ERG Data Research Articles

Novel Machine-Learning Based Framework Using Electroretinography Data for the Detection of Early-Stage Glaucoma.

PurposeEarly-stage glaucoma diagnosis has been a challenging problem in ophthalmology. The current state-of-the-art glaucoma diagnosis techniques do not completely leverage the functional measures' such as electroretinogram's immense potential; instead, focus is on structural measures like optical coherence tomography. The current study aims to take a foundational step toward the development of a novel and reliable predictive framework for early detection of glaucoma using machine-learning-based algorithm capable of leveraging medically relevant information that ERG signals contain.MethodsERG signals from 60 eyes of DBA/2 mice were grouped for binary classification based on age. The signals were also grouped based on intraocular pressure (IOP) for multiclass classification. Statistical and wavelet-based features were engineered and extracted. Important predictors (ERG tests and features) were determined, and the performance of five machine learning-based methods were evaluated.ResultsRandom forest (bagged trees) ensemble classifier provided the best performance in both binary and multiclass classification of ERG signals. An accuracy of 91.7 and 80% was achieved for binary and multiclass classification, respectively, suggesting that machine-learning-based models can detect subtle changes in ERG signals if trained using advanced features such as those based on wavelet analyses.ConclusionsThe present study describes a novel, machine-learning-based method to analyze ERG signals providing additional information that may be used to detect early-stage glaucoma. Based on promising performance metrics obtained using the proposed machine-learning-based framework leveraging an established ERG data set, we conclude that the novel framework allows for detection of functional deficits of early/various stages of glaucoma in mice.

Efficacy of Tamponade of Vitreal Cavity by Perfluororganic Compound Emulsion with Antibiotics Solutions in Treatment of Gram Negative Endopthalmitis (Experimental Study)

The purpose of investigation was assessment of efficacy of the method suggested for treatment of postoperative endophthalmitis on the experimental model of gram negative endophthalmitis. Materials and methods . In order to create experimental model of endophthalmitis phacoemulsification of lens was rendered on 30 rabbits (30 eyes). At the end of surgery 0.1 ml of Escherichia coli microbial suspension containing 100 cells of pathogen was injected intravitreally to all. In 12 hours after the contamination signs of heavy postoperative endophthalmitis appeared in all rabbits. All the rabbits were divided into two groups in dependence of the method of further surgical treatment. 15 rabbits (15 eyes) were in the first group, vitrectomy with intravitreal injection of 1 mg vancomicin + 2.25 mg ceftazidim antibiotics combination was rendered. For 15 rabbits (15 eyes) of the second group vitrectomy with tamponade of vitreal cavity by PFOC and 1 mg vancomicin + 2.25 mg ceftazidim antibiotics combination intravitreal injection was rendered. Results. Treatment of the second group rabbits was more effective in comparison with the first group ( p = 0.0018). According to ERG data visual functions were saved in 6 rabbits of the first group (40 %) and in 10 rabbits of the second group (66.67 %). Besides functional loss anatomic loss of eye was observed in 33.33 % cases in the first group. While eyeball was saved in all 100 % cases of the second group with use of the suggested method. Conclusion. Experimental investigation proved efficacy of the suggested method of endophthalmitis treatment. This method of treatment is universal regardless of disease etiological cause.

The Absence of Toll-Like Receptor 4 Mildly Affects the Structure and Function in the Adult Mouse Retina.

The innate immune Toll-like receptor (TLR) family plays essential roles in cell proliferation, survival and function of the central nervous system. However, the way in which TLRs contribute to the development and maintenance of proper retinal structure and function remains uncertain. In this work, we assess the effect of genetic TLR4 deletion on the morphology and function of the retina in mice. Visual acuity and retinal responsiveness were evaluated in TLR4 knockout and wild type C57BL/6J control mice by means of an optomotor test and electroretinography, respectively, from P20 to P360. Retinal structure was also analyzed in both strains using confocal and electron microscopy. ERG data showed impaired retinal responsiveness in TLR4 KO mice, in comparison to wild type animals. The amplitudes of the scotopic a-waves were less pronounced in TLR4-deficient mice than in wild-type animals from P30 to P360, and TLR4 KO mice presented scotopic b-wave amplitudes smaller than those of age-matched control mice at all ages studied (P20 to P360). Visual acuity was also relatively poorer in TLR4 KO as compared to C57BL/6J mice from P20 to P360, with significant differences at P30 and P60. Immunohistochemical analysis of retinal vertical sections showed no differences between TLR4 KO and C57BL/6J mice, in terms of either photoreceptor number or photoreceptor structure. Horizontal cells also demonstrated no morphological differences between TLR4 KO and wild-type mice. However, TLR4 KO mice exhibited a lower density of bipolar cells (15% less at P30) and thus fewer bipolar cell dendrites than the wild type control mouse, even though both confocal and electron microscopy images showed no morphologic abnormalities in the synaptic contacts between the photoreceptors and second order neurons. Microglial cell density was significantly lower (26% less at P30) in TLR4 KO mice as compared to wild-type control mice. These results suggest that TLR4 deletion causes functional alterations in terms of visual response and acuity, probably through the loss of bipolar cells and microglia, but this receptor is not essential for the processing of visual information in the retina.

Deletion of 3p13 is a late event linked to progression of TMPRSS2:ERG fusion prostate cancer.

IntroductionDeletion of 3p13 is one of the most common alterations in prostate cancer preferentially occurring in tumors with TMPRSS2:ERG fusion. The cause for the striking association between 3p13 loss and ERG fusion is unknown.MethodsHere, we made use of a preexisting heterogeneity prostate cancer tissue microarray including ten tissue spots from ten different tumor areas of 317 cancers to examine the spatial distribution of 3p13 deletions (determined by fluorescence in situ hybridization) in prostate cancer areas with and without ERG overexpression (determined by immunohistochemistry).Results3p13 deletions were found in 61 of 299 (20.4%) and ERG positivity in 174 of 317 (54.9%) interpretable cancers. The likelihood of 3p13 loss was twice as high in ERG-positive cancers (39/152, 25.7%) than in ERG-negative cancers (17/124, 13.7%, P=0.010). At least three tissue spots were interpretable for 3p13 deletion status in 279 cancers: only these were used for heterogeneity assessment. Among these tumors, 58 (20.8%) had a 3p13 deletion and 221 (79.2%) were undeleted. The majority of 3p13-deleted cancers showed marked intratumoral heterogeneity. Areas with and without 3p13 loss were found in 50 (18%) of 279 cancers with three or more interpretable tissue spots, while only eight (3%) tumors had a homogeneous 3p13 loss. Comparison with ERG data revealed that ERG fusion usually precede 3p13 deletions. In total, 26 (66.7%) of 39 cancers with ERG and 3p13 alteration had only focal 3p13 deletions in an otherwise ERG-positive background. In contrast, none of the cancers showed a pattern that would be consistent with 3p13 deletion preceding ERG fusion.ConclusionOur study identifies 3p13 deletion as a highly heterogeneous alteration in prostate cancer preferentially developing at rather late stages of progression in TMPRSS2:ERG fusion-positive tumors.

Clinical utility of assessing PTEN and ERG protein expression in prostate cancer patients: a proposed method for risk stratification.

To assess the prognostic value of ERG and PTEN protein expression as two of the most common genetic aberration in men with prostate cancer managed non-surgically by androgen deprivation therapy (ADT). 463 tumor samples were assessed by double immunohistochemistry stains for ERG and PTEN and data correlated with clinical pathological features including, Gleason score, patients' outcome and ADT. ERG expression and PTEN protein loss were present in 28.2% and 38% of total patients respectively. There was a significant interplay between ERG and PTEN expression with 21.8% PTEN negative tumors being ERG positive (p < 0.001). Both ERG and PTEN showed significant association with lethal disease in all patients and those treated with prior ADT representing castrate-resistant disease. However, only PTEN remained significant in multivariable proportional hazards regression analysis, when including Gleason score and patients' age. Depending on patient's subgroup, intact positive PTEN intensity showed better cancer-specific survival with HR ranging from 0.25 to 0.4 compared to tumors with loss of PTEN expression. Assessing combined marker status, patients with decreased PTEN intensity without ERG positivity showed the worst clinical outcome compared to those with no PTEN loss and no ERG expression, where they had best clinical outcome. Patients with ERG expression with or without PTEN loss showed intermediate risk in relation to lethal disease. This study confirms a significant prognostic role for assessing ERG and PTEN in men with prostate cancer. It supports a role for utilizing combined ERG/PTEN status clinically and prospectively for stratifying PCa patients into different prognostic groups.

High Symmetry of Visual Acuity and Visual Fields in RPGR-Linked Retinitis Pigmentosa.

Mutations in retinitis pigmentosa GTPase regulator (RPGR) cause 70% to 90% of X-linked retinitis pigmentosa (XLRP3) cases, making this gene a high-yield target for gene therapy. This study analyzed the utility of relevant clinical biomarkers to assess symmetry and rate of progression in XLRP3. A retrospective, cross-sectional analysis of 50 XLRP3 patients extracted clinical data including visual acuity (VA), visual fields (I4e and III4e targets), foveal thickness, and ERG data points alongside molecular genetic data. Symmetry was assessed by using linear regression analysis. Kaplan-Meier survival curves (KMCs) and generalized linear mixed model calculations were used to describe disease progression. Ninety-six percent of patients exhibited a rod-cone phenotype, and 4% a cone-rod phenotype. Open reading frame 15 (ORF15) was confirmed as a mutational hotspot within RPGR harboring 73% of exonic mutations. Significant variability, but no clear genotype-phenotype relationship, could be shown between mutations located in exons 1-14 versus ORF15. All biomarkers suggested a high degree of symmetry between eyes but demonstrated different estimates of disease progression. VA and foveal thickness, followed by perimetry III4e, were the most useful endpoints to evaluate progression. KMC estimates predicted a loss of 6/6 vision at a mean of 34 years (±2.9; 95% confidence interval). XLRP3 affects retinal structure and function symmetrically, supporting the use of the fellow eye as an internal control in interventional trials. VA and kinetic visual fields (III4e) seem promising functional outcome measures to assess disease progression. KMC analysis predicted the most severe decline in vision between the third and fourth decade of life.

Prostate cancer risk regions at 8q24 and 17q24 are differentially associated with somatic TMPRSS2:ERG fusion status.

Molecular and epidemiological differences have been described between TMPRSS2:ERG fusion-positive and fusion-negative prostate cancer (PrCa). Assuming two molecularly distinct subtypes, we have examined 27 common PrCa risk variants, previously identified in genome-wide association studies, for subtype specific associations in a total of 1221 TMPRSS2:ERG phenotyped PrCa cases. In meta-analyses of a discovery set of 552 cases with TMPRSS2:ERG data and 7650 unaffected men from five centers we have found support for the hypothesis that several common risk variants are associated with one particular subtype rather than with PrCa in general. Risk variants were analyzed in case-case comparisons (296 TMPRSS2:ERG fusion-positive versus 256 fusion-negative cases) and an independent set of 669 cases with TMPRSS2:ERG data was established to replicate the top five candidates. Significant differences (P < 0.00185) between the two subtypes were observed for rs16901979 (8q24) and rs1859962 (17q24), which were enriched in TMPRSS2:ERG fusion-negative (OR = 0.53, P = 0.0007) and TMPRSS2:ERG fusion-positive PrCa (OR = 1.30, P = 0.0016), respectively. Expression quantitative trait locus analysis was performed to investigate mechanistic links between risk variants, fusion status and target gene mRNA levels. For rs1859962 at 17q24, genotype dependent expression was observed for the candidate target gene SOX9 in TMPRSS2:ERG fusion-positive PrCa, which was not evident in TMPRSS2:ERG negative tumors. The present study established evidence for the first two common PrCa risk variants differentially associated with TMPRSS2:ERG fusion status. TMPRSS2:ERG phenotyping of larger studies is required to determine comprehensive sets of variants with subtype-specific roles in PrCa.

BET bromodomain-mediated interaction between ERG and BRD4 promotes prostate cancer cell invasion.

Prostate cancer (PCa) that becomes resistant to hormone castration and next-generation androgen receptor (AR)-targeted therapies, called castration-resistant prostate cancer (CRPC), poses a significant clinical challenge. A better understanding of PCa progression and key molecular mechanisms could bring novel therapies to light. One potential therapeutic target is ERG, a transcription factor aberrantly up-regulated in PCa due to chromosomal rearrangements between androgen-regulated gene TMPRSS2 and ERG. Here we show that the most common PCa-associated truncated ERG T1–E4 (ERGΔ39), encoded by fusion between TMPRSS2 exon 1 and ERG exon 4, binds to bromodomain-1 (BD1) of bromodomain containing protein 4 (BRD4), a member of the bromodomain and extraterminal domain (BET) family. This interaction is partially abrogated by BET inhibitors JQ1 and iBET762. Meta-analysis of published ERG (T1–E4) and BRD4 chromatin immunoprecipitation-sequencing (ChIP-seq) data demonstrates overlap in a substantial portion of their binding sites. Gene expression profile analysis shows some ERG-BRD4 co-target genes are upregulated in CRPC compared to hormone-naïve counterparts. We provide further evidence that ERG-mediated invasion of PCa cells was significantly enhanced by an acetylation-mimicking mutation in ERG that augments the ERG-BRD4 interaction. Our findings reveal that PCa-associated ERG can interact and co-occupy with BRD4 in the genome, and suggest this druggable interaction is critical for ERG-mediated cell invasion and PCa progression.

270. Optogenetic Activation of Remnant Cone Cells Can Restore Ganglion Cell Light Responses in a Canine Model of Retinitis Pigmentosa

In retinitis pigmentosa, the rod photoreceptor cells are generally lost first followed by a slow loss of cone cells. Remnant cone cell bodies have been observed even after many years of vision loss in retinitis pigmentosa patients. Proof-of-principle studies in retinal degeneration mice have demonstrated vision restoration upon expression of the optogene halorhodopsin in remnant cone cells. However, whether this will work in a large animal model of retinal degeneration is unclear. Here we look at light responses and histology post-treatment with halorhodopsin in a dog model of autosomal recessive retinitis pigmentosa. Halorhodopsin was expressed in the cone cells unilaterally in rcd1 dogs (PDE6β mutation) with mid- to late stage retinal degeneration using recombinant adeno-associated viral vectors. The retinas were imaged using OCT and function was evaluated using ERG and pupillometry. The spiking activity of retinal ganglion cells (RGCs) in retinal patches adjacent to and distant from the point of injection was tested using multi electrode array recordings. Retinal patches were stimulated with 589 nm light of different durations/intensities. OCT revealed significant thinning of the photoreceptor layer in the retinas of the dogs. While the ERG and pupillometry data did not show a significant difference between the treated and untreated eyes, multi-electrode array recordings revealed a restoration of ganglion cell light responses (ON, OFF and ON/OFF-responses to discrete flashes and responses to 4Hz flicker, 589nm light) in the treated retinal patch compared to an untreated control patch of retina. The lowest intensities where responses become clearly detectable for two animals were 0.1 mW/cm2 and 2.8 mW/cm2 probably reflecting different levels of NpHR expression. We observed halorhodopsin expression by histology in the remnant cone cell bodies of the treated retinas. Restoration of ganglion cell responses in the treated retinal patches suggests that the retina can be sensitized to light even after major photoreceptor cell loss. Ongoing work will determine if this restoration of ganglion cell light responses in the dogs translate to being able to navigate in the light.

Long-term evaluation of Leber’s hereditary optic neuropathy-like symptoms in rotenone administered rats

Leber’s hereditary optic neuropathy (LHON) is an inherited disorder affecting the retinal ganglion cells (RGCs) and their axons that lead to the loss of central vision. This study is aimed at evaluating the LHON symptoms in rats administered with rotenone microspheres into the superior colliculus (SC). Optical coherence tomography (OCT) analysis showed substantial loss of retinal nerve fiber layer (RNFL) thickness in rotenone injected rats. Optokinetic testing in rotenone treated rats showed decrease in head-tracking response. Electrophysiological mapping of the SC surface demonstrated attenuation of visually evoked responses; however, no changes were observed in the ERG data. The progressive pattern of disease manifestation in rotenone administered rats demonstrated several similarities with human disease symptoms. These rats with LHON-like symptoms can serve as a model for future investigators to design and implement reliable tests to assess the beneficial effects of therapeutic interventions for LHON disease.

Electroretinogram Monitoring of Dose-Dependent Toxicity after Ophthalmic Artery Chemosurgery in Retinoblastoma Eyes: Six Year Review

PurposeTo report electroretinogram responses of retinoblastoma children under anesthesia before and after treatment with chemotherapeutic drugs (melphalan, topotecan, carboplatin) delivery by ophthalmic artery chemosurgery (OAC).MethodsA cohort study of 81 patients with retinoblastoma treated with OAC. All patients treated with OAC at our center through May 2012 for whom the requisite ERG data were available are included in the analysis. This study recorded the ERG 30 Hz flicker amplitude response changes from baseline, at 3 and 12 months following OAC treatment completion. Both univariate and multivariate linear regression models were evaluated, with generalized estimating equations to correct for correlations within patients. Independent numerical variables included maximum doses and cumulative doses of melphalan, topotecan and carboplatin.ResultsBy univariate analysis, both melphalan and topotecan appear to be associated with changes in ERG amplitude at both 3 and 12 months; but for the most part, these changes are minimal and likely clinically insignificant. By multivariate analysis, maximum and cumulative melphalan have a modest, temporary effect on the ERG amplitude change, which is apparent at 3 months but no longer evident at 12 months after completing treatment. By multivariate analysis, topotecan and carboplatin do not appear to adversely effect the change in ERG response.ConclusionMelphalan has the strongest, and carboplatin the weakest association with reduction in ERG response amplitudes; but for the most part, these changes are minimal and likely clinically insignificant. These conclusions apply only over the dose ranges used here, and should be applied with caution.

TMPRSS2–ERG gene fusions induce prostate tumorigenesis by modulating microRNA miR-200c

Chromosomal translocations that juxtapose the androgen-sensitive TMPRSS2 gene promoter to the oncogenic ETS-family transcription factor ERG result in excessive ERG overexpression in approximately 50% of prostate cancer (PCa) patients. Although numerous studies have investigated ERG-downstream genes, such studies have not attempted to examine miRNAs, which however are emerging to be important regulators of cancer. Through bioinformatics analysis of ChIP-Seq ERG data and miRNA expression profiling data we nominated miR-200c as a direct target of ERG. Experimentation of PCa cells with ERG overexpression or knockdown demonstrated that ERG directly repressed miR-200c expression by physically binding to the ETS motif within its promoter. Consequently, miR-200c was down-regulated in ERG-positive PCa and miR-200c target gene expression was restored. In addition, the expression pattern of miR-200c target genes predicted ERG status in clinical PCa specimens. Furthermore, miR-200c was found important in modulating ZEB1 up-regulation by ERG. Most importantly, miR-200c reconstitution fully reversed ERG-induced epithelial-to-mesenchymal transition, cell migration and invasion. Therefore, our study report miR-200c as a first miRNA target of ERG and a critical inhibitor of PCa cell motility. Therapeutic delivery of miR-200c may provide personalized treatment for patients with the molecular subtype of PCa that harbors TMPRSS2-ERG gene fusions.

Inverse pattern of photoreceptor abnormalities in retinitis pigmentosa and cone-rod dystrophy.

PurposeTo determine the characteristics of the photoreceptor abnormalities in retinitis pigmentosa (RP) and cone–rod dystrophy (CRD).MethodsWe evaluated the photoreceptor abnormalities using spectral-domain optical coherence tomography (SD-OCT) in 28 patients with RP and 17 patients with CRD. The OCT images and full-field electroretinograms were obtained from 21 eyes in normal subjects who were age-matched to patients with RP and CRD and served as controls.ResultsEyes with RP and CRD had markedly decreased rod responses (6.5 and 57.5 % of normal value), maximal responses (9.6 and 51.6 %), cone (16.5 and 25.8 %), and 30-Hz flicker responses (17.8 and 30.1 % of normal value), and their P values were smaller than 0.0003. On comparison of ERG data between RP and CRD, they had statistically significant differences in rod responses (P < 0.0003) and maximal responses (P < 0.0003). However, there were no statistical differences in cone response and a weak difference in 30-Hz flicker responses (P < 0.017). The best-corrected visual acuity was −0.03 ± 0.09 (logMAR, mean ± standard deviation [SD]) in eyes with RP, but 0.57 ± 0.54 in eyes with CRD. SD-OCT showed that eyes with RP had an intact reflective line at the junction between the photoreceptor inner and outer segment (IS/OS) at the fovea, while eyes with CRD had no IS/OS. The extent of the central visual field was correlated with the IS/OS length at the macula in eyes with RP.ConclusionThe distribution patterns of the IS/OS line help to differentiate between RP and CRD.

The effects of hypoxia on the ERG in paediatric cerebral malaria

Cerebral malaria (CM) is a disease of high mortality worldwide. It can be associated with malarial retinopathy (MR) resulting from impaired perfusion within the retinal microvasculature. Areas of capillary non-perfusion (CNP) appear white (retinal whitening) on ophthalmoloscopy. In this study, electrophysiological investigations were performed to investigate the physiological consequences of these hypoxic and ischaemic changes. Children admitted with CM were assessed for inclusion in the study. Those with MR underwent further detailed fundus assessment to quantify retinal whitening and were then designated a severity score. Electrophysiological recordings were performed using a miniganzfeldt stimulator with calibration to the International Society for Clinical Electrophysiology of Visual (ISCEV) standards. ERG data were then analysed with respect to presence of MR and also graded disease severity. Thirty-one children were recruited with a diagnosis of CM, 20 had MR (group 1), and 11 had absent MR (group 2). Statistical analyses of these two groups showed a significant relationship between reduced single flash cone b wave amplitude (CBWA) and increased severity of retinal whitening/CNP (P<0.05). Cone and maximal response b : a wave ratios remained >1 in all subjects. Retinal whitening/CNP in MR is associated with significant changes in ERG cone b wave function. The relatively high b : a ratio is compatible with the high frequency of MR resolution without sequelae.

Persistence of retinal function after selective ophthalmic artery chemotherapy infusion for retinoblastoma

To assess potential retinal viability by electroretinography following selective ophthalmic artery chemotherapy infusion for retinoblastoma. Uncontrolled prospective case series. Patients with advanced retinoblastoma were offered elective ophthalmic artery chemotherapy infusion treatment under an IRB-approved protocol as an alternative to enucleation. The ophthalmic artery was cannulated under fluoroscopic control, and chemotherapeutic agents (melphalan and occasionally carboplatin) were directly infused at doses resulting in very high local tissue concentrations, but low systemic drug levels. Eyes were examined under anesthesia at 1-month intervals, and re-treated as indicated, up to a maximum of six infusions. Electroretinograms were obtained during examination under anesthesia, using ERG-jet contact lens electrodes and a hand-held mini-ganzfeld stimulator. The ERG protocol was similar to ISCEV standards except for briefer adaptation times as necessary to reduce the total anesthesia duration. We report initial results in the first ten patients attempted. Nine eyes were successfully cannulated and perfused. ERG data for these nine patients are reported. [Clinical results have been published elsewhere.] Follow up ranged from 3 to 14 months. Extensive, often total, retinal detachments were present in many of the treated eyes. While regression of tumor mass and vitreous seeds was observed in nearly all the patients, retinal detachment occasionally persisted. ERG responses were extinguished in these eyes. Eyes with largely attached retinas, notwithstanding the presence of large tumors at baseline, remained free of detachment after treatment. Normal or near-normal ERGs in these eyes were repeatedly obtained. Recovery of ERG amplitudes was observed in three patients following treatment. Retinal function can persist and even recover following selective ophthalmic artery chemotherapy infusion for retinoblastoma. Further work is indicated to determine optimal dosing regimens, maximal tolerated dosage, and subsequent visual function in these patients.

Rod and S-cone driven ERG signals at high retinal illuminances

The purpose of the present study was to investigate whether L- and M-cone driven responses can be influenced by concomitant modulation in the rods or the S-cones. In addition, it was studied whether a change in the state of adaptation in L- or M-cones can have a different influence on ERG data when simultaneously the mean number of photoisomerizations in either rods or S-cones is altered. It was found that rods and/or S-cones cannot be neglected when measuring L- or M-cone driven ERGs.

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.

Effects of autologous translocation of the choroid and retinal pigment epithelium on the retinal light response in patients with neovascular age‐related macular degeneration

Abstract Purpose: The aim of the present study was to evaluate potential electrophysiological changes after autologous translocation of the choroid and retinal pigment epithelium for subfoveal choroidal neovascularisation in patients with age‐related macular degeneration. Methods: A consecutive series of 20 patients suffering from subfoveal choroidal neovascularisation secondary to age‐related macular degeneration underwent autologous tranlocation of the choroid and the retinal pigment epithelium The ERG was recorded one day prior to the translocation surgery and no earlier than 4 weeks after the silicone oil removal. Results: The ERG amplitudes were significantly reduced after translocation surgery. The mean b‐wave amplitude reduction of the scotopic ERG was 36,1%. The a‐ and b‐waves of the saturating light response decreased significantly by 42.9 and 43.1 %, respectively. The photopic a‐ and b‐wave amplitudes were significantly lower after the translocation surgery resulting in a mean reduction of 23.7 and 40.1 %, respectively. Furthermore, the mean amplitude of the flicker ERG showed a mean decrease by 26.2%. Conclusions: The present study indicates that a significant electrophysiological decrease is caused by autologous translocation of the choroid and retinal pigment epithelium. However, this surgical procedure proved to substantially reduce the neuroretinal trauma when compared with the ERG data of historical controls that underwent 360° retinotomy and macular translocation.

Clinical and ERG data in a family with autosomal dominant RP and Pro-347-Arg mutation in the rhodopsin gene.

In a family with autosomal dominant retinitis pigmentosa, documented over six generations, a previously undescribed point mutation in the rhodopsin gene could be identified. The mutation found in the six affected members examined but in none of the controls, including healthy members of the family, was a point mutation in codon 347 predicting a substitution of the amino acid arginine for proline, designated Pro-347-Arg. Six affected members from two generations were examined clinically and with ganzfeld rod and cone electroretinography. The cone and, more dramatically, the rod electroretinograms were reduced to residual b-wave amplitudes or were non-detectable as early as ages 18 to 22 years. The Pro-347-Arg mutation resulted in a subjectively and clinically homogeneous phenotype: early onset of night blindness before age 11, relatively preserved usable visual fields until about age 30, blindness at ages 40 to 60, and change from an initial apparently sine pigmento to a hyperpigmented and atrophic fundus picture between 30 and 50 years of age.

Ultraviolet Light from the Nighttime Sky Enhances Retinal Sensitivity of Limulus.

Here we report that stimulation of the median ocelli of the horseshoe crab, Limulus polyphemus, by UV light from the nighttime sky enhances the sensitivity of the lateral eyes to visible light. At night a circadian clock in the brain of Limulus generates and transmits neural activity via efferent optic nerve fibers to the lateral eyes and median ocelli (8), significantly increasing their sensitivity (9,lO). Experiments carried out in the laboratory show that illumination of the median ocelli at night with UV light enhances the clock’s efferent output and thus further increases the sensitivity of the lateral eyes and median ocelli (11). We tested whether this occurs under natural conditions; that is, whether ocellar exposure to UV light from the nighttime sky increases visual sensitivity of the lateral eyes. We carried out our experiments in an outdoor shed located in a remote area of Woods Hole, MA, where no artificial light was detectable at night. We mounted animals securely to a platform in an aquarium so that their gills were irrigated with recirculated seawater, but their lateral eyes and median ocelli remained above water. An opaque chamber was placed over the right lateral eye of each animal to occlude the eye from ambient light. A wick electrode and light emitting diode (LED) within the chamber allowed us to record electroretinograms (ERGS) from the eye in its dark-adapted state while the animal was exposed to normal diurnal changes in illumination. A computerbased system recorded ERGS every 30 min in response to a 10 ms light flash from the LED (12). Changes in the amplitude of the ERG of the occluded right eye provided a measure of the clock’s effect on retinal sensitivity and the ocellar influence on the clock’s action. Animals (n = 7) were maintained in this apparatus for approximately one month. During this period, ERGS were monitored while the median ocelli were either fully exposed, covered by a UV blocking filter (blocks y < 420 nm), a UV bandpass filter (ymaX = 360 nm, 54 nm bandwidth at half maximum) or occluded to block all incident light. Figure 1 shows the ERG data recorded from the lateral eye of an animal during five days of a month-long experiment (1990). The amplitude of the ERG increased at night and decreased during the day. The extent of the change depended, in part, on the light incident on the median ocelli. Fully exposing the ocelli to the nighttime sky on 19