dependent decline that requires optimized multifocal electroretinogram (mfERG) recording procedures.MethodsConventional and four-frame global-flash mfERG recordings were obtained approximately 15, 60, and 150 minutes after the induction of propofol anesthesia (20 pigs) and isoflurane anesthesia (nine pigs). In six of the propofol-anesthetized pigs, the mfERG recordings were split in 3-minute segments. Two to 4 weeks after initial recordings, an intraocular injection of tetrodotoxin (TTX) was given and the mfERG was rerecorded as described above. Data were analyzed using mixed models in SAS statistical software.ResultsPropofol significantly decreases the conventional and global-flash amplitudes over time. The only significant effect of isoflurane is a decrease in the global-flash amplitudes. At 15 minutes after TTX injection several of the mfERG amplitudes are significantly decreased. There is a linear correlation between the conventional P1 and the global-flash DR mfERG-amplitude (R2 = 0.82, slope = 0.72, P < 0.0001). There is no significant difference between the 3-minute and the prolonged mfERG recordings for conventional amplitudes and the global-flash direct response. The global flash–induced component significantly decreases with prolonged mfERG recordings.ConclusionsA 3-minute mfERG recording and a single stimulation protocol is sufficient in anesthetized pigs. Recordings should be obtained immediately after the induction of anesthesia. The effect of TTX is significant 15 minutes after injection, but is contaminated by the effect of anesthesia 90 minutes after injection. Therefore, the quality of mfERG recordings can be further improved by determining the necessary time-of-delay from intraocular injection of a drug to full effect.Translational RelevanceGeneral anesthesia is a possible source of error in mfERG recordings. Therefore, it is important to investigate the translational relevance of the results to mfERG recordings in children in general anesthesia.

Senescent Changes and Topography of the Dark-Adapted Multifocal Electroretinogram.

PurposeTo investigate the topographic changes of the dark-adapted multifocal electroretinogram (mfERG) across adulthood in the central retina and compare the topography between macular versus extramacular, nasal versus temporal, and inferior versus superior retinal areas.MethodsSixty-five subjects (18–88 years) received a comprehensive dilated eye examination to ensure the health of their retina and were tested with a dark-adapted mfERG protocol using a 61-hexagon pattern. The lens absorption of each subject was also estimated using a heterochromatic flicker photometry (HFP) paradigm.ResultsThe response amplitude and latency of the dark-adapted mfERG showed a significant change with age, which was best described with a linear model. All the retinal areas examined demonstrated similar aging effects. The extramacular and temporal retina showed higher response amplitude and faster response latency when compared with the macular and nasal retinae, respectively. No difference was found in response amplitude and latency between the inferior and superior retina. The HFP results also showed a significant correlation with age, consistent with senescent increases in short wavelength absorption by the crystalline lens. However, the change in lens absorption did not exceed the magnitude of the change in response amplitude and latency.DiscussionOur results indicate that there is a decline in dark-adapted retinal activity as measured with the mfERG. These aging processes affect rods and rod-bipolar cells. Their decrease in response can be attributed to both optical and neural factors.

Preserved functional and structural integrity of the papillomacular area correlates with better visual acuity in retinitis pigmentosa.

PurposeLinking multifocal electroretinography (mfERG) and optical coherence tomography (OCT) findings with visual acuity in retinitis pigmentosa (RP) patients.DesignProspective, cross-sectional, nonintervention study.SubjectsPatients with typical RP and age-matched controls, who underwent SD-OCT (spectral domain OCT) and mfERG, were included.MethodsMfERG responses were averaged in three zones (zone 1 (0°-3°), zone 2 (3°-8°), and zone 3 (8°-15°)). Baseline-to-trough- (N1) and trough-to-peak amplitudes (N1P1) of the mfERG were compared with corresponding areas of the OCT. The papillomacular area (PMA) was analyzed separately. Correlations between best-corrected visual acuity (BCVA, logMAR) and each parameter were determined.Main outcome measuresComparing structural (OCT) and functional (mfERG) measures with the BCVA.ResultsIn RP patients, the N1 and N1P1 responses showed positive association with the central retinal thickness outside zone 1 (P≤0.002), while the central N1 and the N1P1 responses in zones 1, 2, and 3-with the BCVA (P≤0.007). The integrity of the IS/OS line on OCT showed also a positive association with the BCVA (P<0.001). Isolated analysis of the PMA strengthened further the structure-function association with the BCVA (P≤0.037). Interactions between the BCVA and the OCT, respectively, the mfERG parameters were more pronounced in the RP subgroup without macular edema (P≤0.020).ConclusionIn RP patients, preserved structure-function of PMA, measured by mfERG amplitude and OCT retinal thickness, correlated well with the remaining BCVA. The subgroup analyses revealed stronger links between the examined parameters, in the RP subgroup without appearance of macular edema.

The Multifocal On- and Off-Responses in the Human Diabetic Retina.

The characteristics of the on- and off-responses in the human diabetic retina by a “long-duration” multifocal electroretinogram (mfERG) paradigm were investigated. Changes in the retinal antagonistic interaction were also evaluated in the early stage of diabetes mellitus (DM). Twenty type II diabetic patients with no or mild non-proliferative diabetic retinopathy (NPDR) and twenty-one age-matched healthy controls were recruited for “long-duration” mfERG measurements. A 61-hexagon mfERG stimulus was displayed under two chromatic conditions (white/black and blue/black) at matched luminance. The amplitudes and implicit times of the on-response components (N1, P1 and N2) and off-response (P2) components were analysed. The blue stimulation generally triggered greater mfERG amplitudes in P1, N2 and P2 (p<0.05) than those from white stimulation in both control and diabetic groups. The diabetic group showed significantly greater N2 amplitude than the controls under white stimulation in mid-retinal regions (Rings 2 and 4) (p<0.05). When the stimulus was changed from white to blue, the diabetic group showed a smaller percentage change in N2 amplitude than the controls in peripheral retinal region (Ring 5) (p<0.02). When a stimulus is changed from white (broad-band spectral stimulation) to blue (narrow-band spectral stimulation), a decrease in the involvement of lateral antagonism would be expected. The larger amplitude of the on-response component (N2) in the diabetic patients suggested an imbalance of lateral antagonism, and the lesser percentage change of N2 amplitude in the diabetic group may indicate an impairment of the cross-talk at the middle retinal level in early stages of DM.

Fixation stability and implication for multifocal electroretinography in patients with neovascular age-related macular degeneration after anti-VEGF treatment.

To quantify fixation stability in patients with neovascular age-related macular degeneration (nAMD) at baseline, 3 and 6months after anti-vascular endothelial growth factor (anti-VEGF) treatment and furthermore asses the implications of an unsteady fixation for multifocal electroretinography (mfERG) measurements. Fifty eyes of 50 nAMD patients receiving intravitreal anti-VEGF treatment with either bevacizumab or ranibizumab and eight eyes of eight control subjects were included. Fixation stability measurements were performed with the Eye-Link eyetracking system and the retinal area in degrees2 (deg2) containing the 68% most frequently used fixation points (RAF68) was calculated. MfERG P1 amplitude and implicit time were analyzed in six concentric rings and as a summed response. Patients were examined at baseline, 3 and 6months. Four different mfERG recordings were performed for the control subjects to mimic an involuntary unstable fixation: normal central fixation, 2.4°, 4.8°, and 7.1° fixation instability. For control subjects, a fixation instability of 2.4° (corresponding to the central hexagon) did not reduce mfERG ring amplitudes significantly, whereas 4.8° and 7.1° fixation instability reduced the amplitudes significantly in rings 1 and 2 (p < 0.001) as well as in the peripheral rings in the 7.1° instability condition (p < 0.001). Fixation stability improved non-significantly for patients at 3 and 6months. The size of the retinal area of fixation was at baseline, 3 and 6months negatively correlated to visual acuity (VA) (rbaseline = -0.65, r3 months = -0.60, and r6 months = -0.66 respectively, p < 0.001) and mfERG amplitudes of the three innermost rings (rbaseline = -0.29, p = 0.042, r3months = -0.43, p = 0.003 and r6months = -0.31, p = 0.042). The VA cutoff for a fixation area less than 5deg2 (approximately the central hexagon) was 65, 77, and 68 ETDRS letters (corresponding a maximal Snellen equivalent of 0.31) at baseline, 3 and 6months, respectively. MfERG amplitudes in recordings of nAMD patients are at substantial risk of being reduced due to poor fixation as a large number of patients may use a fixation area of more than 5deg2. Fixation monitoring during recording as well as interpretation of results should be performed with care, especially in patients with poor visual acuity.

The effect of nutritional supplementation on the multifocal electroretinogram in healthy eyes.

Previous studies have demonstrated an increase in macular pigment optical density (MPOD) with lutein (L)-based supplementation in healthy eyes. However, not all studies have assessed whether this increase in MPOD is associated with changes to other measures of retinal function such as the multifocal ERG (mfERG). Some studies also fail to report dietary levels of L and zeaxanthin (Z). Because of the associations between increased levels of L and Z, and reduced risk of AMD, this study was designed to assess the effects of L-based supplementation on mfERG amplitudes and latencies in healthy eyes. Multifocal ERG amplitudes, visual acuity, contrast sensitivity, MPOD and dietary levels of L and Z were assessed in this longitudinal, randomized clinical trial. Fifty-two healthy eyes from 52 participants were randomly allocated to receive a L-based supplement (treated group), or no supplement (non-treated group). There were 25 subjects aged 18-77 (mean age ± SD; 48 ± 17) in the treated group and 27 subjects aged 21-69 (mean age ± SD; 43 ± 16) in the non-treated group. All participants attended for three visits: visit one at baseline, visit two at 20 weeks and visit three at 40 weeks. A statistically significant increase in MPOD (F = 17.0, p ≤ 0.001) and shortening of mfERG ring 2 P1 latency (F = 3.69, p = 0.04) was seen in the treated group. Although the results were not clinically significant, the reported trend for improvement in MPOD and mfERG outcomes warrants further investigation.

Is multifocal electroretinography an early predictor of glaucoma?

To investigate the potential use of mfERG as an objective functional test that can express inner and outer retinal changes during the early stages of glaucoma. One hundred and twenty-six eyes of 126 patients were included. There were 30 healthy (Group 1), 28 glaucoma suspect (Group 2), 48 early glaucoma (Group 3), and 20 advanced glaucoma cases (Group 4). After complete ophthalmic examination, Humphrey visual field analysis and mfERG were performed. These examinations were performed three times at 6-month intervals, and only the last examination results were used for the analysis. Visual fields global indices and mfERG implicit time and amplitudes were evaluated and analyzed by ring system (central 5°, 5°-10°, 10°-15° and >15°). One-way ANOVA and ROC curve analysis were used for statistical analysis. There was no statistically (one-way ANOVA) significant differences in patient age between groups (p = 0.126). For all rings, we detected statistically significant differences for the mean implicit time (latency) of the N1, P1, and N2 components between the advanced glaucoma and control subjects and between the advanced glaucoma and glaucoma suspects. The N2 amplitudes were significantly decreased in all rings in the advanced glaucoma patients when compared with control subjects. The N2 amplitude was significantly different between healthy subjects (Group 1) and early glaucoma subjects (Group 3) in the central 2° and 2°-5° rings. We used MedClac ROC curve analysis to identify the best parameters for discriminating between control subjects (Group 1) and early glaucoma patients (Group 3). The N2 implicit time for the central 2° ring (p < 0.0001), N2 amplitude for the central 2° ring (p = 0.0001), P1 implicit time for the 2°-5° ring (p = 0.0001), N2 implicit time for the 2°-5° ring (p = 0.0003), and N2 amplitude for the 2°-5° ring (p = 0.001) had ≥0.7 AUC values and were the best parameters in the ROC curve analyses that included the VFA parameters Alterations of amplitudes and implicit times of N2 response in the central area may be able to detect glaucoma earlier than VFA. In addition, with progression to advanced glaucoma these changes can be significant in all retinal areas. Although implicit times of all mfERG components are significantly delayed in glaucoma, both delayed implicit time and decreased amplitude of N2 wave in the central area are effective predictors in early glaucoma diagnosis.