Mf ERG Research Articles

A New Classification for Retinitis Pigmentosa Including Multifocal Electroretinography to Evaluate the Disease Severity

Aim: To establish a useful and objective classification for retinitis pigmentosa (RP) to evaluate the disease severity. Methods: This is a retrospective cross-sectional study. Visual acuity (VA), visual field (VF) width, ellipsoid zone width on optic cohorence tomography (OCT) and multifocal electroretinography (mf ERG) values were obtained from medical records of patients with RP. A scoring criterion was developed wherein each variable was assigned a score from 0 to 5 depending on its distribution. The cumulative score (from 0 to 20) was used to classify disease severity from grade 0 to 5. The scores were correlated with each other and the final grade. Results: Data of 152 eyes of 92 patients who had the results of all tests were reviewed. The mean age was 41.2 years. The mean VA of the patients was 0.13 ± 0.16 Snellen lines. The majority of patients had a VA less than 20/40 (88.6%), a visual field smaller than 20˚ (78%), and an ellipsoid zone width smaller than 7˚ (84.4%). The majority of the patients (85.4%) were in advanced stage of the disease (Grade 4 and 5). Conclusions: We present a simple, objective and easy to use disease severity classification for RP which can be used to categorize patients and to evaluate and compare treatment results.

First Year Results of Suprachoroidal Adipose Tissue Derived Mesenchymal Stem Cell Implantation in Degenerative Macular Diseases.

Background and ObjectivesThis study shows the clinical data of 1-year follow-up of 8 patients with degenerative macular diseases who received suprachoroidal adipose tissue derived mesenchymal stem cell (ADMSC) implantation.Methods and ResultsThis prospective, single-center, phase 1/2 study enrolled 8 eyes of 8 patients with degenerative macular diseases of various reasons who underwent suprachoroidal implantation of ADMSCs. All patients had severe visual field defects and severe visual loss. All patients had defective multifocal electroretinography (mf ERG). The worse eye of the patient was selected for the operation. Patients were evaluated on the first day, first month, sixth month and at 1 year postoperatively. Best corrected visual acuity (BCVA), anterior segment and fundus examination, color photography, optical coherence tomography (OCT) and visual field (VF) examination were carried out at each visit. Fundus fluorescein angiography (FFA) and mfERG recordings were performed at the end of the sixth months. All 8 patients completed the 1 year follow-up. None of them had any systemic or ocular complications. Seven of the patients experienced visual acuity improvement, visual field improvement and improvement in the mfERG recordings. We found choroidal thickening in OCT of the four treated eyes.ConclusionsEven though the sample size is small, stem cell treatment with suprachoroidal implantation of ADMSCs seems to be safe and the improvements were encouraging. To optimize the cell delivery technique and to evaluate the effects of this therapy on visual acuity and the quality of life of these patients, future studies with larger number of cases will be necessary.

WAGNER syndrome: anatomic, functional and genetic characterization of a Portuguese family.

To report the clinical (anatomic and functional) and genetic findings of Wagner Syndrome (WS) in a Portuguese family. Nine members of the family agreed to be examined. All had complete clinical eye examinations. The proband and selected patients underwent color fundus photography, spectral domain optical coherence tomography (SD-OCT), automatic static white-on-white computerized perimetry, and electrophysiology assessment (flash ERG, multifocal(mf) ERG and dark adaptometry). A pedigree was constructed based on interviews with known affected subjects. Genomic DNA samples derived from venous blood were collected from all affected family members examined. Twenty-eight family members are affected. This family has the typical features of Wagner Syndrome, namely an empty vitreous cavity with veils, mild myopia and cataract. Four examined patients underwent vitreoretinal surgery due to abnormal peripheral vitreoretinal adhesions with peripheral retinal traction (n=3). Retinal detachment was observed in 5 of the examined subjects. Four of them occurred between the ages of 5 and 15years. Chorioretinal atrophy is also a frequent finding which results in moderate to severe visual field and advanced rod-cone dystrophy from younger ages, also confirmed by absence of scotopic function on dark adaptation. The macular dysfunction on mfERG was profound and of early onset. A heterozygous mutation in intron 7 of the VCAN gene (c.4004-1G>A) was found. We described a rare autosomal dominant vitreoretinopathy with near complete penetrance in a Portuguese family. Abnormal peripheral vitreoretinal adhesions, retinal detachment and chorioretinal atrophy are present in most of the examined individuals at young ages. Early onset of advanced visual field and electrophysiologic abnormalities were observed in this family. We also added relevant information to the literature by reporting our experience in surgical management of Wagner Syndrome patients with, and at risk of, retinal detachment.

Correlation of Macular Thickness, Multifocal ERG with Visual Acuity in Oculocutaneous Albinism (OCA)

Background and Aim: Ocular albinism is known to have nystagmus and foveal hypoplasia. A study was done to evaluate the correlation of visual acuity with macular thickness (MT) and mf ERG. Materials and Methods: A total of 20 eyes (10 patients) with OCA were selected. Macular thickness was evaluated with optical coherence tomography and mf ERG was done in all the patients. Results: Mean age was 16.1 ± 7.3 years. The patients were divided into three groups based on their visual acuity > 6/12 (group A), 6/18 - 6/24 (group B), 6/36 or less (group C). Mean MT in patients with visual acuity in group A, B and C was 194.8 ± 26.7, 220 ± 12.3 and 243.5 ± 17.3 microns respectively. The amplitudes of first positive wave (P1) and first negative wave (N1) for the central ring in mf ERG in patients of group A, B and C was 1.1 ± 0.5 (P1), 0.7 ± 0.2 (N1), 0.6 ± 0.5 (P1), 0.3 ± 0.2 (N1), 0.7 ± 0.2 (P1), 0.3 ± 0.1 (N1) microvolts respectively. The vision correlated well with the macular thickness. The mf ERG potentials (P1 and N1) do not correlate with the visual acuity. Conclusion: We believe that the visual acuity in albinotic patients is affected by the macular thickness but the electric potentials do not depend on the visual acuity.

Upper hemiretinal occult retinopathy

AbstractPurpose To emphasize the significance of photopsias and positive scotomas as subjective indicators of occult retinopathy.Methods The patient’s depiction of his photopsias led to a diagnostic work‐up by white and red static and kinetic perimetry, OCT, and visual electrophysiology.Results Within the OD lower visual field our patient encountered a rapid loss of color vision. In dark environs, coloured photopsias showed up in this region, in bright environs, a positive black scotoma developped over time. Kinetic perimetry revealed a relative lower hemifield scotoma by white and an absolute one by red targets. On static perimetry, a distinct lower hemifield scotoma improved for white but persisted for red stimuli during 3 years of follow up. Retinal origin of the scotoma was proven by mf ERG. Serology for anti‐retinal antibodies remained negative. Difficult to detect by ophthalmoscopy, an affection of the OS / RPE layer in the corresponding fundus area was proven by SD OCT.Conclusion Coloured photopsias in dark, a black positive scotoma in bright envorons are salient symptoms of this upper hemifield occult retinopathy. OCT, visual fields and electrodiagnostic findings point towards a variant of AZOOR (acute zonal occult outer retinopathy).

Acute macular neuroretinopathy: contribution of spectral-domain optical coherence tomography and multifocal ERG

Acute macular neuroretinopathy is a rare disease which occurs in young women and causes sudden paracentral scotoma and typical reddish-brown macular lesions. We report two cases of young women suffering from acute macular neuroretinopathy which we observed with spectral-domain Spectralis HRA-OCT and multifocal ERG at 3 and 7months. Imaging revealed an early hyper-reflectivity of the photoreceptor layer, which changed into hyporeflectivity in the first week and remained the same in the following months, whereas visual field improved. Our findings show involvement primarly of the outer retina, and confirm OCT and mf ERG as important tools for diagnosis and follow-up of pathologic changes in AMNR, as other diagnostic tests often remain normal.

Oligocone Trichromacy: Clinical and Molecular Genetic Investigations

To describe the phenotype and genotype of patients with a diagnosis of oligocone trichromacy (OT). Six unrelated patients had a detailed ophthalmic examination including color vision testing, a Goldmann visual field test, fundus photography, and full-field electroretinography (ffERG). Five patients also underwent multifocal (mf)ERG, autofluorescence recording, and optical coherence tomography (OCT). Genetic analysis included sequencing of all coding regions and flanking introns of CNGA3, CNGB3, GNAT2, KCNV2, and PDE6C. All patients had subnormal visual acuity, a history of congenital nystagmus, and subjectively normal or near-normal color vision; five patients reported photophobia. Clinical examinations revealed largely normal fundi, normal Goldmann visual field results with the IV/4e target, and normal color discrimination or mild color vision deficiency. Electrophysiological investigations showed either complete absence of recordable cone responses or severely reduced amplitudes. All retinal layers were identifiable by OCT, which also showed thinning of the peripheral retina. Genetic analysis revealed two causative CNGB3 mutations in one patient and single heterozygous mutations of unknown significance in CNGB3 and PDE6C in two other patients. Oligocone trichromacy is a heterogeneous condition with respect to both phenotypic appearance and genetic background. The finding of mutations in genes known to be involved in complete and incomplete achromatopsia supports the notion that some forms of OT is an extreme form of incomplete achromatopsia with preferential loss of peripheral cones.

Autologous Transplantation of Retinal Pigment Epithelium–Bruch’s Membrane Complex for Hemorrhagic Age-Related Macular Degeneration

To evaluate a surgical procedure for patients with hemorrhagic age-related macular degeneration (AMD). This procedure consisted of excision of the choroidal neovascular membrane and transplantation of autologous retinal pigment epithelium (RPE)-Bruch's membrane complex. The RPE-Bruch's membrane complex for transplantation was surgically developed by dissecting Bruch's membrane with the choriocapillaris from the medium size choroidal vessel layer at the midperipheral region of the choroid. Twenty-one eyes of 21 patients had this surgical procedure. Visual function tests included best corrected visual acuity (BCVA), multifocal (mf)ERG, and microperimetry. Optical coherence tomography (OCT), fluorescein angiography, and autofluorescence examinations were performed to study the status of the transplanted graft. Among the 21 eyes, 17 with complete clinical data and qualified follow-up durations, which were 20.35 +/- 10.31 months on average, were analyzed in this series. On the last follow-up visit, the mean for the ETDRS scores increased from 28.65 +/- 23.99 before surgery to 47.76 +/- 17.22 after surgery. Microperimetry showed that after surgery, seven eyes gained central fixation at the 12-month follow-up examination. However, two eyes lost their central fixation on the last follow-up visit. Fourteen (82.35%) of the transplanted patches preserved normal color without depigmentation. Among the 21 eyes, proliferative vitreoretinopathy (PVR) occurred in 3 (14.29%), and a recurrent neovascular membrane was observed in one eye (4.76%). The transplantation of the autologous RPE-Bruch's membrane complex can increase the visual acuity of patients with hemorrhagic AMD. The surviving transplanted graft with functional overlying retina was observed after surgery.

Electroretinography and macular edema in diabetic retinopathy

Abstract Purpose To examine the electrophysiological symptoms in patients with preproliferative and proliferative diabetic retinopathy (PPDR, PDR) with macular edema (ME). Methods 24 patients with type II diabetes were investigated. OCT presented a focal, diffuse and clinically significant ME. ISCEV standard ERG methods, as well as chromatic macular and multifocal ERG (mf ERG), long‐duration flash ERG, pattern ERG (PERG) and retinocortical time (RTT) were performed. Results ERG changes were similar in PPDR and PDR with ME. Full‐field and flicker ERG were normal or subnormal depending on the localization of the pathological process in retina. The amplitude and interpeak latency of OPs were significantly changed. A different amplitude reduction of macular chromatic ERG to red, green and blue stimuli and prolonged b‐wave latency to green and blue stimuli were revealed. The retinal density of bioelectrical activity and amplitudes of N1, P1 components were decreased. A long‐duration flash ERG showed normal or subnormal ON‐response and diminished OFF‐response. The pathological macular and mf ERG were attended by pathological full‐field and flicker ERG in certain cases. N95 component oPERG was changed in amplitude and implicit time. The RTT was prolonged in most of the patients. Conclusion The ERG signs point to extent inclusion in pathological process of different retinal structures and layers. PERG and RTT changes indicate initial functional damage of the optic nerve. It is necessary to compare OCT and ERG data for understanding of mechanisms of visual disturbance in DR. The number of cases in which clinical and functional signs did not correspond to each other must be a subject to deep analysis before choosing a medical or laser treatment.

Function of macular area in retinopathy of prematurity

Abstract Purpose: To assess the bioelectric activity of the retina at different stages of the retinopathy of prematurity (RP). Methods: 21 children with RoP (stage 1‐4, 6‐14 years old, born at 27‐32 week of gestation with the birth weight of 730‐1800g) were examined. In 4 of children the prophylactic laser coagulation of avascular retina was performed in the active phase. Visual acuity (VA) at the stage 1 of RoP amounted to 0,75; at the stage 2: 0,5; at the stage 3: 0,25 and at the stage 4: 0,02. Macular (MBN Moscow) and mf ERG( Roland Concult Germany) were examined. Results: There was no correlation between VA values and parameters of multifocal (mf) and macular (m) ERG. Patients with RP of stage1 showed a moderate reduction of b‐wave magnitude of mERG at its normal latency. This correlated with mfERG data in central hexagons 15 degrees. The magnitude and latency of mERG were changed to a great extent in RP patients of stages 2‐3. The waves N1 and P1 of mERG were also heavily decreased at normal latency. The patients with severe retinal abnormalities, like retinal detachment, have subnormal mERG‐values with prolonged latency, and moderate decrease of retinal density in the central ring and considerable changes with eccentricity in mfERG. Conclusions: RP patients 1‐4 stages showed considerable impairment of macular functionindependent of the ophthalmoscopic changes. Even occult or weak‐manifested of the diseases in the macula might be accompanied with the moderate decrease of macular bioelectric activity, including the abrupt abnormalities of the electrogenesis and neuronal interactions in the macular area. Decline VA d'not always had relation with RP. The pathophysiologic rationale of the latter needs to be elucidated in the future studies.

Local and multifocal ERG in age‐related macular degeneratıon.

Abstract Purpose: To assess the macular ERG responses in different forms of AMD with OCT‐visualisation. Methods: 60 patients (120 eyes) wıth AMD, aged 57‐82, were examined. The groups were formed based on clinical examination, OCT and fluorescein angiography data. Local ERG (L‐ERG) to a red and green stımulus was recorded wıth MBN ERG system (Russıa). Multıfocal ERG was recorded wıth RETIscan system (Roland Consult, Germany). Results: In group 1 wıth hard drusen (18 eyes) ERG responses were in normal range. In group 2 with soft confluent drusen (18 eyes) a‐wave implicit tıme (IT) was prolonged (p=0,007);N1 of mfERG in normal range. b‐wave amplitude of L‐ERG to red stimulus was reduced (p=0,014), P1 of mf‐ERG reduced in fovea and parafovea (р<0,001). In a group 3а (31 eyes) wıth focal RPE atrophy,a‐wave IT of M‐ERG prolonged (p=0,002), P1 reduced in fovea (p=0,04). In a group 3b (16 eyes) with focal RPE atrophy and hyperpigmentation (VA 0,4‐0,1) a‐ and b‐wave reduced (p<0,001),P1 reduced in fovea and parafovea (р<0,05), N1 in foveal hexagone (p=0,04). In a group 4a with CNV with CMO foveal and parafoveal b‐wave amplitude reduced (p<0,05), P1 and N1 reduced (р<0,001). P1 in paramacular ring was reduced (р<0,05). In group 4b with RPE‐detachment a‐wave prolonged, a‐and b‐wave reduced, P1 and N1 reduced (р<0,001). Conclusions: The most sensitive indicators of macular dysfunction in AMD are the implicit time of a‐wave to a red stimulus local ERG and P1 response density of mf ERG in foveal hexagone. Normal amplitude and implicit time of N1 in soft drusen and early RPE‐atrophy in eyes with prolonged a‐wave of local ERG provides the evidence of smaller contibution of cones to N1 of FOK of mf ERG.

Macular function in severe disbinocular amblyopia

Abstract Purpose: To evaluate the mechanisms of the visual function impairment in severe disbinocular amblyopia (SDA). Methods: 41 children with SDA 5‐17 years old; visual acuity 0,03‐0,1; parafoveal, paramacular, peripheric fixation were examined. Mixed, pattern, macular multifocal ERG examination (MBN Moscow and Roland Consult Germany) and topography, contrast, colour sensitivity and spatial contrast sensitivity were performed. Results: The impairment of the color sensitivity to unsaturated red, green and blue was found. The most changes were found for the green in of 7º from the macula. No changes in the mixed, macular and flicker 30 Hz ERG was found. Although some patients showed a supernormal a‐wave of the macular ERG as well as a subnormal b‐wave, supernormal flicker 30 Hz ERG and moderately subnormal pattern ERG. Mf ERG showed the decreased rates of retinal density in the 1st and 2nd ring with normal rates of N1 and P2 in all central hexagons. SDA with non‐central fixation in 2D display is manifested with the zone of maximal bioelectric activity noticeably shifted from the fixation point. Together with the stable central fixation there is a near‐to‐the‐norm retinal density in central rings as well as with the eccentricity, while the maximal bioelectric activity at the non‐central fixation coincides with the presumed projection. Conclusions: Changes in the color and contrast sensitivity and in the retinal bioelectric activityin SDA has a functional character. Rate of the found changes differs from those in other retinal and optic nerve pathologies and retrochiasmial changes in children. There might exist an abnormality of photoreceptor and neuronal interactions among other mechanisms of visual function impairment in ADA.

Assessment of Central Retinal Function in Patients with Advanced Retinitis Pigmentosa

To assess central retinal function in patients with advanced retinitis pigmentosa (RP) using the multifocal (mf)ERG and static perimetry. Patients with RP; a nonrecordable, full-field (ff)ERG; and visual acuity (VA) of </= 1.0 logMAR were included. All patients underwent mfERG testing (103 hexagons, and 2.67 and 5.33 cd . s . m(-2) flash intensities) and static perimetry (103 corresponding areas) in the better eye. First-order kernel mfERGs were analyzed for total noise, signal-to-noise ratio, response amplitude, and implicit time. The number of areas with recordable mfERG responses were counted and compared with visual field (VF) sensitivity. Twenty-nine patients aged 16 to 68 years with a VA of 0.02 to 1.0 logMAR and a kinetic VF of 10 degrees to 60 degrees in diameter were included. mfERGs were successfully performed in 22 of 29 patients. Responses were detected in at least one stimulated area in 22 of 22 patients, with an overall response detection of 9.8% in all stimulated areas and no difference between flash intensities. All responses were diminished severely in response density P1-N1, with normal P1 implicit time in 50% of the recordings. No predictive factors for recordable mfERG responses were identified. VF results were recorded reliably in 27 of 29 patients, with a 40% response detection rate. mfERG responses were recordable in at least one area in all successfully tested patients with advanced RP. Response detection and performance was significantly higher for static perimetry. Static perimetry may be a more sensitive primary outcome measure of central vision function than the mfERG in patients with advanced RP and nonrecordable ffERGs.

In diabetic retinopathy, foveal thickness of 300 μm seems to correlate with functionally significant loss of vision

To study the relationship between foveal thickness assessed by optical coherence tomography (OCT) and foveal function measured with multi focal electroretinography (mfERG) in patients with non-proliferative diabetic retinopathy, and with no previous laser treatment. Twenty-six eyes from 18 diabetic patients (13 men), aged 59 years, (range 28-79 years), diabetes duration 15 years, (range 2-27 years), with a macular thickness between 200 and 600 microm were evaluated by mfERG, visual acuity (ETDRS score) and OCT. Mean amplitudes and implicit times of the mfERG responses were analyzed within the four innermost (14 degrees) of the six concentric rings. For comparison with the results from the OCT (diameter of measured area = 6 mm) we analyzed the summed response from the first and second ring (central zone), corresponding to the central area of the OCT. The third(zone 2) and fourth (zone 3)of the four innermost of the six concentric rings measured by the mfERG corresponding to the second and third area of OCT. An increased macular thickness in the central area of the OCT correlated to reduced amplitudes (r = -0.541; P = 0.004) and prolonged implicit times (r = 0.548; P = 0.004) in the central zone of the mfERG, and inversely correlated with visual acuity, -0.49; P = 0.045. Retinal thickness in the second area was correlated to prolonged implicit times in the second mfERG zone (r = -0.416; P = 0.034). No correlations were found for the third area of the OCT. When macular thickness exceeded 300 mum the decrease of amplitudes and prolonged implicit times, measured by mfERG, seemed to be more pronounced. In conclusion increased macular thickness is correlated with reduced amplitudes and prolonged implicit times on the mf ERG and worse visual acuity.

Outcome of Transplantation of Autologous Retinal Pigment Epithelium in Age-Related Macular Degeneration: A Prospective Trial

To present the outcome of a consecutive series of patients who had foveal choroidal neovascularization (fCNV) in age-related macular degeneration (AMD) and were treated with subretinal surgery combined with simultaneous transplantation of autologous retinal pigment epithelial (RPE) cells. Patients with fCNV who were not eligible for laser or photodynamic therapy were included in the study. They underwent subretinal membrane excision with simultaneous transplantation of autologous RPE cells. Eyes with membrane excision alone served as the control. Tests included best corrected visual acuity for far and near with Early Treatment Diabetic Retinopathy Study (ETDRS) and Jaeger charts, multifocal (mf)ERG, central visual field analysis, optical coherence tomography (OCT), and angiography, before surgery, and 1 month and 3 months after treatment, and at 3-month intervals thereafter. The results of final examinations of 53 eyes are presented. In 39 eyes, RPE transplantation was performed (group 1); 14 eyes had membrane excision alone (group 2). In group 1, visual acuity improved significantly, two or more lines in 21 (53.8%) patients; remained stable in 12 patients (30.8%); and decreased two or more lines in 6 patients (15.4%; P=0.0062). In group 2, the corresponding values were 21.1%, 57.8%, and 21.1% (P=0.5377 NS). Statistical analysis of results in the two groups showed a trend in favor of group 1 (P=0.9714). The difference in reading acuity was significant between the two groups (mean change in group 1: 1.85 +/- 0.42 vs. 0.43 +/- 0.47 in group 2; P=0.0001). mfERG response density changes were significantly different between groups 1 and 2 (P=0.0094). No significant decreases in central visual field defects were detected. OCT showed the postoperative median retinal thickness in the lesion area in group 1 to be higher (242.31 +/- 12.30 microm) than in group 2 (202.07 +/- 10.68 microm), showing a trend (P=0.0682). Patients undergoing fCNV removal with autologous transplantation of RPE reached significantly better reading acuity and higher mfERG-response density than control subjects. The results provide evidence that autologous transplantation of RPE is a beneficial supplement to membrane excision alone in patients with fCNV in AMD and may be regarded as a reasonable treatment option.

Preoperative and postoperative assessment by multifocal electroretinography in the management of optic disc pits with serous macular detachment

Purpose To evaluate the macular function by means of multifocal electroretinogram (MF ERG) in eyes with congenital optic disc pit and serous macular detachment. The evaluation was performed before and after the successful surgical intervention. Design Nonrandomized, comparative (self-controlled), interventional trial. Participants Ten patients (10 eyes) with optic disc pit with serous macular detachment were treated with the macular buckling procedure and followed up from March 1999 through May 2001. Methods In all patients included in the study, MF ERG was recorded before and after treatment. For recording, the VERIS III system (Visual Evoked Response Imaging System; Tomey, Nagoya, Japan) was used. Main outcome measures The retinal response densities were studied before and after treatment in areas 1 and 2 and were compared with visual acuity. Results The MF ERG before treatment showed decreased retinal response densities in all 10 cases. Twelve months after the surgical intervention, the electrical response densities in areas 1 (foveal area) and 2 (parafoveal area) improved. Further improvement was noted in 3 of the 10 patients who completed a follow-up of 18 months after treatment. In 8 of the 10 patients, postoperative visual acuity also increased. In the remaining two patients, visual acuity did not change after treatment, despite improvement of the retinal response densities. Conclusions In eyes with congenital optic disc pit with serous macular detachment, the decrease in retinal electrophysiologic response before treatment was not limited to the fovea, but also involved the perifoveal area. In all 10 eyes 12 months after treatment, the electrical activities in areas 1 and 2 improved. This improvement was not always followed by an increase in visual acuity. In 2 of the 10 patients, visual acuity remained unchanged. The values of retinal response densities before treatment cannot be used alone as a prognostic factor for the postoperative functional retinal results. It should also be stressed that the results of this study cannot be compared with the results of studies where spontaneous resolution of the macular detachment occurred.