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Glaucoma is a neurodegenerative disease, our study aimed to evaluate the potential effects of Palmitoylethanolamide (PEA) supplementation on RGCs function by PERG examination, and to record effects on intraocular pressure, visual field and quality of life. It was a single centre, randomized, prospective, single blind, two treatment, two period crossover study on stable glaucoma patients on topical monotherapy comparing current topical therapy alone or additioned with PEA 600 mg one tablet a day. At baseline, at 4 and at 8 months, all patients underwent to complete ophthalmic examination, pattern electroretinogram, visual field, and quality of life evaluation. 40 patients completed the study: mean age 66.6 ± 7.6 years; 21 (52.5%) male; 35 POAG (87.5%). At baseline, most patients had an early visual field defect, the IOP was well controlled. At the end of the PEA 600 mg supplementation, a significantly higher (mean 0.56 μV, 95% CI 0.30–0.73, p < 0.001) in the P50-wave amplitude was observed; in the PEA period a significantly lower IOP (− 1.6 mmHg, 95% CI − 2 to 1.2, p < 0.001) and higher quality of life scores (+ 6.7, 95% CI 4–9.9, p < 0.001) were observed. Our study is the first to show promising effects of PEA on PERG and on quality of life in glaucoma patients.

Purpose To compare the effect of variable pupil size on the flicker electroretinogram (ERG) between a stimulus having constant luminance and a stimulus having constant retinal illuminance (constant Troland) that compensates for pupil size. Methods Subjects ( n  = 18) were tested with 12 pairs of the stimuli. The stimulus pair consisted of the ISCEV standard constant luminance stimulus (3 cd·s/m 2 with a 30 cd/m 2 background) and a constant retinal illuminance stimulus (32 Td·s with a 320 Td background) selected to provide the same stimulus and background when the pupil diameter is 3.7 mm. Half the subjects were artificially dilated, and their response was measured before and during the dilation. The natural pupil group was used to assess intra- and inter-subject variability. The artificially dilated group was used to measure the flicker ERG’s dependence on pupil size. Results With natural pupils, intra-subject variability was lower with the constant Troland stimulus, while inter-subject variability was similar between stimuli. During pupil dilation, the constant Troland stimulus did not have a dependence on pupil size up to 6.3 mm and had slightly larger amplitudes with longer implicit times for fully dilated pupils. For the constant luminance stimulus, waveform amplitudes varied by 22% per mm change in pupil diameter, or by 48% over the 2.2 mm diameter range measured in dilated pupil size. There was no difference in inter-subject variability between constant Troland natural pupils and the same subjects with a constant luminance stimulus when dilated (i.e., the ISCEV standard condition). Conclusions These results suggest that a constant Troland flicker ERG test with natural pupils may be advantageous in clinical testing. Because of its insensitivity to pupil size, constant Troland stimuli should produce smaller reference ranges, which in turn should improve the sensitivity for detection of abnormalities and for monitoring changes. In addition, the test can be administered more efficiently as it does not require artificial dilation. Clinical Trial registration number This trial is registered at ClinicalTrials.gov (NCT02466607).

Purpose To compare the effects of indocyanine green (ICG)-, brilliant blue G (BBG)-, or triamcinolone acetonide (TA)-assisted internal limiting membrane (ILM) peeling during macular hole (MH) surgery on the different components of the focal macular electroretinograms (fmERGs). Methods Forty-eight eyes of 48 patients with a macular hole were randomly divided into those undergoing ICG-, BBG-, or TA-assisted vitrectomy ( n  = 16 for each group). All patients had combined cataract and macular hole surgery with ILM peeling. The fmERGs were recorded before, and 1, 3, 6, 9, and 12 months postoperatively. The amplitudes and implicit times of the a- and b-waves, the amplitudes of the sum of the oscillatory potentials (ΣOPs), and the photopic negative responses (PhNRs) were analyzed. Results The amplitudes of all of the components of the fmERGs gradually increased with time after surgery ( P  < 0.005). The implicit times of the a- and b-waves were significantly prolonged at 1 month ( P  < 0.01) and then gradually returned to the baseline times. No significant differences were found in these changes among the groups. In pooled data from the 48 patients, the PhNR amplitude increased more than the a- and b-waves and the ΣOPs amplitudes at every time point after 3 months ( P  < 0.005). Conclusions The lack of significant differences on the different components of the fmERGs indicates that none of the three agents was toxic to the macula. After closure of a MH, the function of the retinal ganglion cells may recover more than that of the other neural elements in the macular area.

Background The aims of this study were to determine the longitudinal effects of myopia on full-field electroretinogram (ffERG) in children, and whether there were any effects due to atropine treatment. Methods Fifty children, enrolled in the atropine treatment for myopia study, were randomly selected and 35 children consented to undergo ffERG at baseline (prior to atropine treatment), 24 months (at end of treatment) and 32 months (8 months after cessation of treatment). An extended ISCEV ffERG protocol was used for all recordings. The relationship between axial length (AL) and the following scotopic and photopic ffERG responses was analyzed: a- and b-wave amplitude and implicit time, saturated amplitude ( V max ), and retinal sensitivity (logK). Results Reliable ffERG recordings with acceptable level of noise were obtained on all 3 visits from 29 children (mean age: 9.5 ± 0.8 years and mean spherical equivalent: −5.0 ± 1.6 D). At baseline, the correlation detected between AL and logK was 0.37 ( p  = 0.047). There was no significant correlation between AL and V max or any scotopic and photopic ffERG amplitude and implicit time measures. Longitudinal data suggested a reduction in photopic a- and b-wave and 30 Hz flicker response amplitudes over time. Multivariate analysis showed that the change in 30 Hz flicker response amplitude was likely to be associated with AL change. There was no evidence that changes in other responses were associated with age, baseline AL, or atropine dose used. Conclusion Retinal sensitivity was reduced in myopic children. There was a gradual decline in cone function over time which was not influenced by atropine treatment.

Purpose The purpose of this study was to assess the role of various diagnostic tests in early detection of retinal changes in β-thalassemia major patients. Methods Thirty-eight visually asymptomatic β-thalassemia major patients receiving regular blood transfusions and iron-chelation therapy with deferoxamine (group A, n  = 13), deferasirox (group B, n  = 11) or deferoxamine with deferiprone (group C, n  = 14) and fourteen age- and sex- matched healthy individuals were included in the study. All participants underwent ophthalmoscopy, full-field electroretinography (ERG), visual evoked potentials (VEP), multifocal electroretinography (mfERG), fundus autofluorescence (FAF) imaging and optical coherence tomography (OCT) scans. Results Retinal pigment epithelium changes were present in two cases. Scotopic ERG demonstrated decreased a-wave amplitude in groups A, B and C ( p  = 0.03, p  = 0.002 and p  = 0.002, respectively) and decreased b-wave amplitude in groups B and C ( p  = 0.002 and p  = 0.01, respectively) compared to controls. Photopic ERG showed delayed b-wave latency in groups A and C ( p  = 0.03 and p  = 0.03, respectively) ERG maximal combined response and VEP response did not differ between groups. MfERG showed reduced retinal response density in ring 1 in groups A, B, C ( p  < 0.001, p  < 0.001, p = 0.001, respectively) and ring 2 in group B ( p  = 0.02) and delayed latency in ring 5 in groups A and B ( p  = 0.04 and p  = 0.04, respectively). Abnormal FAF images appeared in three cases and OCT abnormalities in one case, whereas no changes were observed in controls ( p  = 0.55 and p  = 1.00, respectively). Conclusions Full-field ERG and mfERG are more sensitive tools for detecting early retinal changes in β-thalassemia patients compared with ophthalmoscopy, VEP, FAF imaging and OCT scans.

Background In infant ERG recordings skin electrodes frequently result in a better compliance. In order to assess the quality of such recordings, we compared the recording characteristics of DTL microfiber and Neuroline surface electrodes using a modified ISCEV protocol in the Mini Ganzfeld ERG. Methods A prospective cohort study on healthy adult subjects was conducted at the Department of Ophthalmology, University of Basel, Switzerland. Thirty healthy volunteers were tested. The microfiber electrode (DTL Plus Electrode) was placed across the cornea, above the lower eyelid. The Neuroline skin electrode was placed on the surface of the lower lid on the opposite eye. The eye on which each electrode type was placed was randomised. Amplitudes of the rod, standard combined, standard flash cone, light-adapted 3.0 Hz flicker and red cone responses were analysed, as well as their respective implicit times. Results Both electrode recordings showed the same waveform characteristics. Responses with the Neuroline electrode were significantly weaker than those from the DTL electrode. Amplitudes of the rod, standard combined, standard flash cone, light-adapted 3.0 Hz flicker and red cone responses were up to four times larger when recorded with the DTL electrode ( p  < 0.005, ANOVA). Implicit times of the red cone ERGs were slightly faster for the Neuroline skin electrode recordings ( p  ≤ 0.039). Conclusions Comparison of full-field ERG recordings with microfiber DTL and Neuroline skin electrodes showed that DTL electrodes produce larger ERGs. Hence, we provide evidence that both electrode types allow successful full-field ERG recording, although separate normative data for both electrodes are necessary.

To evaluate retinal neuropathy in patients with diabetic macular edema (DME) with multifocal electroretinograph (mfERG), and to evaluate the simultaneous impact of retinal neuropathy and vasculopathy on visual acuity in subtypes of DME. This prospective, controlled, investigative study conducted at a tertiary eye care center of Northern India included 79 eyes of 50 treatment-naïve patients with DME (Group 1), 94 eyes of 50 diabetic patients without diabetic retinopathy (Group 2), and 100 eyes of 100 normal volunteers as controls. Comprehensive ocular evaluation along with mfERG and optical coherence tomography (OCT) were performed for all patients. N1 and P1 mfERG waveforms in the two central-most rings of macula were evaluated for amplitudes and implicit time. OCT was used to sub-classify types of DME and evaluate macular thickness, ellipsoid zone (EZ), and external limiting membrane (ELM) disruption. Best-corrected visual acuity (BCVA) relative to other variables was the primary outcome measure. The three groups were compared for all the parameters inclusive of OCT and mfERG patterns. Further, OCT subtypes of DME were analyzed for mfERG waveform patterns. All mfERG values were significantly lower in Group 1 and Group 2 as compared to Group 3 (P < .05). BCVA strongly correlated with central macular thickness, EZ, and ELM disruption scores in Group 1 (P = .001), but correlated modestly with mfERG waveform amplitudes in Group 1 patients with intact EZ and ELM only. BCVA correlated with mfERG amplitudes in patients with neurosensory detachment, but not in those with cystoid macular edema. Neural changes set in before the clinical changes related to vasculopathy manifest in diabetic patients. Neuroretinopathy in patients with DME affects all retinal layers symmetrically in early stages, but impacts the middle retinal layers severely in advanced disease form. BCVA correlates with electrophysiological changes till the time morphological features are visible when stronger correlation is seen with anatomical disruption. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:626-631.].

The clinical multifocal electroretinogram (mfERG) is an electrophysiological test of local retinal function. With this technique, many local ERG responses are recorded quasi-simultaneously from the cone-driven retina under light-adapted conditions. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV: www.iscev.org ), replaces the ISCEV guidelines for the mfERG published in 2007. Standards for performance of the basic clinical mfERG test with a stimulus array of 61 or 103 hexagons, as well as for reporting the results, are specified.

Visual electrophysiology measurements are important for ophthalmic diagnostic testing. Electrodes with combined optical transparency and softness are highly desirable, and sometimes indispensable for many ocular electrophysiology measurements. Here we report the fabrication of soft graphene contact lens electrodes (GRACEs) with broad-spectrum optical transparency, and their application in conformal, full-cornea recording of electroretinography (ERG) from cynomolgus monkeys. The GRACEs give higher signal amplitude than conventional ERG electrodes in recordings of various full-field ERG responses. High-quality topographic mapping of multifocal ERG under simultaneous fundus monitoring is realized. A conformal and tight interface between the GRACEs and cornea is revealed. Neither corneal irritation nor abnormal behavior of the animals is observed after ERG measurements with GRACEs. Furthermore, spatially resolved ERG recordings on rabbits with graphene multi-electrode array reveal a stronger signal at the central cornea than the periphery. These results demonstrate the unique capabilities of the graphene-based electrodes for in vivo visual electrophysiology studies. The electrical response of the eye to optical stimulus is important in disease diagnosis but current electrodes used have limitations. Here, the authors report on the development of soft transparent graphene-based contact lens electrodes for electroretinogram recording and test the device in vivo.

Purpose To evaluate the effects of cilostazol, an antiplatelet and vasodilation agent, on the retinal function of patients with non-proliferative diabetic retinopathy (NPDR) using a full-field electroretinogram (ffERG). Methods A total of 20 eyes from 20 patients were enrolled as the cilostazol-treated group, and 16 eyes from 16 patients were enrolled as the control group to assess the functional effects of cilostazol. Ophthalmologic examinations including fundus fluorescein angiography (FFA), fundus color photography, optical coherence tomography (OCT), and ffERG responses were recorded at baseline and after 1 year of cilostazol treatment. The number of microaneurysms on FFA, the number of exudates on fundus photographs, and central macular thickness (CMT) on OCT were compared between the two groups. Recording of ffERG was also performed at baseline and repeated after 1 year of treatment. The mean implicit times and amplitudes of a- and b-waves in each ffERG response were analyzed to evaluate the retinal function. Results CMT and the numbers of microaneurysms and exudates showed no significant change in the cilostazol-treated group. There was no significant change in ffERG parameters between baseline and 1 year after the treatment in each group. The mean changes in implicit times from the cilostazol-treated group were significantly less than in the control group in b-waves from dark-adapted 3 ERG ( p  = 0.017) and 10 ERG responses ( p  = 0.047). On the other hand, the mean changes in amplitudes were not significant after 1 year of cilostazol treatment, but there were slight increases in amplitudes of dark-adapted 0.01 ERG and 10 ERG in the cilostazol-treated group. Conclusions These results suggest that cilostazol administration could reduce the implicit times of ffERG in patients with NPDR. It may be beneficial to preserve the retinal function in the diabetic retina, and additional research with larger populations and extended duration are needed to clarify the efficacy and safety of cilostazol for these patients.