Contrast Discrimination and Global Form Perception in Primary Open-Angle Glaucoma and Primary Angle-Closure Glaucoma.

Purpose: This study explored early (contrast discrimination) and intermediate (global form perception) visual processing in primary subtypes of glaucoma: primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). We aimed to understand early and intermediate visual processing in POAG and PACG, matched for similar visual field defect severity. Methods: Early visual processing was measured using a contrast discrimination task described by Porkorny and Smith (1997), and intermediate processing using a global form perception task using glass pattern coherence thresholds. Thresholds were determined centrally and at a single midperipheral location (12.5°) in a quadrant without visual field defects. Controls were tested in corresponding quadrants to individuals with glaucoma. Results: Sixty participants (20 POAG, 20 PACG, and 20 age-matched controls), aged 50 to 77 years, were included. Visual field defects were matched between POAG and PACG, with mean deviation values of -6.53 ± 4.46 (range: -1.5 to -16.85) dB and -6.2 ± 4.24 (range: -1.37 to -16.42) dB, respectively. Two-Way ANOVA revealed significant differences in thresholds between the glaucoma groups and the control group for both contrast discrimination and global form perception tasks, with higher thresholds in the glaucoma groups. Post hoc analyses showed no significant contrast discrimination difference between POAG and PACG, but POAG had significantly higher thresholds than PACG for form perception. Conclusions: In form perception, POAG showed slightly worse performance than PACG, suggesting that individuals with POAG may experience more severe functional damage than PACG of similar visual field severity.

[Thresholds and variability of retinal light sensitivity in each point of the examined visual field]. / Porogovye znacheniya i variabel'nost' svetochuvstvitel'nosti setchatki v kazhdoi tochke issleduemogo polya zreniya.

PURPOSE: This study assesses the light sensitivity and its variability in each point of the visual field in patients without glaucoma and with different stages of glaucoma. MATERIAL AND METHODS: The data of a prospective analytical case-control study involving 500 patients were analyzed. The initial examination of all patients was performed using basic ophthalmological methods, including static perimetry. Retinal light sensitivity and its variability were assessed in 54 points corresponding to the Humphrey 24-2 program. Mean deviation and pattern standard deviation of light sensitivity were calculated for each point. RESULTS: The lowest light sensitivity values in patients with moderate glaucoma were found in the periphery of the nasal sector, at point No. 27 - 14.4 dB, and at points No. 24-26 along the horizontal axis from the nasal side - from 17.7 to 22.7 dB. The maximum variability of light sensitivity was found in the nasal sector on both sides of the horizontal line - from 10.7 to 11.5 dB. The average light sensitivity above the horizontal axis in patients with advanced glaucoma was 10.8 dB, which is 2 dB higher than in the lower half of the visual field - 8.8 dB. The highest light sensitivity values were found at points No. 24 - 17.7 dB and No. 31 - 16.78 dB, the lowest - at point No. 32 - 4.5 dB. The average variability values of light sensitivity in the upper half of the visual field were 9.6 dB, which is 1 dB less than in the lower half of the visual field - 10.6 dB. CONCLUSION: According to our data, points No. 32 and No. 40 are of particular interest in the diagnostic plan. In these loci, the highest light sensitivity values were determined in early and moderate glaucoma. However, the values in these points decrease significantly in advanced glaucoma. It can be assumed that changes in light sensitivity in these loci at the early stages of glaucoma may be a predictor of glaucoma progression.

The speed of sight: Individual variation in critical flicker fusion thresholds.

The critical flicker fusion threshold is a psychophysical measure commonly used to quantify visual temporal resolution; the fastest rate at which a visual system can discriminate visual signals. Critical flicker fusion thresholds vary substantially among species, reflecting different ecological niches and demands. However, it is unclear how much variation exists in flicker fusion thresholds between healthy individuals of the same species, or how stable this attribute is over time within individuals. In this study, we assessed both inter- and intra-individual variation in critical flicker fusion thresholds in a cohort of healthy human participants within a specific age range, using two common psychophysical methods and three different measurements during each session. The resulting thresholds for each method were highly correlated. We found a between-participant maximum difference of roughly 30 Hz in flicker fusion thresholds and we estimated a 95% prediction interval of 21 Hz. We used random-effects models to compare between- and within-participant variance and found that approximately 80% of variance was due to between-individual differences, and about 10% of the variance originated from within-individual differences over three sessions. Within-individual thresholds did not differ significantly between the three sessions in males, but did in females (P<0.001 for two methods and P<0.05 for one method), indicating that critical flicker fusion thresholds may be more variable in females than in males.

Intra-individual consistency of vestibular perceptual thresholds.

Vestibular perceptual thresholds quantify sensory noise associated with reliable perception of small self-motions. Previous studies have identified substantial variation between even healthy individuals' thresholds. However, it remains unclear if or how an individual's vestibular threshold varies over repeated measures across various time scales (repeated measurements on the same day, across days, weeks, or months). Here, we assessed yaw rotation and roll tilt thresholds in four individuals and compared this intra-individual variability to inter-individual variability of thresholds measured across a large age-matched cohort each measured only once. For analysis, we performed simulations of threshold measurements where there was no underlying variability (or it was manipulated) to compare to that observed empirically. We found remarkable consistency in vestibular thresholds within individuals, for both yaw rotation and roll tilt; this contrasts with substantial inter-individual differences. Thus, we conclude that vestibular perceptual thresholds are an innate characteristic, which validates pooling measures across sessions and potentially serves as a stable clinical diagnostic and/or biomarker.

Visual field asymmetries in visual word form identification.

Visual performance across the visual fields interacts with visual tasks and visual stimuli, and visual resolution decreases as a function of eccentricity, varying at isoeccentric locations. In this study, we investigated the extent of asymmetry and the rate of change in visual acuity threshold for visual word form (VWF) identification at horizontal and vertical azimuths across the fovea, and at eccentricities of 1°, 2°, 4°, 6° and 8° for 10%, 20%, 40%, and 80% contrast levels, to determine whether and how the eccentricities, meridians, and contrasts modulated the VWF identification acuity threshold. The stimuli were 16 traditional Chinese characters of similar legibility. Participants pressed a key to indicate the character presented, either monocularly or binocularly, at one of 21 randomly selected locations. A staircase procedure was used to determine the threshold, and a multiple linear regression model was used to fit the linear cortical magnification factor (CMF). We found that (1) the asymmetry was most pronounced on the vertical and superior azimuths, (2) the asymmetry between the right and left azimuths was not significant, (3) the CMF was significantly smaller on the vertical azimuth than on the horizontal azimuth, (4) the CMF was smaller on the superior vertical azimuth than on the inferior azimuth, and (5) monocular viewing and low contrast enhanced the CMF difference between azimuths. In conclusion, vertical and horizontal azimuths, location of eccentricity, contrast levels of word symbols, and monocular/binocular viewing have different effects on visual field asymmetry and cortical magnification factors.

A Bayesian observer model reveals a prior for natural daylights in hue perception.

Incorporating statistical characteristics of stimuli in perceptual processing can be highly beneficial for reliable estimation from noisy sensory measurements but may generate perceptual bias. According to Bayesian inference, perceptual biases arise from the integration of internal priors with noisy sensory inputs. In this study, we used a Bayesian observer model to derive biases and priors in hue perception based on discrimination data for hue ensembles with varying levels of chromatic noise. Our results showed that discrimination thresholds for isoluminant stimuli with hue defined by azimuth angle in cone-opponent color space exhibited a bimodal pattern, with lowest thresholds near a non-cardinal blue-yellow axis that aligns closely with the variation of natural daylights. Perceptual biases showed zero crossings around this axis, indicating repulsion away from yellow and attraction towards blue. These biases could be explained by the Bayesian observer model through a non-uniform prior with a preference for blue. Our findings suggest that visual processing takes advantage of knowledge of the distribution of colors in natural environments for hue perception.

Detection of Threshold-Level Stimuli Modulated by Temporal Predictions of the Cerebellum.

The cerebellum has the reputation of being a primitive part of the brain that mostly is involved in motor coordination and motor control. Older lesion studies and more recent electrophysiological studies have, however, indicated that it is involved in temporal perception and temporal expectation building. An outstanding question is whether this temporal expectation building cerebellar activity has functional relevance. In this study, we collected magnetoencephalographic data from 30 healthy participants performing a detection task on at-threshold stimulation that was presented at the end of a sequence of temporally regular or irregular above-threshold stimulation. We found that behavioral detection rates depended on the degree of irregularity in the sequence preceding it. We also found cerebellar responses evoked by above-threshold and at-threshold stimulation. The evoked responses to at-threshold stimulation differed significantly, depending on whether it was preceded by a regular or an irregular sequence. Finally, we found that detection performance across participants correlated significantly with the differences in cerebellar evoked responses to the at-threshold stimulation, demonstrating the functional relevance of cerebellar activity in sensory expectation building. We furthermore found evidence of thalamic involvement, as indicated by responses in the beta band (14-30 Hz) and by significant modulations of cerebello-thalamic connectivity by the regularity of the sequence and the kind of stimulation terminating the sequence. These results provide evidence that the temporal expectation building mechanism of the cerebellum, what we and others have called an internal clock, shows functional relevance by regulating behavior and performance in sensory action that requires acting and integrating evidence over precise timescales.

Performance on a contour integration task as a function of contour shape in schizophrenia and controls.

Contour Integration (CI) is the ability to integrate elemental features into objects and is a basic visual process essential for object perception and recognition, and for functioning in visual environments. It is now well documented that people with schizophrenia (SZ), in addition to having cognitive impairments, also have several visual perceptual deficits, including in CI. Here, we retrospectively characterize the performance of both SZ and neurotypical individuals (NT) on a series of contour shapes, made up of Gabor elements, that varied in terms of closure and curvature. Participants in both groups performed a CI training task that included 7 different families of shapes (Lines, Ellipse, Blobs, Squiggles, Spiral, Circle and Letters) for up to 40 sessions. Two parameters were manipulated in the training task: Orientation Jitter (OJ, i.e., orientation deviations of individual Gabor elements from ideal for each shape) and Inducer Number (IN, i.e., number of Gabor elements defining the shape). Results show that both OJ and IN thresholds significantly differed between the groups, with higher (OJ) and lower (IN) thresholds observed in the controls. Furthermore, we found significant effects as a function of the contour shapes, with differences between groups emerging with contours that were considered more complex, e.g., due to having a higher degree of curvature (Blobs, Spiral, Letters). These data can inform future work that aims to characterize visual integration impairments in schizophrenia.

Surround masking reveals binocular adding and differencing channels.

Recent studies suggest that binocular adding S+ and differencing S- channels play an important role in binocular vision. To test for such a role in the context of binocular contrast detection and binocular summation, we employed a surround masking paradigm consisting of a central target disk surrounded by a mask annulus. All stimuli were horizontally oriented 0.5c/d sinusoidal gratings. Correlated stimuli were identical in interocular spatial phase while anticorrelated stimuli were opposite in interocular spatial phase. There were four target conditions: monocular left eye, monocular right eye, binocular correlated and binocular anticorrelated, and three surround mask conditions: no surround, binocularly correlated and binocularly anticorrelated. We observed consistent elevation of detection thresholds for monocular and binocular targets across the two binocular surround mask conditions. In addition, we found an interaction between the type of surround and the type of binocular target: both detection and summation were relatively enhanced by surround masks and targets with opposite interocular phase relationships and reduced by surround masks and targets with the same interocular phase relationships. The data were reasonably well accounted for by a model of binocular combination termed MAX (S+S-), in which the decision variable is the probability summation of modeled S+ and S- channel responses, with a free parameter determining the relative gains of the two channels. Our results support the existence of two channels involved in binocular combination, S+ and S-, whose relative gains are adjustable by surround context.

Improving the robustness of the Sequentially Optimized Reconstruction Strategy (SORS) for visual field testing.

Perimetry, or visual field test, estimates differential light sensitivity thresholds across many locations in the visual field (e.g., 54 locations in the 24-2 grid). Recent developments have shown that an entire visual field may be relatively accurately reconstructed from measurements of a subset of these locations using a linear regression model. Here, we show that incorporating a dimensionality reduction layer can improve the robustness of this reconstruction. Specifically, we propose to use principal component analysis to transform the training dataset to a lower dimensional representation and then use this representation to reconstruct the visual field. We named our new reconstruction method the transformed-target principal component regression (TTPCR). When trained on a large dataset, our new method yielded results comparable with the original linear regression method, demonstrating that there is no underfitting associated with parameter reduction. However, when trained on a small dataset, our new method used on average 22% fewer trials to reach the same error. Our results suggest that dimensionality reduction techniques can improve the robustness of visual field testing reconstruction algorithms.

Why am I overwhelmed by bright lights? The behavioural mechanisms of post-stroke visual hypersensitivity.

After stroke, patients can experience visual hypersensitivity, an increase in their sensitivity for visual stimuli as compared to their state prior to the stroke. Candidate behavioural mechanisms for these subjective symptoms are atypical bottom-up sensory processing and impaired selective attention, but empirical evidence is currently lacking. In the current study, we aimed to investigate the relationship between post-stroke visual hypersensitivity and sensory thresholds, sensory processing speed, and selective attention using computational modelling of behavioural data. During a whole/partial report task, participants (51 stroke patients, 76 orthopedic patients, and 77 neurotypical adults) had to correctly identify a single target letter that was presented alone (for 17-100 ms) or along a distractor (for 83ms). Performance on this task was used to estimate the sensory threshold, sensory processing speed, and selective attention abilities of each participant. In the stroke population, both on a group and individual level, there was evidence for impaired selective attention and -to a lesser extent- lower sensory thresholds in patients with post-stroke visual hypersensitivity as compared to neurotypical adults, orthopedic patients, or stroke patients without post-stroke sensory hypersensitivity. These results provide a significant advancement in our comprehension of post-stroke visual hypersensitivity and can serve as a catalyst for further investigations into the underlying mechanisms of sensory hypersensitivity after other types of acquired brain injury as well as post-injury hypersensitivity for other sensory modalities.

Effect of the rs2821557 Polymorphism of the Human Kv1.3 Gene on Olfactory Function and BMI in Different Age Groups.

The sense of smell plays an important role in influencing the eating habits of individuals and consequently, their body weight, and its impairment has been associated with modified eating behaviors and malnutrition problems. The inter-individual variability of olfactory function depends on several factors, including genetic and physiological ones. In this study, we evaluated the role of the Kv1.3 channel genotype and age, as well as their mutual relationships, on the olfactory function and BMI of individuals divided into young, adult and elderly groups. We assessed olfactory performance in 112 healthy individuals (young n = 39, adult n = 36, elderly n = 37) based on their TDI olfactory score obtained through the Sniffin' Sticks test and their BMI. Participants were genotyped for the rs2821557 polymorphism of the human gene encoding Kv1.3 channels, the minor C allele of which was associated with a decreased sense of smell and higher BMIs compared to the major T allele. The results show that TT homozygous subjects obtained higher TDI olfactory scores and showed lower BMIs than CC homozygous subjects, in all age groups considered. Furthermore, the positive effect of the T allele on olfactory function and BMI decreased with increasing age. The contribution of the genetic factor is less evident with advancing age, while the importance of the age factor is compensated for by genetics. These results show that genetic and physiological factors such as age act to balance each other.

An observational study of olfactory functions in total laryngectomees.

OBJECTIVE: To evaluate the olfactory acuity and quality of life in patients who have undergone total laryngectomy. The study also aims to identify any specific patient-related risk factors linked to worse olfactory outcomes. METHODS: This is a prospective cross-sectional study conducted at the University Malaya Medical Centre. A total of 30 patients who have undergone total laryngectomy were assessed objectively using the Sniffin' Sticks test and compared against normal age-matched Malaysians. Subsequently, they also filled out the modified Questionnaire on Olfactory Disorders. Correlations of patient demographics, disease and treatment variables against olfactory outcomes were conducted. RESULTS: All subjects suffered olfactory impairment, with 66.7% of them being anosmic after total laryngectomy. The Sniffin' Sticks test demonstrated a statistically significant difference between laryngectomees and the normal age-matched Malaysian population in all three subtests for odor threshold, discrimination and identification. 37% of patients developed olfactory adaptive methods, which resulted in higher olfactory scores and a better quality of life. There were no patient demographics, disease or treatment variables associated with a poorer olfactory outcome identified. CONCLUSION: Olfactory impairment should not be overlooked among patients after total laryngectomy. Although as many as a third of patients developed some sort of olfactory adaptive behavior, early rehabilitation should be integrated into the multidisciplinary rehabilitation program after total laryngectomy.

Potential application of electronic odor diffuser in olfaction testing.

OBJECTIVE: Different olfactory tests have been performed by otorhinolaryngologists in different parts of the world. For example, the University of Pennsylvania Smell Identification Test (UPSIT) has been used in the U.S., whereas the Sniffin' Sticks Test has been used in Europe, and similarly, T&T olfactometry is used in Japan. Although audiometers with electronic oscillators have long been used in hearing tests, electronic odor generators are not typically used in olfaction tests. We attempted an olfactory test using the AROMASTIC® (SONY, Tokyo, Japan), an electronically controlled device that can diffuse five different odors. METHODS: Forty participants who had visited an outpatient olfactory clinic were included in this study. The participants were instructed to answer whether they could smell the five different odors during the AROMASTIC® screening test (AS-test), and the number of odors smelled was summed and scored (AS-score). The patients also underwent T&T olfactometry concurrently. RESULTS: The AS-scores and T&T olfactometry detection and recognition thresholds showed significant correlations, confirming that the AS-test is a valid olfactory test. CONCLUSION: Electronic odor diffusers may be useful for olfaction tests.

Motion-Acuity Test for Visual Field Acuity Measurement with Motion-Defined Shapes.

The standard visual acuity measurements rely on stationary stimuli, either letters (Snellen charts), vertical lines (vernier acuity) or grating charts, processed by those regions of the visual system most sensitive to the stationary stimulation, receiving visual input from the central part of the visual field. Here, an acuity measurement is proposed based on discrimination of simple shapes, that are defined by motion of the dots in the random dot kinematograms (RDK) processed by visual regions sensitive to motion stimulation and receiving input also from the peripheral visual field. In the motion-acuity test, participants are asked to distinguish between a circle and an ellipse, with matching surfaces, built from RDKs, and separated from the background RDK either by coherence, direction, or velocity of dots. The acuity measurement is based on ellipse detection, which with every correct response becomes more circular until reaching the acuity threshold. The motion-acuity test can be presented in negative contrast (black dots on white background) or in positive contrast (white dots on black background). The motion defined shapes are located centrally within 8 visual degrees and are surrounded by RDK background. To test the influence of visual peripheries on centrally measured acuity, a mechanical narrowing of the visual field to 10 degrees is proposed, using opaque goggles with centrally located holes. This easy and replicable narrowing system is suitable for MRI protocols, allowing further investigations of the functions of the peripheral visual input. Here, a simple measurement of shape and motion perception simultaneously is proposed. This straightforward test assesses vision impairments depending on the central and peripheral visual field inputs. The proposed motion-acuity test advances the capability of standard tests to reveal spare or even strengthened vision functions in patients with injured visual system, that until now remained undetected.

Olfactory threshold as a biomarker of long-term relapse activity in multiple sclerosis.

BACKGROUND: Olfactory threshold (OT) is a marker of short-term inflammatory activity in multiple sclerosis (MS). OBJECTIVE: To investigate whether OT predicts long-term MS clinical disease course. METHODS: This was a 6-year prospective longitudinal study on MS patients at the MS clinic Innsbruck. Clinical visits assessing the occurrence of relapses, Expanded Disability Status Scale (EDSS) scores, and disease-modifying treatment (DMT), were conducted biannually. OT testing was performed at baseline (BL), year 1 (Y1), year 2 (Y2) and year 6 (Y6), using the threshold subscore of the "Sniffin' Sticks" test. Cognitive function was assessed by the Symbol Digit Modalities Test. RESULTS: Of 139 MS patients, 92 were eligible for Y6 follow-up. 68% experienced relapses, 53% EDSS worsening, 29% progression independent of relapse activity (PIRA) and 41% cognitive deterioration. OT scores were lower at BL, Y1 and Y2 in patients requiring DMT escalation. In multivariable analysis, higher OT scores at BL, Y1, Y2 and Y6 were associated with lower risk of relapse (hazard ratio, HR: 0.65-0.92) and EDSS worsening (HR: 0.86-0.89), while no associations were found for PIRA and cognitive deterioration. CONCLUSIONS: OT is a potential surrogate marker for long-term inflammatory disease activity and DMT failure in MS.

Factors influencing olfactory function in an adult general population sample: the CHRIS study.

The sense of smell allows for the assessment of the chemical composition of volatiles in our environment. Different factors are associated with reduced olfactory function, including age, sex, as well as health and lifestyle conditions. However, most studies that aimed at identifying the variables that drive olfactory function in the population suffered from methodological weaknesses in study designs and participant selection, such as the inclusion of convenience sample or only of certain age groups, or recruitment biases. We aimed to overcome these issues by investigating the Cooperative Health Research in South Tyrol (CHRIS) cohort, a population-based cohort, by using a validated odor identification test. Specifically, we hypothesized that a series of medical, demographic and lifestyle variables is associated with odor identification abilities. In addition, our goal was to provide clinicians and researchers with normative values for the Sniffin' Sticks identification set, after exclusion of individuals with impaired nasal patency. We included 6,944 participants without acute nasal obstruction and assessed several biological, social, and medical parameters. A basic model determined that age, sex, years of education, and smoking status together explained roughly 13% of the total variance in the data. We further observed that variables related to medical (positive screening for cognitive impairment and for Parkinson's disease, history of skull fracture, stage 2 hypertension) and lifestyle (alcohol abstinence) conditions had a negative effect on odor identification scores. Finally, we provide clinicians with normative values for both versions of the Sniffin' Sticks odor identification test, i.e. with 16 items and with 12 items.

Effect of wearing masks on odor detection and recognition.

BACKGROUND: The effect of wearing masks on olfaction remains unclear. OBJECTIVES: This study aimed to clarify the differences between the effects of no masks, surgical masks, and N95 respirator masks by conducting both identification and threshold olfaction tests. METHODS: Young, healthy volunteers aged ≥ 18 years and < 30 years without awareness of apparent olfactory disorder were included. All participants filled out a questionnaire on olfaction and completed an acuity smell identification test (Open Essence test) and an olfactory threshold test (T&T olfactometry) while wearing no masks, surgical masks, or N95 respirator masks. RESULTS: In the Open Essence tests, the no-mask group score was significantly higher than those of the surgical- and N95-mask groups. Using T&T olfactometry, the median-detection threshold of the no-mask group was significantly lower than that of the surgical-mask group, and the surgical-mask group threshold was significantly lower than that of the N95-mask group. Similar patterns were observed for the median-recognition threshold. CONCLUSIONS: Wearing masks, especially an N95 mask, reduces the ability to detect and identify odors. This disadvantage should be considered by professionals such as healthcare workers, who require proper olfaction to perform appropriate tasks.

Odor dilution sorting as a clinical test of olfactory function: normative values and reliability data.

Clinical assessment of an individual's sense of smell has gained prominence, but its resource-intensive nature necessitates the exploration of self-administered methods. In this study, a cohort of 68 patients with olfactory loss and 55 controls were assessed using a recently introduced olfactory test. This test involves sorting 2 odorants (eugenol and phenylethyl alcohol) in 5 dilutions according to odor intensity, with an average application time of 3.5 min. The sorting task score, calculated as the mean of Kendall's Tau between the assigned and true dilution orders and normalized to [0,1], identified a cutoff for anosmia at a score ≤ 0.7. This cutoff, which marks the 90th percentile of scores obtained with randomly ordered dilutions, had a balanced accuracy of 89% (78% to 97%) for detecting anosmia, comparable to traditional odor threshold assessments. Retest evaluations suggested a score difference of ±0.15 as a cutoff for clinically significant changes in olfactory function. In conclusion, the olfactory sorting test represents a simple, self-administered approach to the detection of anosmia or preserved olfactory function. With balanced accuracy similar to existing brief olfactory tests, this method offers a practical and user-friendly alternative for screening anosmia, addressing the need for resource-efficient assessments in clinical settings.

Genetic Factors Associated with the Development of Neuropathy in Type 2 Diabetes.

Neuropathy is a serious and frequent complication of type 2 diabetes (T2DM). This study was carried out to search for genetic factors associated with the development of diabetic neuropathy by whole exome sequencing. For this study, 24 patients with long-term type 2 diabetes with neuropathy and 24 without underwent detailed neurological assessment and whole exome sequencing. Cardiovascular autonomic function was evaluated by cardiovascular reflex tests. Heart rate variability was measured by the triangle index. Sensory nerve function was estimated by Neurometer and Medoc devices. Neuropathic symptoms were characterized by the neuropathy total symptom score (NTSS). Whole exome sequencing (WES) was performed on a Thermo Ion GeneStudio S5 system determining the coding sequences of approximately 32,000 genes comprising 50 million base pairs. Variants were detected by Ion Reporter software and annotated using ANNOVAR, integrating database information from dbSNP, ClinVar, gnomAD, and OMIM. Integrative genomics viewer (IGV) was used for visualization of the mapped reads. We have identified genetic variants that were significantly associated with increased (22-49-fold) risk of neuropathy (rs2032930 and rs2032931 of recQ-mediated genome instability protein 2 (RMI2) gene), rs604349 of myosin binding protein H like (MYBPHL) gene and with reduced (0.07-0.08-fold) risk (rs917778 of multivesicular body subunit 12B (MVB12B) and rs2234753 of retinoic acid X receptor alpha (RXRA) genes). The rs2032930 showed a significant correlation with current perception thresholds measured at 5 Hz and 250 Hz for n. medianus (p = 0.042 and p = 0.003, respectively) and at 5 Hz for n. peroneus (p = 0.037), as well as the deep breath test (p = 0.022) and the NTSS (p = 0.023). The rs2032931 was associated with current perception thresholds (p = 0.003 and p = 0.037, respectively), deep breath test (p = 0.022), and NTSS (p = 0.023). The rs604349 correlated with values measured at 2000 (p = 0.049), 250 (p = 0.018), and 5 Hz (p = 0.005) for n. medianus, as well as warm perception threshold measured by Medoc device (p = 0.042). The rs2234753 showed correlations with a current perception threshold measured at 2000 Hz for n. medianus (p = 0.020), deep breath test (p = 0.040), and NTSS (p = 0.003). There was a significant relationship between rs91778 and cold perception threshold (p = 0.013). In our study, genetic variants have been identified that may have an impact on the risk of neuropathy developing in type 2 diabetic patients. These results could open up new opportunities for early preventive measures and might provide targets for new drug developments in the future.