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OBJECTIVE: The purpose of this study was to evaluate the age-dependency of amplitudes and implicit times in the electroretinograms (ERGs) of healthy individuals and provide clinicians and researchers with a reference for a variety of stimulus paradigms. DESIGN AND METHODS: Full-field electroretinography was conducted on 73 healthy participants aged 14-73 using an extended ISCEV standard protocol that included an additional 9 Hz flicker stimulus for assessing rod function and special paradigms for isolated On-Off and S-cone responses. Correlation coefficients and best-fit regression models for each parameter's age-dependency were calculated. RESULTS: Dark-adapted ERGs, in particular, displayed notable age-related alterations. The attenuation and delay of the b-wave with higher age were most significant in the dark-adapted, rod-driven 0.001 cd s/m2 flash ERG. The age-dependent reduction of the a-wave amplitude was strongest in the standard dark-adapted 3 cd s/m2 flash condition. Cone-driven, light-adapted responses to either flash or flicker stimuli displayed comparatively small alterations at higher age. S-cone function tended to diminish at an early age, but the effect was not significant in the whole population. CONCLUSION: The results suggest that rod and cone function decline at different rates with age, with rods being generally more affected by aging. Nonetheless, response amplitudes displayed a wide variability across the whole sample.

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In this study, we describe a comprehensive 3D magnetic resonance imaging (MRI) protocol designed to assess major tissue and fluid components in the brain. The protocol comprises four different sequences: 1) magnetization transfer prepared Cones (MT-Cones) for two-pool MT modeling to quantify macromolecular content; 2) short-TR adiabatic inversion-recovery prepared Cones (STAIR-Cones) for myelin water imaging; 3) proton-density weighted Cones (PDw-Cones) for total water imaging; and 4) highly T2 weighted Cones (T2w-Cones) for free water imaging. By integrating these techniques, we successfully mapped key brain components-namely macromolecules, myelin water, intra/extracellular water, and free water-in ten healthy volunteers and five patients with multiple sclerosis (MS) using a 3T clinical scanner. Brain macromolecular proton fraction (MMPF), myelin water proton fraction (MWPF), intra/extracellular water proton fraction (IEWPF), and free water proton fraction (FWPF) values were generated in white matter (WM), grey matter (GM), and MS lesions. Excellent repeatability of the protocol was demonstrated with high intra-class correlation coefficient (ICC) values. In MS patients, the MMPF and MWPF values of the lesions and normal-appearing WM (NAWM) were significantly lower than those in normal WM (NWM) in healthy volunteers. Moreover, we observed significantly higher FWPF values in MS lesions compared to those in NWM and NAWM regions. This study demonstrates the capability of our technique to volumetrically map major brain components. The technique may have particular value in providing a comprehensive assessment of neuroinflammatory and neurodegenerative diseases of the brain.

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Unlike humans, teleosts like zebrafish exhibit robust retinal regeneration after injury from endogenous stem cells. However, it is unclear if regenerating cone photoreceptors regain physiological function and integrate correctly into post-synaptic circuits. We used two-photon calcium imaging of living adult retina to examine photoreceptor responses before and after light-induced lesions. To assess functional recovery of cones and downstream outer retinal circuits, we exploited color opponency; UV cones exhibit intrinsic Off-response to blue light, but On-response to green light, which depends on feedback signals from outer retinal circuits. Accordingly, we assessed the presence and quality of Off- vs. On-responses and found that regenerated UV cones regain both Off-responses to short-wavelength and On-responses to long-wavelength light within 3 months after lesion. Therefore, physiological circuit functionality is restored in regenerated cone photoreceptors, suggesting that inducing endogenous regeneration is a promising strategy for human retinal repair.

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Vision plays a crucial role in the survival of animals, and the visual system has particularly selectively evolved in response to the visual environment, ecological niche, and species habitats in vertebrate species. To date, a horizontal streak of retinal ganglion cell (RGC) distribution pattern is observed across mammal species. Here, we report that the giant panda's vertically oriented visual streak, combined with current evidence of the animal's forward-placed eyes, ocular structure, and retinal neural topographic distribution patterns, presents the emergence of a well-adapted binocular visual system. Our results suggest that the giant panda may use a unique way to processing binocular visual information. Results of mathematical simulation are in favor of this hypothesis. The topographic distribution properties of RGCs reported here could be essential for understanding the visual adaptation and evolution of this living fossil.

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Introduction: The potential neuroprotective and regenerative properties of electrical stimulation (ES) were studied in rhodopsin knockout mice (Rho -/- ), a murine model of inherited retinal degeneration. The study focused on assessing the impact of varying ES frequencies on visual functions and photoreceptor cell survival in Rho -/- mice. Methods: To elucidate the impact of electrical stimulation on cone survival, Rho -/- mice received either sham or transpalpebral ES using biphasic ramp or rectangular waveforms at 100 µA amplitude, starting at six weeks of age. The treatment duration spanned from one to three weeks. The optimal treatment frequency of ES sessions was determined by applying ES every one, two, or three days in three separate groups of Rho -/- mice. The sham group received daily treatments without the application of ES. Results: Our study revealed significant improvement of visual function in Rho -/- mice following daily or every-other-day noninvasive transpalpebral ES, as evidenced by electroretinogram and optomotor response-based visual behavior assays. Concurrently, assessment of outer nuclear thickness and immunohistochemistry for the cone photoreceptor cell marker PNA demonstrated pronounced increases in the survival of rods and cones and improvement in the morphology of the inner and outer segments. Discussion: This study underscores the protective effect of non-invasive ES in rhodopsin knockout-induced retinal degenerative disorders, providing a foundation for developing targeted therapeutic interventions for retinitis pigmentosa.

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Local translation in growth cones plays a critical role in responses to extracellular stimuli, such as axon guidance cues. We previously showed that brain-derived neurotrophic factor activates translation and enhances novel protein synthesis through the activation of mammalian target of rapamycin complex 1 signaling in growth cones of dorsal root ganglion neurons. In this study, we focused on 40S ribosomal protein S6 (RPS6), 60S ribosomal protein P0/1/2 (RPP0/1/2), and actin filaments to determine how localization of ribosomal proteins changes with overall protein synthesis induced by neurotrophins. Our quantitative analysis using immunocytochemistry and super-resolution microscopy indicated that RPS6, RPP0/1/2, and actin tend to colocalize in the absence of stimulation, and that these ribosomal proteins tend to dissociate from actin and associate with each other when local protein synthesis is enhanced. We propose that this is because stimulation causes ribosomal subunits to associate with each other to form actively translating ribosomes (polysomes). This study further clarifies the role of cytoskeletal components in local translation in growth cones.

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This research work aimed to identify the main components that are responsible for the sedative properties of hop cones and allocate their targets. This investigation was performed through molecular docking, molecular dynamic simulations, root mean square fluctuation (RMSF) analysis, and DFT calculation techniques. The tested compounds from Humulus lupulus were compared to diazepam and paroxetine. Molecular docking showed that two-thirds of the compounds had a good affinity to gamma-aminobutyric acid (GABA), outperforming diazepam, while only three surpassed paroxetine on the SERT. Compounds 3,5-dihydroxy-4,6,6-tris(3-methylbut-2-en-1-yl)-2-(3-methylbutanoyl)cyclohexa-2,4-dien-1-one (5) and (S,E)-8-(3,7-dimethylocta-2,6-dien-1-yl)-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one (15) showed stable binding and favorable energy parameters, indicating their potential for targeting GABA receptors and the SERT. This study provides a basis for future clinical research on these promising compounds.

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Background: The primary objective of revision total knee surgery is to achieve solid bone fixation. Generally, this could be accomplished using sleeves and long stems, which require substantial remaining bone stock and may increase the risk of stem tip pain. An alternative approach involves the use of customized diaphyseal cones, which can preserve the integrity of the bone canal. This study evaluates the impact of employing femoral diaphyseal cones with various stem lengths on stress distribution and relative motion. Methods: CT scan data from five patients were used to generate the 3D model of the femur, cement, customized stems, and cones, along with assigning patient-specific material for each candidate's femur. Three different stem lengths, both with and without the customized cone, were assessed under three gait loading conditions to compare the resulting Von Mises stress distribution and relative motion. Results: Analysis indicated that the use of customized femoral cones moderately increases stress distribution values up to 30 % while significantly reducing relative motion at the femoral canal-cone interface by nearly 60 %. The presence of the cone did not significantly alter relative motion with varying stem lengths, although stem length variation without a cone substantially affected these values. Conclusion: Incorporating cones alongside stems enhances metaphyseal fixation, reduces stress shielding, potentially allowing for the use of shorter stems. Furthermore, cones promote osseointegration by minimizing relative motion, ultimately improving prosthetic stability.

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In recent years, optoretinography has become an important functional imaging method for the retina, as light-evoked changes in the photoreceptors have been demonstrated for a large number of different OCT systems. Full-field swept-source optical coherence tomography (FF-SS-OCT) is particularly phase-stable, and it is currently the only technique sensitive enough to detect the smaller functional changes in the inner plexiform layer (IPL). However, the resolution of state-of-the art FF-SS-OCT systems is not high enough to distinguish individual photoreceptors. This makes it difficult to separate rods from cones. In this work, we circumvent this problem by separating the functional changes in rods and cones by their different temporal dynamics to the same light stimulus. For this purpose, a mathematical model was developed that represents the measured signals as a superposition of two impulse responses. The developed model describes the measured data under different imaging conditions very well and is able to analyze the sensitivity and temporal dynamics of the two photoreceptor types separately.

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The number of revision total knee arthroplasties (TKAs) performed annually continues to rise. This article is a summary of a symposium on revision TKAs presented at the 2023 American Association of Hip and Knee Surgeons annual meeting. It will provide an overview of the surgical tips and tricks for exposure and component removal, use of metaphyseal fixation and stems to manage bone loss and optimize fixation, constraint in TKA, as well as how to manage extensor mechanism disruptions with a synthetic mesh reconstruction. LEVEL OF EVIDENCE: V.

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There is a surprisingly strong effect on color appearance when low levels of luminance contrast are added to visual targets in which only S-cones are modulated. This phenomenon can be studied with checkerboard patterns composed of alternating S-cone-modulated checks and gray checks. + S checks look purple when surrounded by slightly brighter gray checks but look highly desaturated (lavender, almost white) when surrounded by darker gray checks. -S checks change in hue with luminance contrast; they look yellow when surrounded by darker gray checks but are greener when surrounded by lighter checks. Psychophysical paired comparisons confirm these perceptions. Furthermore, visual evoked potentials (VEPs) recorded from human posterior cortex indicate that signals evoked by low luminance contrast interact nonlinearly with S-cone-evoked signals in early cortical color processing. Our new psychophysics and electrophysiology results prove that human perception of color appearance is not based on neural computations within a separate, isolated color system. Rather, signals evoked by color contrast and luminance contrast interact to produce the colors we see.

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Response surface methodology (RSM) was employed to optimize the process parameters of the supercritical carbon dioxide extraction of hop cones in terms of their antifungal properties against Fusarium culmorum and Aspergillus niger. The effects of temperature (40-50 °C), pressure (200-300 bar), and CO2 consumption (25-75 kgCO2/kg) on the extraction yield, content of α- and ß-acids, as well as pathogens' growth inhibition were investigated. Both pressure and CO2 consumption had a significant effect on antifungal properties. It was observed that the best results for antifungal properties were obtained when hop cones were extracted with pure carbon dioxide at the temperature of 50 °C, under the pressure of 300 bar with CO2 consumption at the level of 75 kgCO2/kg of feed for extraction. The highest antifungal properties of hop cone supercritical carbon dioxide extracts were analyzed as 100% for Fusarium culmorum and 68% for Aspergillus niger, calculated as the growth inhibition of tested pathogens. The aim of the study was to determine the optimum values of extraction parameters to achieve the maximum response and enable us to investigate the interaction of these parameters on the antifungal properties of hop cone extracts.

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The role of local of growth cone (GC) manipulation in adult regenerative systems is largely unexplored despite substantial translational importance. Here we investigated collaboration among Rac1 GTPase, its partnering ERM proteins and PTEN in adult sensory neurons and adult nerve regeneration. We confirmed expression of both Rac1 and ERM in adults and noted substantial impacts on neurite outgrowth in naïve and pre-injured adult sensory neurons. PTEN inhibition added to this outgrowth. Rac1 activation acted directly on adult GCs facilitating both attractive turning and advancement. In vivo regeneration indices including electrophysiological recovery, return of sensation, walking, repopulation of myelinated axons and reinnervation of the target epidermis indicated benefits of local Rac1 activation. These indices suggested maximal GC activation whereas local PTEN inhibition offered only limited added improvement. Our findings provide support for the concept of manipulating adult GCs, by emphasizing local Rac1 activation in directing therapy for nerve repair.

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The ambient daylight variation is coded by melanopsin photoreceptors and their luxotonic activity increases towards midday when colour temperatures are cooler, and irradiances are higher. Although melanopsin and cone photoresponses can be mediated via separate pathways, the connectivity of melanopsin cells across all levels of the retina enables them to modify cone signals. The downstream effects of melanopsin-cone interactions on human vision are however, incompletely understood. Here, we determined how the change in daytime melanopsin activation affects the human cone pathway signals in the visual cortex. A 5-primary silent-substitution method was developed to evaluate the dependence of cone-mediated signals on melanopsin activation by spectrally tuning the lights and stabilizing the rhodopsin activation under a constant cone photometric luminance. The retinal (white noise electroretinogram) and cortical responses (visual evoked potential) were simultaneously recorded with the photoreceptor-directed lights in 10 observers. By increasing the melanopsin activation, a reverse response pattern was observed with cone signals being supressed in the retina by 27% (p = 0.03) and subsequently amplified by 16% (p = 0.01) as they reach the cortex. We infer that melanopsin activity can amplify cone signals at sites distal to retinal bipolar cells to cause a decrease in the psychophysical Weber fraction for cone vision.

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OBJECTIVE: Both porous metal cones and metaphyseal sleeves are excellent implants for reconstructing severe bone defects in the knee joint, but they both exhibit design limitations. The porous metal cone, especially, has significant room for improvement in its shape design. The existing porous metal cones often feature a conical external surface with a relatively small taper, potentially compromising both rotational and axial stability. To improve both axial and rotational stability in porous metal cones, we developed a 3D-printed stepped porous metal cone. This study aimed to assess the short-term clinical outcome of the 3D-printed stepped porous metal cone and to compare it with the clinical outcome of patients who underwent revision total knee arthroplasty (rTKA) with the metaphyseal sleeves during the same period. METHOD: Patients who underwent total knee arthroplasty revision with metaphyseal bone defect reconstruction from 2019 to 2021 were retrospectively analyzed. A total of 61 patients were enrolled in the study, including 15 patients using 3D-printed stepped porous metal cones and 46 patients using metaphyseal metal sleeves. Thirty patients using metaphyseal sleeves were screened by propensity score matching method and compared with those using stepped cones. Analysis included the American Knee Society Score, the Hospital for Special Surgery knee score, the Western Ontario and McMaster Universities Arthritis index, the Short Form 12 (SF-12) health survey, and radiographic assessment with a mean follow-up of 28.5 ± 8.3 months. To conduct comparative analyses, unpaired Student's t-tests were employed for continuous variables, while categorical variables were analyzed using the appropriate Fisher exact or chi-squared test. RESULTS: In this study, the survival rates of both the stepped cone and metaphyseal sleeve were 100%. There was no statistically significant difference in postoperative knee function scores between the two groups (p > 0.05). However, patients in the cone group had significantly higher mental component summary scores on the SF-12 scale (p < 0.05) and higher increases in mean postoperative physical component summary scores than patients in the sleeve group (p < 0.05). In addition, patients in the cone group experienced fewer intraoperative and postoperative complications compared to the sleeve group. CONCLUSION: The 3D-printed stepped porous metal cone can effectively reconstruct bone defects in complex rTKA and provide satisfactory early clinical and radiographic results. The 3D-printed stepped cone provides a more stable structure similar to the sleeve while maintaining the original benefits of the cone making it a promising choice for rTKA.

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Porous-activated carbons (ACs) derived from Moroccan pine cones (PC) were synthesised by a two step-chemical activation/carbonisation method using phosphoric acid (PC-H) and zinc chloride (PC-Z) as activating agents and used for the adsorption of bisphenol A (BPA) from water. Several techniques (TGA/DTA, FT-IR, XRD, SEM and BET) were used to determine the surface area and pore characterisation and variations during the preparation of the adsorbents. The modification significantly increased the surface area of both ACs, resulting in values of 1369.03 m2 g-1 and 1018.86 m2 g-1 for PC-H and PC-Z, respectively. Subsequent adsorption tests were carried out, varying parameters including adsorbent dosage, pH, initial BPA concentration, and contact time. Therefore, the highest adsorption capacity was observed when the BPA molecules were in their neutral form. High pH values were found to be unfavourable for the removal of bisphenol A from water. The results showed that BPA adsorption kinetics and isotherms followed pseudo-second-order and Langmuir models. Thermodynamic studies indicated that the adsorption was spontaneous and endothermic. Besides, the regeneration of spent adsorbents demonstrated their reusability. The adsorption mechanisms can be attributed to physical adsorption, hydrogen bonds, electrostatic forces, hydrophobic interactions, and π-π intermolecular forces.

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Sudden phase changes are related to cortical phase transitions, which likely change in frequency and spatial distribution as epileptogenic activity evolves. A 100 s long section of micro-ECoG data obtained before and during a seizure was selected and analyzed. In addition, nine other short-duration epileptic events were also examined. The data was collected at 420 Hz, imported into MATLAB, downsampled to 200 Hz, and filtered in the 1-50 Hz band. The Hilbert transform was applied to compute the analytic phase, which was then unwrapped, and detrended to look for sudden phase changes. The phase slip rate (counts/s) and its acceleration (counts/s2) were computed with a stepping window of 1-s duration and with a step size of 5 ms. The analysis was performed for theta (3-7 Hz), alpha (7-12 Hz), and beta (12-30 Hz) bands. The phase slip rate on all electrodes in the theta band decreased while it increased for the alpha and beta bands during the seizure period. Similar patterns were observed for isolated epileptogenic events. Spatiotemporal contour plots of the phase slip rates were also constructed using a montage layout of 8 × 8 electrode positions. These plots exhibited dynamic and oscillatory formation of phase cone-like structures which were higher in the theta band and lower in the alpha and beta bands during the seizure period and epileptogenic events. These results indicate that the formation of phase cones might be an excellent biomarker to study the evolution of a seizure and also the cortical dynamics of isolated epileptogenic events.

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BACKGROUND: Highly porous metal tibial metaphyseal cones (TMCs) are commonly utilized in revision total knee arthroplasty (TKA) to address bone loss and obtain biologic fixation. Mid-term (5 to 10 year) studies have previously demonstrated excellent survivorship and high rates of osseointegration, but longer-term studies are lacking. We aimed to assess long-term (≥ 10 year) implant survivorship, complications, and clinical and radiographic outcomes after revision TKA with TMCs. METHODS: Between 2004 and 2011, 228 revision TKAs utilizing porous tantalum TMCs with stemmed tibial components were performed at a single institution and were retrospectively reviewed. The mean age at revision was 65 years, the mean body mass index was 33, and 52% were women. Implant survivorship, complications, and clinical and radiographic outcomes were assessed. The mean follow-up was 6.3 years. RESULTS: The 10-year survivorship free of aseptic loosening leading to TMC removal was 97%, free of any TMC removal was 88%, free of any re-revision was 66%, and free of any reoperation was 58%. The most common indications for re-revision were periprosthetic joint infection, instability, and aseptic femoral component loosening. The 10-year nonoperative complication rate was 24%. The mean Knee Society scores increased from 38 preoperatively to 69 at 10 years. There were 8 knees that had evidence of partial, progressive tibial radiolucencies at 10 years. CONCLUSIONS: Porous tantalum TMCs demonstrated persistently durable longer-term survivorship with a low rate of implant removal. The rare implant removals for component loosening or instability were offset by those required for periprosthetic joint infection, which accounted for 80% of cone removals. Porous tantalum TMCs provide an extremely reliable tool to address tibial bone loss and achieve durable long-term fixation in revision TKA. LEVEL OF EVIDENCE: IV.

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BACKGROUND: Tibial bone defects are commonly encountered in revision total knee arthroplasty (rTKA) and can be managed with metaphyseal cones or sleeves. Few studies have directly compared tibial cones and sleeves in rTKA, and none have limited this comparison to the most severe tibial defects. The purpose of this study was to evaluate and compare the outcomes of metaphyseal cones and sleeves for tibial reconstruction in rTKA regarding implant fixation and clinical outcomes. METHODS: A retrospective review was conducted on patients undergoing rTKA in which metaphyseal cones or sleeves were utilized for addressing metaphyseal bone loss (34 cones and 18 sleeves). Tibial bone loss was classified according to the Anderson Orthopaedic Research Institute bone defect classification, with types 2B and 3 being included. Patient-reported outcomes and postoperative complications were collected, and a radiographic evaluation of osseointegration or loosening was performed. RESULTS: There were 52 knees included (34 cones, 18 sleeves), with a median follow-up of 41.0 months. All-cause implant survival was 100% at 2 years and 96% (95% confidence interval: 76 to 99%) at 4 years, with 98% of tibial components demonstrating osseointegration at the final follow-up. During follow-up, there were a total 11 revisions, of which 1 sleeve was revised secondary to implant loosening. Tibial sleeves had a higher risk of revision compared to tibial cones (P < .01), and sleeves fixed with a hybrid technique were more likely to need revision than cones fixed by the same method (P = .01). CONCLUSIONS: Porous metaphyseal tibial cones and tibial metaphyseal sleeves both performed well at a 41-month median follow-up with no difference in aseptic survivorship between the 2 constructs. Both demonstrate high rates of osseointegration, low rates of aseptic failure, and significant improvement in Knee Society Scores in patients with severe tibial defects in rTKA.

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(1) Background. Diabetes mellitus (DM), called the first non-infectious epidemic of the modern era, has long-term health consequences leading to a reduced quality of life, long-term disabilities, and high mortality. Diabetic retinopathy (DR) is a neurovascular complication of diabetes and accounts for about 80% cases of vision loss in the diabetic population. The adaptive optics (AO) technique allows for a non-invasive in vivo assessment of retinal cones. Changes in number or morphology of retinal cones may be one of the first indicators of DR. (2) Methods. This study included 68 DM1 patients (17 women) aged 42.11 ± 9.69 years with a mean duration of diabetes of 22.07 ± 10.28 years, and 41 healthy volunteers (20 women) aged 41.02 ± 9.84 years. Blood pressure, BMI, waist circumference, and metabolic control measures were analysed. Cones' morphological parameters were examined with a retinal camera with Imagine Eyes adaptive optics (rtx1). Statistical analysis was carried out with IMB SPSS version 23 software. (3) Results. Neither study group differed significantly in age, BMI, blood pressure, or eyeball length. Intraocular pressure (IOP) was statistically significantly higher in DM1 patients but remained within physiological range in both groups. Analysis of cone parameters showed a statistically significant lower mean regularity of cones (Rmean) in the DM1 group compared to control group (p = 0.01), with the lowest value in the group with DM1 and hypertension (p = 0.014). In addition, DM1 patients tended to have fewer cones. (4) Conclusions. Our study revealed abnormalities in cone and vessel parameters and these abnormalities should be considered as risk factors for the development of DR. Complementing an eye examination with AO facilitates non-invasive in vivo cellular imaging of the retina. Lesions like those detected in the eye may occur in the brain and certainly require further investigation.