The 52nd ISCEV International Symposium Abstract Issue

Purpose

We have monitored retinal function in patients treated for retinoblastoma (primarily, but not exclusively by intra-arterial chemotherapy infusion) by electroretinography (ERG) recordings for the past 7 years. We here present data from 599 ERG studies of 108 patients, in which a complete ERG protocol including both photopic and scotopic recordings was performed, in justification of our frequent practice of reporting primarily 30-Hz photopic flicker amplitude data.

Methods

Patients referred for treatment of retinoblastoma underwent ERG recordings during examination under anesthesia whenever possible: at baseline and following most treatment sessions. Correlations were calculated for the complete datasets between the four primary amplitude response parameters: photopic single flash b-wave, photopic 30-Hz flicker peak-to-trough, scotopic rod-isolating b-wave, and scotopic maximal flash b-wave.

Results

Using our adaptation of the International Society for Clinical Electrophysiology of Vision-recommended standard ERG protocol, ERG responses of eyes of patients with untreated retinoblastoma or following traditional or intra-arterial treatment for retinoblastoma show very high correlations between 30-Hz flicker amplitude responses and three other standard photopic and scotopic ERG response amplitudes. Reductions in ERG amplitudes seen in these eyes following treatment show no significant difference between retinal dysfunction estimated using rod- or cone-dominated responses.

Conclusion

These observations support the use of photopic response amplitudes (especially in response to 30-Hz flicker) as the primary ERG outcome measure in studies of treated and untreated eyes with retinoblastoma when more complete ERG protocols may be impractical.     

Rod- versus cone-driven ERGs at different stimulus sizes in normal subjects and retinitis pigmentosa patients

Purpose

To study how rod- and cone-driven responses depend on stimulus size in normal subjects and patients with retinitis pigmentosa (RP), and to show that comparisons between responses to full-field (FF) and smaller stimuli can be useful in diagnosing and monitoring disorders of the peripheral retina without the need for lengthy dark adaptation periods.

Method

The triple silent substitution technique was used to isolate L-cone-, M-cone- and rod-driven ERGs with 19, 18 and 33% photoreceptor contrasts, respectively, under identical mean luminance conditions. Experiments were conducted on five normal subjects and three RP patients. ERGs on control subjects were recorded at nine different temporal frequencies (between 2 and 60 Hz) for five different stimulus sizes: FF, 70°, 60°, 50° and 40° diameter circular stimuli. Experiments on RP patients involved rod- and L-cone-driven ERG measurements with FF and 40° stimuli at 8 and 48 Hz. Response amplitudes were defined as those of the first harmonic component after Fourier analysis.

Results

In normal subjects, rod-driven responses displayed a fundamentally different behavior than cone-driven responses, particularly at low temporal frequencies. At low and intermediate temporal frequencies (≤ 12 Hz), rod-driven signals increased by a factor of about four when measured with smaller stimuli. In contrast, L- and M-cone-driven responses in this frequency region did not change substantially with stimulus size. At high temporal frequencies (≥ 24 Hz), both rod- and cone-driven response amplitudes decreased with decreasing stimulus size. Signals obtained from rod-isolating stimuli under these conditions are likely artefactual. Interestingly, in RP patients, both rod-driven and L-cone-driven ERGs were similar using 40° and FF stimuli.

Conclusion

The increased responses with smaller stimuli in normal subjects to rod-isolating stimuli indicate that a fundamentally different mechanism drives the ERGs in comparison with the cone-driven responses. We propose that the increased responses are caused by stray light stimulating the peripheral retina, thereby allowing peripheral rod-driven function to be studied using the triple silent substitution technique at photopic luminances. The method is effective in studying impaired peripheral rod- and cone- function in RP patients.

     

Flicker cone function in normal and day blind sheep: a large animal model for human achromatopsia caused by CNGA3 mutation

Purpose

Recently we reported on day blindness in sheep caused by a mutation in the CNGA3 gene, thus making affected sheep a naturally occurring large animal model for therapeutic intervention in CNGA3 achromatopsia patients. The purpose of this study was to characterize flicker cone function in normal and day blind sheep, with the aim of generating a normative data base for ongoing gene therapy studies.

Methods

Electoretinographic (ERG) cone responses were evoked with full-field conditions in 10 normal, 6 heterozygous carriers and 36 day blind sheep. Following light adaptation (10 min, 30 cd/m²), responses were recorded at four increasing light intensities (1, 2.5, 5 and 10 cd s/m²). At each of these intensities, a single photopic flash response followed by 8 cone flicker responses (10–80 Hz) was recorded. Results were used to generate a normative data base for the three groups. Differences between day blind and normal control animals were tested in two age-matched groups (n = 10 per group).

Results

The normal sheep cone ERG wave is bipartite in nature, with critical flicker fusion frequency (CFF) >80 Hz. In all four flash intensities, the single photopic flash a-wave and b-wave amplitudes were significantly lower (p < 0.005), and implicit times significantly delayed (p < 0.0001), in day blind animals. In all four flash intensities, CFF values were significantly lower (p < 0.0001) in day blind sheep.

Conclusions

Cone function is severely depressed in day blind sheep. Our results will provide a normative data base for ongoing gene therapy studies.     

Electroretinograms and level of aqueous vascular endothelial growth factor in eyes with hemicentral retinal vein occlusion or branch retinal vein occlusion

Purpose

Hemicentral retinal vein occlusion (hCRVO) is a disease related to CRVO but not to branch retinal vein occlusion (BRVO). We reported a significant correlation between aqueous vascular endothelial growth factor (VEGF) levels and the implicit time of 30-Hz flicker electroretinogram (ERG) in CRVO eyes. The purpose of this study was to compare aqueous VEGF levels and ERG components between hCRVO and BRVO eyes.

Methods

The medical records of patients with macular edema secondary to hCRVO (12 eyes) or BRVO (16 eyes) and received an intravitreal injection of bevacizumab (IVB) at the Nagoya University Hospital from July 2009 to May 2013 were reviewed. Full-field ERGs were recorded before the IVB. Aqueous humor was collected just before the IVB to measure VEGF concentration. Differences in aqueous VEGF level and ERG components between hCRVO and BRVO eyes were determined.

Results

Mean aqueous VEGF concentration in hCRVO eyes was significantly higher than that in BRVO eyes (504 vs. 148 pg/ml, P < 0.05). The implicit time of 30-Hz flicker ERG was significantly longer in hCRVO than in BRVO eyes (33.5 vs. 29.8 ms, P < 0.01).

Conclusion

The significant difference in VEGF levels in aqueous and implicit times of 30-Hz flicker ERG suggest that retinal ischemia is more manifest in hCRVO than in BRVO eyes.     

Ocular manipulation reduces both ipsilateral and contralateral electroretinograms

Purpose

To determine the electroretinogram (ERG) changes in eyes manipulated in the course of local ablative therapy (transpupil thermotherapy (TTT), cryotherapy or both) or scleral depression and in un-manipulated fellow, healthy eyes.

Methods

This prospective observational report summarizes 73 ERG studies in 42 patients with retinoblastoma; a study consisted of ERGs of one or both eyes (if present) followed by ocular manipulation (scleral depression, cryotherapy, transpupillary thermotherapy, pressure applied to orbital implant in an anophthalmic socket, or a 5- or 10-min delay without mechanical manipulation) followed by a repeat of the ERGs. Each patient was studied with only a single manipulation modality on any given date: 23 patients were studied only once, and 19 patients were included in more than one study occasion.

Results

Following local ablative treatment of patients with unilateral retinoblastoma, the photopic response decreased significantly in both the treated eye and the untouched fellow, healthy eye. Following scleral depression of the diseased eye, the photopic response immediately decreased in the diseased eye by a mean of 16 μV (21 %, p = .006) and, in the fellow, healthy eye by 40 μV (23 %, p = .0005). Following scleral depression of the fellow, healthy eye, the photopic response immediately decreased by a mean of 11 μV (4 %, p = .37) in the fellow, healthy eye, and by 16 μV (28 %, p = .01) in the diseased eye.

Conclusions

Following physical ocular manipulation, the amplitude of the photopic response decreased in the manipulated, but also the untouched healthy, fellow eyes. These findings may account for some of the variation in clinical ERG recordings, particularly that observed following ocular manipulation by TTT, laser or even scleral depression.     

Changes in the harmonic components of the flicker electroretinogram during light adaptation

Purpose

To evaluate the nature and extent of changes in the fundamental and harmonic components of the 31-Hz flicker electroretinogram (ERG) during light adaptation.

Methods

Full-field ERGs were recorded from five visually normal subjects (ages 21–60 years). Following 30 min of dark adaptation, the subjects were exposed to a uniform adapting field of 50 cd/m². The field, which was presented for approximately 15 min, was intermittently modulated sinusoidally at 31.25 Hz. The ERG was recorded during the sinusoidal modulation, and Fourier analysis was used to obtain the amplitude and phase of the fundamental (F), second (2F), and third (3F) harmonic response components.

Results

F amplitude increased by almost a factor of two over approximately 6 min (time constant, τ, of 3.0 min). The 2F amplitude increased by a smaller amount, a factor of 1.4, and the time-course was approximately eight times faster than that of F (τ = 0.4 min). The 3F amplitude increased by a factor of 4.6, an increase that was larger than F or 2F, with a time-course that was between that of F and 2F (τ = 1.4 min). F phase was unaffected by light adaptation, whereas the 2F and 3F phases both increased by approximately 45° over similar time-courses (τ = 2.0 min).

Conclusions

Light adaptation had different effects on the fundamental, second, and third harmonic components of the 31-Hz flicker ERG, which resulted in a change in waveform shape during light adaptation. The previously reported flicker ERG amplitude growth is driven primarily, but not entirely, by changes in the fundamental.     

New photic stimulating system with white light-emitting diodes to elicit electroretinograms from zebrafish larvae

Purpose

The zebrafish is an established animal model commonly used in biological, neuroscience, and genetic research. We have developed a new light stimulating system using white light-emitting diodes (LEDs) to elicit ERGs from zebrafish larvae. The purpose of this study was to record full-field ERGs and to evaluate the inter-trial reliability of the ERGs recorded with our system from zebrafish larvae.

Methods

The stimulating device used white LEDs that were attached to a stereomicroscope, and the location of the recording electrode on the cornea could be monitored while the eye was being stimulated. Full-field scotopic and photopic ERGs were recorded from larvae at the age of 5–7 days post-fertilization (dpf). Intensity–response curves were constructed from the ERGs. Inter-trial reliability of the ERGs recorded by our system was evaluated.

Results

This stimulating system could be used for efficient and reliable ERG recordings from 5–7 dpf larvae. The amplitudes, implicit times, and the waveforms of the scotopic and photopic ERGs were similar to those reported in earlier studies. Inter-trial reliability of the amplitudes of the photopic ERG b-waves was excellent with an intra-class correlation coefficient of 0.98.

Conclusion

We conclude that this new light stimulation system using white LEDs attached to a stereomicroscope will be helpful in recording reliable ERGs from zebrafish larvae.

     

Changes in the ERG d-wave with vigabatrin treatment in a pediatric cohort

Purpose

Vigabatrin (VGB), a treatment for the childhood epilepsy, infantile spasms (IS), is implicated in visual field constriction. Electroretinograms (ERGs) are used as a substitute for visual field testing in infants. We use the VGB-associated ERG reduction (VAER), defined as reduction in age-corrected light adapted 30 Hz flicker amplitude from a pre-treatment measurement in the absence of other retinal defects, as an indicator of retinal toxicity resulting from VGB use. The d-wave ERG response is predominantly the result of OFF-bipolar cell depolarization response to light offset. The purpose of this study is to evaluate the ERG d-wave response as a marker for VAER toxicity in an infant population.

Methods

One hundred children with IS treated with VGB (median age at baseline: 7.6 months; range 1.7–38.4) were tested for the cone-OFF response elicited to a 250 cd s m² flash with 200 ms duration (long flash ERG). Diagnosis of VAER requires baseline testing of the flicker ERG and at least one follow up ERG; Fifty-one patients fulfilled this criteria. Fifty-eight children received the long flash ERG at baseline. Thirteen retinally normal controls with a median age of 32 months (5.7–65) were also tested. Amplitude and implicit time of the d-wave response were measured manually.

Results

Longer duration of treatment was associated with reduced d-wave amplitude (ANOVA p < 0.05) in patients taking VGB. Nine patients demonstrated VAER during the course of the study. D-wave amplitude was reduced in the IS group with VAER compared to those without VAER (p < 0.05).

Conclusions

Vigabatrin associated retinal defects may be reflected in reduction of the cone d-wave amplitude.     

Constant luminance (cd·s/m<Superscript>2</Superscript>) versus constant retinal illuminance (Td·s) stimulation in flicker ERGs

Purpose

To compare the effect of variable pupil size on the flicker electroretinogram (ERG) between a stimulus having constant luminance and a stimulus having constant retinal illuminance (constant Troland) that compensates for pupil size.

Methods

Subjects (n = 18) were tested with 12 pairs of the stimuli. The stimulus pair consisted of the ISCEV standard constant luminance stimulus (3 cd·s/m² with a 30 cd/m² background) and a constant retinal illuminance stimulus (32 Td·s with a 320 Td background) selected to provide the same stimulus and background when the pupil diameter is 3.7 mm. Half the subjects were artificially dilated, and their response was measured before and during the dilation. The natural pupil group was used to assess intra- and inter-subject variability. The artificially dilated group was used to measure the flicker ERG’s dependence on pupil size.

Results

With natural pupils, intra-subject variability was lower with the constant Troland stimulus, while inter-subject variability was similar between stimuli. During pupil dilation, the constant Troland stimulus did not have a dependence on pupil size up to 6.3 mm and had slightly larger amplitudes with longer implicit times for fully dilated pupils. For the constant luminance stimulus, waveform amplitudes varied by 22% per mm change in pupil diameter, or by 48% over the 2.2 mm diameter range measured in dilated pupil size. There was no difference in inter-subject variability between constant Troland natural pupils and the same subjects with a constant luminance stimulus when dilated (i.e., the ISCEV standard condition).

Conclusions

These results suggest that a constant Troland flicker ERG test with natural pupils may be advantageous in clinical testing. Because of its insensitivity to pupil size, constant Troland stimuli should produce smaller reference ranges, which in turn should improve the sensitivity for detection of abnormalities and for monitoring changes. In addition, the test can be administered more efficiently as it does not require artificial dilation.

Clinical Trial registration number

This trial is registered at ClinicalTrials.gov (NCT02466607).

     

Contribution of retinal ganglion cells to the mouse electroretinogram

Purpose

To quantify the direct contribution of retinal ganglion cells (RGCs) on individual components of the mouse electroretinogram (ERG).

Methods

Dark- and light-adapted ERGs from mice 8 to 12 weeks after optic nerve transection (ONTx, n = 14) were analyzed through stimulus response curves for a- and b-waves, oscillatory potentials (OPs), positive and negative scotopic threshold response (p/n STR), and the photopic negative response (PhNR) and compared with unoperated and sham-operated controls, as well as to eyes treated with 6-cyano-7-nitroquinoxaline-2,3-dion (CNQX).

Results

We confirmed in mice that CNQX intravitreal injection reduced the scotopic a-wave amplitude at high flash strength, confirming a post-receptoral contribution to the a-wave. We found that ONTx, which is more specific to RGCs, did not affect the a-wave amplitude and implicit time in either photopic or scotopic conditions while the b-wave was reduced. Both the pSTR and nSTR components were reduced in amplitude, with the balance between the two components resulting in a shortening of the nSTR peak implicit time. On the other hand, amplitude of the PhNR was increased while the OPs were minimally affected.

Conclusion

With an intact a-wave demonstrated following ONTx, we find that the most robust indicators of RGC function in the mouse full-field ERG were the STR components.     

Full-field electroretinogram findings in children in the atropine treatment for myopia (ATOM2) study

Background

The aims of this study were to determine the longitudinal effects of myopia on full-field electroretinogram (ffERG) in children, and whether there were any effects due to atropine treatment.

Methods

Fifty children, enrolled in the atropine treatment for myopia study, were randomly selected and 35 children consented to undergo ffERG at baseline (prior to atropine treatment), 24 months (at end of treatment) and 32 months (8 months after cessation of treatment). An extended ISCEV ffERG protocol was used for all recordings. The relationship between axial length (AL) and the following scotopic and photopic ffERG responses was analyzed: a- and b-wave amplitude and implicit time, saturated amplitude (V _max), and retinal sensitivity (logK).

Results

Reliable ffERG recordings with acceptable level of noise were obtained on all 3 visits from 29 children (mean age: 9.5 ± 0.8 years and mean spherical equivalent: ?5.0 ± 1.6 D). At baseline, the correlation detected between AL and logK was 0.37 (p = 0.047). There was no significant correlation between AL and V _max or any scotopic and photopic ffERG amplitude and implicit time measures. Longitudinal data suggested a reduction in photopic a- and b-wave and 30 Hz flicker response amplitudes over time. Multivariate analysis showed that the change in 30 Hz flicker response amplitude was likely to be associated with AL change. There was no evidence that changes in other responses were associated with age, baseline AL, or atropine dose used.

Conclusion

Retinal sensitivity was reduced in myopic children. There was a gradual decline in cone function over time which was not influenced by atropine treatment.     

Psychophysically determined full-field stimulus thresholds (FST) in retinitis pigmentosa: relationships with electroretinography and visual field outcomes

Purpose

The purpose of this study is to describe the relationships between full-field stimulus threshold (FST), electroretinography (ERG), and visual field (VF) outcomes in retinitis pigmentosa (RP).

Methods

Data from 47 patients with RP (n = 94 eyes) were evaluated. Patients were submitted to comprehensive ophthalmological examination including measurement of best-corrected visual acuity (BCVA), 30-2 threshold static VF, and microperimetry. Full-field ERG (ISCEV standard) was recorded, and achromatic FST was measured using a Diagnosys Espion system with the ColorDome? LED full-field stimulator (Diagnosys LLC, Lowell, MA, USA).

Results

BCVA mean ± SD was 0.31 ± 0.03 logMAR, and FST mean ± SD was ?18.45 ± 9.53 dB. No significant correlation was found between BCVA and FST. In contrast, statistically significant correlations were found between FST and static 30-2 VF mean deviation (r = ?0.389; P < 0.01), microperimetry mean threshold (r = ?0.607; P < 0.01). Dark and light-adapted ERGs were detectable in 28 and 48 eyes, respectively. Nevertheless, considering only the eyes with recordable ERG responses, moderate correlations were found between combined dark-adapted a-wave amplitude (r = ?0.560; P < 0.01), b-wave amplitude (r = ?0.643; P < 0.001), 30-Hz flicker response (r = ?0.501; P < 0.01), and FST, and high correlation with FST for cone b-wave amplitude (r = ?0.715; P < 0.01).

Conclusions

FST could be successfully determined in RP patients with a wide range of vision loss. FST results showed stronger correlations with full-field ERG amplitude than with sensitivity measured with visual field tests. FST is as an alternative to VF or ERG for assessment of retinal function in patients unable to do visual fields or with non-detectable ERGs.     

Disease progression in autosomal dominant cone–rod dystrophy caused by a novel mutation (D100G) in the GUCA1A gene

Purpose

To document longitudinal fundus autofluorescence (FAF) and electroretinogram (ERG) findings in a family with cone–rod dystrophy (CRD) caused by a novel missense mutation (D100G) in the GUCA1A gene.

Methods

Observational case series.

Results

Three family members 26–49 years old underwent complete clinical examinations. In all patients, funduscopic findings showed intraretinal pigment migration, loss of neurosensory retinal pigment epithelium, and macular atrophy. FAF imaging revealed the presence of a progressive hyperautofluorescent ring around a hypoautofluorescent center corresponding to macular atrophy. Full-field ERGs showed a more severe loss of cone than rod function in each patient. Thirty-hertz flicker responses fell far below normal limits. Longitudinal FAF and ERG findings in one patient suggested progressive CRD. Two more advanced patients exhibited reduced rod response consistent with disease stage. Direct sequencing of the GUCA1A gene revealed a new missense mutation, p.Asp100Gly (D100G), in each patient.

Conclusion

Patients with autosomal dominant CRD caused by a D100G mutation in GUCA1A exhibit progressive vision loss early within the first decade of life identifiable by distinct ERG characteristics and subsequent genetic testing.     

The importance of electrode position in visual electrophysiology

Purpose

The DTL fibre electrode is commonly used to record the electric potentials elicited by stimulation of the retina. Two positions are commonly used: it is placed either on the cornea along the lower lid or in the conjunctival fornix. The PERG and OPs have previously been examined and compared under both conditions. The aim of this study was to examine the ERG, flicker response and on–off responses with differing electrode positions.

Methods

Before recruitment, all subjects underwent an ophthalmological examination. We enrolled 13 normal control subjects into the study aged 13–64 years, all with a visual acuity of ≥1.0. We recorded scotopic and photopic ERGs, flicker and on–off responses, for both electrode positions. On the first day, one eye had the electrode placed on the cornea along the lower lid and the other eye had it positioned in the conjunctival sac. On a second day, the recordings were repeated with the alternative electrode placements.

Results

ERG, on–off and flicker responses were all smaller by between 20 and 25% when the DTL electrode was positioned in the conjunctival sac, compared to when it was positioned on the cornea, as did the scatter in the data points. This indicates that there is no advantage clinically for one or the other placement.

Conclusions

Our results confirm other reports examining the effect of electrode position on electrophysiological potentials. When recording with the DTL electrode, it is important to ensure that it is placed at the same position in repeat recordings or in multicentre trials and that it is stable and does not move during recording.

     

Wellenfrontaberrationen und subjektive optische Qualität nach wellenfrontgeführter LASIK

Purpose

To investigate the clinical impact of the postoperative ocular wavefront error (WFE) on subjective quality of vision (SQV) after LASIK.

Method

Forty-one myopic eyes of 21 patients underwent uneventful LASIK (median –4.63 D). Preoperatively and 1 month postoperatively, WFE measurements were performed and overall SQV was assessed for two lighting conditions (photopic and mesopic) with a questionnaire. Three different WFE representations were computed for a pupil diameter of 6 mm: (1) the visual quality metric VSOTF (visual Strehl ratio based on the optical transfer function), (2) RMS (root mean square) values of the Zernike orders 2–5, and (3) individual Zernike coefficient for orders 2–5. The impact of the postoperative WFE on SQV was calculated using linear regression analysis.

Results

For photopic conditions R² was 0.24 for model 1 (VSOTF), 0.31 for model 2 (RMS values), and 0.29 for model 3 (Zernike coefficients). Second-and fifth-order aberrations had significant influence on SQV. For mesopic conditions, results were similar.

Conclusion

Subjective quality of vision after wavefront-guided LASIK could be explained partially by the ocular WFE.     

Decreased retinal–choroidal blood flow in retinitis pigmentosa as measured by MRI

Purpose

To evaluate retinal and choroidal blood flow (BF) using high-resolution magnetic resonance imaging (MRI) as well as visual function measured by the electroretinogram (ERG) in patients with retinitis pigmentosa (RP).

Methods

MRI studies were performed in 6 RP patients (29–67 years) and 5 healthy volunteers (29–64 years) on a 3-Tesla scanner with a custom-made surface coil. Quantitative BF was measured using the pseudo-continuous arterial spin-labeling technique at 0.5 × 0.8 × 6.0 mm. Full-field ERGs of all patients were recorded. Amplitudes and implicit times of standard ERGs were analyzed.

Results

Basal BF in the posterior retinal-choroid was 142 ± 16 ml/100ml/min (or 1.14 ± 0.13 μl/mm²/min) in the control group and was 70 ±19 ml/100ml/min (or 0.56 ± 0.15 μl/mm²/min) in the RP group. Retinal–choroidal BF was significantly reduced by 52 ± 8 % in RP patients compared to controls (P<0.05). ERG a- and b-wave amplitudes of RP patients were reduced, and b-wave implicit times were delayed. There were statistically significant correlations between a-wave amplitude and BF value (r=0.9, P<0.05) but not between b-wave amplitude and BF value (r =0.7, P=0.2).

Conclusions

This study demonstrates a novel non-invasive MRI approach to measure quantitative retinal and choroidal BF in RP patients. We found that retinal–choroidal BF was markedly reduced and significantly correlated with reduced amplitudes of the a-wave of the standard combined ERG.     

Dark-adapted oscillatory potentials in preterm infants with and without retinopathy of prematurity

Purpose

To describe the appearance and maturation of dark-adapted oscillatory potentials (OPs) in electroretinograms (ERGs) recorded from preterm infants, and to determine any effect of retinopathy of prematurity (ROP).

Methods

Dark-adapted ERGs were recorded in conjunction with screening for ROP and at outpatient follow-up, using a flash luminance of 11.3 scot cd s m^?2 (4.06 phot cd s m^?2). Eligible infants were born before 31 weeks’ gestation and/or weighed ≤1,250 grams at birth.

Results

Presence or absence of OPs was established for 68 ERG recordings from 38 infants at maturities ranging from 30 weeks’ postmenstrual age (PMA) to 28 weeks’ post-term corrected age. 20 infants did not develop ROP, eight developed stage 1, one stage 2 and one stage 3 disease which regressed spontaneously. Eight infants received treatment for threshold ROP. OPs were present in 50 % of infants at 36 weeks’ PMA and in all by 50 weeks’ PMA. The earliest appearance of OPs was at 30+5 weeks’ PMA. Individual OP amplitudes increased and peak time of individual OPs decreased with increasing maturity. For infants with threshold ROP summed OP amplitudes tended to be smaller prior to treatment (6.5 vs 9.9μV, P = 0.09) and were significantly smaller by 50 weeks’ PMA (14 vs 30μV, P = 0.007). OP1 was less likely to be present in infants who developed stage 3 or worse ROP (P = 0.000).

Conclusions

Dark-adapted OPs are recordable in some preterm infants from 30 weeks’ PMA. Relative suppression of early OPs is a potential marker for developing ROP.     

Liquid crystal display screens as stimulators for visually evoked potentials: flash effect due to delay in luminance changes

Purpose

The cathode-ray tube (CRT) screen has recently been replaced by liquid crystal display (LCD) screens as visual stimulators for pattern-reversal visually evoked potentials (p-VEPs). The aim of the study was to evaluate the usefulness of LCD screen to elicit p-VEPs.

Methods

The waveforms of the p-VEPs elicited by a LCD panel were compared with those elicited by a conventional CRT screen. The changes in the luminance of each screen were measured with a photodiode, and the mean luminance change was measured with a luminance meter. VEPs and electroretinograms (ERGs) were also recorded when the monitor was covered by a diffuser.

Results

The p-VEPs elicited by the LCD consisted of the N75 and P100 components of the conventional VEPs and had good reproducibility. The average latency of these components was significantly delayed by 9.8 ms for N75 and 10.2 ms for P100, and the N75-P100 amplitude was significantly larger than the conventional p-VEP elicited by the CRT screen. During the reversal phase, especially from black-to-white, the luminance of the LCD screen was transiently reduced, and it elicited a flash VEP and ERG. A reduction in the contrast of the checks minimized the transient change in the luminance, and the VEP waveform was more similar to that elicited by the CRT screen.

Conclusions

The results suggest that when an LCD monitor is used as an alternative visual stimulator to elicit p-VEPs, the delay in the luminance change and the flash effect needs to be taken into account.     

Comparison of cathode ray tube and liquid crystal display stimulators for use in multifocal VEP

Purpose

To compare the modified signal-to-noise ratio (SNR*) of multifocal visual evoked potential (mfVEP) responses elicited by a cathode ray tube (CRT) and liquid crystal display (LCD) monitor in normal subjects.

Methods

An LCD monitor and CRT monitor were luminance and contrast matched. Luminance stability and the effect of viewing angle on luminance and contrast was measured for both screens. The SNR* of mfVEP responses from 15 normal subjects was compared between the stimulators using repeated measures analysis of variance.

Results

The CRT monitor took 10 min from switch on to reach the desired luminance compared to 60 min for the LCD monitor. LCD luminance was sensitive to variations in ambient temperature, fluctuating by 10 cd/m^?2 over approximately 20–27 °C, whereas CRT luminance was stable. Luminance variation from the centre to the edge of the CRT screen was 8 % when viewed perpendicularly and 28 % when viewed at an angle of 25°, compared to 24 and 46 %, respectively, for the LCD screen. Contrast was >94 % and varied by <3 % across both monitors for both viewing conditions. There was no significant difference in SNR* between responses elicited by the two stimulators (p = 0.76).

Conclusions

CRT and LCD stimulators elicited mfVEP responses with similar SNR* in normal subjects. This study highlighted practical issues with the use of LCD monitors as visual stimulators, particularly with regard to warm-up time, luminance stability and luminance uniformity.     

Progressive retinal degeneration in a girl with Knobloch syndrome who presented with signs of ocular albinism

Purpose

We report for the first time electroretinographic (ERG) evidence of progressive retinal abnormalities in a girl who presented in infancy with ocular features of albinism and gradually developed choroidal sclerosis and patchy retinal atrophy leading to a diagnosis of Knobloch syndrome (KS, OMIM 267750, COL18A1).

Methods

At age 2 months, nystagmus and esotropia prompted ophthalmic evaluation. The appearance of choroidal sclerosis and atrophic retinal patches led to further evaluation at age 8 years. Genetics consultation was obtained in infancy and again at age 8 years as retinal findings evolved. Full field ERG responses in both scotopic and photopic conditions were recorded at both ages and compared to those in healthy control subjects.

Results

At age 2 months ERG response parameters were within normal limits for age and tyrosinase (TYR) gene sequencing revealed one novel mutation, p.S466F, and the temperature-sensitive polymorphism, p.R402Q, suggesting the diagnosis of oculocutaneous albinism type 1 (OCA1). At age 8 years, there was significant attenuation of both scotopic and photopic ERG responses. Genetic re-analysis led to the identification of a homozygous mutation, c.3213dupC, in the COL18A1 gene, thus confirming the diagnosis of Knobloch syndrome.

Conclusions

Our patient with Knobloch syndrome developed abnormal ERG responses similar to those found in col18a1 knockout mice. Thus, we have documented progressive attenuation of the scotopic and photopic responses in KS.