Glaucoma is a chronic, progressive eye disease affecting the optic nerve, which may cause visual damage and blindness. In this study, we present a machine-learning investigation to classify patients with glaucoma (case group) with respect to normal participants (control group). We examined 172 eyes at the Ophthalmology Clinic of the \"Elpis\" General Hospital of Athens between October 2022 and September 2023. In addition, we investigated the glaucoma classification in terms of the following: (a) eye selection and (b) gender. Our methodology was based on the features extracted via two diagnostic optical systems: (i) conventional optical coherence tomography (OCT) and (ii) a modern RETeval portable device. The machine-learning approach comprised three different classifiers: the Bayesian, the Probabilistic Neural Network (PNN), and Support Vectors Machines (SVMs). For all cases examined, classification accuracy was found to be significantly higher when using the RETeval device with respect to the OCT system, as follows: 14.7% for all participants, 13.4% and 29.3% for eye selection (right and left, respectively), and 25.6% and 22.6% for gender (male and female, respectively). The most efficient classifier was found to be the SVM compared to the PNN and Bayesian classifiers. In summary, all aforementioned comparisons demonstrate that the RETeval device has the advantage over the OCT system for the classification of glaucoma patients by using the machine-learning approach.

OBJECTIVE: To investigate the objective function of the inner retinal layer in each stage of primary open angle glaucoma (POAG) using the photopic negative response (PhNR) measured by RETeval full-field electroretinography (ERG), and to identify which PhNR parameter is the most useful.
METHODS: Ninety eyes of 90 patients with POAG (30 with mild POAG (mean deviation (MD) ≥ -6 dB) and 60 with moderate-to-advanced POAG (MD < -6 dB)) and 76 eyes of 76 control cases were examined. We investigated six PhNR parameters and their relationships with the results of the Humphrey 30-2 visual field test and the thickness of the circumpapillary retinal nerve fiber layer (cpRNFL) obtained from optical coherence tomography. The following PhNR parameters were assessed: base-to-trough (BT), peak-to-trough (PT), 72msPhNR, the W-ratio, P-ratio, implicit time (IT), and a-wave and b-wave amplitudes on ERG.
RESULTS: All PhNR parameters other than IT significantly differed between the all POAG (all stages) and control groups and between the moderate-to-advanced POAG and control groups. BT and 72msPhNR in the mild POAG group, significantly differed from those in the control group. Regarding the relationships between PhNR parameters and the visual field and between these parameters and cpRNFL thickness, correlations were observed between all PhNR parameters, except PT and IT, and both the visual field and cpRNFL thickness in the all and moderate-to-advanced POAG groups. 72msPhNR correlated with cpRNFL thickness in the mild POAG group. The area under the receiver operating characteristic curve was greater for BT than for the other PhNR parameters in both the mild and moderate-to-advanced POAG groups. The discriminant linear function for examining the presence or absence of POAG and the threshold for diagnosis were quantitatively obtained as follows. Regarding BT: discriminant = 0.505 × BT + 2.017; threshold = positive for POAG, negative for no POAG; correct answer rate = 80.7%. Concerning 72msPhNR: discriminant = 0.533 × 72msPhNR + 1.553; threshold = positive for POAG and negative for no POAG; correct answer rate = 77.1%.
CONCLUSIONS: RETeval-measured PhNR parameters were useful for an objective evaluation of visual function in moderate-to-advanced POAG. BT appeared to be the most diagnostically useful parameter.

To report abnormal full-field electroretinograms (ERGs) in a patient with cystoid macular edema (CME) induced by systemic paclitaxel.
This is an observational case report. Full-field ERGs were recorded to evaluate the retinal function using the RETeval system and conventional ERGs using contact lens electrodes with built-in white light-emitting diodes. Optical coherence tomography (OCT) was also used to assess the retinal morphology.
A 70-year-old man, who was diagnosed with gastric cancer, had undergone gastrectomy. Subsequently, systemic paclitaxel was administered once a week as an adjuvant therapy. After the tenth course of paclitaxel, he experienced blurred vision in both eyes and visited our department of ophthalmology. OCT revealed the presence of CME in both eyes, and the RETeval flicker ERGs showed a marked reduction in the amplitudes and a prolongation of the implicit times in both eyes. Conventional ERGs showed that the amplitudes of the oscillatory potentials (OPs) were also severely attenuated. The abnormal OCT findings and reduced visual acuity recovered to normal at 1 and 2 months, respectively, after the discontinuation of paclitaxel. However, the flicker ERGs did not recover to normal values until 4 months after the discontinuation of paclitaxel.
These results suggest that the ERGs can be used to monitor the changes in the overall retinal function in patients receiving paclitaxel.

The study reports a case with metastatic cutaneous malignant melanoma that developed Vogt-Koyanagi-Harada-like uveitis during pembrolizumab treatment. The uveitis improved by discontinuation of pembrolizumab and use of oral and topical steroids. Full-field flicker ERGs were used to monitor the retinal function before and after the steroid treatments.
A 68-year-old women presented with blurred vision in both eyes 3 months after beginning pembrolizumab adjuvant therapy for a malignant melanoma on the lower thigh. Optical coherence tomography showed a serous retinal detachment (SRD) in the right eye and marked choroidal thickening in both eyes. Fluorescein angiography showed spotted hyperfluorescence in the right eye and leakage of fluorescein from both optic disks. Indocyanine green angiography showed dark hypofluorescent spots in both eyes. She was diagnosed with Vogt-Koyanagi-Harada-like uveitis induced by pembrolizumab and discontinued the pembrolizumab. She was then treated with oral prednisolone and topical betamethasone. One week later, the symptoms were improved, and 1 month later the choroidal thickening in both eyes and the SRD of the right eye were not present. The implicit time of the full-field flicker ERGs recorded by RETeval system was significantly delayed at the initial examination but improved within a few weeks after the steroid replacement treatment.
Our case with Vogt-Koyanagi-Harada-like uveitis induced by pembrolizumab had a reduction in the degree of uveitis after discontinuation of the pembrolizumab and use of oral prednisolone and topical betamethasone. Flicker ERGs were helpful in monitoring the retinal function before and after the steroid treatment.

BACKGROUND: A new handheld electroretinographic (ERG) recording system can record ERGs without mydriasis. However, this RETeval system cannot record ERGs from both eyes simultaneously. Thus, the purpose of this study was to determine whether the sequence of the ERG recordings will alter the results.
METHODS: We studied 30 eyes of 30 healthy subjects. The flicker ERGs were recorded with the RETeval system without mydriasis and were elicited by 8, 16 and 32 photopic Td-s. The flicker ERGs were recorded at two sessions. Session 1, the ERGs were recorded from the right eye and then the left eye, and Session 2, ERGs were recorded from the left eye then the right eye. We compared the implicit times, amplitudes and pupil diameters of the right eye between these two sessions.
RESULTS: The implicit time of the flicker ERGs was significantly shorter (p < 0.001), and the pupil diameters were significantly smaller (p = 0.013) at Session 2 than Session 1 but only for the lower stimulus intensity of eight Td-s. There was a significant correlation of the differences in the implicit times and the differences in the pupil diameter between the two sessions (r = 0.406, p = 0.026).
CONCLUSIONS: The results indicate that the implicit times of the fundamental components of RETeval flicker ERGs can be affected by the sequence of recordings for lower stimulus intensities. This was most likely due to the differences of the pupil diameter during the recordings. We recommend that stronger stimuli be used to record the RETeval flicker ERGs to minimize the effects of the sequence of recordings.

To determine whether there is a significant correlation between the amplitude of the photopic negative response (PhNR) and the peripapillary retinal nerve fiber layer thickness (pRNFLT) in eyes of young, healthy subjects.
We analyzed 136 eyes of 136 young, healthy subjects (89 males and 47 females; age, 20-29 years). The PhNRs were recorded with the RETeval system without mydriasis using red flashes on a blue background. PhNR amplitude was measured at two points: at 72 ms (P72) and at the negative trough following the b-wave (Pmin). Univariate and multivariable linear regression analyses were performed to identify the independent variables that were significantly correlated with P72 and Pmin. The variables included age, sex, axial length, pRNFLT, intraocular pressure (IOP), a-wave amplitude, b-wave amplitude, and pupillary area during the electroretinogram recordings.
The amplitudes of P72 and Pmin were significantly larger in female subjects (P = 0.021 and P = 0.001, respectively). Univariate analyses showed that PhNR amplitudes were significantly correlated with pRNFLT (P72: r = 0.246, P = 0.004; Pmin: r = 0.219, P = 0.011). Female sex was significantly and negatively correlated with P72 (r = -0.206; P = 0.016) and Pmin (r = -0.271; P = 0.001). Multivariable regression analyses showed that greater pRNFLT was an independent factor significantly associated with a larger P72 (r = 0.283; P = 0.004) and Pmin (r = 0.299; P = 0.002). Female sex was an independent factor that was significantly associated with a larger Pmin (r = -0.208; P = 0.022).
These findings indicate that PhNR amplitude is significantly associated with pRNFLT and female sex in young, healthy subjects.
The amplitude of the PhNR recorded with RETeval is smaller in subjects with thinner pRNFLT not only in glaucoma patients but also in young healthy subjects.

To report our findings in a case of lens fragment-induced uveitis associated with supernormal flicker electroretinograms (ERGs) twenty months after the cataract surgery.
This is an observational case report. Full-field flicker ERGs were recorded with the RETeval system. Optical coherence tomography (OCT) and slit-lamp biomicroscopy were used to assess the uveitis during the follow-up period.
A 70-year-old man, who had undergone cataract surgery 20 months earlier, visited our hospital with a complaint of decreased vision in his right eye. Slit-lamp biomicroscopy revealed corneal edema and a lens fragment was detected in the inferior part of the anterior chamber. OCT showed cystoid macular edema, and flicker ERGs showed a marked increase in the amplitude and a delay in the implicit time in the right eye. These abnormalities of the flicker ERGs improved gradually after the removal of lens fragment and application of topical anti-inflammatory medications.
Our case of lens-induced uveitis had supernormal flicker ERG amplitudes. Clinicians should be aware that eyes with uveitis can have larger-than-normal ERG amplitudes.

The anti-epileptic drug vigabatrin is associated with reduction in light-adapted 30-Hz flicker electroretinogram (ERG) amplitude. Ophthalmological assessments, including ERGs, monitor retinal health during vigabatrin treatment. RETeval™ is a hand-held ERG device adapted for dilation-free ERG assessment. To evaluate the usefulness of RETeval™ for vigabatrin ERG assessment, we evaluated intra-visit reliability and clinical feasibility of RETeval™ ERG assessment in children under 3 years of age undergoing vigabatrin treatment.
In this prospective study, children underwent 30-Hz flicker ERG assessment with RETeval™ before routine vigabatrin monitoring including sedated-ERG using the Espion E2 Colour Dome. Intraclass correlation coefficient (ICC) statistics identified the degree of intra-visit reliability from two repeated measurements of the same participant within one testing session. The omega squared (ω2) statistic identified the level of association between RETeval™ and Espion light-adapted 30-Hz flicker responses.
Nine children completed RETeval™ ERG testing. The intra-visit ICCs for the RETeval™ 30-Hz flicker amplitude (µV) were high: 0.81 (right eye) and 0.86 (left eye), while the implicit times (ms) were 0.79 (right eye) and 0.42 (left eye). The RETeval™ 30-Hz flicker amplitude was positively associated with the Espion 30-Hz flicker response (ω2 = 0.71). The Bland-Altman plot showed no bias in the mean difference of amplitudes between the two systems.
This is the first study to assess the utility of RETeval™ device in children under 3 years of age undergoing vigabatrin treatment. RETeval™ demonstrated high intra-visit reliability with responses consistent with the standard Espion ERG. RETeval™ may be beneficial for assessment of retinal toxicity in young children treated with vigabatrin.

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).
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.
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.
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.

To determine if the RETeval system can be used for the screening of diabetic retinopathy (DR) to provide early diagnosis.
The subjects were 42 diabetic patients selectively recruited by examination of their medical records to have varying severities of DR. The severity of DR was classified into four groups according to the International Clinical Diabetic Retinopathy Disease Severity Scale. Full-field electroretinograms (ERG) without mydriasis were obtained by the DR assessment protocol of the RETeval system. Macular retinal nerve fiber layer (RNFL) thickness was measured by optical coherence tomography. We compared the DR assessment protocol results and the macular RNFL thickness among four groups. Moreover, an analysis was conducted on whether there was any correlation among the DR assessment protocol results, duration of diabetes mellitus, and RNFL thickness individually for each group of patients.
The mean ages and mean duration of diabetes mellitus of the four groups were similar. The DR assessment protocol results in the moderate-severe nonproliferative DR, and proliferative DR groups were significantly higher than those in the other groups (p < 0.001). The mean macular RNFL thickness was similar in all groups. No significant correlation was found between the DR assessment protocol results and duration of DM and the RNFL thickness.
Our results suggest that the RETeval full-field ERG system can be used as an adjunctive tool for the mass screening of DR, while macular RNFL thickness would not be useful.