Acuity VEP: improved with machine learning Abstract Purpose Acuity-VEP approaches basically all use the information obtained across a number of check sizes (or spatial frequencies) to derive a measure of acuity. Amplitude is always used, sometimes combined with phase or a noise measure. In our approach, we employ steady-state brief-onset low-contrast checkerboard stimulation and obtain amplitude and significance for six different check sizes, yielding 12 numbers. The rule-based “heuristic algorithm” (Bach et al. in Br J Ophthalmol 92:396–403, 2008. https://doi.org/10.1136/bjo.2007.130245) is successful in over 95% with a limit of agreement (LoA) of ± 0.3LogMAR between behavioral and objective acuity for 109 cases. We here aimed to test whether machine learning techniques with this relatively small dataset could achieve a similar LoA. Methods Given recent advances in machine learning (ML), we applied a wide class of ML algorithms to this dataset. This was done within the “caret” framework of R using altogether 89 methods, of which rule-based and multiple regression approaches performed best. For cross-validation, using a jackknife (leave-one-out) approach, we predicted each case based on an ML model having been trained on all remaining 108 cases. Results The ML approach predicted visual acuity well across many different types of ML algorithms. Using amplitude values only (discarding the p values) improved the outcome. Nearly half of the tested ML algorithms achieved an LoA better than the heuristic algorithm; several “Random Forest”- or “multiple regression”-type algorithms achieved an LoA of below ± 0.3. In the cases where the heuristic approach failed, acuity was predicted successfully. We then applied the ML model trained with the Bach et al. [1] dataset to a new dataset from 2018 (78 cases) and found both for the heuristic algorithm and for the ML approach an LoA of ± 0.259, a nearly one-line improvement. Conclusions The ML approach appears to be a useful alternative to rule-based analysis of acuity-VEP data. The achieved accuracy is comparable or better (in no case the ML-based acuity differed more than ± 0.29 LogMAR from behavioral acuity), and testability is higher, nearly 100%. Possible pitfalls are examined.

Visual evoked and event-related brain potentials in HIV-infected adults: a longitudinal study over 2.5 years Abstract Purpose The aim of this neurophysiological study was to monitor changes in the visual and cognitive function of HIV-infected patients treated with combination antiretroviral therapy. Methods Eleven adult Czech HIV+ patients, with a mean age of 35 years and CD4 cell count ≥ 230 × 106 cells/L of blood at the time of enrollment, underwent four to six examinations over the course of 2.5 years to evaluate pattern-reversal and motion-onset visual evoked potentials (P-VEPs and M-VEPs), visually driven oddball event-related potentials (ERPs) and Montreal Cognitive Assessments. In addition to evaluating the intraindividual change in the observed parameters, we also compared patient data to data from eleven age- and gender-matched controls. Results We did not find any significant differences in P-VEPs between the patients and controls or in the paired comparison of the first and last visit. The only significant finding for P-VEPs was a linear trend in prolongation of the 20′ P-VEP P100 peak time. In M-VEPs, we found a significant intergroup difference in the N160 peak time recorded during the first visit for peripheral M-VEPs only. During the last visit, all N160 peak times for patients differed significantly from those of the control group. The only intervisit difference close to the level of significance was for peripheral M-VEPs, which confirmed the trend analysis. No significant differences between patients and controls were found in the ERPs, but the P300 peak time showed a significant difference between the first and last visits, as confirmed by the trend. Patient reaction time was not significantly delayed at the first visit; however, it was prolonged with time, as confirmed by the trend. Conclusion Our aim was to evaluate whether antiretroviral treatment in HIV+ patients is sufficient to preserve brain visual function. The optic nerve and primary visual cortex function tested by the P-VEPs seem to be preserved. The prolongation of the M-VEPs suggests an individually detectable decline in CNS function, but these changes did not show a progression during the follow-up. From a longitudinal perspective, the trends in peak time prolongation of the 20′ P-VEP, peripheral M-VEP, ERP and reaction time suggest a faster decline than that caused by aging in healthy populations, as previously described in a cross-sectional study.

Full-field electroretinography, visual acuity and visual fields in Usher syndrome: a multicentre European study Abstract Purpose Usher syndrome (USH) is a multisensory deficiency involving vision, hearing and the vestibular system. The purpose of this study is to report on the functional data (i.e. electroretinography, visual fields, visual acuity) of patients with retinitis pigmentosa (RP) due to Usher syndrome that were collected in a multicentre European study (TREATRUSH). Methods A total of 268 genetically confirmed USH patients underwent electrophysiological examinations in the context of multimodal ophthalmological examination in the study (75 USH1, 189 USH2 and four USH3). Full-field electroretinography (ERG) was performed according to ISCEV standards, visual field determination was carried out with either the Octopus or Goldmann perimeters and visual acuity was examined with either ETDRS or Snellen charts. The data were compared between USH subtypes (USH1/USH2/USH3) and correlated with age. Results Visual acuity decreases significantly with age for both USH1 and USH2 (p < 0.001), without a difference between the two cohorts. When corrected for age, the preserved kinetic visual field was significantly larger in USH2 than in USH1 (p = 0.04). Furthermore, the preserved kinetic visual field area showed a significant decrease with age (based on an exponential fit) in both USH1 and USH2 (p < 0.001). In USH1 patients, however, the visual field was already vastly reduced at an early age. The ERG results were abnormal in all patients. Detectable data for scotopic ERG were obtained from nine patients, and data of photopic ERG were obtained from 24 patients, without a difference between USH1 and USH2 subtypes. Conclusions There are differences in the phenotypes of RP in USH subtypes, most visible in the progression of visual fields between USH1 and USH2. The perimetric reduction occurs earlier in USH1 than in USH2. In both subtypes, visual acuity decreases significantly with age and the ERG is not detectable already at early ages.

Objective and quantitative assessment of visual acuity and contrast sensitivity based on steady-state motion visual evoked potentials using concentric-ring paradigm Abstract Purpose The traditional assessment of visual acuity and contrast sensitivity depends more on subjective judgments. Steady-state motion visual evoked potentials (SSMVEPs) can provide an objective and quantitative method to evaluate visual functions such as visual acuity and contrast sensitivity. Here, we explored the possibility of objective SSMVEP visual acuity and contrast sensitivity testing, and compared its performance with that of psychophysical methods. Methods In this study, we designed a specific concentric ring with oscillating expansion and contraction SSMVEP paradigm to assess visual acuity and contrast sensitivity. By changing the parameters of the paradigm, the SSMVEP paradigm with different contrasts and spatial frequencies corresponding to different visual acuity and contrast sensitivity was designed. Moreover, we proposed a threshold determination criterion to define the corresponding objective SSMVEP visual acuity and contrast sensitivity. Results We tested visual acuity and contrast sensitivity of sixteen healthy adults utilizing this paradigm with an electroencephalography system. Our data suggested that there was no significant difference between objective visual acuity and contrast sensitivity measurements based on the SSMVEPs and subjective psychophysical ones. Conclusion Our study proved that SSMVEPs can be an objective and quantitative method to measure visual acuity and contrast sensitivity.

Can VEP-based acuity estimates in one eye be improved by applying knowledge from the other eye? Abstract Purpose It is desirable to make VEP-based acuity estimates match standard subjective acuity numerically, as the latter is familiar to ophthalmologists and optometrists. This is achieved by applying an empirical conversion factor, and previous studies found the resulting values to be within ±1 octave of subjective acuity. This leaves room for improvement. In the present study, we tested for the case of a monocular acuity deficit whether the known difference between subjective and objective acuity in the trusted fellow eye can be used to get a more precise objective estimate in the eye of which the acuity is to be estimated. In other words, we tested whether it would make sense to determine a patient-specific conversion factor. Methods In 19 subjects, we obtained monocular objective and subjective acuity estimates with both eyes. Normal vision and artificially degraded vision were tested. Subjective acuity was taken as the veridical value. We computed the differences between objective and subjective acuity and reasoned that if these were correlated between eyes and acuity levels, the valid information from the trusted healthy eye could be used to improve the precision of the acuity estimate in the other, potentially impaired, eye. Results The difference between objective and subjective acuity values was neither correlated significantly between eyes, nor was it correlated significantly between acuity levels. Conclusions Knowledge about the discrepancy between objective and subjective acuity values in one eye does not help improving the accuracy of acuity estimates in the other eye. The lack of a significant correlation between eyes even at the same acuity level suggests that a major part of the discrepancies between subjective acuity and VEP-based acuity is not the result of factors that would equally apply to both eyes, such as cortical morphology.

Electrophysiological and pupillometric measures of inner retina function in nonproliferative diabetic retinopathy Abstract Purpose To evaluate three measures of inner retina function, the pattern electroretinogram (pERG), the photopic negative response (PhNR), and the post-illumination pupil response (PIPR) in diabetics with and without nonproliferative diabetic retinopathy (NPDR). Methods Fifteen non-diabetic control subjects and 45 type 2 diabetic subjects participated (15 have no clinically apparent retinopathy [NDR], 15 have mild NPDR, and 15 have moderate/severe NPDR). The pERG was elicited by a contrast-reversing checkerboard pattern, and the PhNR was measured in response to a full-field, long-wavelength flash presented against a short-wavelength adapting field. The PIPR was elicited by a full-field, 450 cd/m2, short-wavelength flash. All responses were recorded and analyzed using conventional techniques. One-way ANOVAs were performed to compare the pERG, PhNR, and PIPR among the control and diabetic groups. Results ANOVA indicated statistically significant differences among the control and diabetic subjects for all three measures. Holm-Sidak post hoc comparisons indicated small, nonsignificant reductions in the pERG (8%), PhNR (8%), and PIPR (10%) for the NDR group compared to the controls (all p > 0.25). In contrast, there were significant reductions in the pERG (35), PhNR (34%), and PIPR (30%) for the mild NPDR group compared to the controls (all p < 0.01). Likewise, there were significant reductions in the pERG (40%), PhNR (32%), and PIPR (32%) for the moderate/severe NPDR group compared to the controls (all p < 0.01). Conclusion Abnormalities of the pERG, PhNR, and PIPR suggest inner retina neural dysfunction in diabetics who have clinically apparent vascular abnormalities. Taken together, these measures provide a noninvasive, objective approach to study neural dysfunction in these individuals.

Central and peripheral steady-state visual evoked potentials in children with optic pathway gliomas Abstract Purpose Treatment of optic pathway gliomas is prompted by neuroradiological evidence of tumor growth, usually associated with progressive visual loss. Despite therapy, approximately 40% will show visual deterioration. Treatment outcome is largely based on the preservation of vision. However, current visual function assessment is often unreliable in children with optic pathway gliomas who have limited collaboration. Thus, there is a need for new clinical tools to evaluate visual functions in these children. The aim of the study was to assess the value of steady-state visual evoked potentials as a tool to assess function in the central and peripheral visual fields of children with optic pathway gliomas. Method Ten patients with optic pathway gliomas and 33 healthy controls (ages 3 to 18 years) were tested using steady-state visual evoked potentials. The dartboard stimulus consisted of one central circle alternating at 16 reversals/s and one peripheral hoop alternating at 14.4 reversals/s, separated by a hoop of gray space. It was presented monocularly at 30% and 96% contrasts. Results Results indicated that central signal-to-noise ratios were significantly lower in children with optic pathway gliomas compared to controls. However, no significant group difference was detected in the peripheral visual field. Conclusion Steady-state visual evoked potentials could eventually be implemented in the clinical assessment and follow-up of central visual field deficits in uncooperative or nonverbal children but seem to have limited usefulness for evaluation of peripheral visual field deficits. Additional studies are needed to identify testing parameters for full visual field assessment.

Electrophysiological measures of dysfunction in early-stage diabetic retinopathy: No correlation between cone phototransduction and oscillatory potential abnormalities Abstract Purpose To define the relationship between abnormalities in the activation phase of cone phototransduction and the oscillatory potentials (OPs) of the light-adapted electroretinogram in diabetics who have mild or no retinopathy. Methods Subjects included 20 non-diabetic controls and 40 type-2 diabetics (20 had no clinically apparent diabetic retinopathy [NDR] and 20 had mild nonproliferative DR). Single flash responses for a series of stimulus retinal illuminances were measured under light-adapted conditions using conventional techniques. The a-waves of the responses were fit with a delayed Gaussian model to derive Rmp3 (maximum amplitude of the massed photoreceptor response) and S (phototransduction sensitivity). OPs were extracted from the responses by conventional band-pass filtering. Results Analysis of variance (ANVOA) indicated that both diabetic groups had significant OP amplitude and S reductions compared to the controls, whereas Rmp3 did not differ significantly among the groups. Although log OP amplitude and log Rmp3 were significantly correlated for the control subjects for each flash retinal illuminance (all r > 0.49, p < 0.03), log OP amplitude and log Rmp3 were not correlated for either diabetic group for any flash retinal illuminance (all r ≤ 0.36, p ≥ 0.13). Log OP amplitude and log S were generally not correlated significantly for the control or diabetic groups. Conclusion OP amplitude losses do not appear to be related to reduced cone sensitivity in early-stage diabetic retinopathy. This suggests that diabetes may separately affect cone function, as evidenced by cone phototransduction sensitivity losses, and inner-retina function, as evidenced by OP amplitude losses.

Rathke’s cleft cyst presenting as incomplete cavernous sinus syndrome and disc edema: a case report with literature review Abstract Purpose To report a Rathke’s cleft cyst (RCC) presenting as unilateral incomplete cavernous sinus syndrome and disc edema Method Case report with literature review Results We present an 18-year-old girl who has been experiencing intermittent binocular diplopia for 1 month. Upon examination, the best corrected visual acuity was 20/20 (OU). Pronounced limitation of ocular motility with ptosis in her right eye was noted. Her pupil constricted normally. However, a relative afferent pupillary defect in the right eye was observed. Fundus examination showed disc edema in the right eye without peripapillary hemorrhage. Moreover, her thyroid function and acetylcholine receptor antibody levels were normal. Brain magnetic resonance imaging revealed a 1.6-cm mass at the suprasellar fossa and optic nerve sheath of right eye enhancement. She underwent transsphenoidal surgery, and pus-like formation was noted. Pathological findings were consistent with RCCs. After the cyst was removed, her ocular motility remarkably improved and ptosis subsided. Conclusion A case of RCC presenting as multiple cranial nerve palsy was reported. RCCs are benign and usually asymptomatic. Symptomatic RCCs often manifest as headache or visual problems, such as reduced visual acuity and visual field defect. Multiple cranial nerve involvement is uncommon and indicates inflammation or compression of the cavernous sinus and optic nerve. Neuropathy may resolve after surgery; therefore, surgery is indicated for symptomatic RCCs. Further, RCC should be included in the differential diagnosis of patients with disc edema.

Use of diffusing filters for artificially reducing visual acuity when testing equipment and procedures Abstract Purpose When evaluating ophthalmological devices and procedures, for instance those for visual electrophysiology, it is often desirable to perform tests with reduced acuity. Doing this with individuals with actual visual impairments has a number of disadvantages, such as considerable recruitment efforts, especially when a specific acuity range is targeted, and little control about the actual perceptual characteristics of the impairment, which are normally not fully known. Lenses with positive diopters or blurring filters that are placed in front of the eyes of visually normal observers promise a simple solution to the problem. However, defocus results in considerable spurious resolution, and previous studies suggest that the frequently used Bangerter occluders are not optimal for the purpose. The present study therefore reviews a number of other options and tests a selection of filters with respect to their effect on acuity and contrast sensitivity with the aim of identifying filters that primarily degrade acuity while mostly sparing contrast sensitivity. Methods First, we screened several filters for potential usefulness. The Freiburg Acuity and Contrast Test was then used to measure visual acuity and contrast sensitivity with a subset of three filters (Luminit LSD 0.5° and 1°, and LEE 420) and, for comparison, with a Bangerter occluder with a nominal acuity grade of 0.1. A qualitative comparison of the filters’ effect on the checkerboard-reversal VEP was also performed. Results With both Luminit filters, variability in acuity across participants was relatively small, and at least with the 0.5° version, contrast sensitivity was relativity little affected. The LEE filter and the Bangerter occluder resulted in more variability and, compared to the effect on acuity, a relatively strong reduction in contrast sensitivity. Comparing the Luminit 0.5° and 1° filters, the reduction of acuity was not proportional to physical stimulus degradation. The effect on VEP responses was consistent with the psychophysical data. Conclusions The Luminit filters, which have a Gaussian light diffusion profile, appear to be a good choice for artificial reduction of acuity.