Flash Electroretinogram Research Articles

Correlations Between Dark-Adapted Rod Threshold Elevations and ERG Response Deficits in Duchenne Muscular Dystrophy.

PurposeThe purpose of this study was to characterize changes in the full-field flash electroretinogram (ERG) in association with psychophysical dark-adapted visual thresholds in patients with genetically characterized Duchenne muscular dystrophy (DMD) either lacking Dp427 (Up 30) or at least Dp260 in addition to Dp427 (Down 30).MethodsTwenty-one patients with DMD and 27 age-similar controls participated in this study. Dark-adapted (0.01, 3.0, and 10 cd.s/m² flashes) and light-adapted (3.0 cd.s/m² flash) ERGs were recorded following International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocols. Visual detection thresholds to 625-nm (cone function) and 527-nm (rod function) light-emitting diode (LED) flashes (2 degree diameter) were measured during a dark adaptation period after a 1-minute exposure to a bleaching light (3000 cd/m²). Initially, 8 minutes of interleaved 625-nm and 527-nm thresholds were measured. After an additional 5 minutes of dark-adaptation, a second set of threshold measurements to 527-nm stimuli was performed during the subsequent 6 minutes.ResultsDark-adapted b-wave amplitude was significantly reduced to all strengths of flash and a-wave in response to the strong flash stimulus was delayed (15.6 vs. 14.7 ms, P < 0.05) in patients with Down 30 compared with controls. Dark-adapted cone thresholds did not differ among the groups (−2.0, −1.8, and −1.7 log cd/m² for Down 30, Up 30, and controls, respectively, P = 0.21). In contrast, dark-adapted rod thresholds were elevated (F(2,36) = 8.537, P = 0.001) in patients with Down 30 (mean = −3.2 ± 1.1 log cd/m²) relative to controls (mean = −4.2 ± 0.3 log cd/m²). Dark-adapted b-wave amplitudes were correlated with dark-adapted rod sensitivity in patients with DMD (Spearman Rho = 0.943, P = 0.005). The changes were much smaller or absent in patients with intact Dp260.ConclusionsDp260 is particularly required for normal rod-system function in dark adaptation.

Safety and Long-term Scleral Biomechanical Stability of Rhesus Eyes after Scleral Cross-linking by Blue Light

ABSTRACT Purpose: To assess the safety and long-term scleral biomechanical stability of rhesus eyes after blue light scleral CXL by investigating the biomechanical and microstructural changes. Methods: Seven rhesus monkeys (14 eyes) were observed in this study. All right eyes received blue light scleral CXL at the superior temporal equatorial sclera, and the left eyes served as controls. Biological ocular parameters were followed up to 1 year after scleral CXL. Stress-strain measurements of three rhesus sclera were measured, three rhesus retinas were examined histologically by H&E and TUNEL staining. And the microstructure of both the sclera and retina were observed by transmission electron microscopy at 1 year. Results: As for the retinal thickness, choroidal thickness, flow density of retinal superficial vascular networks and flash electroretinography (f-ERG) results, no significant differences were observed between the paired eyes at 1 year (P >.05). At the same time, the scleral collagen fibril distribution was much tighter, and the scleral biomechanical properties were significantly increased in the experimental eyes. However, apoptotic cells and retinal ultrastructural changes could still be found in the retina of the experimental eyes. Conclusion: This study demonstrates that blue light scleral CXL could effectively increase the scleral stiffness of the rhesus eye for at least 1 year, but ultrastructural change was still observed in the retina of scleral CXL eye. Therefore, the long-term intraocular safety of the blue light scleral CXL technique for preventing myopia progression should be investigated further.

Repeated measurements of ERGs and VEPs using chloral hydrate sedation and propofol anesthesia in young children.

Sedation with chloral hydrate or anesthesia using propofol allow ocular examination and testing in young children, but these drugs may affect electrophysiologic recordings. We compared the flash and pattern ERGs and VEPs recorded with each drug in a cohort of young children enrolled in a prospective study of optic nerve hypoplasia (ONH) syndrome. ERGs and VEPs to light-adapted, standard, full-field flashes, to standard and steady-state pattern-reversal (PR) were recorded with cycloplegia in 9 participants. Age range at the first session, with chloral hydrate was 8-23 mo; at the second session with propofol it was 20-29 mo. Examiners masked to the drug and clinical conditions measured the waveforms for longitudinal, paired comparisons between the sessions. Flash ERG amplitudes did not differ between sessions; peak times were longer at the second session (propofol) by clinically insignificant amounts (< 2ms, p = 0.002). Standard PERGs had larger amplitudes and later peaks in the second session (propofol) than with chloral hydrate (P50 2.9 vs 4.7μV, p = 0.016 and 43 vs 52ms, p < 0.001; N95 4.0 vs 6.1μV, p = 0.003 and 91 vs 98.5ms p = 0.034.). These differences were present for those with an interval of > 10 mo between sessions (n = 5, 10 eyes) but not for those with a shorter inter-test interval (< 8 mo, p > 0.05, n = 4). Magnitudes of the steady-state PERGs did not differ between tests but the waveforms had earlier peaks at the second test with propofol. Flash VEP waveforms were present in 10/18 eyes and showed 72% agreement for recordability between sessions. Standard pattern VEPs were recordable in only a few eyes in this cohort with ONH. Light-adapted flash ERG waveforms were generally similar with chloral hydrate and with propofol. Larger PERGs with later peaks, found in the second session (propofol) could reflect maturation of the PERG generators, as the differences found were associated with a greater age difference between the sessions, but we do not rule out that small differences in the waveforms may be drug-related. There are insufficient VEP data from these children with ONH to identify drug-related or maturational effects on VEPs.

Imaging the pediatric retina: An overview.

Recent decade has seen a shift in the causes of childhood blinding diseases from anterior segment to retinal disease in both developed and developing countries. The common retinal disorders are retinopathy of prematurity and vitreoretinal infections in neonates, congenital anomalies in infants, and vascular retinopathies including type 1 diabetes, tumors, and inherited retinal diseases in children (up to 12 years). Retinal imaging helps in diagnosis, management, follow up and prognostication in all these disorders. These imaging modalities include fundus photography, fluorescein angiography, ultrasonography, retinal vascular and structural studies, and electrodiagnosis. Over the decades there has been tremendous advances both in design (compact, multifunctional, tele-consult capable) and technology (wide- and ultra-wide field and noninvasive retinal angiography). These new advances have application in most of the pediatric retinal diseases though at most times the designs of new devices have remained confined to use in adults. Poor patient cooperation and insufficient attention span in children demand careful crafting of the devices. The newer attempts of hand-held retinal diagnostic devices are welcome additions in this direction. While much has been done, there is still much to do in the coming years. One of the compelling and immediate needs is the pediatric version of optical coherence tomography angiography. These needs and demands would increase many folds in future. A sound policy could be the simultaneous development of adult and pediatric version of all ophthalmic diagnostic devices, coupled with capacity building of trained medical personnel.

Ocular Characteristics of Patients With Bardet-Biedl Syndrome Caused by Pathogenic BBS Gene Variation in a Chinese Cohort.

Bardet–Biedl syndrome (BBS; OMIM 209900) is a rare genetic disease causing damage to multiple organs and affecting patients’ quality of life in late adolescence or early adulthood. In this study, the ocular characteristics including morphology and function, were analyzed in 12 BBS patients from 10 Chinese families by molecular diagnostics. A total of five known and twelve novel variants in four BBS genes (BBS2, 58.33%; BBS4, 8.33%; BBS7, 16.67%; and BBS9, 16.67%) were identified in 10 Chinese families with BBS. All patients had typical phenotypes of retinitis pigmentosa with unrecordable or severely damaged cone and rod responses on full-field flash electroretinography (ffERG). Most of the patients showed unremarkable reactions in pattern visual evoked potential (PVEP) and multifocal electroretinography (mfERG), while their flash visual evoked potentials (FVEP) indicated display residual visual function. Changes in the fundus morphology, including color fundus photography and autofluorescence (AF) imaging, were heterogeneous and not consistent with the patients’ functional tests. Overall, our study expands the variation spectrum of the BBS gene, showing that the ocular characteristics of BBS patients are clinically highly heterogeneous, and demonstrates the usefulness of a combination of the ffERG and FVEP assessments of visual function in the advanced stage of retinopathy in BBS.

Delayed on- and off-retinal responses of cones pathways in regular cannabis users: An On-Off flash electroretinogram case-control study

The retina is considered a useful area for investigating synaptic transmission abnormalities in neuropsychiatric disorders, including as a result of using cannabis, the most widely consumed illicit substance in the developed world.The impact of regular cannabis use on retinal function has already been evaluated, using pattern and flash electroretinogram (ERG) to demonstrate a delay in ganglion and bipolar cell response. Using multifocal ERG, it was showed that the delay to be preferentially located in the central retina. ERG tests do not separately examine the impact of cannabis on the On and Off pathways. The purpose of this study is to assess On and Off pathway function using On-Off ERG.We conducted an On-Off ERG test in 42 regular cannabis users and 26 healthy controls. The protocol was compliant with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Amplitude and peak time were measured for the a-, b- and d-waves.Results in the regular cannabis users showed a significant increase in the latencies of both the b- and the d-wave (p = 0.020, p = 0.022, respectively, Mann-Whitney U test), with no change in the wave amplitudes. A-wave peak time and amplitude were unchanged.These findings are reflective of an effect of regular cannabis use on the On and Off pathways and are consistent with previous findings which also identified increases in retinal neuron response times. We confirm here that regular cannabis use impacts the post-receptoral cones pathway at the level of bipolar cells, affecting the On and Off pathways.

Retinal dysfunctions in regular tobacco users: The retina as a window to the reward circuit in addictive disorders

The nicotine contained in tobacco is a neuromodulator which affects neurotransmission within the brain. The retina is an easy way to study central synaptic transmission dysfunctions in neuropsychiatric disorders. The purpose of this study is to assess the impact of regular tobacco use on retinal function using pattern (PERG), flash (fERG) and multifocal (mfERG) electroretinogram (ERG).We recorded PERG, fERG and mfERG for 24 regular tobacco users and 30 healthy non-smoking subjects. The protocol was compliant with International Society for Clinical Electrophysiology of Vision standards. The amplitudes and peak times (PT) of P50, N95 waves (PERG), a-, b- and oscillatory potentials (fERG), and N1, P1, N2 (mfERG) were evaluated.Compared to non-smokers, the results (Mann–Whitney U test, Bonferroni correction) for tobacco users suggested a significant increase of ~ 1 ms in the PT of light-adapted 3.0 fERG b-wave (p = 0.002). Using mfERG, we observed the following increases in tobacco users: in ring 3 for P1 PT of ~1,5 ms and in ring 5 for P1 PT of ~ 1 ms and for N2 PT of ~ 1 ms (p = 0.002, p = 0.002 and p = 0.006).It is our hypothesis that these results reflect the consequences of regular tobacco use on retinal synaptic transmission, and more specifically on dopaminergic and cholinergic transmission. We deduce that the retina may provide a crucial site of investigation for neurotransmission modulation of the reward circuit in regular tobacco users.

Altered visual processing in the mdx52 mouse model of Duchenne muscular dystrophy

The mdx52 mouse model of Duchenne muscular dystrophy (DMD) is lacking exon 52 of the DMD gene that is located in a hotspot mutation region causing cognitive deficits and retinal anomalies in DMD patients. This deletion leads to the loss of the dystrophin proteins, Dp427, Dp260 and Dp140, while Dp71 is preserved. The flash electroretinogram (ERG) in mdx52 mice was previously characterized by delayed dark-adapted b-waves. A detailed description of functional ERG changes and visual performances in mdx52 mice is, however, lacking. Here an extensive full-field ERG repertoire was applied in mdx52 mice and WT littermates to analyze retinal physiology in scotopic, mesopic and photopic conditions in response to flash, sawtooth and/or sinusoidal stimuli. Behavioral contrast sensitivity was assessed using quantitative optomotor response (OMR) to sinusoidally modulated luminance gratings at 100% or 50% contrast. The mdx52 mice exhibited reduced amplitudes and delayed implicit times in dark-adapted ERG flash responses, particularly in their b-wave and oscillatory potentials, and diminished amplitudes of light-adapted flash ERGs. ERG responses to sawtooth stimuli were also diminished and delayed for both mesopic and photopic conditions in mdx52 mice and the first harmonic amplitudes to photopic sine-wave stimuli were smaller at all temporal frequencies. OMR indices were comparable between genotypes at 100% contrast but significantly reduced in mdx52 mice at 50% contrast. The complex ERG alterations and disturbed contrast vision in mdx52 mice include features observed in DMD patients and suggest altered photoreceptor-to-bipolar cell transmission possibly affecting contrast sensitivity. The mdx52 mouse is a relevant model to appraise the roles of retinal dystrophins and for preclinical studies related to DMD.

Organic visual loss measured by kinetic perimetry and retinal electrophysiology in children with functional amblyopia.

To demonstrate an organic (retinal) amblyogenic defect in functional amblyopes not responding to treatment. Twenty-four children (Mean age: 5.9 ± 1.8years; range: 4-10years) with functional amblyopia were recruited for this study. All these children underwent complete ophthalmic and orthoptic evaluation. In addition, Kinetic Goldman Visual Fields (KGVF), Spectral Domain Optical Coherence Tomography (SD-OCT), full field flash electroretinograms (ffERG) and multifocal electroretinograms (mfERG) were also performed. Ratios were subsequently derived by comparing the amplitudes obtained from the amblyopic eye (AE) to the good eye (GE) for the a- and b-waves of the ffERG, as well as for the ring analysis of the mfERG. KGVF showed a central scotoma of varying size (3°-7°) and density (absolute to relative), with increasing target size in 14/24 patients whose best post-treatment vision in the AE ranged from 20/100 to 20/40. The scotoma decreased in size and density with improving vision until a plateau of recovery was reached. The remaining 10/24 patients with a vision ≥ 20/30 showed no scotoma. SD-OCT showed no significant difference between the AE and GE. ffERG and mfERG were obtained in 18/24 patients. The ffERG AE/GE ratio was abnormal in 7 patients, 5 of which had large scotomas on KGVF. The mfERG ring 1 AE/GE ratio was significantly (p < .05) attenuated in 9/18 patients out of which 3 were no longer amblyopic. However, there was no significant difference (p > .05) in ring 1 AE/GE amplitude ratio between those who achieved 20/50-20/40 (.81 ± .26) and those with ≥ 20/25(.86 ± .25). The combined findings of central scotoma on KGVF and mfERG anomalies in patients who did not achieve optimal vision with treatment suggest an underlying organic defect impairing macular function.

Temporal Contrast Sensitivity Increases despite Photoreceptor Degeneration in a Mouse Model of Retinitis Pigmentosa.

The detection of temporal variations in amplitude of light intensity, or temporal contrast sensitivity (TCS), depends on the kinetics of rod photoresponse recovery. Uncharacteristically fast rod recovery kinetics are facets of both human patients and transgenic animal models with a P23H rhodopsin mutation, a prevalent cause of retinitis pigmentosa (RP). Here, we show that mice with this mutation (RhoP23H/+) exhibit an age-dependent and illumination-dependent enhancement in TCS compared with controls. At retinal illumination levels producing ≥1000 R*/rod/s or more, postnatal day 30 (P30) RhoP23H/+ mice exhibit a 1.2-fold to 2-fold increase in retinal and optomotor TCS relative to controls in response to flicker frequencies of 3, 6, and 12 Hz despite significant photoreceptor degeneration and loss of flash electroretinogram (ERG) b-wave amplitude. Surprisingly, the TCS of RhoP23H/+ mice further increases as degeneration advances. Enhanced TCS is also observed in a second model (rhodopsin heterozygous mice, Rho+/−) with fast rod recovery kinetics and no apparent retinal degeneration. In both mouse models, enhanced TCS is explained quantitatively by a comprehensive model that includes photoresponse recovery kinetics, density and collecting area of degenerating rods. Measurement of TCS may be a non-invasive early diagnostic tool indicative of rod dysfunction in some forms of retinal degenerative disease.

Visual Abnormalities Associate With Hippocampus in Mild Cognitive Impairment and Early Alzheimer's Disease.

Background and Objective: Alzheimer's disease (AD) has been shown to affect vision in human patients and animal models. This study was conducted to explore ocular abnormalities in the primary visual pathway and their relationship with hippocampal atrophy in patients with AD and mild cognitive impairment (MCI). The aim of this study was to investigate the potential value of ocular examinations as a biomarker during the AD progression.Methods: Patients with MCI (n = 23) or AD (n = 17) and age-matched cognitively normal controls (NC; n = 19) were enrolled. Pattern visual-evoked potentials (PVEP), flash electroretinogram (FERG) recordings and optical coherence tomography (OCT) were performed for all participants. Hippocampal volumes were measured by 3T magnetic resonance imaging. Cognitive function was assessed by Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Pearson correlation was employed to analyze the potential associations between ocular abnormalities and hippocampal volumes. Hierarchical regression models were conducted to determine associations between cognitive performances and ocular abnormalities as well as hippocampal volumes after adjusting for confounding factors including age, sex, cognitive reserve, and APOE4 status.Results: PVEP amplitude of P100 waveform was significantly decreased in AD patients compared to MCI and normal individuals. In FERG test, delayed latencies of rod response, rod cone response and 3.0 flicker time were found in cognitively impaired groups, indicating dysfunctions of both the rod and cone systems in the disease progression. OCT test revealed reduced macular retinal nerve fiber layer (m-RNFL) thickness in MCI and AD patients, which significantly correlated with brain structure of hippocampus particularly vulnerable during the progression of AD. Interestingly, P100 amplitude showed a significant association with hippocampal volumes even after adjusting confounding factors including age, sex, and cognitive reserve. Hierarchical regression analysis further demonstrated that m-RNFL thickness, as well as hippocampal volumes, significantly associated with ADAS-cog scores.Conclusion: P100 amplitude and m-RNFL thickness showed significant correlations with brain structure involved in AD-related neurodegeneration, and therefore proved to be potential indicators of brain imaging pathologies.

Retinal Screening of Prolactinoma Patients Using Flash Electroretinography

Aim: Prolactinoma is the most pituitary adenomas that affect young women at fertile age. Visual impairment is a common presentation of this condition. Retina is a part of visual system may be affected in these patients. Flash electroretinography is one of the techniques to screen the retina. The aim of present work is to search for probable adverse effect of prolactinoma on retina using flash electro-retinography. Patients and Method: Fifteen female patients (30 eyes) with age range of 20-40 years were selected. The patients had healthy visual system as for as visual acuity, field of vision and magnetic resonance imaging of brain were concerned. The amplitude and latency of electroretinogram b-wave was recorded for these patients and 15 age and sex matched controls with healthy visual system. Results: The mean age was 29.4±6.68 and 29.13±6.82 in case and control groups respectively. The mean visual acuity was 0.00±0.00 (LogMar) in both groups. The difference in values were not statistically significant as far as age (P = 0.967) and visual acuity (P=1) were concerned. The values obtained for amplitude were 113.93 ± 9.14 and 114.4 ± 6.83 in case and control groups respectively. On other hand the values for latency were 34.13 ± 1.56 and 34.13 ± 1.65 in case and control groups respectively. The values for ERG were not statistically significant as for as amplitude and latency (P = 0.682 and P = 0.925 respectively) of ERG, b-wave were concerned. Conclusion: Prolactinoma does not affect retina of the patients as for as flash electroretinography is concerned.

Retrospective and prospective study of progressive retinal atrophy in dogs presented to the veterinary hospital of the Federal University of Parana, Brazil.

Background:Progressive retinal atrophy (PRA) is one of the main causes of blindness in dogs. Despite its clinical importance, there is limited epidemiological information available, particularly in South America.Aim:The main objective of this study was to perform a retrospective, and prospective analysis of PRA in dogs admitted at the Veterinary Hospital of the Federal University of Paraná, Brazil.Methods:Medical records of dogs admitted between 2014 and 2018 were selected through the archives of the Comparative Ophthalmology Laboratory. A total of 130 dogs with medical records indicating clinical signs suggestive of PRA, independent of the electroretinography confirmation, were selected. In order to investigate common characteristics, each patient’s clinical history, ophthalmic examination, and visual status were reviewed (obstacle course, pupillary light reflex, dazzle reflex, visual tracking to a cotton ball, and menace responses). Additionally, a prospective study was performed, where flash electroretinography was performed on 30 animals with clinical signs suggestive of PRA, and 14 animals were selected for fundus photography. Data were assessed through descriptive and inferential statistics.Results:A total of 2,055 dogs were evaluated between January 2014 and December 2018. Of those, 130 animals were presumptively diagnosed with PRA (6.33%), consisting of 18 different breeds and 27 dogs with a mixed pedigree. Poodles were the most prevalent breed (n = 26; 20.00%), followed by Cocker Spaniels (n = 19; 14.62%). In the reported caseload, Pomeranians showed a considerably higher odds ratio for PRA development (15.36%).Conclusion:Pomeranians presented a high odds ratio, suggesting that further studies may be performed with breeds with a high potential for developing this disease.

AAV-CRB2 protects against vision loss in an inducible CRB1 retinitis pigmentosa mouse model

Loss of Crumbs homolog 1 (CRB1) or CRB2 proteins in Müller cells or photoreceptors in the mouse retina results in a CRB dose-dependent retinal phenotype. In this study, we present a novel Müller cell-specific Crb1KOCrb2LowMGC retinitis pigmentosa mouse model (complete loss of CRB1 and reduced levels of CRB2 specifically in Müller cells). The Crb double mutant mice showed deficits in electroretinography, optokinetic head tracking, and retinal morphology. Exposure of retinas to low levels of dl-α-aminoadipate acid induced gliosis and retinal disorganization in Crb1KOCrb2LowMGC retinas but not in wild-type or Crb1-deficient retinas. Crb1KOCrb2LowMGC mice showed a substantial decrease in inner/outer photoreceptor segment length and optokinetic head-tracking response. Intravitreal application of rAAV vectors expressing human CRB2 (hCRB2) in Müller cells of Crb1KOCrb2LowMGC mice subsequently exposed to low levels of dl-α-aminoadipate acid prevented loss of vision, whereas recombinant adeno-associated viral (rAAV) vectors expressing human CRB1 (hCRB1) did not. Both rAAV vectors partially protected the morphology of the retina. The results suggest that hCRB expression in Müller cells is vital for control of retinal cell adhesion at the outer limiting membrane, and that the rAAV-cytomegalovirus (CMV)-hCRB2 vector is more potent than rAAV-minimal CMV (CMVmin)-hCRB1 in protection against loss of vision.

Seizure triggered by flicker electroretinogram in a patient with no history of epilepsy

PurposeIt is well known that repetitive flash stimulation may trigger seizures in susceptible individuals. Nevertheless, reports of such incidents occurring during recording of a flash electroretinogram (ERG) are extremely rare. Here, we describe the case of a photic-induced seizure triggered during an ERG recording in the absence of a history of epilepsy or other paroxysmal events.MethodsA 14-year-old male patient presented with reduced visual acuity and impaired mesopic vision. Ophthalmological exams confirmed the patient’s complaints but were inconclusive as to the underlying pathophysiology. An ERG recording was performed, during which the 30-Hz flicker stimulus triggered a seizure.ResultsThe ERG was essentially normal, with the exception of a 7-Hz rhythm superimposed onto the flicker ERG response that was recorded when the seizure developed.ConclusionsThe present case highlights the possibility that the 30-Hz ERG flash stimulus triggers a seizure in patients with no previous paroxysmal events. Literature evidence suggests that the likelihood of such an incident could be reduced by stimulating monocularly.

Houttuynia cordata Thunb rescues retinal ganglion cells through inhibiting microglia activation in a rat model of retinal ischemia-reperfusion.

To determine whether Houttuynia cordata Thunb (HCT) can increase the survival of the retinal ganglion cells (RGCs) and inhibit microglia activation following retinal ischemia-reperfusion (RIR) injury. Rat model of RIR was induced by transient elevation of the intraocular pressure (IOP). HCT was orally administered for 2d before the performance of retinal RIR model and once a day for the next 14d. After 14d of RIR injury, the rats were sacrificed for further analysis. Survival RGCs were stained with haematoxylin and eosin (H&E). Apoptosis of RGCs was detected by TUNEL staining. Retinal function was examined by flash-electroretinography (F-ERG). Retinal microglia were labeled using Iba-1, one specific marker for microglia. The mRNA expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) were assessed by quantitative real time reverse transcription polymerase chain reaction (qRT-PCR). Systemic HCT treatment significantly reduced RGCs death by H&E staining and exhibited an anti-apoptotic effect as assessed by TUNEL staining at day 14 after RIR injury. HCT greatly improved the retinal function as examined by F-ERG. The number of activated microglia significantly increased after RIR injury, which was significantly attenuated by HCT treatment. Besides, RIR injury induced a strong upregulation of pro-inflammatory genes TNF-α, iNOS and IL-1β mRNAs at day 14 post injury, which was suppressed by HCT. Neuroprotective effects of HCT encourage the survival of RGCs through inhibiting microglia activation due to RIR injury. Together these results support the use of HCT as promising therapy for the ischemic events of the retina diseases.

Evaluation of amblyopic eyes with optical coherence tomography angiography and electrophysiological tests.

Purpose:To investigate the structural and functional changes of the retina and optic nerve in amblyopia.Methods:Eighteen patients with unilateral anisometropic amblyopia and 27 age-matched healthy controls were involved in this study. All patients underwent optical coherence tomography angiography (OCTA), pattern visual evoked potential (pVEP), and flash electroretinogram (fERG).Results:There was no statistically significant difference in terms of the foveal avascular zone (FAZ), perifoveal superficial density, whole superficial density, parafoveal deep density, perifoveal deep density among the eyes (P > 0 0.05). Significant differences were found only in superficial capillary plexus (SCP) vessel density in whole (P = 0.029) and parafoveal (P = 0.008) image. In electrophysiological tests, while VEP latencies of the amblyopic eyes increased compared to nonamblyopic eyes and controls (P = 0.027), VEP amplitudes decreased in amblyopic and nonamblyopic eyes compared to controls (P = 0.01), amplitudes of the rod (P = 0.027) and cones (P < 0.001) also decreased in amblyopic eyes compared to nonamblyopic and healthy eyes. When we assessed the correlation between the parameters of OCTA and electrophysiological test, only a significant correlation was found between parafoveal SCP vessel density and VEP amplitudes (r = 0.341).Conclusion:We found a significant decrease only in SCP vessel density of the OCTA parameters in amblyopic eyes compared to healthy eyes. We detected a significant relationship between parafoveal SCP vessel density and VEP parameters, which might be associated with the underlying pathophysiology of the amblyopia.

Acute unilateral inner retinal dysfunction with photophobia: importance of electrodiagnosis.

To establish with negative electroretinogram (ERG) the clinical entity of eight patients with unilateral severe photophobia, essentially normal fundus, good visual acuity, and severe cone and rod dysfunction. Multicenter retrospective observation case series. Comprehensive ophthalmologic examinations were performed, including best-corrected visual acuity (BCVA), full-field ERGs and multifocal ERGs (mfERGs), fundus photographs, and OCT. Systemic and genetic examinations were performed. The mean (± SD) age at the onset was 60.0 ± 8.4years, and the six patients noticed severe photophobia in the affected eye in spite of almost normal fundus appearance and good BCVA. The dark-adapted bright flash ERGs in the affected eye had relatively well-preserved a-waves and depressed b-waves, i.e., a negative ERG. Cone ERGs and both b- and d-waves of the photopic long-duration ERGs were almost undetectable. Rod ERGs were severely reduced; however, only two patients complained of night blindness. In five patients, the mfERGs were extinguished in the periphery but preserved in the central retina, resulting in good BCVA. Electrophysiological findings indicated a severe diffuse dysfunction of the inner retina affecting bipolar cells of both ON- and OFF-pathways, and in five patients there was a reduction in the thickness of the inner nuclear layer. In seven patients the retinal arteries were attenuated. Anti-retinal antibodies were detected in the serum of two patients. No genetic causes were found. The common features in the eight patients with unilateral negative ERGs suggest a new disease entity of unilateral acute inner retinal layer dysfunction. In most patients, the only subjective complain was photophobia.

Using retinal function to define ischemic exclusion criteria for animal models of glaucoma

Most animal models of glaucoma rely on induction of ocular hypertension (OHT), yet such models can suffer from high IOPs leading to undesirable retinal ischemia. Thus, animals with IOPs exceeding a threshold (e.g. > 60 mmHg) are often excluded from studies. However, due to the intermittent nature of IOP measurements, this approach may fail to detect ischemia. Conversely, it may also inappropriately eliminate animals with IOP spikes that do not induce ischemic damage. It is known that acute ischemia selectively impairs inner retinal function, which results in a reduced b-wave amplitude. Here, we explore the potential of using electroretinography (ERG) to detect ischemic damage in OHT eyes. 74 Brown Norway rats received a unilateral injection of magnetic microbeads to induce OHT, while contralateral eyes served as controls. IOP was measured every 2–3 days for 14 days after microbead injection. Retinal function was evaluated using dark-adapted bright flash ERG (2.1 log cd•s/m2) prior to, and at 7 and 14 days after, injection. We investigated two criteria for excluding animals: (IOP Criterion) a single IOP measurement > 60 mmHg; or (ERG Criterion) a b-wave amplitude below the 99.5% confidence interval for naïve eyes. 49 of 74 rats passed both criteria, 7 of 74 failed both, and 18 passed one criterion but not the other. We suggest that ERG testing can detect unwelcome ischemic damage in animal models of OHT. Since brief IOP spikes do not necessarily lead to ischemic retinal damage, and because extended periods of elevated IOP can be missed, such ERG-based criteria may provide more objective and robust exclusion criteria in future glaucoma studies.

Comparison among Short Time Fourier Transform and Continuous Wavelet Transform Techniques in Flash Erg Signals Processing

Flaş Elektroretinogram sinyalleri gözün retina tabakasının flaş bir ışık ile uyarılması sonucu ortaya çıkan elektriksel potansiyellerdir. Bu sinyale ait iki temel bileşeni olan ‘a’ ve ‘b’ dalgaları retina tabakasının değerlendirilmesinde önem arz etmektedir. Bunun için farklı sinyal işleme tekniklerinden yararlanılmaktadır. Yapılan bu çalışmada sağlıklı bireylerden kaydedilen flaş Elektroretinogram sinyallerinin rod, maksimum kombine ve kon yanıtları kullanılarak Kısa Zamanlı Fourier Dönüşümü ve Sürekli Dalgacık Dönüşümü yöntemleriyle sinyallerin ‘a’ ve ‘b’ dalgaları analizi edilmiştir. Bu doğrultuda dalgaların lokasyonlarının tespit edilmesinde hangi yöntemin daha başarılı olduğu irdelenmiştir. Gerçekleştirilen analizler sonucunda her üç yanıtta da dalgaların analizi için Sürekli Dalgacık Dönüşümünün daha başarılı bir yöntem olduğu tespit edilmiştir. Bunun yanı sıra Sürekli Dalgacık Dönüşümünde rod ve kon yanıtları için Coiflet, Gauss, Meksika şapka ve Morlet dalgacıklarının, maksimum kombine yanıtı için ise Morlet dalgacığının kullanılması halinde dalgaların lokasyonlarının daha doğru bir şekilde tespit edebileceği saptanmıştır.