Accelerated hydroxychloroquine toxic retinopathy.

PURPOSE: To report a case series of patients with retinal toxicity due to hydroxychloroquine (HCQ) within a short span of treatment. METHODS: A retrospective review of case records of patients with accelerated HCQ toxicity within 1 year of starting the treatment was done. Systemic co-morbidities, details of HCQ treatment, details of ocular examination, and results of multimodal investigations were noted. RESULTS: Nine patients (1 male, 8 females) with age ranging from 40 to 73 years (mean 54.2 ± 13.4 years) who showed accelerated HCQ toxicity were included. None had systemic conditions or drug history predisposing to early HCQ toxicity. The treatment duration ranged from 2 to 11 months and the cumulative HCQ dose ranged from 18 to 120 g (mean 45.0 ± 33.0 g). The visual acuity was normal in 8 (88.9%) patients and retinal evaluation was normal in 4 (44.4%). Optical coherence tomography was abnormal in 4 (44.4%). Six (66.6%) cases had reduced sensitivity in the parafoveal point on visual field testing. All 9 cases had multifocal electroretinographic changes diagnostic of HCQ toxicity. The HCQ treatment was stopped in 8 and continued with reduced dose in 1 patient. The mean duration of follow-up was 11.2 ± 9.6 months during which 5 patients showed improved mfERG and 1 patient had a stable mfERG. Visual fields improvement was noted in 2 cases. CONCLUSIONS: Patients on HCQ need to be kept on regular monitoring with more frequent follow-ups to detect signs of early onset toxicity and prevent permanent visual impairment. mfERG is an important diagnostic tool for HCQ toxicity.

ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update).

This document developed by the International Society for Clinical Electrophysiology of Vision (ISCEV) provides guidance for calibration and verification of stimulus and recording systems specific to clinical electrophysiology of vision. This guideline provides additional information for those using ISCEV Standards and Extended protocols and supersedes earlier Guidelines. The ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update) were approved by the ISCEV Board of Directors 01, March 2023.

Effect of spatial averaging on the amplitude ring ratio in multifocal electroretinography.

PURPOSE: The purpose of this study was to evaluate the effect of spatial averaging on the multifocal electroretinography (mfERG) amplitude ring ratios used in screening for hydroxychloroquine (HCQ) toxicity. METHODS: This was a retrospective review of the records of patients screened for HCQ retinopathy at the USF Eye Institute (University of South Florida) during the period of 2015-2020. Patients were tested binocularly with Diagnosys mfERG system (Diagnosys LLC, Lowell, MA). Only the records of patients referred internally were used. The effects of the lowest level (level 1, or 8%) of spatial averaging on the P1 amplitude ring ratios used for screening of HCQ maculopathy: R1/R2, R2/R5, R5/R3 and R5/R4, were evaluated. RESULTS: The records of 40 patients (4 males, 36 females) aged 54.4 ± 14.1 years were selected for analysis. The use of spatial averaging had a significant effect on P1 amplitudes, and on the ring ratios and this effect was correlated with the magnitude of the amplitudes and the ratios. Spatial averaging diminished P1 amplitude significantly in ring 1 (p < 0.0001) and increased it slightly in ring 4 (p < 0.05), while it had no effect on the amplitude of the other three rings. Although as a group spatial averaging had a moderate effect on the R1/R2 ratio (~ -15%), on an individual basis the range was wide, from -36 to 43%. The effect on the other ring ratios was similar: The average group effect was ~ -5%, ~ -3.4% and ~ -4% for R2/R5, R5/R3 and R5/R4 ratios, but individual effects ranged from 0.18% to -27.3%, 0.9% to -14.2% and 0.9% to -26.2%, respectively. CONCLUSIONS: For all ring ratios used in this analysis, spatial averaging has a substantial effect on the ring ratio, which could affect the interpretation of the results. Therefore, use of spatial averaging should be avoided when analyzing mfERG results for HCQ screening.

Unilaterally extinguished electroretinograms in an eye with normal visual acuity and visual field.

PURPOSE: This study reports a case of unilateral retinopathy with extinguished full-field ERGs (ffERGs), wherein the visual acuity was 16/16 and the visual field was spared. METHODS: Observational case report. RESULTS: A 39-year-old female had developed nyctalopia in her left eye. Two years later, she visited an ophthalmologist who noted a bilaterally reduced pigmentation of the fundus. Her best-corrected visual acuity was 16/16 in both the eyes. Goldmann perimetry demonstrated that her visual field was bilaterally fully spared. ffERGs measurement was performed in accordance with the ISCEV standard protocol and indicated that her right eye was normal. However, all ERG responses were severely attenuated in her left eye. Multifocal ERG responses were found to be normal in the right eye and extinguished in the left eye except for residual responses that were exclusively located at the center. During the 7 years of the follow-up period, the visual field in the left eye, which was once normal, became shaded, and the development of a ring scotoma was identified. The visual field in the right eye is still full. CONCLUSIONS: The pathogenesis of this patient's condition still remains unknown, while unilateral retinitis pigmentosa, unilateral pigmentary retinopathy, acute zonal occult outer retinopathy, and autoimmune retinopathy can all be considered as possible explanations. The uniqueness of this case study is that the extinguished ERG responses are predictive of the functional alteration in the affected eye, when the initial visual acuity and the visual field were normal.

Autologous neurosensory free-flap retinal transplantation for refractory chronic macular hole-outcomes evaluated by OCT, microperimetry, and multifocal electroretinography.

PURPOSE: To report the safety, anatomical and functional outcomes of autologous neurosensory retinal transplant in patients with a refractory large unclosed macular hole. PATIENTS AND METHODS: This is a prospective case series of four patients with large chronic macular hole that underwent vitrectomy and free-flap neurosensory retinal transplantation surgery with silicone oil tamponade. The hole was closed with an autologous retinal transplant of an approximate diameter of 1.5-1.8 mm, harvested outside the vascular arcades. Anatomical and functional outcomes were assessed using best-corrected visual acuity (BCVA-Snellen), optical coherence tomography (OCT), OCT angiography, microperimetry (MP), and multifocal electroretinography (mfERG). RESULTS: There were 2 male and 2 female patients with median age of 73 (60-81) years. The median follow-up period was 17 (13-23) months. The median preoperative size of the macular hole was 1872.5 (868-2591) µm at the widest basal diameter and 828 (556-1099) µm at the minimum diameter. Surgery resulted in the anatomical closure of the macular hole in all cases. The OCT showed structural integration of the transplant and reappearance of the inner segment ellipsoid to different extents. The BCVA improved from preoperative 0.1 (6/60; + 1.0 logMAR), 0.1 (6/60; + 1.0 logMAR), 0.05 (6/120; + 1.3 logMAR), and 0.005 (6/1200; + 2.3 logMAR) to 0.2 (6/30; + 0.7 logMAR) postoperatively in cases 1, 2, and 4, and to 0.1 (6/60; + 1.0 logMAR) in case 3. MP showed retinal function in the region corresponding to the area of the transplant (circle of 1.8 mm in diameter) in all patients after the surgery (median sensitivity in that region was 4.0 dB, range 1.8-12.4 dB). Improvement was noted in the patient that had MP performed before the surgery (mean sensitivity improved from 0 to 1.8 dB). Detectable function was mostly located in the peripheral regions of the transplant. Multifocal ERG showed abnormal function of the central ring and normal function of the second ring in 3 of 4 cases. The OCT angiography showed normal perfusion, without signs of neovascularization. There were no intra- or postoperative complications. CONCLUSION: Autologous retinal transplantation surgery is a successful technique for closing of large refractory macular holes. The procedure is safe and provides good anatomical results. Visual acuity, microperimetry, and mfERG suggest some gradual functional integration of outer regions of the transplants, but no central functional restitution has been detected as yet.

Electrophysiological and SD-OCT findings in patients receiving chloroquine therapy in relation to cumulative dosage and duration of treatment.

PURPOSE: Assessment of multifocal ERG (mfERG) changes in patients treated with chloroquine and their correlation with morphological abnormalities, detected by spectral-domain optical coherence tomography in relation to cumulative dosage. METHODS: Data from 37 eyes of 20 patients were retrospectively collected, and one randomly selected eye per patient was considered for statistical analysis. Eyes were divided into three groups according to mfERG and visual acuity findings: normal, early and advanced maculopathy. Functional measures of the first three mfERG rings were compared with retinal thickness measures of the corresponding OCT ETDRS circles. Data on cumulative dose and duration of therapy were also evaluated. RESULTS: The mean mfERG values progressively decreased according to the stage of the disease. In particular in the early maculopathy group, amplitudes were significantly reduced in all the three central rings. The mean ring ratio R1/R2 was abnormal only in the early maculopathy group. OCT thickness measures were significantly lower in all the three ETDRS circles in the advanced maculopathy group, and in the paracentral circle in the early maculopathy group. Considering all the eyes, there was a statistically significant correlation between functional and morphological values (p < 0.001). High chloroquine cumulative dosages were always associated with retinal toxic effects, whereas lower cumulative dosages generated different levels of toxicity. CONCLUSIONS: This study shows a strong association between mfERG ring values and the corresponding OCT thickness measures; however, mfERG may enhance early detection of functional changes in patients treated with chloroquine, especially in ambiguous cases. At low chloroquine cumulative dosages, different subjects might have different susceptibilities to the drug.

Correlation between electroretinography, foveal anatomy and visual acuity in albinism.

BACKGROUND: Albinism patients have poor visual acuity in addition to hypopigmentation. Their foveal anatomy is abnormal, but correlation with function is incompletely understood. This study correlates retinal electrophysiology, visual acuity and optical coherence tomography (OCT) anatomy in albinism patients and compares with age-similar controls. METHODS: Institutional Review Board approval was obtained (IRB# 201408782). Patients were recruited from clinical practice. Inclusion criteria were at least three clinical features of albinism including iris transillumination, nystagmus, fundus hypopigmentation, or foveal hypoplasia on OCT and/or molecular genetic confirmation. Diagnosys (Lowell, Mass) full-field ERG (ffERG) and VERIS multifocal ERG (mfERG; Electro-Diagnostic Imaging, Milpitas, California) were obtained using standard International Society for Clinical Electrophysiology of Vision protocols. The mfERG protocol was a 4-min 103-hexagon protocol covering approximately 40° in diameter of central retina. Control subjects without albinism were recruited by in-hospital notices and invitations in clinic. OCT central thickness was recorded, and an OCT foveal score was calculated. Nonparametric permutation testing was utilized to determine the statistical significance. RESULTS: A total of 16 albinism patients and 19 age-similar controls were recruited. Four of 16 albinism patients had no nystagmus. Seventeen non-albinism controls had no ocular disorder other than refractive error. Two controls had infantile nystagmus with normal maculas on OCT. There was no statistically significant difference in mfERG amplitude or latency between albinism patients with or without nystagmus (lowest p = 0.68; 0.54, respectively). mfERG: 12 of 16 (75%) albinism patients had average ring 1 amplitudes within one standard deviation of controls despite having abnormal foveal anatomy on OCT. Patients averaged shorter latencies in rings 1 and 2 than controls (p = 0.005, p = 0.02). Patients averaged higher amplitudes than controls in rings 4, 5 and 6 (p = 0.03, p = 0.006, p = 0.004). There was no significant correlation between visual acuity and mfERG amplitudes in any ring (smallest p = 0.15). ffERG: Patients averaged higher amplitudes on 30 Hz flicker (p = 0.008). In all conditions, albinism patients had higher amplitude a-waves (p ≤ 0.03). B-waves were higher amplitude than controls in light-adapted 3.0 (p = 0.03). There was no statistical correlation between ffERG amplitudes and visual acuity (smallest p = 0.45). OCT: In albinism patients, thicker central macula on OCT correlated with lower mfERG amplitudes in all rings except for ring 1 (p < 0.05) and lower ffERG a-wave amplitudes on dark-adapted 0.01 (p = 0.003). Macular thickness on OCT did not correlate with visual acuity (p = 0.51); OCT foveal score did (p = 0.0004). CONCLUSIONS: Amplitude of mfERG does not correlate with visual acuity in any ring in patients with albinism. The slope of the change in amplitude from central to peripheral rings on the mferg is significantly different in albinism patients versus controls whether or not nystagmus is present. The decreased slope of change in amplitudes from center to periphery of the macula in albinism patients indicates changes in macular topography that are more important to visual deficits than the foveal depression.

Müller cells and choriocapillaris in the pathogenesis of geographic atrophy secondary to age-related macular degeneration.

PURPOSE: To better understand the pathophysiology of geographic atrophy (GA), secondary to age-related macular degeneration, eyes affected by unilateral GA (and CNV in the fellow eye; U-GA group) or by bilateral GA (B-GA group) were evaluated using an integrated morpho-functional approach and quantifying biomarker of retinal macroglial activity. METHODS: Patients with U-GA and B-GA and foveal-sparing were consecutively enrolled in a prospective study. All included eyes underwent fundus photography, fundus autofluorescence (FAF), foveal retinal and choroidal thicknesses (RT, CT), contrast sensitivity, best-corrected visual acuity (BCVA), low-luminance VA (LLVA) and low-luminance deficit (LLD), and mesopic and scotopic microperimetry and multifocal electroretinography (mfERG). Glial fibrillary acidic protein (GFAP), biomarker of Müller cell activation, was quantified in the aqueous humor (AH). RESULTS: Forty eyes of 40 patients (18 in the U-GA group and 22 in the B-GA group) were studied. RT, GA area, BCVA, contrast sensitivity, mfERG, and microperimetry (at both background luminances) were not different between groups. CT was significantly thinner in U-GA compared to B-GA group (p = 0.020). Both LLVA and LLD were significantly worse in the B-GA vs U-GA group (p = 0.033 and p = 0.048, respectively). GFAP intraocular concentration was significantly higher in the B-GA group (p = 0.01). CONCLUSIONS: Different pathophysiologic mechanisms may be responsible for GA in unilateral (with CNV in the fellow eye) compared to bilateral GA cases. In unilateral cases, a thinner choroid seems to play a key role. Whereas, in bilateral cases, Müller cells and their supported photoreceptors may be primarily involved.

ISCEV guide to visual electrodiagnostic procedures.

Clinical electrophysiological testing of the visual system incorporates a range of noninvasive tests and provides an objective indication of function relating to different locations and cell types within the visual system. This document developed by the International Society for Clinical Electrophysiology of Vision provides an introduction to standard visual electrodiagnostic procedures in widespread use including the full-field electroretinogram (ERG), the pattern electroretinogram (pattern ERG or PERG), the multifocal electroretinogram (multifocal ERG or mfERG), the electrooculogram (EOG) and the cortical-derived visual evoked potential (VEP). The guideline outlines the basic principles of testing. Common clinical presentations and symptoms are described with illustrative examples and suggested investigation strategies.

Fixation stability and implication for multifocal electroretinography in patients with neovascular age-related macular degeneration after anti-VEGF treatment.

PURPOSE: To quantify fixation stability in patients with neovascular age-related macular degeneration (nAMD) at baseline, 3 and 6 months after anti-vascular endothelial growth factor (anti-VEGF) treatment and furthermore asses the implications of an unsteady fixation for multifocal electroretinography (mfERG) measurements. METHODS: Fifty eyes of 50 nAMD patients receiving intravitreal anti-VEGF treatment with either bevacizumab or ranibizumab and eight eyes of eight control subjects were included. Fixation stability measurements were performed with the Eye-Link eyetracking system and the retinal area in degrees2 (deg2) containing the 68 % most frequently used fixation points (RAF68) was calculated. MfERG P1 amplitude and implicit time were analyzed in six concentric rings and as a summed response. Patients were examined at baseline, 3 and 6 months. Four different mfERG recordings were performed for the control subjects to mimic an involuntary unstable fixation: normal central fixation, 2.4°, 4.8°, and 7.1° fixation instability. RESULTS: For control subjects, a fixation instability of 2.4° (corresponding to the central hexagon) did not reduce mfERG ring amplitudes significantly, whereas 4.8° and 7.1° fixation instability reduced the amplitudes significantly in rings 1 and 2 (p < 0.001) as well as in the peripheral rings in the 7.1° instability condition (p < 0.001). Fixation stability improved non-significantly for patients at 3 and 6 months. The size of the retinal area of fixation was at baseline, 3 and 6 months negatively correlated to visual acuity (VA) (rbaseline = -0.65, r3 months = -0.60, and r6 months = -0.66 respectively, p < 0.001) and mfERG amplitudes of the three innermost rings (rbaseline = -0.29, p = 0.042, r3 months = -0.43, p = 0.003 and r6 months = -0.31, p = 0.042). The VA cutoff for a fixation area less than 5 deg2 (approximately the central hexagon) was 65, 77, and 68 ETDRS letters (corresponding a maximal Snellen equivalent of 0.31) at baseline, 3 and 6 months, respectively. CONCLUSIONS: MfERG amplitudes in recordings of nAMD patients are at substantial risk of being reduced due to poor fixation as a large number of patients may use a fixation area of more than 5 deg2. Fixation monitoring during recording as well as interpretation of results should be performed with care, especially in patients with poor visual acuity.

Correlation between N2 amplitude of multifocal ERGs and retinal sensitivity and retinal nerve fiber layer thickness in glaucomatous eyes.

PURPOSE: To determine whether there are significant correlations between the N2 amplitude of the multifocal electroretinograms (mfERGs) and the retinal sensitivity and retinal nerve fiber layer (RNFL) thickness in glaucomatous and normal eyes. METHODS: Thirty-eight glaucomatous and 11 normal eyes were studied. The mfERGs were elicited by red stimuli presented on a blue background. The responses from the central five elements within a 20° stimulated area were analyzed. The retinal sensitivity was determined by Humphrey Field Analyzer and the RNFL thickness by spectral-domain optical coherence tomography. The correlations between the N2 amplitude and the retinal sensitivity and the RNFL thickness were calculated. RESULTS: The N2 amplitude was significantly smaller in the glaucomatous eyes than the normal eyes in all areas (P < 0.05). There was a significant correlation between the N2 amplitude and the retinal sensitivity (1/Lambert linear unit) of the HFA for the superior retina (r = 0.36, P = 0.01), for the central retina (r = 0.54, P < 0.0001), and for the inferior retina (r = 0.51, P = 0.0001). There were significant correlations between the N2 amplitude and the RNFL thicknesses in the superior retina (r = 0.49, P = 0.0003), the central retina (r = 0.79, P < 0.0001), and the inferior retina (r = 0.52, P = 0.0001) for both normal and glaucomatous eyes. CONCLUSIONS: These results indicate that the activity of the retinal ganglion cells contribute to the amplitude of the N2 of the mfERGs and thus can be used as an objective monitor of retinal ganglion cell function.

What monitor can replace the cathode-ray tube for visual stimulation to elicit multifocal electroretinograms?

To compare a conventional cathode-ray tube (CRT) screen to organic light-emitting diode (OLED) and liquid crystal display (LCD) screens as visual stimulators to elicit multifocal electroretinograms (mfERGs), mfERGs were recorded from seven eyes of seven healthy volunteers (21 ± 2 years). The mfERGs elicited by a conventional CRT screen (S710, Compaq Computer Co.) were compared to those elicited by a studio-grade master OLED monitor (PVM-1741, Sony, Japan) and a conventional LCD (S1721, Flexscan, Eizo Nanao Corp., Japan). The luminance changes of each monitor were measured with a photodiode. CRT, OLED, and LCD screens with a frame frequency of 60 Hz were studied. A hexagonal stimulus array with 61 stimulus elements was created on each monitor. The serial white stimuli of the OLED screen at 60 Hz did not fuse, and that of the LCD screens fused. The amplitudes of P1 and P2 of the first-order kernels of the mfERGs were not significantly different from those elicited by the CRT and OLED screens, and the P1 amplitude of the first-order kernel elicited by the LCD stimuli was significantly smaller than that elicited by the CRT in all the groups of the averaged hexagonal elements. The implicit times were approximately 10 ms longer in almost all components elicited by the LCD screen compared to those elicited by the CRT screen. The mfERGs elicited by monitors other than the CRT should be carefully interpreted, especially those elicited by LCD screens. The OLED had good performance, and we conclude that it can replace the CRT as a stimulator for mfERGs; however, a collection of normative data is recommended.

Full-field and multifocal electroretinogram in non-diabetic controls and diabetics with and without retinopathy.

OBJECTIVE: To compare retinal function assessed by full-field electroretinography (ffERG) and multifocal electroretinography (mfERG) in diabetes without retinopathy, diabetes with moderate non-proliferative diabetic retinopathy (NPDR) and in the absence of diabetes. METHODS: Scotopic and photopic ffERG and mfERG was made in non-fasting volunteers, including 26 diabetic participants without retinopathy, 22 diabetic participants with moderate NPDR and 22 participants without diabetes using full International Society for Clinical Electrophysiology of Vision protocols. RESULTS: Of the ffERG responses, significant deviation (p ≤ 0.05, corrected for multiple sampling and other relevant confounders) from the non-diabetic participants was seen in the diabetic participants only for the OP1-OP3 oscillatory amplitudes and the OP2 implicit time. This finding was independent of whether retinopathy was present or not. For the mfERG, minor amplitude or implicit time deviations were found for a small number of rings (R2, R4 and R5). Receiver of operating characteristic analysis showed that the single most prominent abnormality of the ffERG in diabetes, regardless of whether retinopathy was present or not, was the OP2 implicit time (area under the curve ≥ 0.80). CONCLUSION: This bi-modal study of electroretinographic characteristics found that the most prominent anomaly associated with diabetes was a prolongation of the implicit time of the OP2 of the scotopic ffERG, while the most prominent added effect of non-proliferative diabetic retinopathy was a further prolongation of the OP2 implicit time. Although the variation in ERG characteristics is far too large for diagnostic purposes, the close association of the oscillatory potentials with the amacrine cells of the retina indicate that their function is particularly sensitive to diabetes.

Multifocal ERG and Microperimetry Changes in Response to Ranibizumab Treatment of Neovascular AMD: Randomized Phase 2 Open-Label Study.

PURPOSE: To compare monthly versus pro re nata (PRN) ranibizumab injections in the treatment of exudative macular degeneration (AMD) while assessing the utility of microperimetry (MP) and multifocal electroretinography (mfERG) testing when monitoring response to treatment. METHODS: A randomized exploratory trial comparing the efficacy of monthly versus PRN dosing of ranibizumab (0.5 mg or 2.0 mg) for patients with exudative AMD over 12 months. High-resolution optical coherence tomography (HR-OCT) studies were used to guide PRN treatment and any cystic spaces or subretinal fluid prompted retreatment. Macular function was assessed using mean sensitivity on MP and N1-P1 response density on mfERG. Best-corrected visual acuity (BCVA) was measured with Early Treatment Diabetic Retinopathy Study (ETDRS) letters and anatomic response assessed with central foveal thickness (CFT) using HR-OCT studies. RESULTS: The 12-month study was completed by 43 patients in the PRN cohort and 33 patients in the monthly cohort. Mean BCVA improved by 6.0 ± 1.3 ETDRS letters in the PRN cohort compared to 7.3 ± 2.8 ETDRS letters in the monthly cohort (p=0.68). A reduction in mean CFT of 64.5 ± 13.3 and 96.3 ± 22.0 µm occurred in the PRN and monthly cohorts, respectively (p=0.22). Macular function assessed with mfERG decreased comparably in both the PRN and monthly cohorts (p=0.33). For all patients, average mean sensitivity significantly improved by 1.7 ± 0.5 dB (p<0.05) and N1-P1 response density significantly decreased by 0.52 ± 0.21 nV/deg2 (p<0.05). CONCLUSION: Both PRN and monthly treatment of exudative AMD with ranibizumab improve visual function as assessed by BCVA and MP. Macular thickening also improved as demonstrated by HR-OCT findings. However, the decreased retinal function noted by mfERG suggests that some loss of retinal function still occurs despite effective treatment. These measures of visual function may be useful in assessing retinal health and response to treatment in future clinical trials.

Relationship between functional and structural retinal changes in myopic eyes.

BACKGROUND: The aim of this study was to investigate the retinal structure in different grades of myopia and correlate it with the functional changes detected with multifocal electroretinogram (mf-ERG) and try to show the most important determining factors. METHODS: The study included 80 participants divided into four groups according to their spherical equivalent refractive error, namely, emmetropia (within ± 0.50 D), mild myopia group (greater than -0.50 to -3.00 D), moderate myopia group (more than -3.00 to -6.00 D) and high myopia group (greater than -6.00 D). Full ophthalmologic examination was performed for all participants, including visual acuity (VA), slitlamp examination, Goldmann applanation tonometry, indirect ophthalmoscopy, axial length (AL) measurement, retinal nerve fibre layer thickness assessment and mf-ERG stimulation. RESULTS: Axial length was significantly higher in myopes than emmetropes; also it was higher the greater the degree of myopia. There was a reduction in the amplitude and prolongation of implicit times of mf-ERG in myopia. Also P1 implicit time of the mf-ERG response was prolonged the greater the degree of myopia. The retinal nerve fibre layer was significantly thinner in myopic groups than the emmetropic group. The thinning of the retinal nerve fibre layer increased the more the degree of myopia. Multiple regression analysis of myopic patients showed that AL is the most important determinant of most of the mf-ERG five-rings retinal response density (RRD), mf-ERG four-quadrant (Q) RRD, most of the five-rings P1 amplitude and all five-rings latencies. The most important determinant factors of mean Q RRD were VA, AL and retinal nerve fibre layer thickness. CONCLUSION: The retina of the myope is subject to both structural and functional alterations compared to that of the emmetrope. Significant correlations exist between the functional and structural changes and can be explained on bases of longer AL and increasing myopic refraction.

Impact of a Digital Power Line Filter in the 2-Global-Flash Multifocal Electroretinogram of Glaucoma Patients Compared to Controls.

PURPOSE: To assess the effect of a 50 Hz power line digital filter on the response to a 2-global-flash multifocal electroretinogram (mfERG) in primary open angle glaucoma (POAG) compared to control. MATERIALS AND METHODS: A 2-global-flash mfERG (VERIS™) was recorded (23 control, 34 POAG). Eight recordings were noise contaminated: 4 control, 4 POAG. Response averages from the central 10° and 7 surrounding groups were analyzed with and without a 50 Hz digital filter for the following mfERG response epochs: direct component (15-45 ms), 1st (45-75 ms) and 2nd (75-105 ms) induced components. RESULTS: A digital 50 Hz filter had little effect on uncontaminated with noise waveforms but, in noisy recordings, changed the waveform dramatically to resemble uncontaminated waveforms. In controls' 50 Hz-filtered uncontaminated with noise mfERGs differed significantly from unfiltered responses in induced components. Uncontaminated with noise recordings from glaucoma patients did not differ with or without the notch filter (p > 0.1 for all three epochs of mfERG). The mfERG response in the central 10°in glaucoma patients differed significantly from controls, whether the notch filter was used or not (p < 0.001). CONCLUSIONS: A 50 Hz notch filter allows grossly contaminated waveforms to be analyzed in a meaningful manner. With a 50 Hz filter, glaucoma patients still differed significantly from normal.

Multifocal Electroretinography in the Presence of Temporal and Spatial Correlations and Eye Movements.

Releasing patients from the fixation task, and permitting them to view natural stimuli such as movies, would provide increased comfort, and potentially additional signs of retinal function, when recording multifocal electroretinograms (mfERGs). Techniques must be developed to handle the difficulties that arise from these alternative stimulation strategies. Multifocal stimuli were presented to volunteer human subjects with and without fixation. Retinocentric analyses were performed to deal with shifts of the stimulus across the retina in the presence of eye movements. Artificial scotomas that moved with the eyes to simulate local retinal defects were presented to assess whether such defects might be detectable in the presence of eye movements. Temporal and spatial correlations in the stimulus can be discounted, permitting retinal kernels to be measured in response to natural stimuli. Responses to temporally natural stimuli tend to have slightly stronger amplitudes because of the presence of low temporal frequencies in these stimuli. The effects of eye movement artifacts can be reduced, permitting similar kernels to be obtained in the absence and presence of eye movements. Convergence to stable kernels took slightly longer in the presence of temporal correlations or eye movements. Artificial scotomas can be localized with these methods. It may be possible to perform multifocal ERG recordings in the clinic using more flexible, natural techniques. However, work is needed to achieve results comparable to those routinely obtained with conventional methods.

Near-infrared reflectance bull's eye maculopathy as an early indication of hydroxychloroquine toxicity.

IMPORTANCE: In some patients, hydroxychloroquine ocular toxicity may progress even following cessation of therapy. Any leverage the clinician may use to allow earlier detection may avert significant vision loss. OBSERVATION: We report three cases suggesting that bull's eye maculopathy seen on near-infrared reflectance with a confocal scanning laser ophthalmoscope could be an early, objective manifestation of hydroxychloroquine ocular toxicity, and with progression of the disease this near-infrared "bull's eye" change may disappear. CONCLUSION AND RELEVANCE: Alerting clinicians to this observation may allow a larger case series to corroborate the hypothesis that bull's eye maculopathy detected by near-infrared reflectance may represent an early sign of hydroxychloroquine toxicity.

Continuous-wavelet-transform analysis of the multifocal ERG waveform in glaucoma diagnosis.

The vast majority of multifocal electroretinogram (mfERG) signal analyses to detect glaucoma study the signals' amplitudes and latencies. The purpose of this paper is to investigate application of wavelet analysis of mfERG signals in diagnosis of glaucoma. This analysis method applies the continuous wavelet transform (CWT) to the signals, using the real Morlet wavelet. CWT coefficients resulting from the scale of maximum correlation are used as inputs to a neural network, which acts as a classifier. mfERG recordings are taken from the eyes of 47 subjects diagnosed with chronic open-angle glaucoma and from those of 24 healthy subjects. The high sensitivity in the classification (0.894) provides reliable detection of glaucomatous sectors, while the specificity achieved (0.844) reflects accurate detection of healthy sectors. The results obtained in this paper improve on the previous findings reported by the authors using the same visual stimuli and database.

Male-female differences in diabetic retinopathy?

The purpose of this paper is to review male-female differences in the incidence and prevalence of diabetes and diabetic retinopathy. These differences will be established primarily through results from our present research and a review of related literature. Previously, we have demonstrated that neuroretinal dysfunction can be used to predict the location of future retinopathy up to three years before it is manifest. Our current research suggests that, for type 2 diabetes, the normal differences in neuroretinal function between nondiabetic males and females under 50 years of age are altered in patients with type 2 diabetes. Furthermore, local neuroretinal function in type 2 diabetes is more abnormal in adult males compared with adult females. The literature also suggests that there are male-female differences in the occurrence of diabetes. In adolescence, the incidence of type 1 diabetes is greater in males, whereas in type 2 diabetes, the incidence is greater in females. This excess of females in type 2 diabetes shifts to a more equal incidence between the two sexes in adults. In addition, advanced retinopathy in type 1 diabetes appears to be more common in males, and the presence and severity of diabetic retinopathy at the time of diagnosis in type 2 diabetes appears to be more associated with male sex. Although the reasons for male-female differences identified in this review are unknown, sex appears to be a significant factor in certain aspects of diabetes incidence and diabetic retinopathy.