Pattern Electroretinogram Amplitude Research Articles

Hemifield-based analysis of pattern electroretinography in normal subjects and patients with preperimetric glaucoma

This prospective cross-sectional study investigated the visual function of preperimetric glaucoma (PPG) patients based on hemifield (HF) pattern electroretinogram (PERG) amplitudes. Thirty-two (32) normal subjects and 33 PPG patients were enrolled in control and PPG groups, respectively. All of the participants had undergone full ophthalmic examinations, including spectral-domain optical coherence tomography (SD-OCT), visual field (VF) examination and pattern electroretinography (PERG). The PERG parameters along with the HF ratios of SD-OCT and PERG were compared between the control and PPG groups. Pairwise Pearson's correlation coefficients and linear regression models were fitted to investigate the correlations. The PERG N95 amplitudes were significantly lower in the PPG group (P < 0.001). The smaller/larger HF N95 amplitude ratio of the PPG group was found to be smaller than that of the control group (0.73 ± 0.20 vs. 0.86 ± 0.12; P = 0.003) and showed positive correlations with affected HF average ganglion cell-inner plexiform layer (GCIPL) thickness (r = 0.377, P = 0.034) and with average GCIPL thickness (r = 0.341, P = 0.005). The smaller/larger HF N95 amplitude ratio did not significantly change with age (β = − 0.005, P = 0.195), whereas the full-field N95 amplitude showed a negative correlation with age (β = − 0.081, P < 0.001). HF analysis of PERG N95 amplitudes might be particularly useful for patients with early glaucoma.

Pattern electroretinogram, blue-yellow visual evoked potentials and the risk of developing visual field defects in glaucoma suspects: a longitudinal “survival” analysis with a very long follow-up

PurposeEstimating glaucoma suspects’ risk for visual field defects helps to avoid under- and over-treatment. In this retrospective, longitudinal cohort study with a very long follow-up, we studied whether pattern electroretinograms (PERG) amplitudes and blue-on-yellow visual evoked potential (BY-VEP) latencies can predict visual field defects.MethodsParticipants of the Erlangen Glaucoma Study were examined with PERG and BY-VEP between 9/1991 and 8/2001. Stimuli were created using an optical bench with Maxwellian view and consisted of vertical gratings (0,88 cpd) in a 32° field for both PERG and BY-VEP. Patients were treated according to clinical standards and performed standard automated perimetry (SAP) annually. Retrospectively, patients with normal SAP at baseline were selected. Primary endpoint was conversion to perimetric glaucoma. Predictive value was modeled using Kaplan–Meier analyses and a multivariate cox proportional hazards model with the continuous variables PERG amplitude, BY-VEP peak time and SAP square-root of loss variance (sLV) after stratification for Jonas classification of the optic discs.ResultsOf 412 patients (288: Jonas 0, 103: I, and 21: II; baseline age: 20–60 years), 65 converted to perimetric glaucoma during follow-up (0.5–23.3 years; median 5.5 years). Optic disc classification was a strong risk factor for conversion (log rank p < 0.0001), and patients with more advanced changes progressed earlier. In the multivariate analysis (log rank p = 0.005), only PERG amplitude remained an independent risk factor after stratification for optic disc morphology (p = 0.021), with a ~ 30% higher risk per μV amplitude decrease.ConclusionsPERG helps to estimate glaucoma suspects’ risk for visual field defects.

The Inflammasome-Dependent Dysfunction and Death of Retinal Ganglion Cells after Repetitive Intraocular Pressure Spikes.

The dysfunction and selective loss of retinal ganglion cells (RGCs) is a known cause of vision loss in glaucoma and other neuropathies, where ocular hypertension (OHT) is the major risk factor. We investigated the impact of transient non-ischemic OHT spikes (spOHT) on RGC function and viability in vivo to identify cellular pathways linking low-grade repetitive mechanical stress to RGC pathology. We found that repetitive spOHT had an unexpectedly high impact on intraocular homeostasis and RGC viability, while exposure to steady OHT (stOHT) of a similar intensity and duration failed to induce pathology. The repetitive spOHT induced the rapid activation of the inflammasome, marked by the upregulation of NLRP1, NLRP3, AIM2, caspases -1, -3/7, -8, and Gasdermin D (GSDMD), and the release of interleukin-1β (IL-1β) and other cytokines into the vitreous. Similar effects were also detected after 5 weeks of exposure to chronic OHT in an induced glaucoma model. The onset of these immune responses in both spOHT and glaucoma models preceded a 50% deficit in pattern electroretinogram (PERG) amplitude and a significant loss of RGCs 7 days post-injury. The inactivation of inflammasome complexes in Nlrp1-/-, Casp1-/-, and GsdmD-/- knockout animals significantly suppressed the spOHT-induced inflammatory response and protected RGCs. Our results demonstrate that mechanical stress produced by acute repetitive spOHT or chronic OHT is mechanistically linked to inflammasome activation, which leads to RGC dysfunction and death.

Morpho-Functional Assessment of Retinal Ganglion Cells and Visual Pathways in Patients with Optic Disc Drusen: Superficial Drusen Visible Height as a Marker of Impairment.

The aim of this study was to assess the morpho-functional involvement of the retinal ganglion cells (RGCs) and of the visual pathways in patients with superficial (ODD-S) or deep (ODD-D) optic disc drusen. This study enrolled 17 patients with ODD (mean age of 59.10 ± 12.68 years) providing 19 eyes and 20 control subjects (mean age 58.62 ± 8.77 years) providing 20 eyes. We evaluated the following: best-corrected visual acuity, visual field mean deviation (MD), the amplitude (A) of Pattern Electroretinogram (PERG), the implicit time (IT) and A of Visual Evoked Potentials (VEPs), retinal nerve fiber layer thickness (RNFL-T) and ganglion cell thickness (GC-T). In ODD-S eyes, the drusen visible height was measured. ODD-D and ODD-S were detected in 26.3% and 73.7% of ODD eyes, respectively. Significantly (p < 0.01) reduced MD, PERG A, VEP amplitude, RNFL-T and GC-T values and significantly (p < 0.01) increased VEP IT values were found in the ODD Group as compared to the Control one. In the ODD Group, no significant correlation (p > 0.01) between PERG As and VEP ITs was found. In ODD-S, the visible height was significantly correlated (p < 0.01) with reduced MD, PERG As and RNFL-T and with increased PSD and VEP IT values. Our findings suggest that ODD might induce morpho-functional changes in RGCs and their fibers and an unrelated visual pathway dysfunction leading or not leading to visual field defects. The observed morpho-functional impairment should be ascribed to an alteration in retrograde (from the axons to the RGCs) and anterograde (from the RGCs up to the visual cortex) axoplasmic transport. In ODD-S eyes, a minimum visible height of 300 microns represented the threshold for the abnormalities, suggesting that "the higher the ODD, the worse the impairment".

Pattern Electroretinogram in Ocular Hypertension, Glaucoma Suspect and Early Manifest Glaucoma Eyes: A Systematic Review and Meta-analysis

To provide standardized confidence limits of the transient pattern electroretinogram (tPERG) P50 and N95 and steady state pattern electroretinogram (ssPERG) amplitudes in normal controls as compared to ocular hypertension (OHT), glaucoma suspect (GS), or early manifest glaucoma (EMG) eyes. The identification of standardized confidence limits in the context of pattern electroretinogram (PERG) might overcome the high intrinsic variability of the measure, and it might lead to a more intuitive understanding of the results as well as to an easier comparison of data from multiple tests, sites, and operators. The study protocol was prospectively registered on the International Prospective Register of Systematic Reviews (ID: CRD42022370032). A literature search was conducted on PubMed, Web of Science, and Scopus. Studies comparing PERG raw data in normal control eyes as compared to OHT, GS, or EMG were included. The risk of bias was assessed using the National Institute for Health and Clinical Excellence quality assessment tool. The main outcome was the P50, N95, and ssPERG amplitude difference between the control and the study groups' eyes. The standardized mean difference was calculated as a measure of the effect size for the primary outcome. A subanalysis was conducted based on the type of electrodes adopted for the PERG measurements (invasive vs. noninvasive). Of the 4580 eligible papers, only 23 were included (1754 eyes). Statistically significant amplitude differences were found in the P50, N95, and ssPERG amplitudes between normal controls and OHT, GS, and EMG eyes. The highest standardized mean difference values were observed in the ssPERG amplitude in all 3 sets of comparison. The subanalysis did not reveal any statistically significant differences between invasive and noninvasive recording strategies. The use of standardized values as the main outcome measures in the context of the PERG data analysis is a valid approach, normalizing several confounding factors which have affected the clinical utility of PERG both for individual patients and in clinical trials. Steady state PERG apparently better discriminates diseased eyes compared to tPERG. The adoption of skin-active electrodes is able to adequately discriminate between healthy and diseased statuses. Proprietary or commercial disclosure may be found after the references.

Fluoxetine Protects Retinal Ischemic Damage in Mice.

To evaluate the neuroprotective effect of the topical ocular administration of fluoxetine (FLX) in a mouse model of acute retinal damage. Ocular ischemia/reperfusion (I/R) injury in C57BL/6J mice was used to elicit retinal damage. Mice were divided into three groups: control group, I/R group, and I/R group treated with topical FLX. A pattern electroretinogram (PERG) was used as a sensitive measure of retinal ganglion cell (RGC) function. Finally, we analyzed the retinal mRNA expression of inflammatory markers (IL-6, TNF-α, Iba-1, IL-1β, and S100β) through Digital Droplet PCR. PERG amplitude values were significantly (p < 0.05) higher in the I/R-FLX group compared to the I/R group, whereas PERG latency values were significantly (p < 0.05) reduced in I/R-FLX-treated mice compared to the I/R group. Retinal inflammatory markers increased significantly (p < 0.05) after I/R injury. FLX treatment was able to significantly (p < 0.05) attenuate the expression of inflammatory markers after I/R damage. Topical treatment with FLX was effective in counteracting the damage of RGCs and preserving retinal function. Moreover, FLX treatment attenuates the production of pro-inflammatory molecules elicited by retinal I/R damage. Further studies need to be performed to support the use of FLX as neuroprotective agent in retinal degenerative diseases.

Assessment of the uniform field electroretinogram for mouse retinal ganglion cell functional analysis.

The uniform field electroretinogram (UF-ERG) has been suggested as an alternative to the pattern electroretinogram (PERG) for non-invasive assessment of retinal ganglion cell (RGC) function in primates. We evaluated the validity of the UF-ERG to assess mouse RGC activity in vivo. Unilateral optic nerve crush (ONC) was performed on adult C57BL/6J mice. Contralateral eyes with uncrushed optic nerves and eyes from surgically naive mice served as experimental controls. Electrophysiological visual assessment was performed at 12weeks post-ONC. Flash-mediated visual-evoked cortical potentials (VEPs) were measured to confirm the robustness of the ONC procedure. Full-field flash ERGs were used to interrogate photoreceptor and retinal bipolar cell function. RGC function was assessed with pattern ERGs. Summed onset and offset UF-ERG responses to alternating dark and light uniform field flash stimuli of different intensities and wavelengths were recorded from ONC and control eyes, and relative differences were compared to the PERG results. Following electrophysiological analysis, RGC loss was monitored by immunohistochemical staining of the RGC marker protein, RBPMS, in post-mortem retinal tissues. ONC dramatically impacts RGC integrity and optic nerve function, demonstrated by reduced RGC counts and near complete elimination of VEPs. ONC did not affect scotopic ERG a-wave and b-wave amplitudes, while PERG amplitudes of eyes subjected to ONC were reduced by approximately 50% compared to controls. Summation of ON and OFF UF-ERG responses did not reveal statistically significant differences between ONC and control eyes, regardless of visual stimulus. PERG responses are markedly impaired upon ONC, while UF-ERG responses are not significantly affected by surgical trauma to RGC axons in mice. The more closely related pattern and uniform field ERGs recorded in primates suggests species-specific differences in RGC features or subpopulations corresponding to PERG and UF-ERG response generators, limiting the utility of the UF-ERG for mouse RGC functional analysis.

Depression scores are associated with retinal ganglion cells loss

BackgroundLight is a known factor affecting mood and the circadian system. Light deficit is linked to deteriorated transduction of photic information to the brain, and reduced amplitude of the perceived circadian light signaling. Retinal ganglion cells (RGCs) loss due to advanced glaucoma can be a factor compromising light perception, with consequences for circadian rhythms, sleep and mood. This study aimed to estimate associations of RGCs loss with a depression score by multiple regression, accounting for other features of glaucoma. MethodsOne hundred and fifteen patients diagnosed with primary open-angle glaucoma completed the Beck Depression Inventory II questionnaire. The damage to their RGCs was assessed by high-definition optical coherence tomography (HD-OCT) and their function by pattern electroretinogram (PERG). On fifteen of these patients, 24-h salivary melatonin patterns were determined under light-controlled laboratory conditions, and analysis of eight clock related gene polymorphisms was performed. ResultsBackward stepwise multiple regression revealed that the BDI score was the strongest factor that was most closely associated with the HD-OCT-based percentage of global RGCs loss (standardized coefficient, b* = 0.784, p < 0.001), surpassing other related factors, including age, intraocular pressure, visual field loss, and PERG amplitude. A high BDI score was associated with the GNβ3 825C > T polymorphism (dbSNP rs5443). LimitationsThis study did not specifically address damage to intrinsically photoreceptive RGCs. The gene study is based on a limited number of volunteers. ConclusionsDepression scores are strongly associated with RGCs loss, increasing abruptly above a threshold of 15 %, supporting the hypothesis that RGCs loss in advanced glaucoma may affect non-visual photic transduction and lead to mood disturbances.

Comparison of different gene-therapy methods to treat Leber hereditary optic neuropathy in a mouse model.

Therapies for Leber hereditary optic neuropathy (LHON), in common with all disorders caused by mutated mitochondrial DNA, are inadequate. We have developed two gene therapy strategies for the disease: mitochondrial-targeted and allotopic expressed and compared them in a mouse model of LHON. A LHON mouse model was generated by intravitreal injection of a mitochondrialtargeted Adeno-associated virus (AAV) carrying mutant human NADH dehydrogenase 4 gene (hND4/m.11778G>A) to induce retinal ganglion cell (RGC) degeneration and axon loss, the hallmark of the human disease. We then attempted to rescue those mice using a second intravitreal injection of either mitochondrial-targeted or allotopic expressed wildtype human ND4. The rescue of RGCs and their axons were assessed using serial pattern electroretinogram (PERG) and transmission electron microscopy. Compared to non-rescued LHON controls where PERG amplitude was much reduced, both strategies significantly preserved PERG amplitude over 15 months. However, the rescue effect was more marked with mitochondrial-targeted therapy than with allotopic therapy (p = 0.0128). Post-mortem analysis showed that mitochondrial-targeted human ND4 better preserved small axons that are preferentially lost in human LHON. These results in a pre-clinical mouse model of LHON suggest that mitochondrially-targeted AAV gene therapy, compared to allotopic AAV gene therapy, is more efficient in rescuing the LHON phenotype.

Assessment of digital light processing (DLP) projector stimulators for visual electrophysiology

IntroductionVisual electrophysiology tests require the use of precise and calibrated visual display units (VDUs). Existing VDUs for presenting structured stimuli are now mostly obsolete, with modern solutions limited or unsuitable for clinical testing. Digital light processing (DLP) laser projectors have recently become commercially available and this study aimed to assess their suitability as VDUs for visual electrophysiology testing.MethodsThis study consisted of two sections. The first was a photometric study of two DLP laser projectors (Viewsonic LS831WU and HiSense 100L5FTUK) to assess luminance, contrast, spectral and temporal characteristics of the stimulus. The second was a physiological study comparing pattern electroretinograms (PERG) and visual evoked potentials (PVEPs) amplitudes and peak-times recorded using a DLP laser projector, photometrically and spatially matched to existing plasma VDUs at our institution (Pioneer Electronics Corporation, PDP422MXE).ResultsThe Viewsonic DLP laser projector was capable of high luminance levels (0–587.5 cd/m2) whilst maintaining contrast above 93%. The temporal properties showed fast rise and fall times of 0.5–1 ms and 0.5–1 ms, respectively, without any transient luminance change with reversals. The device required a warm-up time of at least 2 min until reaching near maximal luminance. The second (Hisense) device was observed to have a detrimental input lag jitter so was not used for any further analysis. PERGs and PVEPs showed high agreement and correlation (r = 0.766–0.905) between the Viewsonic DLP device and existing plasma VDUs. No significant differences were observed for P50 and P100 peak-time (p = > 0.05), however P50, N95 and P100 amplitudes were all significantly larger for the DLP device (p = < 0.05).DiscussionThe DLP laser projector tested in this study is a viable and practical replacement VDU for clinical electrophysiology tests of vision. The device is easily capable of meeting ISCEV standards, and showed PERG and PVEP amplitudes larger than existing systems despite photometric and spatial matching. The DLP laser projectors are capable of very large field sizes so are beneficial for paediatric testing or those wishing to examine large field responses. Importantly, it was observed that some devices may suffer input lag jitter, therefore, individual calibration and assessment of DLP projection systems is an important consideration before clinical implementation.

Microglia depletion exacerbates retinal ganglion cell loss in a mouse model of glaucoma.

To test whether depletion of microglia in the optic nerve head has a beneficial effect on retinal ganglion cell numbers and function, we depleted microglia by oral administration of the CSF1R antagonist PLX5622. Then, ocular hypertension was induced by unilateral injection of magnetic microbeads into the anterior chamber. Visual function was assessed with pattern electroretinography and measurement of the optomotor reflex. Retinal ganglion cell bodies and axons were counted and gene expression patterns in optic nerve head astrocytes were tested on freshly dissociated astrocytes. PLX5622 efficiently depleted microglia in the retina and the optic nerve head, but about 20% of microglia persisted in the myelinated optic nerve proper even after prolonged exposure to the drug. PLX5622 did not affect ganglion cell function by itself. Elevation of the IOP for four weeks led to the expected decrease in visual acuity and pattern ERG amplitude. Microglia ablation did not affect these parameters. Ganglion cell and axon numbers were counted histologically post mortem. Mice in the microglia depletion group showed a moderate but significantly greater loss of ganglion cells than the control group. At four weeks post microbead injection, gene expression patterns in optic nerve head astrocytes are consistent with an A2 (or neuroprotective) pattern. Microglia depletion blunted the up-regulation of A2 genes in astrocytes. In conclusion, microglia depletion is unlikely to protect retinal ganglion cells in early glaucoma.

Attenuated Amplitude of Pattern Electroretinogram in Glaucoma Patients with Choroidal Parapapillary Microvasculature Dropout

This study aims to investigate whether parapapillary choroidal microvasculature dropout (MvD) is related to visual function measured by pattern electroretinogram (PERG) in glaucomatous eyes with β-zone parapapillary atrophy (PPA). A total of 79 patients with open angle glaucoma and preperimetric glaucoma with β-zone PPA was included in this cross-sectional study. Through the deep layer of the Swept-source optical coherence tomography angiography image, the angular width and the area of MvD were measured. Visual function was evaluated with a standard automated perimetry and PERG. N95 and P50 PERG amplitudes in eyes with MvD were noticeably decreased compared to those without MvD (p = 0.004 and p = 0.007, respectively), although the mean deviation was not significantly different (p = 0.107). The lower N95 amplitude was associated with the presence of MvD (β = −0.668, p = 0.017) and wider angular width of MvD (B = −7.612, p = 0.014). Old age (p = 0.001), average ganglion cell’s inner plexiform layer thickness (p = 0.003), and the presence of MvD (p = 0.020) were significantly related to low N95 amplitude. Association between the presence and extent of the MvD and PERG amplitudes suggests that the presence of MvD has relevance to the generalized dysfunction of retinal ganglion cells.

Melatonin, circadian rhythms and glaucoma: current perspective.

Melatonin, circadian rhythms and glaucoma: current perspective.

Cannabinol modulates neuroprotection and intraocular pressure: A potential multi-target therapeutic intervention for glaucoma

ObjectivesGlaucoma is characterized by progressive damage of the retinal ganglion cells (RGCs), resulting in irreversible vision loss. Cannabinoids (CBs) ameliorate several factors that contribute to the progression of glaucoma, including increased intraocular pressure (IOP), degeneration of RGC and optical nerve (ON) damage. However, a direct correlation of specific CBs with the molecular events pertaining to glaucoma pathology is not well established. Therefore, this study aims to evaluate the role of cannabinol (CBN) on RGC protection, modulation of IOP, and its effects on the level of extracellular matrix (ECM) proteins using both in vitro and in vivo models of glaucoma. Methods and resultsWhen exposed to elevated hydrostatic pressure, CBN, in a dose-dependent manner, protected differentiated mouse 661W retinal ganglion precursor-like cells from pressure-induced toxicity. In human trabecular meshwork cells (hTM), CBN attenuated changes in the ECM proteins, including fibronectin and α-smooth muscle actin (α-SMA), as well as mitogen-activated protein kinases (phospho-ERK1/2) in the presence or absence of transforming growth factor-beta 2 (TGF-β2) induced stress. Ocular pharmacokinetic parameters were evaluated post-intravitreal (IVT) CBN delivery in vivo. Furthermore, we demonstrated that IVT-administered CBN improved pattern electroretinogram (pERG) amplitudes and reduced IOP in a rat episcleral vein laser photocoagulation model of glaucoma. ConclusionCBN promotes neuroprotection, abrogates changes in ECM protein, and normalizes the IOP levels in the eye. Therefore, our observations in the present study indicate a therapeutic potential for CBN in the treatment of glaucoma.

Replication of Reduced Pattern Electroretinogram Amplitudes in Depression With Improved Recording Parameters.

Background: The retina has gained increasing attention in non-ophthalmological research in recent years. The pattern electroretinogram (PERG), a method to evaluate retinal ganglion cell function, has been used to identify objective correlates of the essentially subjective state of depression. A reduction in the PERG contrast gain was demonstrated in patients with depression compared to healthy controls with normalization after remission. PERG responses are not only modulated by stimulus contrast, but also by check size and stimulation frequency. Therefore, the rationale was to evaluate potentially more feasible procedures for PERG recordings in daily diagnostics in psychiatry.Methods: Twenty-four participants (12 patients with major depression (MDD) and 12 age- and sex-matched healthy controls) were examined in this pilot study. We investigated PERG amplitudes for two steady-state pattern reversal frequencies (12.5/18.75 rps) and four sizes of a checkerboard stimulus (0.8°, 1.6°, 3.2°, and 16°) to optimize the PERG recordings in MDD patients.Results: Smaller PERG amplitudes in MDD patients were observed for all parameters, whereby the extent of the reduction appeared to be stimulus-specific. The most pronounced decline in the PERG of MDD patients was observed at the higher stimulation frequency and the finest pattern, whilst responses for the largest check size were less affected. Following the PERG ratio protocol for early glaucoma, where similar stimulus dependent modulations have been reported, we calculated PERG ratios (0.8°/16°) for all participants. At the higher frequency (18.75 rps), significantly reduced ratios were observed in MDD patients.Conclusion: The “normalization” of the PERG responses—via building a ratio—appears to be a very promising approach with regard to the development of an objective biomarker of the depressive state, facilitating inter-individual assessments of PERG recordings in patients with psychiatric disorders.

Neural Conduction Along Postretinal Visual Pathways in Glaucoma.

Purpose: This study was conducted in order to evaluate retinal ganglion cell (RCG) function and the neural conduction along the postretinal large and small axons and its correlation with retinal nerve fiber layer thickness (RNFL-T) in open-angle glaucoma (OAG) eyes.Methods: Thirty-seven OAG patients (mean age: 51.68 ± 9.83 years) with 24–2 Humphrey mean deviation (MD) between −2.5 and −20 dB and IOP <21 mmHg on pharmacological treatment (OAG group) and 20 age-matched controls (control group) were enrolled. In both groups, simultaneous pattern electroretinograms (PERG) and visual evoked potentials (VEP), in response to checks stimulating macular or extramacular areas (the check edge subtended 15′ and 60′ of visual arc, respectively), and RNFL-T (measured in superior, inferior, nasal, and temporal quadrants) were assessed.Results: In the OAG group, a significant (ANOVA, p < 0.01) reduction of 60′ and 15′ PERG P50-N95 and VEP N75-P100 amplitudes and of RNFL-T [overall (average of all quadrants) or temporal] with respect to controls was found; the values of 60′ and 15′ PERG P50 and VEP P100 implicit times and of retinocortical time (RCT; difference between VEP P100 and PERG P50 implicit times) were significantly (p < 0.01) increased with respect to control ones. The observed increased RCTs were significantly linearly correlated (Pearson’s test, p < 0.01) with the reduced PERG amplitude and MD values, whereas no significant linear correlation (p < 0.01) with RNFL-T (overall or temporal) values was detected.Conclusions: In OAG, there is an impaired postretinal neural conduction along both large and small axons (increased 60′ and 15′ RCTs) that is related to RGC dysfunction, but independent from the RNFL morphology. This implies that, in OAG, the impairment of postretinal neural structures can be electrophysiologically identified and may contribute to the visual field defects, as suggested by the linear correlation between the increase of RCT and MD reduction.

The Retinal Ganglion Cell Response to Blast-Mediated Traumatic Brain Injury Is Genetic Background Dependent.

PurposeThe purpose of this study was to examine the influence of genetic background on the retinal ganglion cell (RGC) response to blast-mediated traumatic brain injury (TBI) in Jackson Diversity Outbred (J:DO), C57BL/6J and BALB/cByJ mice.MethodsMice were subject to one blast injury of 137 kPa. RGC structure was analyzed by optical coherence tomography (OCT), function by the pattern electroretinogram (PERG), and histologically using BRN3A antibody staining.ResultsComparison of the change in each group from baseline for OCT and PERG was performed. There was a significant difference in the J:DOΔOCT compared to C57BL/6J mice (P = 0.004), but not compared to BALB/cByJ (P = 0.21). There was a significant difference in the variance of the ΔOCT in J:DO compared to both C57BL/6J and BALB/cByJ mice. The baseline PERG amplitude was 20.33 ± 9.32 µV, which decreased an average of −4.14 ± 12.46 µV following TBI. Baseline RGC complex + RNFL thickness was 70.92 ± 4.52 µm, which decreased an average of −1.43 ± 2.88 µm following blast exposure. There was not a significant difference in the ΔPERG between J:DO and C57BL/6J (P = 0.13), although the variances of the groups were significantly different. Blast exposure in J:DO mice results in a density change of 558.6 ± 440.5 BRN3A-positive RGCs/mm2 (mean ± SD).ConclusionsThe changes in retinal outcomes had greater variance in outbred mice than what has been reported, and largely replicated herein, for inbred mice. These results demonstrate that the RGC response to blast injury is highly dependent upon genetic background.

Blue light blind-spot stimulation upregulates b-wave and pattern ERG activity in myopes

Upregulation of retinal dopaminergic activity may be a target treatment for myopia progression. This study aimed to explore the viability of inducing changes in retinal electrical activity with short-wavelength light targeting melanopsin-expressing retinal ganglion cells (ipRGCs) passing through the optic nerve head. Fifteen healthy non-myopic or myopic young adults were recruited and underwent stimulation with blue light using a virtual reality headset device. Amplitudes and implicit times from photopic 3.0 b-wave and pattern electroretinogram (PERG) were measured at baseline and 10 and 20 min after stimulation. Relative changes were compared between non-myopes and myopes. The ERG b-wave amplitude was significantly larger 20 min after blind-spot stimulation compared to baseline (p < 0.001) and 10 min (p < 0.001) post-stimulation. PERG amplitude P50-N95 also showed a significant main effect for ‘Time after stimulation’ (p < 0.050). Implicit times showed no differences following blind-spot stimulation. PERG and b-wave changes after blind-spot stimulation were stronger in myopes than non-myopes. It is possible to induce significant changes in retinal electrical activity by stimulating ipRGCs axons at the optic nerve head with blue light. The results suggest that the changes in retinal electrical activity are located at the inner plexiform layer and are likely to involve the dopaminergic system.

Correlations between visual morphological, electrophysiological, and acuity changes in chronic non-arteritic ischemic optic neuropathy.

To study whether there is a correlation between the macular and optic nerve morphological condition and the retinal ganglion cells (RGCs) and visual pathways' function, and to investigate whether visual acuity (VA) changes might be related to the morpho-functional findings in chronic non-arteritic ischemic optic neuropathy (NAION). In this retrospective study, 22 patients (mean age 62.12 ± 6.87) with chronic unilateral NAION providing 22 affected and 22 fellow eyes without NAION (NAION-FE), and 20 (mean age 61.20 ± 7.32) healthy control subjects were studied by spectral domain optical coherence tomography (Sd-OCT) for investigating macular thickness (MT) and volume (MV) of the whole (WR), inner (IR) and outer retina (OR), and the peripapillary retinal nerve fiber layer thickness (RNFL-T) measured overall and for all quadrants. Also, simultaneous 60' and 15' pattern electroretinogram (PERG) and visual evoked potentials (VEP) and VA were assessed. Differences of MT and MV of WR, IR, OR, and RNFL-T overall and for all quadrants, PERG amplitude (A), VEP implicit time (IT), and A and VA values between NAION eyes and controls were assessed by one-way analysis of variance. Pearson's test was used for regression analysis. A p value < 0.01 was considered as significant. In NAION eyes as compared to NAION-FE eyes and controls, significant (p < 0.01) changes of MT, MV of WR and IR, RNFL-T, 60' and 15' PERG A, VEP IT and A, and VA were found. No significant (p > 0.01) OR changes were observed between groups. In NAION eyes, significant (p < 0.01) correlations between MV of WR and IR and 15' PERG A were found. Overall, RNFL-T values were significantly correlated (p < 0.01) with those of 60' PERG A and VEP IT and A; temporal RNFL-T values were correlated (p < 0.01) with 15' PERG A and VEP IT and A ones. Temporal RNFL-T, MV-IR, and 15' PERG A as well as VEP IT were significantly (p < 0.01) correlated with VA. Significant (p < 0.01) linear correlations between 60' and 15' PERG A findings and the corresponding values of 60' and 15' VEP A were also found. Our findings suggest that in chronic NAION, there is a morpho-functional impairment of the IR, with OR structural sparing. VA changes are related to the impaired morphology and function of IR, to the temporal RNFL-T reduction and to the dysfunction of both large and small axons forming the visual pathway.

Relationship between N95 Amplitude of Pattern Electroretinogram and Optical Coherence Tomography Angiography in Open-Angle Glaucoma.

Purpose: The pattern electroretinogram (PERG) is useful to detect retinal ganglion cell (RGC) damage in patients with glaucoma. Optical coherence tomography angiography (OCTA) measures retinal vessel density (VD), which is known to be reduced in glaucoma. There may be correlations between parameters of the PERG and OCTA in open-angle glaucoma (OAG). Methods: In total, 95 eyes of 95 OAG patients and 102 eyes of 102 normal controls were included in this study. N35, P50, and N95 latency along with P50 and N95 amplitude were obtained using the PERG. Retinal VD was measured around the peripapillary and macular area according to the ETDRS grid (concentric circles with diameters of 1, 3, and 6 mm), which is named a center (≤1 mm), an inner (1–3 mm), an outer (3–6 mm), and a full (≤6 mm) area. Pearson correlation analysis was done between parameters, and partial correlation analysis was done after adjusting confounding factors. Results: P50 amplitude, N95 amplitude, and VD of most measured areas were significantly lower in the OAG group compared to the normal group. N95 amplitude showed a statistically significant correlation with parameters of optical coherence tomography and visual field, peripapillary outer and full VD, and macular outer and full VD even after adjusting confounding factors. There was no significant correlation between parameters in the normal group. Conclusions: N95 amplitude was associated with structural and functional change including VD reduction in OAG. Microvascular alterations may be associated with dysfunctional changes of RGC recorded by the PERG in OAG.