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Introduction: Nephronophthisis 12 is a rare condition and only two cases have been reported to associate with retinopathy. Herein we present the third case in scientific literature, and the first with vision-quality exams., Clinical Case: The case was a 28-year-old male with the mutations c.626C > T (p.Pro209Leu) and c.1317T > G (p.Tyr439*). Bilateral atrophy of outer retinal layers and retinal pigmented epithelium were observed, resembling a bull's eye maculopathy. Visual acuity, as well as contrast sensitivity dropped with mesopic conditions. He presented more difficulties in differentiating colors within blue-yellow range, and some degree of halos were detected. Multifocal electroretinogram detected little retinal function, and visual field detected a full scotoma. He referred poorer quality of life due to emotional wellbeing, more than to difficulties in reading or accessing information., Conclusion: Although rare, nephronophthisis 12 may be caused by genetic mutations that associate severe retinopathy., Competing Interests: Declarations. Conflict of interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Informed consent: Informed consent was obtained the participant included in the study. Human rights: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Vitamin A is a lipid-soluble compound that is critical in maintaining phototransduction. Ocular manifestations of hypovitaminosis A may present with anterior segment signs of xeropthalmia, with advanced cases also causing classic retinal and electrophysiologic changes of vitamin A deficiency retinopathy. We present a case of vitamin A deficiency retinopathy, with corresponding retinal imaging and electrophysiology, in an adult patient with celiac disease and liver fibrosis., Methods: A single case report was conducted in Toronto, Canada., Results: A 77-year-old male with known celiac disease and liver fibrosis presented progressively worsening vision noticed primarily when driving. Vision was 20/50 OD and 20/200 OS. Bitot spots were noted on anterior segment examination. Fundus photography demonstrated bilateral peripheral macular hypopigmentation and far-peripheral granular retinal hypopigmentation with focal yellow dots and hyper-pigmented deposits. Optical coherence tomography (OCT) imaging demonstrated indistinct outer retinal banding with mild outer nuclear layer thinning, focal hyper-reflective deposits, and a thin choroid bilaterally. Full-field electroretinography (ERG) testing demonstrated reduced rod-isolated and combined rod-cone response amplitudes, and multifocal ERG testing demonstrated blunted individual responses throughout the field. The patient was treated with pulse vitamin A therapy. After 6 months of therapy, ERG responses were back within reference range, and the outer retinal changes reversed; visual acuity improved to 20/30 OD and 20/40 OS., Conclusion: This case represents the classic findings of vitamin A deficiency retinopathy on fundus examination and electrophysiologic testing secondary to gastrointestinal pathology. Prompt treatment of high dose vitamin A supplementation led to improvement of full-field and multifocal ERG results, as well as reconstitution of outer retinal architecture., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Multiple myeloma (MM) is a plasma cell dyscrasia leading to proliferation of monoclonal plasma cells. Ocular involvement in multiple myeloma is uncommon but can occur. The ocular manifestations of MM may include the cornea, uvea, and retinal vasculature. We present a rare case of autoimmune retinopathy associated with smoldering MM., Case: A 76-year-old female with no significant past medical or ocular history presented with four months of worsening vision, difficulty with night driving, and loss of peripheral vision. Examination was notable for pallor of the optic nerves and vascular attenuation. Visual field testing demonstrated significant and progressive field loss in both eyes. An electroretinogram was extinguished under all conditions. Serum protein electrophoresis showed a significant elevation of IgG with an M-spike, and a subsequent bone marrow biopsy was performed showing 12.5% plasma cells, consistent with the diagnosis of MM. CAR antibody testing was positive for anti-enolase, anti-GAPDH, and anti-Rab6 antibodies, consistent with autoimmune retinopathy., Discussion: Autoimmune retinopathy associated with MM is exceedingly rare. Management of this condition is challenging, as treatment of the underlying disease does not often lead to improvement in visual symptoms. Ultimately, visual prognosis is very poor, and both patients and clinicians should be aware of the guarded visual potential., Conclusion: The association of autoimmune retinopathy with multiple myeloma is rare. It is crucial for physicians to be aware of such manifestations to ensure timely and appropriate diagnosis and management for patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We present our findings in two cases of retinal dysfunction caused by syphilitic outer retinopathy. CASE 1: A 59-year-old man visited our clinic complaining of blurred vision in his left eye. Optical coherence tomography (OCT) demonstrated an absence of the ellipsoid zone (EZ) in the left eye. A round yellowish-white lesion was observed in the posterior pole of the left fundus. Fundus autofluorescence (FAF) showed hyperfluorescent areas in the posterior pole of both fundi although no specific ophthalmoscopic findings were seen in the right eye. The amplitudes of the LA 3.0 1 Hz and LA 3.0 30 Hz ERG responses were reduced with better preservation of the rod responses. Based on a strong positivity to the rapid plasma reagin (RPR) assay and the Treponema pallidum hemagglutination (TPHA) test, he was diagnosed with syphilitic outer retinopathy and treated with systemic antibiotics. The treatment resulted in a restoration of the retinal structures and cone function. CASE 2: A 47-year-old man was referred to our clinic complaining of reduced vision in both eyes. Although the ocular fundus appeared normal, FAF showed a diffuse hyperfluorescent area in the posterior pole and multiple hyperfluorescent spots. Indocyanine green angiography showed multiple confluent areas of hypofluorescence. OCT demonstrated irregular EZs in both eyes. The amplitudes of the LA 3.0 1 Hz and LA 3.0 30 Hz ERG responses were slightly reduced with prolonged implicit times. These findings are comparable to the findings in patients with multiple evanescent white dot syndrome. However, the strong positivity to the RPR and TPHA tests led us to diagnose the patient with outer retinopathy caused by syphilis. Systemic administration of antibiotics resulted in the restoration of the retinal structures and retinal function., Conclusions: Syphilitic outer retinopathy affected the retinal structures and function that can be restored by antibiotic treatments.

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.

Objective: To report a unique retinal signaling defect in GNB5-related disease., Methods: A 3-year-old female child underwent detailed systemic and ophthalmological evaluation. The eye examination included fundus photography, spectral domain optical coherence tomography and an extended protocol full-field electroretinography (ERG) including the ISCEV recommended standard steps. The dark-adapted (DA) ERGs were performed to a series of white flashes (range 0.006-30.0 cd s m -2 ) and two red flashes. The DA ERGs to higher stimulus intensities (3.0, 10.0 and 30.0 cd s m -2 ) were tested using a range of inter-stimulus intervals (ISI) of up to 60 s. In addition to standard light-adapted (LA) ERGs, a short-duration (0.5 s) LA 3.0 30-Hz flicker ERG and a long-duration LA ON-OFF ERG were also performed. Genetic testing included microarray, mitochondrial genome testing and whole exome sequencing., Results: The child was diagnosed to have status epilepticus and bradycardia at 6 months of age. Subsequently, she was diagnosed to have global developmental delay and hypotonia. On ophthalmological evaluation, the child fixes and follows light. Fundus evaluation showed mild optic disk pallor; macular SD-OCT was normal. The dim flash DA ERGs (DA 0.006 and DA 0.01 cd s m -2 ) were non-detectable. DA red flash ERGs showed the presence of an x-wave (cone component) and no rod component. The DA 3.0, 10.0 and 30.0 ERGs showed electronegative configuration regardless of the ISI; the averaged a-wave amplitude (4 flashes) was smaller at shorter ISI but became normal at a prolonged ISI (60 s). The LA 30-Hz flicker ERG was severely reduced but detectable for the initial 0.5 s; this became non-detectable after 5 s of averaging. The LA 3.0 2-Hz ERG showed markedly reduced a- and b-wave amplitudes and a reduced b:a ratio; the LA ON-OFF ERGs were non-detectable. WES identified a homozygous null mutation in G protein subunit beta 5 (GNB5; c.1032C>A/p.Tyr344*)., Conclusion: This report identifies for the first time a unique retinopathy associated with biallelic mutations in GNB5. The observed phenotype is consistent with a dual retinal signaling defect reminiscent of features of bradyopsia and rod ON-bipolar dysfunction.

Purpose: To analyze the effects of different methods of measurement on the photopic negative response (PhNR), recorded as part of a standard ISCEV Photopic 3.0 ERG responses from patients with a variety of clinical diagnoses., Methods: ERGs were recorded from both eyes of 97 patients (187 eyes) as part of a standard clinical assessment. The average age was 56.4 ± 15.7 years, the gender balance was 35 M, 62F, and only recordable responses of acceptable quality were included. PhNR was measured at an identifiable trough before (PhNR1) and after the i-wave (PhNR2), and the amplitudes and peak times were compared with a-, b- and i-wave corresponding parameters. PhNR components were measured: from baseline and from b-wave peak. Correlation between PhNR troughs and with ERG parameters were tested for right eyes. The possibility to predict and substitute PhNR2 amplitude from PhNR1 amplitude was also tested., Results: PhNR1 was recordable in 97.3% of eyes and PhNR2 in 85.6%. An identifiable PhNR2 peak was found to occur before 65 ms at ~ 50% of the records, while in ~ 38% of the cases was within 65-75 ms in ~ 12%-after 75 ms. The correlation between the PhNR1 and PhNR2 peaks was quite strong (with coefficients 0.81-0.98, depending on method of measurement, and slopes close to 1). The average difference between predicted and measured PhNR2 was reasonably small in absolute (< 2 µV) and relative (< 2%) terms. The correlations between PhNR amplitudes and other ERG component amplitudes showed different ranges of correlation coefficients depending on the method of measurement: for the a-wave amplitudes the range of coefficients was 0.48-0.73, while for the b-wave amplitudes it was 0.30-0.95 and 0.39-0.65 for i-wave., Conclusion: The strong correlation between the two PhNR troughs could allow using PhNR1 when PhNR2 is poorly defined due to artifacts. Different methods of PhNR measurement lead to different correlations with other ERG parameters, and this needs to be considered when analyzing and comparing PhNR data between studies.

Purpose: To report a case of linezolid-induced reversible retinopathy., Methods: Case report with literature review., Results: Clinical examination and imaging are presented over a 7-month interval, from initial presentation to subsequent follow-up (6 months after discontinuation of linezolid). The subject was found to have not only an optic neuropathy but also severe reversible photoreceptor dysfunction as demonstrated by electrophysiologic testing. Upon discontinuation of linezolid, not only did the patient's visual acuity, visual fields, and visual evoked potential significantly improve, but the electroretinogram did as well., Conclusions: Linezolid has previously been reported to cause a toxic optic neuropathy. Reversible photoreceptor dysfunction on full-field electroretinography has never been reported in conjunction with linezolid toxicity. This novel case suggests that linezolid toxicity should be considered in cases of photoreceptor dysfunction.

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum protocol for clinical testing but encourages more extensive testing where appropriate. This ISCEV extended protocol describes an extension of the ISCEV full-field ERG standard, in which methods to record and evaluate the growth of the dark-adapted (DA) ERG b-wave with increasing stimulus energy are described. The flashes span a range that includes the weakest flash required to generate a reliable DA ERG b-wave and that required to generate a maximal b-wave amplitude. The DA ERG b-wave stimulus-response series (also known historically as the "intensity-response" or "luminance-response" series) can more comprehensively characterize generalized rod system function than the ISCEV standard ERG protocol and may be of diagnostic or prognostic value in disorders that cause generalized rod system dysfunction.

Purpose: The aim of this study was to develop a simple and reliable method for the objective assessment of visual acuity by optimizing the stimulus used in commercially available systems and by improving the methods of evaluation using a nonlinear function, the modified Ricker model., Methods: Subjective visual acuity in the normal subjects was measured with Snellen targets, best-corrected, and in some cases also uncorrected and with plus lenses (+ 1 D, + 2 D, + 3 D). In patients, subjective visual acuity was measured best-corrected using the Freiburg Visual Acuity Test. Sweep VEP recordings to 11 spatial frequencies, with check sizes in logarithmically equidistant steps (0.6, 0.9, 1.4, 2.1, 3.3, 4.9, 7.3, 10.4, 18.2, 24.4, and 36.5 cpd), were obtained from 56 healthy subjects aged between 17 and 69 years (mean 42.5 ± 15.3 SD years) and 20 patients with diseases of the lens (n = 6), retina (n = 8) or optic nerve (n = 6). The results were fit by a multiple linear regression (2nd-order polynomial) or a nonlinear regression (modified Ricker model) and parameters compared (limiting spatial frequency (sf limiting ) and the spatial frequency of the vertex (sf vertex ) of the parabola for the 2nd-order polynomial fitting, and the maximal spatial frequency (sf max ), and the spatial frequency where the amplitude is 2 dB higher than the level of noise (sf threshold ) for the modified Ricker model., Results: Recording with 11 spatial frequencies allows a more accurate determination of acuities above 1.0 logMAR. Tuning curves fitted to the results show that compared to the normal 2nd-order polynomial analysis, the modified Ricker model is able to describe closely the amplitudes of the sweep VEP in relation to the spatial frequencies of the presented checkerboards. In patients with a visual acuity better than about 0.5 (decimal), the predicted acuities based on the different parameters show a good match of the predicted visual acuities based on the models established in healthy volunteers to the subjective visual acuities. However, for lower visual acuities, both models tend to overestimate the visual acuity (up to ~ 0.4 logMAR), especially in patients suffering from AMD., Conclusions: Both models, the 2nd-order polynomial and the modified Ricker model performed equally well in the prediction of the visual acuity based on the amplitudes recorded using the sweep VEP. However, the modified Ricker model does not require the exclusion of data points from the fit, as necessary when fitting the 2nd-order polynomial model making it more reliable and robust against outliers, and, in addition, provides a measure for the noise of the recorded results.

Purpose: The full-field electroretinogram (ff-ERG) is a widely used clinical tool to evaluate generalized retinal function by recording electrical potentials generated by the cells in the retina in response to flash stimuli and requires mydriasis. The purpose of this study was to determine the intra-visit reliability and diagnostic capability of a handheld, mydriasis-free ERG, RETeval (LKC Technologies, Gaithersburg, MD, USA), in comparison with the standard clinical ff-ERG by measuring responses recommended by the International Society for Clinical Electrophysiology of Vision (ISCEV)., Methods: This prospective, cross-sectional study included 35 patients recruited at the Hospital for Sick Children (median age = 17, range 11 months-69 years) who had undergone a clinical ff-ERG according to ISCEV standards. For RETeval (n = 35), pupils were undilated in most (n = 29) and sensor strip electrodes were placed under the inferior orbital rim. Stimulus settings on RETeval were equivalent to those used in the clinical ERG. Fifty-seven control participants (median age = 22, range 8-65 years) underwent undilated RETeval ERG to establish standard values for comparison. Patient waveform components with amplitudes < 5th percentile, or implicit times > 95th percentile of normal relative to control data were classified as abnormal for the RETeval system., Results: The RETeval system demonstrated a high degree of within-visit reliability for amplitudes (ICC = 0.82) and moderate reliability for implicit times (ICC = 0.53). Cohen's Kappa analysis revealed a substantial level of agreement between the diagnostic capability of RETeval in comparison with clinical ff-ERG (k = 0.82), with a sensitivity and specificity of 1.00 and 0.82, respectively. Pearson's correlations for clinical ERG versus RETeval demonstrated a positive correlation for amplitudes across the rod (r = 0.65) and cone (r = 0.74) ERG waveforms. Bland-Altman plots showed no bias between the mean differences across all amplitude and implicit time parameters of the two systems., Conclusions: The present study demonstrated that RETeval is a reliable tool with reasonable accuracy in comparison with the clinical ERG. The portable nature of RETeval system enables its incorporation at resource-limited centers where the ff-ERG is not readily available. The avoidance of sedation and pupillary dilation are added advantages of RETeval ERG.

Purpose: Many mfERG displays show normal responses that are larger at the center than peripherally, and the typical linear display of signals is inaccurate with respect to the retinal location of the signals. Printouts do not always indicate retinal or field view, they sometimes emphasize 3-D topographic plots which are not always representative of physiologic signals, and they show ring response densities which are different in every ring and hard to interpret without norms. These problems limit the clinical usefulness of the mfERG and limit communication in the literature. We share our Stanford Display to illustrate possible solutions to these problems., Methods: We have changed the scaling factor for our mfERG unit to produce a trace array with near equal signals everywhere. We display responses is a spatially scaled array, in a retinal view, so that signals appear in their correct anatomic locations relative to a fundus image. The 3-D display is minimized on the page of signal analysis, and we emphasize ring response averages rather than ring response densities., Results: The new scaling and trace array display greatly facilitate the analysis of retinal disease. Regions of loss are easily recognized in their fundus location. Ring ratios based upon response amplitudes all have a normal value of 1.0 which simplifies analysis. A case of early hydroxychloroquine retinopathy demonstrates the use of this Stanford display., Conclusions: Recognition of these recording and display options may help mfERG users to maximize the value of the test. Proper scaling of the mfERG stimulus array facilitates localization of retinal disease and simplifies ring response analysis. Different laboratories will have different priorities for signal analysis, but mfERG displays should always indicate the eccentricity of responses, and the use of a retina or field view.

Purpose: To report a case of deferoxamine-induced retinopathy characterized by electroretinography (ERG), optical coherence tomography angiography (OCT-A), and other multimodal imaging., Methods: This is an observational case report of one patient. Full-field ERG was performed. OCT-A, spectral-domain optical coherence tomography (SD-OCT), color fundus photography, and fundus autofluorescence were used to characterize the retinopathy induced by deferoxamine use., Results: A 64-year-old man with a history of β-thalassemia intermedia presented with worsening visual acuity, nyctalopia, and electronegative ERG. OCT-A revealed atrophy of the choriocapillaris in areas of hypoautofluorescence, corresponding to regions of retinal atrophy. SD-OCT showed disruption of the ellipsoid zone, granular hyperreflective deposits within the retinal pigment epithelium, thinning of the retinal layers, and extensive choroidal sclerosis and atrophy of the retinal pigment epithelium., Conclusion: Deferoxamine-induced retinopathy can manifest with electronegative maximal ERG responses, and OCT-A can be used to detect deferoxamine toxicity.

Purpose: Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. Studies have shown retinal abnormalities in patients and mouse models with HD; however, to our knowledge, no prior research papers evaluated retinal structure and function in a presymptomatic patient with HD. The aim of this report is to present a case of retinal dysfunction in a presymptomatic patient with HD., Methods: We investigated retinal structure and function in a 25-year-old male who tested positive for the gene that causes HD, but did not have any symptoms normally associated with HD. Vision and ocular testing included a comprehensive dilated ophthalmic examination, 24-2 full-threshold Humphrey visual field, spectral-domain optical coherence tomography (SD-OCT), fundus photography, full-field electroretinogram (ERG), and multifocal electroretinogram (mfERG)., Results: Visual electrophysiology testing showed rod and cone functional anomalies in both eyes. Full-field ERG amplitudes were subnormal in both eyes for the dark-adapted (DA) 0.01 ERG, DA 3 ERG, DA 3 oscillatory potentials (OPs), DA 10 ERG, light-adapted (LA) 3 ERG, and LA 30 Hz flicker, but peak times for the six standard ERG responses were not significantly different from normals. mfERGs revealed functional anomalies of the central retina with attenuated P1 amplitudes for five of the six concentric rings in the right eye and all six rings in the left eye. mfERG P1 peak times were normal at all eccentricities. Dilated fundus examination, SD-OCT, and fundus photography were unremarkable in both eyes. The visual field was normal in the right eye, but there was a mild paracentral field defect in the left eye., Conclusions: Our results illustrate that the ERG and mfERG detected early retinal dysfunction in a presymptomatic patient with HD consistent with electroretinogram findings in animal models of HD. However, our report was limited to one patient and additional studies are needed to verify whether the ERG and/or mfERG can uncover neural dysfunction before motor, behavioral, and cognitive abnormalities are discernible in patients with HD.

Introduction: CABP4-related retinal dysfunction is a cone-rod synaptic transmission disorder with electronegative electroretinogram (ERG) waveform. It is a rare retinal dysfunction that can be classified into the incomplete form of congenital stationary night blindness. Absent foveal reflex and overall foveal thinning were previously reported, but in most cases the fundus appearance was described as nearly normal. We report here peculiar macular changes in a patient of French ancestry harbouring CABP4 mutations., Methods: Complete ocular examination and full-field ERG were performed at the initial presentation and follow-up. Multimodal fundus imagining, including spectral-domain optical coherence tomography, colour, infrared reflectance and short-wavelength autofluorescence photographs, was performed during follow-up visits., Results: A 7-month-old infant was addressed to our department for visual unresponsiveness and nystagmus. ERG had an electronegative waveform, even for light-adapted stimuli, thus supporting the diagnosis of photoreceptor-bipolar cell transmission disorder. Genetic investigations discovered a compound heterozygous mutation in CABP4: c.646C > T, p.Arg216*/c.673C > T, p.Arg225*. Multimodal fundus imaging, performed at follow-up visits, showed fine radial folds at the vitreomacular interface and dark foveal dots in both eyes. Optic coherence tomography revealed a focal foveal ellipsoid zone gap., Discussion: Initial presentation was misleading with Leber congenital amaurosis. The electronegative ERG waveform reoriented the genetic investigations and thus establishing a correct diagnosis. To the best of our knowledge, the peculiar fundus changes observed in our patient were never reported before. We hypothesized that a foveal ellipsoid zone interruption discovered in our patient could reflect mostly a cone dysfunction. It was unclear whether the fine radial folds in both maculae were linked with high hyperopia or were an intrinsic feature of the retinal disease., Conclusion: CABP4-related retinal disease is a cone-rod system disorder with possible foveal abnormalities.

Purpose: To characterize the ultrastructural and functional correlates of hydroxychloroquine (HCQ)-induced subclinical bull's eye lesion seen on near-infrared reflectance (NIR) imaging., Methods: An asymptomatic 54-year-old male taking HCQ presented with paracentral ring-like scotoma, abnormal multifocal electroretinography (mfERG) and preserved ellipsoid zone on optical coherence tomography (OCT). Dense raster OCT was performed to create en face reflectivity maps of the interdigitation zone. Macular Integrity Assessment (MAIA) microperimetry and mfERG findings were compared with NIR imaging, en face OCT, retinal thickness profiles and wave-guiding cone density maps derived from flood-illumination adaptive optics (AO) retinal photography., Results: The bull's eye lesion is an oval annular zone of increased reflectivity on NIR with an outer diameter of 1450 µm. This region corresponds exactly to an area of preserved interdigitation zone reflectivity in en face OCT images and of normal cone density on AO imaging. Immediately surrounding the bull's eye lesion is an annular zone (3°-12° eccentricity) of depressed retinal sensitivity on MAIA and reduced amplitude density on mfERG. Wave-guiding cone density at 2° temporal was 25,400 per mm 2 . This declined rapidly to 12,900 and 1200 per mm 2 at 3° and 4°., Conclusion: Multimodal imaging illustrated pathology in the area surrounding the NIR bull's eye, characterized by reduced reflectance, wave-guiding cone density and retinal function. Further studies are required to investigate whether the bull's eye on NIR imaging and en face OCT is prominent or consistent enough for diagnostic use.

Purpose: Dark adaptometry (DA) is a sensitive test for diagnosis of retinal disease. Patients requiring flash electroretinograms (ERGs) benefit from DA for proper diagnosis. Our purpose was to develop a DA test to be administered during the 20-min dark adaptation period of the flash ERG ( www.iscev.org ) using alternating red and blue stimuli to bias responses in favor of cones (red) and rods (blue)., Methods: An ERG Ganzfeld was used to measure DA in 21 normal subjects and 21 patients with retinal disease. Subjects underwent 75 s of preadaptation followed by 20 min of DA using an adaptive staircase to detect alternating flashes of red and blue light. Normative red and blue DA was compared to patients at the 10-min midpoint and 20-min final threshold., Results: At 15 min, normals and patients showed asymptotic plateaus; hence, final thresholds were achieved within 15 min for parameters of this study. In RP and allied conditions (n = 11), 100% showed significantly elevated blue DA thresholds (> 2SD above normal) at 10 and 20 min. In cone diseases, 80% showed abnormal red DA at 10 min and 30% at 20 min, indicating that delayed adaptation is more typical of cone disease., Conclusions: Two-color DA is expediently measured during the DA phase of ERGs providing clinical data which separate rod and cone dysfunction critical for accurate diagnosis of various retinal diseases. It provides an additional benchmark for monitoring function over time and invaluable guidance for patients functioning in dimly lit settings.

Purpose: To compare the retinal toxicity due to hydroxychloroquine (HCQ) use in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) using multifocal electroretinography (mfERG), fundus autofluorescence (FAF) and optical coherence tomography (OCT)., Methods: Patients who were using HCQ due to SLE and RA, and healthy subjects evaluated in this study. Central foveal thickness (CFT), inner-outer segment (IS-OS) junction irregularity, retinal nerve fiber layer thickness, mfERG and FAF measurements were performed to evaluate retinal toxicity., Results: Study included 35 eyes of 35 SLE patients, 40 eyes of 40 RA patients and 20 eyes of 20 healthy subjects. In SLE group, retinal abnormality was found in three eyes with mfERG, in one eye with FAF and in four eyes with OCT. In RA group, retinal abnormality was found in 10 eyes with mfERG, in five eyes with FAF and in nine eyes with OCT. A statistically significant difference was found with respect to mfERG between "eyes with abnormal responses and without abnormal responses" and "eyes with abnormal responses and controls" (p < 0.05). A statistically significant difference was found with respect to CFT between "eyes with IS-OS junction irregularities and without IS-OS junction irregularities" and "eyes with/without IS-OS junction irregularities and controls" (p < 0.05)., Conclusions: The use of HCQ seems to cause retinal toxicity more often in RA patients compared to SLE patients. For the early detection of retinal changes, OCT and mfERG can be used as screening tools due to their higher sensitivity rates compared to other tests.

Purpose: To evaluate discrimination ability of pattern electroretinography (PERG) and photopic negative response (PhNR) between early glaucoma and healthy controls, and their relationship with structural measurements using spectral-domain optical coherence tomography (SD-OCT)., Methods: Cross-sectional study with 34 patients with ocular hypertension (n = 7), suspect glaucoma (n = 17), and early glaucoma (n = 10), plus 24 age-matched controls. The following parameters were analyzed: P50 and N95 amplitude of the PERG, PhNR amplitude and PhNR/b-wave ratio, peripapillary retinal and macular nerve fiber layer (NFL) thicknesses, and ganglion cell complex (GCC) thickness. Data from only one eye per individual were included in the statistical analysis. Descriptive statistics, ANOVA, receiver operating characteristics (ROC) curves, and correlation tests were used for analysis of the variables., Results: PERG N95 and PhNR amplitudes were significantly reduced in suspect and early glaucoma eyes versus controls. Significant differences across ocular hypertensive, suspect, and early glaucoma eyes were found for macular NFL and GCC thickness, but not for any of the ERG parameters. The mean PhNR amplitude did not differ across these groups and was already reduced on average by 46% in ocular hypertensive and early glaucoma eyes and by 52% in suspect glaucoma eyes. The P50 and N95 amplitudes showed similar reduction in suspect and early glaucoma eyes on average by 15 and 26%, respectively. Of the ERG parameters, PhNR amplitude distinguished best between glaucoma and control groups, with an area under ROC curve of 0.90 for suspect glaucoma, and 0.86 for early glaucoma. PhNR/b-wave ratio showed strongest association in suspect glaucoma eyes with peripapillary retinal (r, 0.61) and macular NFL (r, 0.76) thicknesses. In eyes with early glaucoma, peripapillary retinal NFL thickness correlated best with PhNR amplitude (r, 0.71) and PERG P50 amplitude (r, 0.67)., Conclusions: In eyes with suspect glaucoma, important decrease in PhNR amplitude is associated with small changes in peripapillary retinal and macular NFL thicknesses. These findings suggest that PhNR may be a useful and sensitive test in eyes with diagnostic dilemma, although further follow-up of such eyes is required for definitive confirmation.

Purpose: To describe the clinical and genetic findings in a patient with autosomal recessive bestrophinopathy (ARB) and his healthy parents., Methods: The patient and his healthy non-consanguineous parents underwent detailed ophthalmic evaluations including electro-oculography (EOG), spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) imaging. Mutation analysis of the BEST1 gene was performed by Sanger sequencing., Results: The FAF images showed multiple spots of increased autofluorescence, and the sites of these spots corresponded to the yellowish deposits detected by ophthalmoscopy. SD-OCT showed cystoid macular changes and a shallow serous macular detachment. The Arden ratio of the EOG was markedly reduced to 1.1 in both eyes. Genetic analysis of the proband detected two sequence variants of the BEST1 gene in the heterozygous state: a novel variant c.717delG, p.V239VfsX2 and an already described c.763C>T, p.R255W variant associated with Best vitelliform macular dystrophy and ARB. The proband's father carried the c.717delG, p.V239VfsX2 variant in the heterozygous state, and the mother carried the c.763C>T, p.R255W variant in the heterozygous state. The parents who were heterozygous for the BEST1 variants had normal visual acuity, EOG, SD-OCT, and FAF images., Conclusions: In a truncating BEST1 mutation, the phenotype associated with ARB is most likely due to a marked decrease in the expression of BEST1 promoted by the nonsense-mediated decay surveillance mechanism, and it may depend on the position of the premature termination of the codon created.

Purpose: To study the clinical use and efficacy of electrophysiology in children., Methods: This was a retrospective review of all children aged <16 years, who were referred to the Visual Electrophysiology Laboratory at the Singapore National Eye Center between 2003 and 2013., Results: A total of 586 children, median age 8 years (range 0.15-16), were referred for a variety of reasons including investigation of poor vision (40 %), suspected retinal disease or optic nerve/cortical dysfunction (17 %), nystagmus (13 %) and screening or monitoring of a variety of ocular or neurological conditions (12 %). The number of children with vision 6/15 or worse was 418 (71 %), and 103 (18 %) had vision 6/120 or worse in at least one eye. The most common pathology noted was retinal dystrophy or dysfunction (41 %) or optic nerve/cortical dysfunction (12 %). In 30 %, visual electrophysiology was within normal limits, and in 6 %, a conclusive diagnosis could not be obtained., Conclusion: Electrophysiology testing played an important role in the assessment of children and added to the clinical management of the patient.

Purpose: Laser pointer devices have become increasingly available in recent years, and their misuse has caused a number of ocular injuries. Online distribution channels permit trade in devices which may not conform to international standards in terms of their output power and spectral content. We present a case study of ocular injury caused by one such device., Methods: The patient was examined approximately 9 months following laser exposure using full-field and multifocal electroretinography (ERG and MF-ERG), electrooculography (EOG), and optical coherence tomography (OCT), in addition to a full ophthalmological examination. MF-ERG, OCT, and the ophthalmological examination were repeated 7 months after the first examination. The output of the laser pointer was measured., Results: Despite severe focal damage to the central retina visible fundoscopically and with OCT, all electrophysiological examinations were quantitatively normal; however, qualitatively the central responses of the MF-ERG appeared slightly reduced. When the MF-ERG was repeated 7 months later, all findings were normal. The laser pointer was found to emit both visible and infrared radiation in dangerous amounts., Conclusion: Loss of retinal function following laser pointer injury may not always be detectable using standard electrophysiological tests. Exposure to non-visible radiation should be considered as a possible aggravating factor when assessing cases of alleged laser pointer injury.

Purpose: To assess clinical value of visual electrophysiology in identifying causes of visual dysfunction in patients referred from neuro-ophthalmology clinics., Methods: A review of 410 subjects (aged 0.3-88 years) referred for visual electrophysiology from neuro-ophthalmologists between 2009 and 2013 was performed. Subjects were divided into those with unexplained poor vision, visual field defects, visual symptoms or other reasons (e.g. monitoring for drug toxicity or known conditions). Subjects underwent pattern, full-field and multifocal electroretinography (ERG) and pattern visual evoked potential (VEP) tests. Flash and multifocal VEP were included where indicated., Results: Most subjects referred for poor vision (n = 158) had electrophysiology findings suggestive of retinopathy (37 %) or post-retinal pathology (34 %). Those with poorer vision (worse than 6/24) were more likely to have abnormal recordings (86 vs. 62 %, p = 0.002). Among subjects with unexplained visual field defects (n = 102), findings of retinopathy, post-retinal pathology and normal recordings were noted in 31, 24 and 28 %, respectively. Most subjects with other visual symptoms (n = 97) had normal findings (69 %). The multifocal ERG was most sensitive for detecting retinopathy (96 %) and maculopathy (95 %), while pattern VEP was most sensitive for post-retinal pathology (94 %). An indeterminate result was noted in 9 %., Conclusion: Electrophysiology was effective in differentiating between retinopathy, post-retinal pathology and normality in 91 % of subjects. Pre-testing provisional diagnoses of retinopathy and post-retinal pathology were revised in 30 and 42 %, respectively, after electrophysiology. Appreciation of characteristics of each test, correlation with the clinical picture and interpretation of results in totality are required to localize the site of pathology.

Purpose: While optic neuropathy is a well-known cause of visual disturbances in linezolid-treated patients, the possibility of linezolid-related retinopathy has not been investigated. Here, we report a case of retinopathy demonstrated by multifocal electroretinogram (mfERG) in a linezolid-treated patient., Method and Results: A 61-year-old man with extensively drug-resistant pulmonary tuberculosis treated with linezolid for 5 months presented with painless loss of vision in both eyes. The patient's best corrected visual acuity was 20/50 in the right eye and 20/100 in the left eye. Fundus examination revealed mild disc edema, and color vision was defective in both eyes. Humphrey visual field tests showed a superotemporal field defect in the right eye and central and pericentral field defect in the left eye. Optical coherence tomography (OCT) revealed only mild optic disc swelling. In mfERG, central amplitudes were depressed in both eyes. Four months after the cessation of linezolid, visual acuity was restored to 20/20 right eye and 20/25 left eye. The color vision and visual field had improved. The OCT and mfEFG findings improved as well., Conclusions: Although the clinical features were similar to linezolid-induced optic neuropathy, the mfERG findings suggest the possibility of a retinopathy through cone dysfunction.

Purpose: To report the first documented case of aripiprazole-induced chorioretinopathy., Methods and Results: A 47-year-old schizophrenic patient with loss of vision due to an atypical retinopathy was investigated. She had been treated with aripiprazole for 8 years. Multimodal imaging showed in the right eye a large area of retinal atrophy predominating in the outer retina, including the posterior pole up to the upper temporal periphery, and in the left eye a serous retinal detachment. The electroretinogram exhibited decreased and delayed responses of both the rod and cone systems; the electrooculogram showed no light peak., Conclusion: Aripiprazole, an atypical antipsychotic, was introduced more recently than the antipsychotics commonly incriminated in chorioretinopathies, such as thioridazine. Optical coherence tomography was not used to document former cases of antipsychotic-related chorioretinopathies. Although pathophysiological mechanisms are poorly understood, imaging of the present case points toward an involvement of the retinal pigmentary epithelium. Clinicians should be aware of the potential chorioretinal toxicity of new atypical antipsychotics.

Purpose: To describe a follow-up case of vitamin A deficiency (VAD)-related retinopathy with macular involvement monitored with electroretinography and microperimetry., Methods: Flash (ERG), pattern (PERG), and multifocal (mfERG) electroretinography were recorded in parallel with microperimetry before and during 7-month follow-up of vitamin A treatment on a 65-year-old man presented with a 1-year history of night blindness. The patient had undergone ileostomy procedure for Crohn's disease 14 years ago. His best corrected visual acuity was 6/6 in each eye. Fundus examination revealed macular and mid-peripheral yellow-white lesions compatible with drusen., Results: Before treatment, PERG was reduced, and mfERG was reduced and delayed, worse in responses from the central rings. These results revealed evidence of bilateral macular and central cone dysfunction. The flash ERG showed reduced dark-adapted 0.01 ERG (rod response); a-wave of dark-adapted 3.0 and 10.0 ERG was normal but b-wave was reduced (negative configuration); light-adapted 3.0 ERG was slightly reduced. The flash ERG revealed evidence of bilateral generalised retinal dysfunction affecting the rod more than cone system. Microperimetry showed deep reduction in retinal sensitivity. Fixation stability was unstable with eccentric locus. During treatment, ERG and microperimetry demonstrated significant improvements. Fixation stability reached normal values after the third treatment week., Conclusions: This case illustrates the importance of electrophysiological investigation in early VAD-related retinopathy detection correlated with microperimetry. Our findings indicate a more delayed central cone function recovery than that of generalised rod and cone function. There was a marked correlation between ERG and microperimetric changes.

Purpose: To evaluate the effect of long-term chloroquine intake on the multifocal electroretinogram (mfERG) in female patients with and without maculopathy., Methods: Retrospective analysis of the mfERGs recorded in three different groups: (1) patients with bilateral maculopathy having taken chloroquine, (2) patients without maculopathy having taken chloroquine, and (3) healthy control subjects (age-matched to group 2) who never took chloroquine. MfERGs of each group were averaged, and the data of each patient group were compared to the control group. The main outcome measures were N1 and P1 characteristics and the ring ratio analysis., Results: In group 1, 11 female subjects (22 eyes) were included, group 2 consisted of nine patients (18 eyes) and group 3 of seven healthy female subjects (14 eyes). Compared with healthy controls, patients in group 1 showed significantly reduced response densities of both N1 and P1 across all ring eccentricities except ring 5. Implicit times were significantly delayed only concerning N1 (ring 4 and the sum response of the left eye of group 1). P1 implicit times showed no significant alterations in either group. Ring ratios of the response densities were significantly higher mainly concerning group 1 (N1: ring 5/ring 2 and ring 5/ring 4 of the right eye; P1: all ring ratios of the right eye and all ratios except ring 5/ring 1 and ring 5/ring 4 of the left eye). The only ring ratio being significantly higher in group 2 was P1 ring 5/ring 1 ratio of the right eye., Conclusions: In the absence of clinically apparent maculopathy, chloroquine intake was not associated with major alterations of the mfERG.

Purpose: To describe the clinical, functional, and genetic findings in a young Caucasian girl and her father, in whom a mutation of the PAX6 gene was identified., Methods: Detailed histories, eye examinations, and flash electroretinograms (ERGs) were acquired from both patients, and molecular genetic diagnostic testing was performed. Both patients were followed over a 2-year period., Results: At presentation, the proband displayed congenital nystagmus, photophobia, posterior embryotoxon, foveal hypoplasia, and coarse peripheral retinal pigment epithelium mottling. Light-adapted cone-driven ERG responses were delayed and reduced. The father had similar findings, but additionally displayed corneal clouding and pannus, decreased best-corrected visual acuity, and his ERG demonstrated a larger reduction in ERG cone-driven responses. PAX6 testing of the proband revealed a heterozygous mutation in exon 13 resulting in a p.X423Lfs (p.Stop423Leufs) frameshift amino acid substitution, predicting aberrant protein elongation by either 14 or 36 amino acids (p.X423Lext14 or p.X423Lext36) and subsequent disruption of normal protein function., Conclusions: The p.X423Lfs mutation has previously been described in cases of atypical aniridia, but this is the first report demonstrating abnormal cone-driven ERG responses associated with this particular mutation of the PAX6 gene. ERG abnormalities have been documented in other mutations of the PAX6 gene, and we propose that the retinal pathology causing these ERG abnormalities may contribute to the photophobia experienced by patients with aniridia. Systematic ERG testing can aid in the diagnosis of PAX6-related disorders and may prove to be a useful tool to objectively assess responses to future treatments.

Purpose: To describe the morphofunctional findings in a 6-year-old child with a unilateral lesion of the temporal macula called "torpedo maculopathy" throughout a 1-year follow-up., Methods: Evaluation of retinal morphology and function was assessed by means of spectral-domain OCT scans, best-corrected visual acuity, full-field flash electroretinogram (ERG), multifocal electroretinogram (mfERG) and pattern visual evoked potentials (VEP). Patient was examined every 4 months for a 1-year follow-up time., Results: Torpedo maculopathy consisted in a sharply demarcated hypopigmented oval iuxta-macular lesion (1.5 DD wide × 0.7 DD high). The baseline visual acuity of the affected eye was 20/25. OCT showed a sensorial retinal detachment in correspondence with the torpedo lesion. Pattern VEPs revealed a reduced response in left eye, as compared to contralateral eye. Full-field flash ERGs amplitude was normal in both eyes. Multifocal ERG response was reduced at all sites, more significantly at the site of the lesion in the eye with torpedo maculopathy and normal in fellow eye. Visual acuity, fundoscopic evaluation, OCT scans and electrophysiological tests showed no changes from baseline throughout the follow-up time., Conclusions: Torpedo maculopathy, although known as benign, may affect visual function if macular involvement is associated with neuroretinal detachment.

Purpose: The aims of this retrospective study were to compare the results of recommended screening tests for hydroxychloroquine-related retinal toxicity and analyze disparities between the structural and functional findings., Methods: Thirty-four patients (31 women and 3 men) were included in the study. All were evaluated with standard automated perimetry using the 10-2 and/or 24-2 visual field program (Zeiss, Meditec), multifocal electroretinography (mfERG), spectral-domain optical coherence tomography (SD-OCT), and short-wavelength fundus autofluorescent imaging (SW-FAF). The results for the right eye from each patient were analyzed. Visual fields were classified as normal or abnormal based on pattern deviation plots, and mfERGs based on a comparison of R5 ring ratios to values from 20 controls. The SW-FAF images were examined for areas/rings of abnormal hypo- and/or hyperautofluorescence, and the SD-OCT line scans were classified as abnormal based on visual inspection and thickness measurements of the outer segment plus retinal pigment epithelial layer and total receptor layers compared to mean thicknesses from 35 controls., Results: Fifteen patients had abnormal results on at least one test; however, only two patients had abnormal results on all four tests. Excluding SW-FAF, seven of the 15 had abnormal visual fields, mfERG ring ratios, and SD-OCTs. The remaining eight had either abnormal mfERGs and/or visual fields and normal SD-OCTs. We found no evidence of abnormal SD-OCTs in the presence of normal mfERG and visual field results., Conclusions: The findings suggest that functional deficits precede structural changes seen on SD-OCT in these patients.

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 m(2) 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.

The b-wave is a major component of the electroretinogram that reflects the activity of depolarizing bipolar cells (DBCs). The b-wave is used diagnostically to identify patients with defects in DBC signaling or in transmission from photoreceptors to DBCs. In mouse models, an abnormal b-wave has been used to demonstrate a critical role of a particular protein in the release of glutamate from photoreceptor terminals, in establishing the structure of the photoreceptor-to-DBC synapse, in DBC signal transduction, and also in DBC development, survival, or metabolic support. The purpose of this review is to summarize these models and how they have advanced our understanding of outer retinal function.

Introduction: We present the ocular features including full-field electroretinography (ff-ERG) and spectral domain optical coherence tomography (SD-OCT) in a 14-month-old infant with congenital disorder of glycosylation type 1a (PMM2-CDG)., Methods and Results: An infant with failure to thrive, bilateral neurosensory hearing loss, cerebellar hypoplasia, and pericardial effusions was referred to ophthalmic genetics for evaluation. The patient had fix and follow vision, an intermittent esotropia, moderate myopia, a hypo pigmented macula, and mild attenuation of the retinal vasculature. Electroretinography showed severe reduction in both rod and cone-dependent responses with a negative waveform pattern. Handheld SD-OCT revealed severe attenuation of the outer retina throughout the macula, but with preservation of outer retinal structures in the fovea., Conclusion: PMM2-CDG is a rare congenital disorder for which both ff-ERG and SD-OCT were useful in demonstrating early changes in retinal architecture and function.

Purpose: To report new findings in a case of ocular siderosis explored by high resolution angiography and adaptive optics (AO)., Methods: We report data on a 40-year-old man with an intraocular foreign body (IOFB) embedded in the sclera after hammering., Results: Nine months after this accident, the patient presented with full-field electroretinogram (FF-ERG) abnormalities. Subsequent IOFB extraction was performed. One month after the surgery, high resolution angiography showed for the first time small iron particles all over the inner retinal surface. Spreading of these deposits was followed by inflammatory prepapillary new vessels and venous retinal vasculatis, which spontaneously resolved within a few months. ERG responses became slightly electronegative at this time. Clearance of the iron particles was followed over a year with AO and ERG recording. AO revealed an arterial tropism with a decrease in the amount of particles overtime, which may be consistent with macrophagic activity., Conclusion: High resolution angiography and AO are new tools, combined with electrophysiology, to better understand ocular siderosis pathophysiology.

Purpose: To report two cases of visual loss following snake bite., Method: Retrospective review of medical records including history, examination finding, fundus details and investigation reports (visual field, electroretinogram, visual evoked potential and optical coherence tomogram) at two centers., Result: Two cases of snake bite presented to us with reduction of vision at 1 and 3 months after the incident. The subnormal b wave and abnormal pattern electroretinography in one case pointed at inner retinal dysfunction and neurotoxicity as the cause of visual loss in an apparently normal-looking fundus. The electronegative b wave in the other gave us a clue that the optic atrophy was consecutive (secondary to inner retinal dysfunction due to central retinal artery occlusion)., Conclusion: When presented late, diagnosis of visual loss secondary to snake bite becomes difficult and puzzling due to the absence of classical findings. Electrophysiological tests in such cases give us important clue to reach at a definite diagnosis.

Background: In acute posterior multifocal placoid pigment epitheliopathy (APMPPE), little is known about the long-term outcome of electroretinographic macular function. The purpose of this study was to report 2-year follow-up results of multifocal electroretinography (mfERG) in a 26-year-old Japanese woman diagnosed with APMPPE., Methods: Clinical and electrophysiological investigations of a single patient., Results: Best-corrected visual acuity at initial examination was 1.5 and 0.5 in her right and left eyes, respectively. In addition to characteristic fundus lesions bilaterally, fluorescein angiography demonstrated diagnostic early blockage and late staining of the lesions. Optical coherence tomography revealed a hyperreflective spot (corresponding to the lesion) in the outer retinal layer in the right eye and intraretinal fluid in the left eye. On mfERG, the amplitudes were generally preserved, but markedly reduced amplitudes were detected in the central region of the left eye and in the paracentral region of the right eye. Five days later, visual acuity improved to 1.0, and the intraretinal fluid spontaneously disappeared without medication in the left eye. Light-to-dark ratios on electrooculography were 2.68 and 2.23 in the right and left eyes, respectively, both within the normal range. Two years later, visual acuity was 2.0 in both eyes, and ophthalmoscopically, there were neither retinal nor retinal pigment epithelial (RPE) abnormalities. mfERG revealed that the amplitudes were considerably improved (nearly normal level) in both eyes., Conclusions: The outcome suggests that longitudinal macular function in both visual acuity and mfERG may be favorable, unless areas of retinal or RPE alteration remain.

Purpose: To study the effects of filtering bandwidth on the two-global-flash multifocal electroretinogram (mfERG) responses in primary open-angle glaucoma (POAG) compared with control subjects., Methods: A two-global-flash mfERG (VERIS 6.06™, FMS III) was recorded in 20 healthy subjects and 22 POAG patients with a band-pass filter (BPF) of 1-300 Hz (103 Hexagons, M-sequence stimulus: Lmax 100 cd/m(2), Lmin < 1 cd/m(2), global flash: 200 cd/m(2)). The root-mean-square average of the central 10° was calculated. Three response epochs were analysed: the response to the focal flash, at 15-45 ms (DC), and the following two components induced by the effects of the preceding focal flash on the response to the global flashes at 45-75 ms (IC1) and at 75-105 ms (IC2). The following BPF settings were analysed: 1-300 Hz, 3-300 Hz, 10-300 Hz, 100-300 Hz, 200-300 Hz, 1-10 Hz, 1-100 Hz and 1-200 Hz., Results: Filtering at 1-300 Hz showed significantly lower responses in POAG than in control subjects (p < 0.001) for all epochs analysed. At 1-100 Hz, this also held true even though the difference between the groups became smaller. At 1-10 Hz, responses were extremely small and did not differ between POAG and control (p > 0.5). This would suggest a filter setting of 10-300 Hz for mfERG recordings in POAG. However, when a filter setting of 10-300 Hz was compared to 1-300 Hz, with a filter setting of 10-300 Hz, the DC in POAG differed more (p < 0.0001) from normal than with 1-300 Hz (p = 0.0002). For IC1 and IC2, the stronger difference between POAG and control was found with 1-300 Hz (p < 0.0001) rather than with 10-300 Hz (p < 0.0001 and p = 0.0005, respectively). For the 'oscillatory potentials' at 100-300 Hz, POAG and control differed significantly in IC1 and IC2 (p < 0.05), but not in DC (p = 0.8). However, filtering at 200-300 Hz did not show a difference between POAG and control (p > 0.5). Thus, we applied a filter setting of 1-200 Hz, which seemed to be most sensitive in detecting glaucomatous retinal dysfunction (p < 0.0001)., Conclusions: A filter setting of 1-200 Hz appears most sensitive to detect glaucomatous damage if using a two-global-flash mfERG: using a band-pass filter a with lower low-frequency cut-off, containing the 10 Hz component, may be especially important in the small induced components that show glaucomatous damage most sensitively. High frequencies of 100-300 Hz also contain information that differentiates glaucoma from normal and thus should be included in the analysis.

Purpose: To report the clinical case of a 65-year-old male who developed retinal dysfunction following cobalt-chromium toxicity., Methods: A review of the clinical, haematological, radiological and electrophysiological investigations into a single patient was performed in order to form a case report., Results: A 65-year-old male presented to his ophthalmologist with a 1-year history of worsening vision on the background of a multisystem illness including motor axonopathy, pericardiomyopathy and bulbar palsy. His medical history included hypertension, hypercholesterolaemia and a metallic hip prosthesis. Ocular examination revealed significantly reduced visual acuity bilaterally along with very poor colour vision. Cornea, fundi and optic discs all appeared normal. Bilateral moderate nuclear sclerosis was noted. Basic investigations including mitochondrial studies, auto-immune screen and MRI of brain were unremarkable. Further investigations showed significantly elevated plasma cobalt and chromium levels. Electrophysiological studies revealed an abnormality in all phases of the ERG including a negative b-waveform, suggestive of inner retinal pathology. Following subsequent revision of the hip, cobalt and chromium levels decreased and the patient's vision improved. Further electrophysiological testing indicates a persistent ERG abnormality despite a significant improvement in both the patient's visual acuity and colour vision., Conclusions: These results suggest that cobalt-chromium toxicity can cause inner retinal dysfunction.

Oscillatory potentials (OPs) are typically isolated from the electroretinogram (ERG) via linear, time-invariant, bandpass filtering. The use of a highpass cutoff frequency that is too low results in a- and b-wave contamination of the OP signal, while a cutoff frequency that is too high removes significant OP signal energy. Two methods for automated highpass cutoff frequency estimation were developed and evaluated. An OP amplitude analysis method exploited a trend in variation of maximum OP amplitude with cutoff frequency. A second method fit a time-varying exponential model to the rising edge of the b-wave and selected a cutoff frequency based on minimizing the error between the residual ERG signal (the signal formed by subtracting the OP signal from the original ERG signal) and the exponential fit. The performance of each method was evaluated at 11 luminances (0.001-100 scot cd · s/m(2)) in ten wild-type adult mice by comparing the automated selections to expert-selected highpass cutoff frequencies. It was noted that cutoff frequency selection was not critical at the lower luminance levels, but strongly influenced the OP signal shape for higher luminances. At the highest luminance, errors between the OP amplitude and exponential model versus expert selection were -6.3 ± 13 and -8.2 ± 7.3 Hz, respectively. ANOVAs showed that estimations made by the OP amplitude analysis method were generally statistically indistinguishable from the expert identifications. Furthermore, both OP amplitude analysis and exponential fitting error analysis provided excellent fits to the manual selections for the four highest stimulus luminance values.

The red-spotted newt, Notophthalmus viridescens, is one of few adult vertebrate organisms that has retained the remarkable ability to regenerate a complete retina following injury or removal. The aim of this study was to develop a non-invasive method to monitor recovery of components within the retinal circuitry, in vivo, following surgical removal (retinectomy) of the adult newt retina. A novel and reproducible protocol was established for full-field electroretinography in the intact newt retina. Electroretinograms (ERGs) were measured at the corneal surface. The effects of dilation and external body temperature on the ERG amplitudes were measured as well as the reproducibility in recording ERGs in the same animal over time. Retinectomies were conducted on 15 newts, and the a- and b-wave amplitudes were measured prior to retinectomy and at various timepoints after retinectomy. Surgical removal of the retina resulted in an initial loss of ERG a- and b-waves, representing loss of photoreceptor cells and cells of the inner nuclear layer. The ERG amplitudes recovered to baseline levels by 15 weeks post-retinectomy, indicative of subsequent restoration of retinal function after regeneration.

The purpose of this study was to report a patient with acute zonal occult outer retinopathy (AZOOR) unilaterally, who received steroid pulse therapy. A 42-year-old woman presented with photopsias and severe vision loss in her left eye. Visual acuity was 0.04, and Humphrey visual field testing showed overall depression with a mean deviation (MD) value of -25.78 dB in the left eye. Fundus and angiographic examinations found no specific abnormal findings, leading to a diagnosis of AZOOR. Optical coherence tomography showed attenuation of the photoreceptor inner segment/outer segment junction (IS/OS) line. Focal macular electroretinography (fmERG) demonstrated that there were non-detectable responses at 5°, 10° and 15° (in diameter). Following steroid pulse therapy, her visual acuity was 1.0, her MD value improved to -16.08 dB, and there were both partial recovery of the IS/OS line and apparent improvements of fmERG responses (at 10° and 15°). The present findings suggest that steroid pulse therapy might potentially be an effective treatment in some AZOOR patients.

The antiepileptic drug vigabatrin is known to cause retinal and visual dysfunction, particularly visual field defects, in some patients. Electroretinography (ERG) is used in an attempt to identify adverse effects of vigabatrin (VGB) in patients who are not candidates for conventional perimetry. We report data from 114 pediatric patients taking VGB referred for clinical evaluation; median age at test was 22.9 (2.4 to 266.1) months, and median duration of VGB use was 9.7 (0.3 to 140.7) months. Twenty-seven of them were tested longitudinally (3 to 12 ERG tests). ERG responses to full-field stimuli were recorded in scotopic and photopic conditions, and results were compared to responses from healthy control subjects. We found that abnormalities of photoreceptor and post-receptor ERG responses are frequent in these young patients. The most frequently abnormal scotopic parameter was post-receptor sensitivity, log σ, derived from the b-wave stimulus-response function; the most frequently abnormal photopic parameter was the implicit time of the OFF response (d-wave) to a long (150 ms) flash. Abnormal 30-Hz flicker response amplitude, previously reported to be a predictor of visual field loss, occurred infrequently. For the group as a whole, none of the ERG parameters changed significantly with increasing duration of VGB use. Four of the 27 patients tested longitudinally showed systematic worsening of log σ with duration of VGB use. In a subset of patients who underwent perimetry (N = 39), there was no significant association of any ERG parameter with visual field defects. We cannot determine whether the ERG abnormalities we found were due solely to the effects of VGB. We caution against over-reliance on the ERG to monitor pediatric patients for VGB toxicity and recommend further development of a reliable test of peripheral vision to supplant ERG testing.

To refine methods of electroretinographical (ERG) recording for the analysis of low retinal potentials under scotopic conditions in advanced retinal degenerative diseases. Standard Ganzfeld ERG equipment (Diagnosys LLC, Cambridge, UK) was used in 27 healthy volunteers (mean age 28 ± SD 8.5 years) to define the stimulation protocol. The protocol was then applied in clinical routine and 992 recordings were obtained from patients (mean age 40.6 ± 18.3 years) over a period of 5 years. A blue stimulus with a flicker frequency of 9 Hz was specified under scotopic conditions to preferentially record rod-driven responses. A range of stimulus strengths (0.0000012-6.32 scot. cd s/m² and 6-14 ms flash duration) was tested for maximal amplitudes and interference between rods and cones. Analysis of results was done by standard Fourier Transformation and assessment of signal-to-noise ratio. Optimized stimulus parameters were found to be a time-integrated luminance of 0.012 scot. cd s/m² using a blue (470 nm) flash of 10 ms duration at a repetition frequency of 9 Hz. Characteristic stimulus strength versus amplitude curves and tests with stimuli of red or green wavelength suggest a predominant rod-system response. The 9 Hz response was found statistically distinguishable from noise in 38% of patients with otherwise non-recordable rod responses according to International Society for Clinical Electrophysiology of Vision standards. Thus, we believe this protocol can be used to record ERG potentials in patients with advanced retinal diseases and in the evaluation of potential treatments for these patients. The ease of implementation in clinical routine and of statistical evaluation providing an observer-independent evaluation may further facilitate its employment.

We report the clinical findings and macular function of a patient with Bietti crystalline dystrophy. A 39-year-old woman reported visual loss in both eyes and nyctalopia. A complete ophthalmological evaluation, retromode imaging, SD-OCT acquisition, MP1 microperimetry, and multifocal electroretinogram (mfERG) were performed. Microcrystalline deposits in the cornea and the retina with retinal pigment epithelial atrophy were observed. Retromode imaging revealed visualization of normal large choroidal vessels, cystoid macular edema, and small defined glistening lesions. SD-OCT showed changes in the outer retina with numerous microcrystalline deposits. Microperimetry showed an absolute scotoma involving the perimacular area but sparing of the fovea. In both eyes, mfERG analysis suggests a dysfunction of pre-ganglionic retinal elements detectable in the 20 central retinal degrees. The genetic characterization showed an homozygous mutation c.772C > T[p.Leu258Phe] in exon 6. Retromode imaging and SD-OCT were useful tools to determine the extent and the localization of the crystals. Microperimetry should allow evaluation of the progression of the macular changes.

The purpose of this study was to investigate the early alterations of retinal function, assessed with electrophysiology, in newly onset type 2 diabetes patients without vascular retinopathy. Seventeen patients with newly diagnosed type 2 diabetes (duration 7±3 months), without any vascular retinopathy in fundus photographs, were examined with full-field electroretinogram (ERG) and multifocal ERG (mfERG). The results were compared with those of age-matched subjects without diabetes. In the dark-adapted full-field ERG, the a-wave and the 30-Hz flicker implicit times were delayed in diabetes patients compared to controls, P=0.001 and P=0.020. In the first-order kernel of the mfERG, the first positive wave, P1, was delayed in all areas measured. The electrophysiological examinations demonstrate early alterations of retinal function characterised by a delayed a-wave implicit time in the dark-adapted full-field ERG, representing the rod signalling, and alterations in the multifocal ERG reflecting cone and/or postreceptoral function.

A 34-year-old man presented with reduction and distortion of vision in both the eyes. The best-corrected vision was 20/20 parts, N6 in either eye. The external and slit lamp examination of both the eyes was unremarkable. The fundus examination showed multiple intraretinal crystalline deposits at the posterior pole, extending up to midperiphery, tortuous retinal blood vessels with S-shaped deflections, and absent foveal reflex in both the eyes. There were no corneal crystals, and the color vision was defective in both the eyes. Fundus autofluorescence and fundus fluorescein angiogram (FFA) were suggestive of geographic areas of retinal pigment epithelium (RPE) and choriocapillary (CC) loss. OCT revealed subfoveal neurosensory detachment. Flash ERG and EOG were normal except for a slight decrease in amplitude and delay in latency of pattern ERG waveforms. The Humphrey's visual field showed paracentral scotoma with reduction in the amplitude of waveforms from the corresponding area in the multifocal ERG in both the eyes. Systemic evaluation for crystalline retinopathy was unremarkable. He was diagnosed to be a case of Bietti crystalline retinopathy (local/regional variant). The subfoveal neurosensory detachment could represent early RPE dysfunction caused by these crystals and could account for the mild visual disturbance in both the eyes. Retinal vascular tortuosity and neurosensory detachment seen in this case is the first time to be reported in literature.

Purpose: To present a case of melanoma-associated retinopathy (MAR) associated with an intranasal melanoma., Case Report: A 77-year-old Japanese man visited us complaining of night blindness, blurred vision, and color vision difficulties in both eyes. His best-corrected visual acuity was 0.7 in the right and 1.0 in the left eyes. The rod response of the electroretinogram (ERG) was abolished, and the maximum response had a negative waveform. The a-wave of the single-flash cone response was square shaped, and the b-wave was delayed. The ON-response of the long-flash cone ERG was absent, but the OFF-response was preserved. A severe loss of retinal sensitivity was detected by static perimetry. Positron emission tomography showed no abnormal signs. Six months after the initial examination, an intranasal tumor was detected and surgically removed. The final diagnosis based on histopathology was malignant melanoma., Conclusion: Our case demonstrates that MAR can be associated with an intranasal mucosal melanoma. Thus, in cases where the primary lesion cannot be identified in patients with MAR-like symptoms and signs, we recommend that preferential sites of mucosal melanomas be examined.

The effects of chloroquine intake on the retinal function in a Brazilian population of patients were assessed by multifocal electroretinography. Twenty-four randomly chosen eyes of patients treated with chloroquine for rheumatoid arthritis and systemic lupus erythematosus were examined using multifocal electroretinography (mfERG). Control measurements were acquired from 21 randomly chosen eyes of age-matched healthy subjects. None of the study participants had an inherited retinal disease or a Snellen visual acuity reduced to less than 20/40. In patients and control subjects, cumulative chloroquine dose, total daily dose, duration of treatment, retinal examination, visual field defects, visual acuity, and the mfERG were assessed. The average amplitudes and implicit times of the N1, P1, and P2 components of the mfERGs were measured in the central hexagon (R1) and in five rings (R2-R6). The values measured in patients and normal subjects were compared. The P1 amplitudes in R2 were significantly decreased in the patients. In addition, the amplitudes of N1 and N2 in R1 were significantly smaller in the patients. The implicit times of none of the components were significantly different between patients and controls. The response amplitude was not significantly correlated with cumulative dose and duration of intake. There was no correlation with retinal appearance, visual field, and visual acuity. In agreement with earlier data, the central mfERG amplitudes were decreased in chloroquine patients indicating functional alterations in the retina. These changes are also present in a Brazilian population suggesting that the effects of chloroquine are general and that genetic background and life circumstances probably have, if at all, only little effect.

The intent of our study was to evaluate whether the response to a long-duration white stimulus in the multifocal electroretinogram (mfERG) is sufficiently sensitive to detect early retinal dysfunction in glaucoma. On-off mfERGs were recorded from 15 NTG and 15 HTG patients and compared with 14 control subjects. Recording parameters were the following: LED stimulus screen (RETIscan™), 100-ms stimulus duration, 200-ms stimulus interval, 11-min total recording time, stimulus matrix of 61 elements, frame rate: 70 Hz, Lmax: 180 cd/m(2), Lmin: 0 cd/m(2), and filter setting: 1-200 Hz. The second negative response following stimulus onset (N2-on), as well as following stimulus offset (N2-off), was analyzed as an overall response and in quadrants, as well as in 4 small central and four adjoining peripheral areas per quadrant. The latency of the N2-on was significantly delayed in HTG in all response averages tested, while in NTG this was only seen in the overall response and in the small central response averages (P < 0.05). The most sensitive measure in HTG was the latency of the N2-on of the small peripheral response average of the superior temporal quadrant with an area under the ROC curve of 0.881. For NTG, the most representative measure was the latency of the N2-on of the small central response average of the inferior nasal quadrant with an area under the ROC curve of 0.793. Our results showed that in stimulation with long-duration flashes, the second negative response following the on response, representative of the early PhNR, is affected in glaucoma where N2-on showed a latency delay in POAG patients. The latency delay of the N2-on was more prominent for HTG than for NTG.

The purpose of this study was to evaluate the efficacy of topical dorzolamide 2% eye drops on macular function and thickness in a case of enhanced S-cone syndrome (ESCS). A 24-year-old Asian man with enhanced S-cone syndrome treated with topical dorzolamide in the left eye participated in the study. Examinations performed before and during treatment were included visual acuity (VA), contrast sensitivity measured with briefly presented grating targets (grating CS) and the Pelli-Robson chart (P-R CS), microperimetry (MP), and spectral-domain optical coherence tomography (SD-OCT). Following 4 months of treatment, the mean thickness of the central 1-mm foveal subfield of the left eye, as measured by SD-OCT, decreased from 551 to 242 μm. Mean MP sensitivity within the central 12 degrees (28 points) increased from 9.4 dB at baseline to 11.2 dB. Although Pelli-Robson contrast sensitivity improved only minimally in the left eye, grating contrast sensitivity improved by more than a factor of two. Mean log MAR VA was 0.22 OD and 1.00 OS (at baseline), which improved to 0.10 OD and 0.66 OS after 4 months of treatment. The results indicate that in our patient with enhanced S-cone syndrome, treatment with topical dorzolamide was effective in improving macular thickness, VA, microperimetry sensitivity, and grating contrast sensitivity. These measures of retinal structure and function are sensitive tools for evaluating the effects of treatment in enhanced S-cone syndrome patients with cystoid macular edema. Further investigation is warranted to assess the relationships among visual performance for daily activities, visual sensitivity, and macular thickness.