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11 pages, 2175 KB  
Case Report
First Case in Lithuania of an Autosomal Recessive Mutation in the DNAJC30 Gene as a Cause of Leber’s Hereditary Optic Neuropathy
by Liveta Sereikaite, Alvita Vilkeviciute, Brigita Glebauskiene, Rasa Traberg, Arvydas Gelzinis, Raimonda Piskiniene, Reda Zemaitiene, Rasa Ugenskiene and Rasa Liutkeviciene
Genes 2025, 16(9), 993; https://doi.org/10.3390/genes16090993 - 23 Aug 2025
Viewed by 259
Abstract
Background: Leber’s hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and an inherited optic neuropathy. Recently, two different LHON inheritance types have been discovered: mitochondrially inherited LHON (mtLHON) and autosomal recessive LHON (arLHON). Our case report is the first diagnosed case [...] Read more.
Background: Leber’s hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and an inherited optic neuropathy. Recently, two different LHON inheritance types have been discovered: mitochondrially inherited LHON (mtLHON) and autosomal recessive LHON (arLHON). Our case report is the first diagnosed case of arLHON in a patient of Lithuanian descent and confirms the DnaJ Heat Shock Protein Family (Hsp40) Member C30 (DNAJC30) c.152A>G p.(Tyr51Cys) founder variant. Case Presentation: A 34-year-old Lithuanian man complained of headache and sudden, painless loss of central vision in his right eye. On examination, the visual acuity of the right and left eyes was 0.1 and 1.0, respectively. Visual-field examination revealed a central scotoma in the right eye, and visual evoked potentials (VEPs) showed prolonged latency in both eyes. Optical coherence tomography showed thickening of the retinal nerve fiber layer in the upper quadrant of the optic disk in the left eye. Magnetic resonance imaging of the head showed evidence of optic nerve inflammation in the right eye. Blood tests were within normal range and showed no signs of inflammation. Retrobulbar neuritis of the right eye was suspected, and the patient was treated with steroids, which did not improve visual acuity. He later developed visual loss in the left eye as well. A genetic origin of the optic neuropathy was suspected, and a complete mitochondrial DNA analysis was performed, but it did not reveal any pathologic mutations. Over time, the visual acuity of both eyes slowly deteriorated, and the retinal nerve fiber layer (RNFL) thinning of the optic disks progressed. A multidisciplinary team of specialists concluded that vasculitis or infectious disease was unlikely to be the cause of the vision loss, and a genetic cause for the disease was still suspected, although a first-stage genetic test did not yield the diagnosis. Thirty-three months after disease onset, whole-exome sequencing revealed a pathogenic variant in the DNAJC30 gene, leading to the diagnosis of arLHON. Treatment with Idebenone was started 35 months after the onset of the disease, resulting in no significant worsening of the patient’s condition. Conclusion: This case highlights the importance of considering arLHON as a possible diagnosis for patients with optic neuropathy, because the phenotype of arLHON appears to be identical to that of mtLHON and cannot be distinguished by clinicians. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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17 pages, 1921 KB  
Article
Streamlining cVEP Paradigms: Effects of a Minimized Electrode Montage on Brain–Computer Interface Performance
by Milán András Fodor, Atilla Cantürk, Gernot Heisenberg and Ivan Volosyak
Brain Sci. 2025, 15(6), 549; https://doi.org/10.3390/brainsci15060549 - 23 May 2025
Viewed by 598
Abstract
(1) Background: Brain–computer interfaces (BCIs) enable direct communication between the brain and external devices using electroencephalography (EEG) signals, offering potential applications in assistive technology and neurorehabilitation. Code-modulated visual evoked potential (cVEP)-based BCIs employ code-pattern-based stimulation to evoke neural responses, which can then be [...] Read more.
(1) Background: Brain–computer interfaces (BCIs) enable direct communication between the brain and external devices using electroencephalography (EEG) signals, offering potential applications in assistive technology and neurorehabilitation. Code-modulated visual evoked potential (cVEP)-based BCIs employ code-pattern-based stimulation to evoke neural responses, which can then be classified to infer user intent. While increasing the number of EEG electrodes across the visual cortex enhances classification accuracy, it simultaneously reduces user comfort and increases setup complexity, duration, and hardware costs. (2) Methods: This online BCI study, involving thirty-eight able-bodied participants, investigated how reducing the electrode count from 16 to 6 affected performance. Three experimental conditions were tested: a baseline 16-electrode configuration, a reduced 6-electrode setup without retraining, and a reduced 6-electrode setup with retraining. (3) Results: Our results indicate that, on average, performance declines with fewer electrodes; nonetheless, retraining restored near-baseline mean Information Transfer Rate (ITR) and accuracy for those participants for whom the system remained functional. The results reveal that for a substantial number of participants, the classification pipeline fails after electrode removal, highlighting individual differences in the cVEP response characteristics or inherent limitations of the classification approach. (4) Conclusions: Ultimately, this suggests that minimal cVEP-BCI electrode setups capable of reliably functioning across all users might only be feasible through other, more flexible classification methods that can account for individual differences. These findings aim to serve as a guideline for what is currently achievable with this common cVEP paradigm and to highlight where future research should focus in order to move closer to a practical and user-friendly system. Full article
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17 pages, 3769 KB  
Article
Atypical Leber Hereditary Optic Neuropathy (LHON) Associated with a Novel MT-CYB:m.15309T>C(Ile188Thr) Variant
by Sanja Petrovic Pajic, Ana Fakin, Martina Jarc-Vidmar, Maja Sustar Habjan, Lucija Malinar, Kasja Pavlovic, Nina Krako Jakovljevic, Andjelka Isakovic, Sonja Misirlic-Dencic, Marija Volk, Ales Maver, Gregor Jezernik, Damjan Glavac, Borut Peterlin, Ivanka Markovic, Nebojsa Lalic and Marko Hawlina
Genes 2025, 16(1), 108; https://doi.org/10.3390/genes16010108 - 20 Jan 2025
Viewed by 4687
Abstract
Background: The study presents a detailed examination and follow-up of a Slovenian patient with an Leber Hereditary Optic Neuropathy (LHON)-like phenotype and bilateral optic neuropathy in whom genetic analysis identified a novel variant MT-CYB:m.15309T>C (Ile188Thr). Methods: We provide detailed analysis of the [...] Read more.
Background: The study presents a detailed examination and follow-up of a Slovenian patient with an Leber Hereditary Optic Neuropathy (LHON)-like phenotype and bilateral optic neuropathy in whom genetic analysis identified a novel variant MT-CYB:m.15309T>C (Ile188Thr). Methods: We provide detailed analysis of the clinical examinations of a male patient with bilateral optic neuropathy from the acute stage to 8 years of follow-up. Complete ophthalmological exam, electrophysiology and optical coherence tomography (OCT) segmentation were performed. The genotype analysis was performed with a complete screening of the mitochondrial genome. Furthermore, proteomic analysis of the protein structure and function was performed to assess the pathogenicity of a novel variant of unknown significance. Mitochondrial function analysis of the patient’s peripheral blood mononuclear cells (PBMCs) was performed with the objective of evaluating the mutation effect on mitochondrial function using flow cytometry and high-resolution respirometry. Results: The patient had a profound consecutive bilateral visual loss at 19 years of age due to optic neuropathy with characteristics of LHON; however, unlike patients with typical LHON, the patient experienced a fluctuation in visual function and significant late recovery. He had a total of three visual acuity deteriorations and improvements in the left eye, with concomitant visual loss in the right eye and a final visual acuity drop reaching nadir 9 months after onset. The visual loss was characterized by centrocecal scotoma, abnormal color vision and abnormal VEP, while deterioration of PERG N95 followed with a lag of several months. The OCT examination showed retinal nerve fiber layer thinning matching disease progression. Following a two-year period of legal blindness, the patient’s visual function started to improve, and over the course of 5 years, it reached 0.5 and 0.7 Snellen (0.3 and 0.15 LogMAR) visual acuity (VA). Mitochondrial sequencing identified a presumably pathogenic variant m.15309T>C in the MT-CYB gene at 65% heteroplasmy, belonging to haplogroup K. Mitochondrial function assessment of the patient’s PBMCs showed a lower respiration rate, an increase in reactive oxygen species production and the presence of mitochondrial depolarization, compared to an age- and sex-matched healthy control’s PBMCs. Conclusions: A novel variant in the MT-CYB:m.15309T>C (Ile188Thr) gene was identified in a patient with optic nerve damage and the LHON phenotype without any additional systemic features and atypical presentation of the disease with late onset of visual function recovery. The pathogenicity of the variant is supported by proteomic analysis and the mitochondrial dysfunction observed in the patient’s PBMCs. Full article
(This article belongs to the Special Issue Genetics of Eye Development and Diseases)
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12 pages, 1852 KB  
Article
Nondestructive Determination of Tocopherol and Tocotrienol in Vitamin E Powder Using Near- and Mid-Infrared Spectroscopy
by Saowaluk Rungchang, Sila Kittiwachana, Sujitra Funsueb, Chitsiri Rachtanapun, Juthamas Tantala, Phumon Sookwong, Laichheang Yort, Chayanid Sringarm and Sudarat Jiamyangyuen
Foods 2024, 13(24), 4079; https://doi.org/10.3390/foods13244079 - 17 Dec 2024
Cited by 1 | Viewed by 1636
Abstract
Vitamin E is an essential nutrient, but its poor water solubility limits food and pharmaceutical applications. The usability of vitamin E can be enhanced via modification methods such as encapsulation, which transforms the physical state of vitamin E from a liquid to a [...] Read more.
Vitamin E is an essential nutrient, but its poor water solubility limits food and pharmaceutical applications. The usability of vitamin E can be enhanced via modification methods such as encapsulation, which transforms the physical state of vitamin E from a liquid to a powder. This study examined the efficacy of near-infrared (NIR) and mid-infrared (MIR) spectroscopy in identifying and predicting various vitamin E derivatives in vitamin E-encapsulated powder (VEP). An MIR analysis revealed the fundamental C–H vibrations of vitamin E in the range of 2700–3250 cm−1, whereas an NIR analysis provided information about the corresponding combination, first, and second overtones in the range of 4000–9000 cm−1. The MIR and NIR data were analyzed using a principal component analysis to characterize the VEP. Partial least squares (PLS) regression was applied to predict the content of individual vitamin E derivatives. PLS cross-validation revealed that NIR analysis provides more reliable predictive accuracy and precision for the contents of vitamin E derivatives, achieving a higher coefficient of determination for prediction (Q2) (0.92–0.99) than MIR analysis (0.20–0.85). For test set validation, the NIR predictions exhibited a significant level of accuracy, as indicated by a high ratio of prediction to deviation (RPD) and Q2. Furthermore, the PLS models developed using the NIR data had statistically significant predictive performance, with a high RPD (1.54–3.92) and Q2 (0.66–0.94). Thus, NIR spectroscopy is a valuable nondestructive technique for analyzing vitamin E samples, while MIR spectroscopy serves as a useful method for confirming its presence. Full article
(This article belongs to the Section Food Analytical Methods)
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15 pages, 2414 KB  
Article
Interaction of Sensitivity, Emotions, and Motivations During Visual Perception
by Sergey Lytaev
Sensors 2024, 24(22), 7414; https://doi.org/10.3390/s24227414 - 20 Nov 2024
Cited by 1 | Viewed by 2052
Abstract
When an organism is exposed to environmental stimuli of varying intensity, the adaptive changes in the CNS can be explained by several conceptual provisions: the law of motivation–activation by Yerkes and Dodson, the laws of force and pessimal protective inhibition, and the theory [...] Read more.
When an organism is exposed to environmental stimuli of varying intensity, the adaptive changes in the CNS can be explained by several conceptual provisions: the law of motivation–activation by Yerkes and Dodson, the laws of force and pessimal protective inhibition, and the theory of emotion activation. Later, reinforcement sensitivity theory was developed in the fields of psychology and psychophysics. At the same time, cortical prepulse inhibition (PPI), the prepulse inhibition of perceived stimulus intensity (PPIPSI), and the augmentation/reduction phenomenon were proposed in sensory neurophysiology, which expanded our understanding of consciousness. The aim of this study was to identify markers of levels of activity of cognitive processes under normal and in psychopathological conditions while amplifying the information stimulus. For this purpose, we changed the contrast level of reversible checkerboard patterns and mapped the visual evoked potentials (VEPs) in 19 monopolar channels among 52 healthy subjects and 39 patients with a mental illness without an active productive pathology. Their cognitive functions were assessed by presenting visual tests to assess invariant pattern recognition, short-term visual memory, and Gestalt perception. The personalities of the healthy subjects were assessed according to Cattell’s 16-factor questionnaire, linking the data from neurophysiological and cognitive studies to factors Q4 (relaxation/tension) and C (emotional stability). According to the N70 and N150 VEP waves, the healthy subjects and the patients were divided into two groups. In some, there was a direct relationship between VEP amplitude and contrast intensity (21 patients and 29 healthy persons), while in the others, there was an inverse relationship, with a reduction in VEP amplitude (18 patients and 23 healthy persons). The relationship and mechanisms of subjects’ cognitive abilities and personality traits are discussed based on the data acquired from the responses to information stimuli of varied intensity. Full article
(This article belongs to the Section Intelligent Sensors)
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16 pages, 664 KB  
Article
Evaluation of Different Visual Feedback Methods for Brain—Computer Interfaces (BCI) Based on Code-Modulated Visual Evoked Potentials (cVEP)
by Milán András Fodor, Hannah Herschel, Atilla Cantürk, Gernot Heisenberg and Ivan Volosyak
Brain Sci. 2024, 14(8), 846; https://doi.org/10.3390/brainsci14080846 - 22 Aug 2024
Cited by 2 | Viewed by 1726
Abstract
Brain–computer interfaces (BCIs) enable direct communication between the brain and external devices using electroencephalography (EEG) signals. BCIs based on code-modulated visual evoked potentials (cVEPs) are based on visual stimuli, thus appropriate visual feedback on the interface is crucial for an effective BCI system. [...] Read more.
Brain–computer interfaces (BCIs) enable direct communication between the brain and external devices using electroencephalography (EEG) signals. BCIs based on code-modulated visual evoked potentials (cVEPs) are based on visual stimuli, thus appropriate visual feedback on the interface is crucial for an effective BCI system. Many previous studies have demonstrated that implementing visual feedback can improve information transfer rate (ITR) and reduce fatigue. This research compares a dynamic interface, where target boxes change their sizes based on detection certainty, with a threshold bar interface in a three-step cVEP speller. In this study, we found that both interfaces perform well, with slight variations in accuracy, ITR, and output characters per minute (OCM). Notably, some participants showed significant performance improvements with the dynamic interface and found it less distracting compared to the threshold bars. These results suggest that while average performance metrics are similar, the dynamic interface can provide significant benefits for certain users. This study underscores the potential for personalized interface choices to enhance BCI user experience and performance. By improving user friendliness, performance, and reducing distraction, dynamic visual feedback could optimize BCI technology for a broader range of users. Full article
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19 pages, 9860 KB  
Article
High-Density Electroencephalogram Facilitates the Detection of Small Stimuli in Code-Modulated Visual Evoked Potential Brain–Computer Interfaces
by Qingyu Sun, Shaojie Zhang, Guoya Dong, Weihua Pei, Xiaorong Gao and Yijun Wang
Sensors 2024, 24(11), 3521; https://doi.org/10.3390/s24113521 - 30 May 2024
Cited by 3 | Viewed by 1642
Abstract
In recent years, there has been a considerable amount of research on visual evoked potential (VEP)-based brain–computer interfaces (BCIs). However, it remains a big challenge to detect VEPs elicited by small visual stimuli. To address this challenge, this study employed a 256-electrode high-density [...] Read more.
In recent years, there has been a considerable amount of research on visual evoked potential (VEP)-based brain–computer interfaces (BCIs). However, it remains a big challenge to detect VEPs elicited by small visual stimuli. To address this challenge, this study employed a 256-electrode high-density electroencephalogram (EEG) cap with 66 electrodes in the parietal and occipital lobes to record EEG signals. An online BCI system based on code-modulated VEP (C-VEP) was designed and implemented with thirty targets modulated by a time-shifted binary pseudo-random sequence. A task-discriminant component analysis (TDCA) algorithm was employed for feature extraction and classification. The offline and online experiments were designed to assess EEG responses and classification performance for comparison across four different stimulus sizes at visual angles of 0.5°, 1°, 2°, and 3°. By optimizing the data length for each subject in the online experiment, information transfer rates (ITRs) of 126.48 ± 14.14 bits/min, 221.73 ± 15.69 bits/min, 258.39 ± 9.28 bits/min, and 266.40 ± 6.52 bits/min were achieved for 0.5°, 1°, 2°, and 3°, respectively. This study further compared the EEG features and classification performance of the 66-electrode layout from the 256-electrode EEG cap, the 32-electrode layout from the 128-electrode EEG cap, and the 21-electrode layout from the 64-electrode EEG cap, elucidating the pivotal importance of a higher electrode density in enhancing the performance of C-VEP BCI systems using small stimuli. Full article
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11 pages, 748 KB  
Article
Retinal Function in Long-Term Type 1 Diabetes without Retinopathy: Insights from Pattern Electroretinogram and Pattern Visual Evoked Potentials Assessments
by Marta Arias-Alvarez, Maria Sopeña-Pinilla, Guisela Fernandez-Espinosa, Elvira Orduna-Hospital, Ines Vicente-Garza, Anna Bonet-Rodriguez, Javier Acha-Perez, Diego Rodriguez-Mena and Isabel Pinilla
Diagnostics 2024, 14(5), 492; https://doi.org/10.3390/diagnostics14050492 - 25 Feb 2024
Cited by 1 | Viewed by 1541
Abstract
Background: To evaluate changes in pattern electroretinogram (pERG) and pattern visual evoked potentials (pVEP) in patients with long-lasting type 1 diabetes without diabetic retinopathy (DR). Methods: Prospective study involving 92 eyes divided into two groups. The diabetic group included 46 eyes of 23 [...] Read more.
Background: To evaluate changes in pattern electroretinogram (pERG) and pattern visual evoked potentials (pVEP) in patients with long-lasting type 1 diabetes without diabetic retinopathy (DR). Methods: Prospective study involving 92 eyes divided into two groups. The diabetic group included 46 eyes of 23 patients with type 1 diabetes (T1DM); the control group included 23 age-matched healthy subjects. pERG and pVEP were assessed using the RETI-port/scan21 recording software (version 1021.3.0.0). Results: Mean age was 48 ± 9.77 years for the diabetic group and 51.7 ± 4.75 years for the control group. The mean duration of diabetes was 28.88 ± 8.04 years. The mean HbA1c value was 7.29 ± 0.89%. There were no differences in the age or sex distribution. Regarding the pERG, T1DM patients exhibited a significant decrease in the amplitude of the P50 and N95 waves compared to the control group (p = 0.018 and p = 0.035, respectively), with no differences in the peak time of each component. pVEP showed no significant changes in either peak time or amplitude of the different components. Conclusions: Long-term T1DM patients without DR showed changes in the amplitude of pERG waves with preserved peak times. We did not observe modifications in pVEP. pERG may serve as a subclinical marker of ganglion cell damage in long-term T1DM patients. Full article
(This article belongs to the Section Biomedical Optics)
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11 pages, 2227 KB  
Case Report
Leber Hereditary Optic Neuropathy (LHON) in Patients with Presumed Childhood Monocular Amblyopia
by Sanja Petrovic Pajic, Ana Fakin, Maja Sustar Habjan, Martina Jarc-Vidmar and Marko Hawlina
J. Clin. Med. 2023, 12(20), 6669; https://doi.org/10.3390/jcm12206669 - 22 Oct 2023
Cited by 2 | Viewed by 2136
Abstract
Background: Most Leber hereditary optic neuropathy (LHON) cases are bilateral and sequential; however, there are rare unilateral examples, or those in which the delay of onset of vision loss between one and the other eye is longer. In the case of presumed childhood [...] Read more.
Background: Most Leber hereditary optic neuropathy (LHON) cases are bilateral and sequential; however, there are rare unilateral examples, or those in which the delay of onset of vision loss between one and the other eye is longer. In the case of presumed childhood amblyopia in one eye, vision loss in the good eye may be the only symptom of bilateral disease, which was unnoticed in the previously amblyopic eye, or a preexisting episode of LHON in the “amblyopic” eye. The clinical decision in such cases may be difficult and suggestive of other forms of atypical optic neuropathy until confirmed by genetic testing. Case series: We present three genetically confirmed (MT-ND1:m.3700G>A, MT-ND6:m14484 T>C, and MT-ND4:m.11778G>A) patients with subacute vision loss in the previously good eye, with the other eye believed to be amblyopic from childhood and their features different from what would be expected in true amblyopia. In all, electrophysiology testing showed a bilaterally reduced amplitude of PERG with low VEP P100 wave amplitudes and prolonged peak time in both eyes, also unusual for amblyopia. During follow-up, the pallor of the optic discs progressed in all eyes. Significant thinning of the peripapillary retinal nerve fiber layer (pRNFL; retinal nerve fiber layer around the optic disc) and ganglion cell complex (GCC) in the macular region was present. All three patients had a peculiar history. The first patient was treated for presumed hyperopic amblyopia that did not improve since childhood, experienced visual loss in the good eye at the age of 17, and was negative for the three typical LHON mutations. Extended testing confirmed an atypical pathogenic variant MT-ND1:m.3700G>A in homoplasmy. The second patient with presumed strabismic amblyopia had an unusual presentation of vision loss only at the age of 61, and after the exclusion of other causes, a typical MT-ND4:m.11778G>A pathogenic variant was found in homoplasmy. The third case was peculiar as he had presumed strabismic amblyopia since childhood and had some degree of disc pallor in the amblyopic eye upon presenting with loss of vision in the good eye at the age of 21, and a typical pathogenic variant m14484 T>C, p.Met64Val was subsequently confirmed. However, one year after disease onset, he started to experience significant spontaneous functional improvement in the non-amblyopic up to 1.0 Snellen whilst improvement in the presumed amblyopic eye was modest, suggesting preexisting amblyopia. This interestingly extensive improvement was carefully followed by electrophysiology as well as visual acuity and fields. Conclusions: This report shows three different scenarios of presentation of LHON in patients with presumed uniocular amblyopia from childhood. In such cases, the diagnosis may be difficult, and detailed structural and functional evaluation of the optic nerve head is necessary to assess whether an earlier LHON episode was misdiagnosed as amblyopia or whether LHON presented bilaterally on both eyes whilst only being noticed in the previously good eye. Full article
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13 pages, 539 KB  
Review
Visual Evoked Potentials for the Detection of Diabetic Retinal Neuropathy
by Gen Miura
Int. J. Mol. Sci. 2023, 24(8), 7361; https://doi.org/10.3390/ijms24087361 - 17 Apr 2023
Cited by 9 | Viewed by 3656
Abstract
Visual evoked potentials (VEP) are visually evoked signals that extract electroencephalographic activity in the visual cortex that can detect retinal ganglion cells, optic nerves, chiasmal and retrochiasmal dysfunction, including optic radiations, and the occipital cortex. Because diabetes causes diabetic retinopathy due to microangiopathy [...] Read more.
Visual evoked potentials (VEP) are visually evoked signals that extract electroencephalographic activity in the visual cortex that can detect retinal ganglion cells, optic nerves, chiasmal and retrochiasmal dysfunction, including optic radiations, and the occipital cortex. Because diabetes causes diabetic retinopathy due to microangiopathy and neuropathy due to metabolic abnormalities and intraneural blood flow disorders, assessment of diabetic visual pathway impairment using VEP has been attempted. In this review, evidence on the attempts to assess the visual pathway dysfunction due to abnormal blood glucose levels using VEP is presented. Previous studies have provided significant evidence that VEP can functionally detect antecedent neuropathy before fundus examination. The detailed correlations between VEP waveforms and disease duration, HbA1c, glycemic control, and short-term increases and decreases in blood glucose levels are evaluated. VEP may be useful for predicting postoperative prognosis and evaluating visual function before surgery for diabetic retinopathy. Further controlled studies with larger cohorts are needed to establish a more detailed relationship between diabetes mellitus and VEP. Full article
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15 pages, 3883 KB  
Article
Neuroprotective Effects of Erinacine A on an Experimental Model of Traumatic Optic Neuropathy
by Chiao-Ling Hsu, Yao-Tseng Wen, Tzu-Chao Hsu, Chin-Chu Chen, Li-Ya Lee, Wan-Ping Chen and Rong-Kung Tsai
Int. J. Mol. Sci. 2023, 24(2), 1504; https://doi.org/10.3390/ijms24021504 - 12 Jan 2023
Cited by 7 | Viewed by 4183
Abstract
Erinacine A (EA), a natural neuroprotectant, is isolated from a Chinese herbal medicine, Hericium erinaceus. The aim of this study was to investigate the neuroprotective effects of EA in a rat model of traumatic optic neuropathy. The optic nerves (ONs) of adult [...] Read more.
Erinacine A (EA), a natural neuroprotectant, is isolated from a Chinese herbal medicine, Hericium erinaceus. The aim of this study was to investigate the neuroprotective effects of EA in a rat model of traumatic optic neuropathy. The optic nerves (ONs) of adult male Wistar rats were crushed using a standardized method and divided into three experimental groups: phosphate-buffered saline (PBS control)-treated group, standard EA dose-treated group (2.64 mg/kg in 0.5 mL of PBS), and double EA dose-treated group (5.28 mg/kg in 0.5 mL of PBS). After ON crush, each group was fed orally every day for 14 days before being euthanized. The visual function, retinal ganglion cell (RGC) density, and RGC apoptosis were determined using flash visual-evoked potentials (fVEP) analysis, retrograde Fluoro-Gold labelling, and TdT-dUTP nick end-labelling (TUNEL) assay, respectively. Macrophage infiltration of ON was detected by immunostaining (immunohistochemistry) for ED1. The protein levels of phosphor-receptor-interacting serine/threonine-protein kinase1 (pRIP1), caspase 8 (Cas8), cleaved caspase 3 (cCas3), tumour necrosis factor (TNF)-α, tumour necrosis factor receptor1 (TNFR1), interleukin (IL)-1β, inducible nitric oxide synthase (iNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1), and superoxide dismutase 1 (SOD1) were evaluated by Western blotting. When comparing the standard EA dose-treated group and the double EA dose-treated group with the PBS-treated group, fVEP analysis showed that the amplitudes of P1–N2 in the standard EA dose group and the double EA dose-treated group were 1.8 and 2.4-fold, respectively, higher than that in the PBS-treated group (p < 0.05). The density of RGC in the standard EA dose-treated group and the double EA dose-treated group were 2.3 and 3.7-fold, respectively, higher than that in the PBS-treated group (p < 0.05). The TUNEL assay showed that the standard EA dose-treated group and the double EA dose-treated group had significantly reduced numbers of apoptotic RGC by 10.0 and 15.6-fold, respectively, compared with the PBS-treated group (p < 0.05). The numbers of macrophages on ON were reduced by 1.8 and 2.2-fold in the standard EA dose-treated group and the double EA dose-treated group, respectively (p < 0.01). On the retinal samples, the levels of pRIP, Cas8, cCas3, TNF-α, TNFR1, IL-1β, and iNOS were decreased, whereas those of Nrf2, HO-1, and SOD1 were increased in both EA-treated groups compared to those in the PBS-treated group (p < 0.05). EA treatment has neuroprotective effects on an experimental model of traumatic optic neuropathy by suppressing apoptosis, neuroinflammation, and oxidative stress to protect the RGCs from death as well as preserving the visual function. Full article
(This article belongs to the Special Issue CNS Drug Action in Neurodegenerative Diseases 2.0)
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12 pages, 2805 KB  
Article
The Impact of Robotic Fractionated Radiotherapy for Benign Tumors of Parasellar Region on the Eye Structure and Function
by Michal Orski, Rafal Tarnawski, Edward Wylęgała and Dorota Tarnawska
J. Clin. Med. 2023, 12(2), 404; https://doi.org/10.3390/jcm12020404 - 4 Jan 2023
Cited by 4 | Viewed by 1940
Abstract
Purpose: To evaluate the radiation effect of fractionated robotic radiotherapy of benign tumors located in the parasellar region on the anterior and posterior segments of the eye. Methods: A prospective observational study based on the expanded ophthalmological examination. The pre-treatment baseline was used [...] Read more.
Purpose: To evaluate the radiation effect of fractionated robotic radiotherapy of benign tumors located in the parasellar region on the anterior and posterior segments of the eye. Methods: A prospective observational study based on the expanded ophthalmological examination. The pre-treatment baseline was used as a control for the post-radiotherapy follow-up examinations. The study group consists of 34 patients (68 eyes) irradiated using the CyberKnife system. There were ten patients with cavernous sinus meningioma, nine with pituitary adenoma, five with meningioma of the anterior and middle cranial fossa, five with meningioma in the region close to optic chiasm, three with craniopharyngioma, and two with meningioma of the orbit. All patients were treated using three fractions of 600–800 cGy. We assessed the impact of radiation on the eye based on changes in anatomical and functional features. The condition of the eye surface, central corneal thickness (CCT), endothelial cell density (ECD), lens densitometry, central macular thickness (CMT), and retinal nerve fiber layer (RNFL) were the anatomical features assessed. The functional tests were best-corrected visual acuity (BCVA), intraocular pressure (IOP), visual field (VF) and visual-evoked potentials (VEP). An ophthalmologic examination was performed before and 6, 12, 18, and 24 months after radiotherapy. Results: We did not observe any significant changes in BCVA, IOP, CCT, CMT, VF, and VEP, nor in the slit-lamp examination during the two-years observation. We found a significant decrease in ECD at all follow-up measurements. The drop in ECD exceeded approximated age-related physiological loss. The reduction in ECD was not large enough to disrupt corneal function and thus affect vision. We also observed a statistically significant reduction of RNFL in all observation time points. However, there was no correlation between the dose delivered to the optic pathway and the decrease in RNFL thickness. The thinning of the RNFL was not significant enough to impair visual function. Conclusion: Fractionated robotic radiotherapy of the tumors located close to the optical pathway is safe and does not impair patient’s vision. Minor changes found in optic nerve anatomy (RNFL thinning) might be related to radiation effect or tumor compression. The causal relation between low doses of radiation delivered to the cornea and the observed significant but slight decrease in ECD is uncertain. The observed changes did not cause visual disturbances perceivable by the patients. Full article
(This article belongs to the Section Ophthalmology)
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15 pages, 608 KB  
Article
Retinal and Visual Pathways Involvement in Carriers of Friedreich’s Ataxia
by Lucia Ziccardi, Lucilla Barbano, Giulio Antonelli, Ettore Cioffi, Antonio Di Renzo, Valeria Gioiosa, Christian Marcotulli, Andrzej Grzybowski, Carlo Casali and Vincenzo Parisi
Diagnostics 2022, 12(12), 3135; https://doi.org/10.3390/diagnostics12123135 - 12 Dec 2022
Viewed by 1940
Abstract
Friedreich’s ataxia (FRDA) is a rare autosomal recessive neurodegenerative disorder due to the homozygous pathological expansion of guanine-adenine-adenine (GAA) triplet repeats in the first intron of the FXN gene, which encodes for the mitochondrial protein frataxin. In the visual system, the typical manifestations [...] Read more.
Friedreich’s ataxia (FRDA) is a rare autosomal recessive neurodegenerative disorder due to the homozygous pathological expansion of guanine-adenine-adenine (GAA) triplet repeats in the first intron of the FXN gene, which encodes for the mitochondrial protein frataxin. In the visual system, the typical manifestations are ocular motility abnormality, optic neuropathy, and retinopathy. Despite the evidence of ophthalmological impairment in FRDA patients, there is a lack of information about the morpho-functional condition of the retina and of the optic pathways in healthy heterozygous carriers of Friedreich’s ataxia (C-FRDA). Ten C-FRDA subjects (providing 20 eyes) and thirty-five Controls (providing 70 eyes) underwent a complete neurological and ophthalmological examination comprehensive of functional (full-field Electroretinogram (ffERG), multifocal Electroretinogram (mfERG), Visual Evoked Potential (VEP), and Pattern Reversal Electroretinogram (PERG)) and morphological assessments (Optical Coherence Tomography, OCT) of the retina, macula, retinal ganglion cells, and visual pathways. The groups’ data were compared using a two-sample t-test. Pearson’s test was used to investigate the morpho-functional correlations. Statistically significant differences (p < 0.01) between C-FRDA and Control eyes for the values of the following parameters were found: ffERG b-wave amplitude, mfERG Response Amplitude Densities, PERG P50 implicit time and P50-N95 amplitude, VEP P100 implicit time, Retinal Nerve Fiber Layer (RNFL) Overall, and Nasal thickness. The values of the OCT macular volume were not statistically different (p > 0.01) between the two Groups. Therefore, our data suggest that, in C-FRDA, a dysfunction of retinal elements without morphological macular impairment may occur. In addition, a morphological impairment of RNFL associated with an abnormal neural conduction along the visual pathways can be also detected. Full article
(This article belongs to the Special Issue Structure-Function Relationship in Retinal Diseases)
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16 pages, 6443 KB  
Article
Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort
by Fadi Nasser, Susanne Kohl, Anne Kurtenbach, Melanie Kempf, Saskia Biskup, Theresia Zuleger, Tobias B. Haack, Nicole Weisschuh, Katarina Stingl and Eberhart Zrenner
Genes 2022, 13(7), 1218; https://doi.org/10.3390/genes13071218 - 8 Jul 2022
Cited by 12 | Viewed by 4090
Abstract
The aim of this study was to characterize the ophthalmic and genetic features of Bardet Biedl (BBS) syndrome in a cohort of patients from a German specialized ophthalmic care center. Sixty-one patients, aged 5–56 years, underwent a detailed ophthalmic examination including visual acuity [...] Read more.
The aim of this study was to characterize the ophthalmic and genetic features of Bardet Biedl (BBS) syndrome in a cohort of patients from a German specialized ophthalmic care center. Sixty-one patients, aged 5–56 years, underwent a detailed ophthalmic examination including visual acuity and color vision testing, electroretinography (ERG), visually evoked potential recording (VEP), fundus examination, and spectral domain optical coherence tomography (SD-OCT). Adaptive optics flood illumination ophthalmoscopy was performed in five patients. All patients had received diagnostic genetic testing and were selected upon the presence of apparent biallelic variants in known BBS-associated genes. All patients had retinal dystrophy with morphologic changes of the retina. Visual acuity decreased from ~0.2 (decimal) at age 5 to blindness 0 at 50 years. Visual field examination could be performed in only half of the patients and showed a concentric constriction with remaining islands of function in the periphery. ERG recordings were mostly extinguished whereas VEP recordings were reduced in about half of the patients. The cohort of patients showed 51 different likely biallelic mutations—of which 11 are novel—in 12 different BBS-associated genes. The most common associated genes were BBS10 (32.8%) and BBS1 (24.6%), and by far the most commonly observed variants were BBS10 c.271dup;p.C91Lfs*5 (21 alleles) and BBS1 c.1169T>G;p.M390R (18 alleles). The phenotype associated with the different BBS-associated genes and genotypes in our cohort is heterogeneous, with diverse features without genotype–phenotype correlation. The results confirm and expand our knowledge of this rare disease. Full article
(This article belongs to the Special Issue Research on Inherited Retinal Dystrophies)
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13 pages, 655 KB  
Article
cVEP Training Data Validation—Towards Optimal Training Set Composition from Multi-Day Data
by Piotr Stawicki and Ivan Volosyak
Brain Sci. 2022, 12(2), 234; https://doi.org/10.3390/brainsci12020234 - 8 Feb 2022
Cited by 9 | Viewed by 2424
Abstract
This paper investigates the effects of the repetitive block-wise training process on the classification accuracy for a code-modulated visual evoked potentials (cVEP)-based brain–computer interface (BCI). The cVEP-based BCIs are popular thanks to their autocorrelation feature. The cVEP-based stimuli are generated by a specific [...] Read more.
This paper investigates the effects of the repetitive block-wise training process on the classification accuracy for a code-modulated visual evoked potentials (cVEP)-based brain–computer interface (BCI). The cVEP-based BCIs are popular thanks to their autocorrelation feature. The cVEP-based stimuli are generated by a specific code pattern, usually the m-sequence, which is phase-shifted between the individual targets. Typically, the cVEP classification requires a subject-specific template (individually created from the user’s own pre-recorded EEG responses to the same stimulus target), which is compared to the incoming electroencephalography (EEG) data, using the correlation algorithms. The amount of the collected user training data determines the accuracy of the system. In this offline study, previously recorded EEG data collected during an online experiment with 10 participants from multiple sessions were used. A template matching target identification, with similar models as the task-related component analysis (TRCA), was used for target classification. The spatial filter was generated by the canonical correlation analysis (CCA). When comparing the training models from one session with the same session’s data (intra-session) and the model from one session with the data from the other session (inter-session), the accuracies were (94.84%, 94.53%) and (76.67%, 77.34%) for intra-sessions and inter-sessions, respectively. In order to investigate the most reliable configuration for accurate classification, the training data blocks from different sessions (days) were compared interchangeably. In the best training set composition, the participants achieved an average accuracy of 82.66% for models based only on two training blocks from two different sessions. Similarly, at least five blocks were necessary for the average accuracy to exceed 90%. The presented method can further improve cVEP-based BCI performance by reusing previously recorded training data. Full article
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