LKC Technologies Research Articles

The Effect of High-Dose Erythropoietin Perinatally on Retinal Function in School-Aged Children Born Extremely or Very Preterm

To investigate the long-term effects of high-dose recombinant human erythropoietin (rhEPO) administered during the perinatal period on retinal and visual function in children born extremely or very preterm. Randomized, double-blind clinical trial follow-up plus cohort study. Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland. Extremely or very preterm-born children aged 7 to 15 years, previously randomized to receive either high-dose rhEPO or placebo in the perinatal period. participation in an ongoing neuropediatric study (EpoKids), written informed consent. previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Healthy control (HC) children of comparable age were recruited. term birth, informed consent. any ocular/visual abnormality, high refractive error. Intervention status (rhEPO/placebo) was unknown to examiners and subjects at examination, with examiners unblinded only after completion of all analyses. The electroretinogram (ERG) was performed with the RETeval device (LKC Technologies, Inc). Ophthalmological and orthoptic examinations excluded comorbidity in the prematurely born cohort and ocular diseases in the HC group. Scotopic and photopic ERG response amplitudes and peak times (6 amplitudes; 6 peak times). Secondary outcomes were habitual visual acuity and color discrimination performance (for descriptive summary only). No differences in ERG parameters between EPO (n = 52; 104 eyes) and placebo (n = 35; 70 eyes) subgroups were observed (all corrected P > .05). Two cone system-mediated peak times were slightly slower in the placebo than HC (n = 52; 104 eyes) subgroup (coefficient/95% confidence interval = 0.53/0.21-0.85 and 0.36/0.13-0.60; P = .012 and .022); a predominantly rod system-mediated peak time was slightly faster in the EPO than the HC subgroup (coefficient/95% confidence interval = -4.33/-6.88 to -1.78; P = .011). Secondary outcomes were comparable across subgroups. Administration of high-dose rhEPO to infants born extremely or very preterm during the perinatal period has no measurable effects on retinal function in childhood compared to placebo. Premature birth may cause small, likely clinically insignificant effects on retinal function in childhood, which may be partially mitigated by administration of rhEPO during the perinatal period.

Electroretinograms Recorded with Skin Electrodes from Post-Vitrectomy Silicone Oil Filled Eyes with Proliferative Diabetic Retinopathy.

To determine the physiological status of the retina by electroretinography (ERG) using skin electrodes and the RETevalTM system in eyes that had undergone pars plana vitrectomy (PPV) with silicone oil (SO) tamponade. The vitrectomy was performed for a retinal detachment and proliferative diabetic retinopathy (PDR). Retrospective case series. ERGs were recorded with the RETevalTM system (LKC Technologies Inc. Gaithersburg, MD; Welch Allyn, Inc. Skaneateles Falls, NY) from eight eyes with PDR before and after the SO removal. The amplitudes and implicit times of the a- and b-waves of the ERGs before the SO removal were compared to that after the SO removal. ERGs were recordable in four eyes before and after the SO removal and the a- and b-amplitudes improved in three eyes and worsened in one eye after the SO removal. In the remaining four eyes, ERGs were non-recordable both before and after the SO removal. These results indicate that ERGs picked up by skin electrodes can be used to assess the physiology of the retina in eyes with a SO tamponade. The flat ERGs in the SO-filled eye indicated the presence of diffuse retinal damage which was confirmed by the flat ERGs after the SO removal.

The Use of the RETeval Portable Electroretinography Device for Low-Cost Screening: A Mini-Review.

Electroretinography (ERG) provides crucial insights into retinal function and the integrity of the visual pathways. However, ERG assessments classically require a complicated technical background with costly equipment. In addition, the placement of corneal or conjunctival electrodes is not always tolerated by the patients, which restricts the measurement for pediatric evaluations. In this short review, we give an overview of the use of the RETeval portable ERG device (LKC Technologies, Inc., Gaithersburg, MD, USA), a modern portable ERG device that can facilitate screening for diseases involving the retina and the optic nerve. We also review its potential to provide ocular biomarkers in systemic pathologies, such as Alzheimer's disease and central nervous system alterations, within the framework of oculomics.

Electroretinogram as a Screening Tool to Assess Vigabatrin-Induced Retinal Toxicity in Children With Infantile Spasms.

To assess the utility of electroretinogram (ERG) as a screening tool for vigabatrin-induced retinal toxicity in children with infantile spasms. This was an observational cohort study including children with infantile spasms receiving treatment with vigabatrin. A 30-Hz flicker potential ERG, using the RETeval system (LKC Technologies), was done at baseline before starting vigabatrin at 6 months and 1 year. The amplitudes were recorded. Eleven children were included in the study. The most common etiologic factor for infantile spasms was tuberous sclerosis (36.4%) followed by West syndrome (27.3%). The mean age of the children was 7.14 ± 2.9 months, with a range of 3 to 16 months. The mean difference in amplitude was 3.21 ± 2.45 and 5.72 ± 4.18 µV at 6 and 12 months follow-up, respectively (P < .001). Eight of the 11 children (72.7%) showed vigabatrin-induced retinal toxicity, and all 8 children were receiving vigabatrin for more than 6 months. ERG can be used for vigabatrin-induced retinal toxicity monitoring in children with infantile spasms. Vigabatrin-induced retinal toxicity is related to the duration of treatment rather than cumulative dosage. [J Pediatr Ophthalmol Strabismus. 2024;61(4):273-278.].

Electrophysiological Assessment in Birdshot Chorioretinopathy: Flicker Electroretinograms Recorded With a Handheld Device.

PurposeThe flicker electroretinogram (ERG) is a sensitive indicator of retinal dysfunction in birdshot chorioretinopathy (BCR). We explored recordings from a handheld device in BCR, comparing these with conventional recordings in the same patients and with handheld ERGs from healthy individuals.MethodsNon-mydriatic flicker ERGs, using the handheld RETeval system (LKC Technologies), were recorded with skin electrodes at two centers. At one center (group 1), the stimuli (85 Td·s, 850 Td background) delivered retinal illuminance equivalent to international standards; at the other center (group 2), a different protocol was used (32 Td·s, no background). Patients also underwent international standard flicker ERG recordings with conventional electrodes following mydriasis. Portable ERGs from patients were also compared with those from healthy individuals.ResultsThirty-two patients with BCR (mean age ± SD, 56.4 ± 11.3 years) underwent recordings. Portable and standard ERG parameters correlated strongly (r > 0.75, P < 0.01) in both groups. Limits of agreement for peak times were tighter in group 1 (n = 21; −4.3 to +2.0 ms [right eyes], −3.9 to 1.5 ms [left eyes]) than in group 2 (n = 11; −3.4 to +6.9 ms [right eyes], −4.8 to +9.0 ms [left eyes]). Compared with healthy controls (n = 66 and n = 90 for groups 1 and 2, respectively), patients with BCR showed smaller mean amplitudes and longer peak times.ConclusionsPortable ERGs correlated strongly with conventional recordings, suggesting potential in rapid assessment of cone system function in office settings.Translational RelevanceFlicker ERGs, known to be useful in BCR, can be obtained rapidly with a portable device with skin electrodes and natural pupils.

Qualitative and quantitative comparison of ERGs with contact lens and adhesive skin electrodes.

Traditional ERGs recorded using corneal electrodes can be difficult for some patients to tolerate. In the last several years, adhesive skin electrodes have gained in acceptance. In this report we present a qualitative comparison of waveforms as well as a quantitative analysis of correlation of amplitudes and implicit times of simultaneous ERG recordings using contact lens and skin electrodes. 89 subjects were included; all were referred for full-field ERG testing for multiple indications. ERGs (obtained according to ISCEV standards) were recorded simultaneously from both eyes with ERG-jet corneal contact lens electrodes and LKC Technologies Sensor Strip adhesive skin electrodes using multi-channel instrumentation (Diagnosys LLC, Espion3). Waveforms, a-wave and b-wave amplitudes and implicit times were compared. Waveform morphologies were similar between electrode types. Regression coefficients (conversion factors) for a-wave and b-wave amplitudes under both photopic and scotopic conditions were tightly clustered. Regression coefficients for implicit times were nearly equal to 1.0. The regression coefficient for the entire amplitude dataset was 0.349, with an overall correlation of 0. 869 between amplitude recorded with skin and contact lens electrodes. The regression coefficient for the entire implicit time dataset was 0.967, with an overall correlation of 0.964 between skin and contact lens electrodes. Our best estimate for the conversion factor between ERG amplitudes recorded with adhesive skin electrodes and contact lens electrodes is 0.349-amplitudes with skin electrodes are about 1/3 the amplitudes recorded simultaneously from the same eyes with contact lens electrodes, with a high correlation. Implicit times are nearly identical for the two electrode types.

Electroretinography and contrast sensitivity, complementary translational biomarkers of sensory deficits in the visual system of individuals with fragile X syndrome

BackgroundDisturbances in sensory function are an important clinical feature of neurodevelopmental disorders such as fragile X syndrome (FXS). Evidence also directly connects sensory abnormalities with the clinical expression of behavioral impairments in individuals with FXS; thus, positioning sensory function as a potential clinical target for the development of new therapeutics. Using electroretinography (ERG) and contrast sensitivity (CS), we previously reported the presence of sensory deficits in the visual system of the Fmr1−/y genetic mouse model of FXS. The goals of the current study were two-folds: (1) to assess the feasibility of measuring ERG and CS as a biomarker of sensory deficits in individuals with FXS, and (2) to investigate whether the deficits revealed by ERG and CS in Fmr1−/y mice translate to humans with FXS.MethodsBoth ERG and CS were measured in a cohort of male individuals with FXS (n = 20, 18–45 years) and age-matched healthy controls (n = 20, 18–45 years). Under light-adapted conditions, and using both single flash and flicker (repeated train of flashes) stimulation protocols, retinal function was recorded from individual subjects using a portable, handheld, full-field flash ERG device (RETeval®, LKC Technologies Inc., Gaithersburg, MD, USA). CS was assessed in each subject using the LEA SYMBOLS® low-contrast test (Good-Lite, Elgin, IL, USA).ResultsData recording was successfully completed for ERG and assessment of CS in most individuals from both cohorts demonstrating the feasibility of these methods for use in the FXS population. Similar to previously reported findings from the Fmr1−/y genetic mouse model, individuals with FXS were found to exhibit reduced b-wave and flicker amplitude in ERG and an impaired ability to discriminate contrasts compared to healthy controls.ConclusionsThis study demonstrates the feasibility of using ERG and CS for assessing visual deficits in FXS and establishes the translational validity of the Fmr1−/y mice phenotype to individuals with FXS. By including electrophysiological and functional readouts, the results of this study suggest the utility of both ERG and CS (ERG-CS) as complementary translational biomarkers for characterizing sensory abnormalities found in FXS, with potential applications to the clinical development of novel therapeutics that target sensory function abnormalities to treat core symptomatology in FXS.Trial registrationID-RCB number 2019-A01015-52 registered on the 17 May 2019.

Exploratory Study of the Association between the Severity of Idiopathic Intracranial Hypertension and Electroretinogram Photopic Negative Response Amplitude Obtained Using a Handheld Device.

The photopic negative response (PhNR) is a negative component of the photopic flash electroretinogram that follows the b-wave and is thought to arise from the retinal ganglion cells. Reduction in its amplitude in idiopathic intracranial hypertension (IIH) has been previously documented using formal electroretinography. This study explored the use of a handheld device (RETeval, LKC technologies, Gaithersburg, MD, USA) in 72 IIH patients of varying stages and severity (and seven controls) and investigated associations between PhNR parameters and disease severity. PhNR amplitudes at 72 ms (P72) and p-ratio (ratio to b-wave peak value) differed significantly across groups, with a trend towards smaller amplitudes in those with severe IIH, defined as papilloedema with Modified Frisén Scale (MFS) ≥ 3, retinal nerve fibre layer (RNFL) ≥ 150 μm or atrophic papilloedema (p = 0.0048 and p = 0.018 for P72 and p-ratio, respectively). PhNR parameters did not correlate with MFS, RNFL thickness, standard automated perimetry mean deviation or macular ganglion cell layer volume. This study suggests that PhNR measurement using a handheld device is feasible and could potentially augment the assessment of disease severity in IIH. The clinical utility of PhNR monitoring in IIH patients requires further investigation.

Clinical Utility of Electroretinograms for Evaluating Vigabatrin Toxicity in Children.

To determine changes in the clinical treatment of pediatric patients taking vigabatrin for seizure control in response to results of electroretinogram (ERG) performed for retinal toxicity screening. The authors retrospectively reviewed the medical records of patients who received ERGs at Children's Hospital of Colorado from 2009 to 2012. Age, indication for ERG, ERG data, and clinical management of vigabatrin were extracted from the records. ERGs were interpreted according to LKC Technologies normative values. A physician trained in ERG analysis interpreted each ERG. One hundred seventy ERGs were performed during the study period, and 147 ERGs were available for analysis. Every patient received general anesthesia for the procedure. Thirty-three ERGs were performed in 29 patients specifically as screening for retinal toxicity due to vigabatrin use, and 30 were available for analysis. Within this cohort, only 2 ERGs were normal (6.6%), and 28 were abnormal (93.3%). In patients who received abnormal results, 1 patient discontinued vigabatrin in response to the screening. In this study cohort, clinical management generally did not change in response to an abnormal screening result. Given the need for general anesthesia in the pediatric population receiving ERG testing, and minimal change in clinical decision-making in the face of abnormal results, ERG screening for retinal toxicity due to vigabatrin in the pediatric cohort should be reconsidered. [J Pediatr Ophthalmol Strabismus. 2021;58(3):174-179.].

Multimodal Testing Reveals Subclinical Neurovascular Dysfunction in Prediabetes, Challenging the Diagnostic Threshold of Diabetes

Background: There is growing evidence that small nerve fibre and retinal neurovascular damage occur in prediabetes before the onset of type 2 diabetes. Methods: Participants with normoglycaemia, prediabetes or type 2 diabetes underwent corneal confocal microscopy (CCM), electrochemical skin conductance (ESC), optical coherence tomography angiography (OCT-A), and handheld electroretinography (ERG) measurements. Findings: Seventy-five participants with normoglycaemia (n=20), prediabetes (n=29) and type 2 diabetes (n=26) were studied. Compared with normoglycaemia, mean peak ERG amplitudes of retinal responses at low (16 Td·s: 4·05 µV, 95% confidence interval (CI) 0·96-7·13) and high (32 Td·s: 5·20 µV, 95% CI 1·54-8·86) retinal illuminance were lower in prediabetes, as were OCT-A parafoveal vessel densities in superficial (0.051 pixels/mm2, 95% CI 0·005-0·095) and deep (0·048 pixels/mm2, 95% CI 0·003-0·093) retinal layers. There were no differences in CCM or ESC measurements between these two groups. Correlations between HbA1c and peak ERG amplitude at 32 Td·s (r=-0.256, p=0·028), implicit time at 32 Td·s (r=0·422, p=0·0002) and 16 Td·s (r=0·327, p=0·005), OCT parafoveal vessel density in the superficial (r=-0·238, p=0·049) and deep (r=-0·3, p=0·017) retinal layers, corneal nerve fibre length (CNFL) (r=-0·293, p=0·017), and hand ESC (r=-0·244, p=0·035) were observed. HOMA-IR was a predictor of CNFD (β=-0·94, 95% CI -1·66 to -0·21, p=0·012) and CNBD (β=-5·02, 95% CI -10·01 to -0·05, p=0·048). Interpretation: The diagnosis of diabetes is based on historical data showing emergent retinopathy on fundus examination; newer tests reveal abnormal retinal neurovascular structure (OCT-A) and function (ERG) occurring before retinopathy. Funding: This research received no funding support. Declaration of Interests: None of the authors have any relevant financial disclosures to declare. LKC Technologies Inc. and Impeto Medical Inc. provided free use of the RETeval and SUDOSCAN devices, respectively, for this study. CB is part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Ethics Approval Statement: This study adhered to the Declaration of Helsinki (2008) and was approved by an independent National Health Service Research Ethics Committee in November 2018 (REC ID: 18/LO/2126). Written informed consent was obtained from all participants.

Using the RETeval Device in Healthy Children to Establish Normative Electroretinogram Values.

To provide normative data of full-field electro-retinogram (ERG) responses in the pediatric population using the RETeval ERG device (LKC Technologies, Inc) in healthy children without evidence of retinal disease. This was a single-site cross-sectional study of healthy pediatric patients with normal dilated fundus examinations and no known retinal diseases. Participants were recruited to undergo dilated full-field ERG using the handheld RETeval device. The International Society for Clinical Electrophysiology of Vision 5-step protocol was used. Photopic and dark-adapted scotopic responses were recorded using skin electrodes. Main outcome measures were normative RETeval ERG values and correlation of age with measured ERG parameters. Thirty-eight eyes of 20 healthy patients (aged 4 to 17 years) were included in the study. Of the 20 normal patients, 9 were male and 11 were female. Normative mean, median, and range values were recorded for the measured full-field ERG parameters. Pearson correlation was moderately positive between age and oscillatory potential and scotopic dim flash amplitude (r = 0.59, P = .006 for both). A positive correlation was also found between age and cone a-wave implicit time (r = 0.67, P = .001). The handheld RETeval system is a useful tool for obtaining full-field ERGs in children without anesthesia. Moderate positive correlations were observed between age and oscillatory potential and scotopic dim flash amplitude. A strong correlation was found between age and cone a-wave implicit time. The current study provides a baseline of normative full-field ERG values in children. [J Pediatr Ophthalmol Strabismus. 2021;58(1):17-22.].

Comparison of peak times of photopic flicker electroretinogram responses recorded using conventional and portable systems in Birdshot chorioretinopathy

AbstractPurposeAssessing disease activity in Birdshot uveitis can be challenging. The peak time of the 30 Hz flicker photopic electroretinogram (ERG) was shown to be sensitive for detecting retinal dysfunction. ERG testing is not readily available in many eye units. We investigated use of a portable device to obtain recordings in the clinic setting and compared these with conventional recordings.MethodsPatients underwent testing with the portable device (RETeval, LKC Technologies) and conventional equipment (Espion ColorDome, Diagnosys). For portable recordings pupils were undilated and skin electrodes used; for conventional recordings a conductive fibre electrode was used with mydriasis. Flicker ERG peak times were recorded and were deemed abnormal if they exceeded the 95th centile from a healthy cohort (&gt;190 healthy volunteers).Results18 patients with Birdshot uveitis underwent recordings. Recordings with the portable device took c. 3 min and were well‐tolerated. Mean (SD) age was 56.3 (12.8) years. For portable recordings, mean (SD) peak times were 30.1 (3.7) and 30.2 (3.9) ms for right and left eyes respectively. For conventional recordings mean (SD) peak times were 31.4 (3.9) and 31.8 (4.0) ms respectively. Peak times were significantly shorter with the portable device (p = 0.026 and 0.002 for right and left eyes). Correlation between devices was high (0.83 and 0.89 for right and left eyes) and highly significant (p &lt; 0.0001). Strength of agreement between the two methods was good (kappa statistic 0.64; 95% CI, 0.36‐0.92).ConclusionsCorrelation between the portable and conventional ERG recordings was high with a good level of agreement. Recordings were rapid and well‐tolerated. There were significant differences in peak times between the two methods highlighting the importance of normative data specific to each device.

Assessing nonsedated handheld cone flicker electroretingram as a screening test in pediatric patients: comparison to sedated conventional cone flicker electroretinogram

To assess the RETeval (LKC Technologies, Gaithersburg, MD) handheld electroretingram (ERG) device as a screening tool for cone dysfunction in pediatric patients by comparing it to conventional ERG. Patients scheduled for ERG under general anesthesia (GA) underwent three tests: (1) RETeval standard 30Hz cone flicker ERG using skin electrodes prior to GA, (2) E3 Diagnosys (Diagnosys LLC, Lowell, MA) conventional complete standard protocol full-field ERG using bipolar contact lens electrodes and handheld stimulus under GA, and (3) repeat RETeval testing under GA. The 30Hz cone flicker amplitudes and implicit times from the three methods were compared. Negative and positive predictive values were calculated by applying a previously established 5μV amplitude cut-off. Thirty patients ≤18years of age were enrolled. Impaired conventional ERGs were found in 18 patients. Compared to conventional ERG under GA, RETeval cone flicker amplitudes were smaller before GA (mean difference, -42.2±45.3μV) and under GA (-37.1±44.5μV), likely due to skin electrode; and implicit times were shorter before GA (-1.06±2.83ms) and longer under GA (1.28±4.12ms), likely due to GA. Comparing RETeval responses before and under GA, the amplitudes were lower (-3.05±6.82μV), and implicit times were shorter (-2.25±3.28μV) before GA. Overall, the positive predictive value of the RETeval was 85%; the negative predictive value, 90%. The unsedated handheld RETeval 30Hz cone flicker ERG is a feasible screening test for detecting cone dysfunction in pediatric patients. Full-protocol ERG is needed when screening ERG is reduced, equivocal, or clinically warranted.

Electroretinography using the RetEval ERG system in healthy children

Recent innovation has led to the development of the hand-held RetEval™ ERG system (LKC Technologies, Gaithersburg, MD) which utilizes skin electrodes and can be performed without anesthesia. The purpose of this study is to determine reference range values for electroretinography (ERG) in healthy children using the RetEval ERG system.

Effect of varying skin surface electrode position on electroretinogram responses recorded using a handheld stimulating and recording system

PurposeA handheld device (the RETeval system, LKC Technologies) aims to increase the ease of electroretinogram (ERG) recording by using specially designed skin electrodes, rather than corneal electrodes. We explored effects of electrode position on response parameters recorded using this device.MethodsHealthy adult twins were recruited from the TwinsUK cohort and underwent recording of light-adapted flicker ERGs (corresponding to international standard stimuli). In Group 1, skin electrodes were placed in a “comfortable” position, which was up to 20 mm below the lid margin. For subsequent participants (Group 2), the electrode was positioned 2 mm from the lid margin as recommended by the manufacturer. Amplitudes and peak times (averaged from both eyes) were compared between groups after age-matching and inclusion of only one twin per pair. Light-adapted flicker and flash ERGs were recorded for an additional 10 healthy subjects in two consecutive recording sessions: in the test eye, electrode position was varied from 2 to 10–20 mm below the lid margin between sessions; in the fellow (control) eye, the electrode was 2 mm below the lid margin throughout. Amplitudes and peak times (test eye normalised to control eye) were compared for the two sessions.ResultsIncluding one twin per pair, and age-matching yielded 28 individuals per group. Flicker ERG amplitudes were significantly lower for Group 1 than Group 2 participants (p = 0.0024). However, mean peak times did not differ between groups (p = 0.54). For the subjects in whom electrode position was changed between recording sessions, flash and flicker amplitudes were significantly lower when positioned further from the lid margin (p < 0.005), but peak times were similar (p > 0.5).ConclusionsMoving the skin electrodes further from the lid margin significantly reduces response amplitudes, highlighting the importance of consistent electrode positioning. However, this does not significantly affect peak times. Thus, it may be feasible to adopt a more comfortable position in participants who cannot tolerate the recommended position if analysis is restricted to peak time parameters.

Effects of cataracts on flicker electroretinograms recorded with RETeval™ system: new mydriasis-free ERG device.

BackgroundThe purpose of this study was to evaluate the effects of cataracts on the flicker electroretinograms (ERGs) recorded with the RETeval™ system under mydriatic-free conditions.MethodsThis was a retrospective study of 82 eyes of 60 patients with cataracts and 52 eyes of 38 patients who were pseudophakic. Flicker ERGs were recorded with the RETeval™ system (LKC Technologies, Gaithersburg, MD) under mydriatic-free condition with skin electrodes. Flicker ERGs were elicited by white light delivered at a frequency of 28.3 Hz and intensity of 8 Td-s. The implicit times and amplitudes of the ERGs recorded from the Grade 2 cataract, Grade 3 cataract, and pseudophakic groups were compared.ResultsThe mean amplitude was significantly smaller in both cataract groups than the pseudophakic group (Grade 2 cataract vs pseudophakic group, P < 0.0001; Grade 3 cataract vs pseudophakic group, P < 0.0001; Grade 2 cataract vs Grade 3 cataract, P = 0.027).The mean implicit times was significantly longer in both cataract groups than the pseudophakic group (Grade 2 cataract vs pseudophakic group, P = 0.046; Grade 3 cataract vs pseudophakic group, P = 0.0004; Grade 2 cataract vs Grade 3 cataract, P = 0.0084).ConclusionsThe results indicate that the presence of Grade 2 or more cataracts will affect both the amplitude and the implicit time of the flicker ERGs. The presence of cataracts should be taken into consideration when interpreting the flicker ERG recorded with RETeval™.

Disruption of the Chaperonin Containing TCP-1 Function Affects Protein Networks Essential for Rod Outer Segment Morphogenesis and Survival

Type II Chaperonin Containing TCP-1 (CCT, also known as TCP-1 Ring Complex, TRiC) is a multi-subunit molecular machine thought to assist in the folding of ∼ 10% of newly translated cytosolic proteins in eukaryotes. A number of proteins folded by CCT have been identified in yeast and cultured mammalian cells, however, the function of this chaperonin in vivo has never been addressed. Here we demonstrate that suppressing the CCT activity in mouse photoreceptors by transgenic expression of a dominant-negative mutant of the CCT cofactor, phosducin-like protein (PhLP), results in the malformation of the outer segment, a cellular compartment responsible for light detection, and triggers rapid retinal degeneration. Investigation of the underlying causes by quantitative proteomics identified distinct protein networks, encompassing ∼ 200 proteins, which were significantly affected by the chaperonin deficiency. Notably among those were several essential proteins crucially engaged in structural support and visual signaling of the outer segment such as peripherin 2, Rom1, rhodopsin, transducin, and PDE6. These data for the first time demonstrate that normal CCT function is ultimately required for the morphogenesis and survival of sensory neurons of the retina, and suggest the chaperonin CCT deficiency as a potential, yet unexplored, cause of neurodegenerative diseases.

Photopic Negative Response (PhNR) in Normal Subjects

Purpose: To evaluate the nature of photopic negative response (PhNR) in normal subjects. Methods: The electroretinogram (ERG) waves were recorded in 52 eyes of 26 normal subjects with UTAS E-3000 (LKC Technologies Inc., Gaithersberg, MD, USA). Photopic cone response was obtained for analysis from a white flash with white background illumination (group 1) and a red flash with blue background illumination (group 2), after stimulations ranging from 0.007674 cd.s/m2 (-25dB) to 7.736 cd.s/m2 (5dB) with a 5dB interval. Results: PhNRs were observed in all 52 eyes in group 1 stimulated with the white flash at 0.9933 cd.s/m2 (-4dB). PhNRs were also observed in all 52 eyes in group 2 at 2.4297 cd.s/m2 (0dB) after stimulation with the red flash. There was correlation between the amplitudes of PhNR and intensity of stimuli (p

Relative Course of Retinal Nerve Fiber Layer Birefringence and Thickness and Retinal Function Changes after Optic Nerve Transection

To test the hypothesis that alterations of RNFL birefringence precede changes in RNFL thickness in an experimental model of RGC injury and, secondarily, to determine the time course of RGC functional abnormalities relative to RNFL birefringence and thickness changes. RNFL birefringence was measured by scanning laser polarimetry (GDx VCC; Carl Zeiss Meditec, Inc., Dublin, CA). RNFL thickness was measured by spectral domain optical coherence tomography (SD-OCT, Spectralis HRA+OCT; Heidelberg Engineering, GmbH, Heidelberg, Germany). Retinal function was assessed by three forms of electroretinography (ERG): slow-sequence multifocal (mf)ERG (VERIS; EDI, San Mateo, CA); pattern-reversal (P)ERG (Utas-E3000; LKC Technologies, Inc. Gaithersburg, MD); and photopic full-field flash (ff)ERG (Utas-E3000; LKC Technologies). All measurements were obtained in both eyes of four adult rhesus macaque monkeys (Macaca mulatta) during two baseline sessions, and again 1 week and 2 weeks after unilateral optic nerve transection (ONT). ONT was successfully completed in three subjects. RNFL birefringence declined by 15% 1 week after ONT (P = 0.043), whereas there was no significant change in RNFL thickness (+1%, P = 0.42). Two weeks after ONT, RNFL retardance had declined by 39% (P = 0.018), whereas RNFL thickness had declined by only 15% (P = 0.025). RGC functional abnormalities were present 1 week after ONT, including decreased amplitudes relative to baseline of the mfERG high-frequency components (-65%, P = 0.018), the PERG N95 component (-70%, P = 0.007), and the photopic negative response of the ffERG (-44%, P = 0.005). RNFL birefringence declined before and faster than RNFL thickness after ONT. RGC functional abnormalities were present 1 week after ONT, when RNFL thickness had not yet begun to change. RNFL birefringence changes after acute RGC injury are associated with RGC dysfunction. Together, they reflect RGC abnormalities that precede axonal caliber changes and loss.

Indicators of vitamin A status in rural villages in Southern Ethiopia

This study was part of a cross-sectional investigation of the nutritional status of lactating women in two rural villages in Southern Ethiopia conducted in January, 2006. A convenience sample of 108 women living in Wondo Genet and Arsi Negele was utilized. Land ownership was significantly greater in Arsi Negele (p<0.0001), while significantly more goods (lamps, radios, hand torches, bicycles, and carts) were owned in Wondo Genet (p<0.01). Vitamin A status was assessed by food consumption patterns and pupillary response testing. Women in Wondo Genet consumed mango, papaya, and sweet potato more frequently than women in Arsi Negele (p<0.0001). Dark adaptation threshold was assessed using the scotopic sensitivity tester-1 (SST-1, LKC Technologies, Inc, Gaithersburg, MD). This instrument utilizes a hand-held illuminator with light intensity ranging from 0dB to 30dB. Subjects underwent binocular partial bleaching with a digital camera flash (Sony Cyber-shot DSC-W5) and were then dark adapted for 20 minutes in a portable black tent. Pupillary response was evaluated by use of a night vision scope (ELF-1, LOMO America Inc.). Women from Wondo Genet had significantly lower pupillary thresholds than women from Arsi Negele (p<0.02). High pupillary thresholds were consistent with lower consumption of vitamin A source foods. (Supported by The Micronutrient Initiative of Canada, Debub University, and Oklahoma State University).