Reversible axonal swelling and brainstem auditory evoked potential (BAEP) changes were observed in standard chronic (9-month) toxicology studies in dogs treated with ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor, at exposures higher than the approved 50-mg human dose. To evaluate the clinical relevance of the dog toxicity finding, this phase 2a, double-blind study assessed BAEP changes and intraepidermal nerve fiber (IENF) histology in adults with alopecia areata treated with ritlecitinib. Patients were randomized to receive oral ritlecitinib 50 mg once daily (QD) with a 4-week loading dose of 200 mg QD or placebo for 9 months (placebo-controlled phase); they then entered the active-therapy extension and received ritlecitinib 50 mg QD (with a 4-week loading dose of 200 mg in patients switching from placebo). Among the 71 patients, no notable mean differences in change from baseline (CFB) in Waves I-V interwave latency (primary outcome) or Wave V amplitude on BAEP at a stimulus intensity of 80 dB nHL were observed in the ritlecitinib or placebo group at Month 9, with no notable differences in interwave latency or Wave V amplitude between groups. The CFB in mean or median IENF density and in percentage of IENFs with axonal swellings was minimal and similar between groups at Month 9. Ritlecitinib treatment was also not associated with an imbalanced incidence of neurological and audiological adverse events. These results provide evidence that the BAEP and axonal swelling finding in dogs are not clinically relevant in humans.

UNASSIGNED: To investigate association between optic disc parameters analyzed by optical coherence tomography (OCT) and occurrence of peripheral retinal tears in patients with symptomatic posterior vitreous detachment (PVD).
UNASSIGNED: This cross-sectional study enrolled 75 patients with symptoms of acute PVD, who were allocated into two groups based on whether a peripheral retinal tear occurred or not.
UNASSIGNED: When comparing the average retinal nerve fiber layer (RNFL) thickness (μm) between retinal tear and control groups, it was shown that patients with a retinal tear have a significantly higher (87.18 [95% confidence interval (CI), 84.47 to 89.9] vs 81.14 [95% CI, 77.81 to 84.46], P = 0.005) average RNFL thickness. Furthermore, we observed a significant difference (0.13, 0.06 to 0.22 vs 0.07, 0.04 to 0.1, P = 0.036, Mann-Whitney U-test) in the size of cup volume (mm3) between the tear and control groups, respectively. Linear regression showed a significant decrease (P = 0.029) in average RNFL thickness with increasing age, but without a significant difference between the two groups. There was no statistically significant difference between the tear and control groups in terms of rim area, disc area, and average cup-to-disc ratio.
UNASSIGNED: Patients with a higher average RNFL thickness and larger cup volume measured by OCT were more prone to develop a peripheral retinal tear. Increased peripapillary average RNFL thickness due to trauma and subsequent inflammation, possibly related to the more adherent posterior hyaloid membrane to the retina, may also indicate strengthened adhesions in the areas of the peripheral retina where retinal tears occur. OCT analysis of the optic nerve head may be used in everyday clinical practice as a predictor of the development of peripheral retinal tears in patients with symptomatic PVD.

UNASSIGNED:

The aim of this study is to comprehensively determine the types of affected fibers in Parkinson’s disease (PD) patients by employing nerve conduction studies (NCS), sympathetic skin response (SSR) examinations, and current perception threshold (CPT) testing and to analyze the correlation between levodopa use and nerve involvement.

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UNASSIGNED:

This retrospective study included 36 clinically diagnosed PD patients who were recruited between January 2018 and April 2019. All patients underwent NCS, SSR testing, and CPT sensory examinations. Additionally, the PD patients were assessed for disease staging using the Hoehn and Yahr (H-Y) scale. 

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UNASSIGNED:

Fifteen patients were included in the tremor-dominant subtype, ten patients in the rigid-dominant subtype, and eleven patients in the mixed subtype. Eleven patients were using levodopa, while twenty-five patients had never used any anti-Parkinson’s medication. Ten patients (28%) showed abnormal sympathetic skin responses (SSR). The CPT examination revealed sensory abnormalities in twenty-four patients (67%), with eighteen patients (75%) experiencing sensory hypersensitivity and six patients (25%) experiencing sensory hypoesthesia. Twelve patients (33%) had normal CPT results. Among the patients with abnormal CPT findings, seven cases (29%) involved large myelinated fiber damage, twenty-two cases (92%) involved small myelinated fiber damage, and nineteen cases (79%) involved unmyelinated fiber damage. The rate of sensory abnormalities was 64% (7/11) in the levodopa group and 68% (17/25) in the non-levodopa group, with no statistically significant difference between the two groups. 

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UNASSIGNED:

The incidence of abnormal CPT findings in PD patients was higher than that of abnormal SSR responses, suggesting that nerve fiber damage primarily affects small fiber nerves (SFN).

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UNASSIGNED:

E vizsgálat célja, hogy átfogóan meghatározza az érintett rostok típusait Parkinson-kóros (PD-) betegeknél idegvezetési vizsgálatok (NCS), szimpatikus bőrválasz- (SSR-) vizsgálatok és áramérzékelési küszöb- (CPT-) tesztek alkalmazásával, valamint hogy elemezze a levodopahasználat és az idegek érintettsége közötti összefüggést.

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UNASSIGNED:

Ebbe a retrospektív vizsgálatba 36 klinikailag diagnosztizált PD-beteget vontunk be, akiket 2018 januárja és 2019 áprilisa között vizsgáltak klinikánkon. Minden betegnél NCS-, SSR- és CPT szenzoros vizsgálatokat végeztek. A betegeket a Hoehn és Yahr (H-Y) skála segítségével betegségstá-diumba sorolták. 

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UNASSIGNED:

Tizenöt beteg tartozott a tremordomináns-altípusba, 10 beteg a rigiditásdomináns-altípusba és 11 beteg a kevert altípusba. Tizenegy beteg használt levodopát, míg 25 beteg soha nem alkalmazott semmilyen PD-ellenes gyógyszert. Tíz betegnél (28%) mutattak ki kóros szim-patikus bőrreakciót (SSR). A CPT-vizsgálat 24 betegnél (67%) mutatott ki szenzoros eltéréseket, közülük 18 betegnél (75%) szenzoros túlérzékenységet, hat betegnél (25%) pedig szenzoros hypoesthesiát. Tizenkét beteg (33%) CPT-eredményei normálisak voltak. A kóros CPT-leletet mutató betegek közül hét esetben (29%) a nagy myelinizált rostok károsodása, 22 esetben (92%) a kis myelinizált rostok károsodása, 19 esetben (79%) pedig a nem myelinizált rostok károsodása fordult elő. A szenzoros eltérések aránya 64% (7/11) volt a levodopacsoportban és 68% (17/25) a nem levodopacsoportban; a két csoport között nem volt statisztikailag szignifikáns különbség. 

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UNASSIGNED:

A kóros CPT-leletek előfordulási gyakorisága a PD-betegeknél magasabb volt, mint a kóros SSR-válaszoké. Ez arra utal, hogy az idegrostok károsodása elsősorban a kis idegrostokat (SFN) érinti.

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UNASSIGNED: This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs).
UNASSIGNED: A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA). Additionally, optical coherence tomography (OCT) was used to measure the thickness of the retinal nerve fiber layer (RNFL).
UNASSIGNED: The mean SE was -1.58 ± 3.71 diopters (D). The mean AXL was 18.76 ± 0.86 mm. The prevalence rate of high myopia was 17.7%. As myopia aggravated, the AXL increased (r = -0.498, P < 0.001). Compared with non-high myopia, highly myopic eyes had a greater AXL (P < 0.001), less RNFL thickness (P = 0.004), a higher incidence of PPA (P < 0.001), and elevated grades of fundus tessellation (P < 0.001). The binary logistic regression was performed, which showed PPA (odds ratio [OR] = 4.924, 95% confidence interval [CI] = 2.375-10.207, P < 0.001) and higher grades of fundus tessellation (OR = 1.865, 95% CI = 1.474-2.361, P < 0.001) were independent risk characteristics for high myopia.
UNASSIGNED: In NHPs, a higher grade of fundus tessellation and PPA were significant biomarkers of high myopia.
UNASSIGNED: The study demonstrates adult NHPs raised in conditioned rooms have a similar prevalence and highly consistent fundus changes with human beings, which strengthens the foundation for utilizing macaques as an animal model in high myopic studies.

OBJECTIVE: To study the fellow eyes of patients with unilateral primary congenital glaucoma (PCG) using optical coherence tomography angiography (OCTA) and compare them to normal age- and refractive error-matched healthy controls.
METHODS: Using OCTA, the foveal avascular zone (FAZ) area, cup:disk ratio, vessel density (VD) of the optic nerve head (ONH) and peripapillary area and the macular VD in superficial (SCP) and deep vascular complexes in both 3 mm and 6 mm scans of both groups were compared. Clinical data included best-corrected visual acuity (BCVA), cycloplegic refraction, intraocular pressure (IOP), anterior and posterior segments examination findings, including ONH cup:disk ratio.
RESULTS: A total of 48 eyes of 48 children (24 eyes in each group) were included. There was no difference in the mean retinal nerve fiber layer thickness, cup:disk ratio, baseline visual acuity, or spherical equivalent between groups (P > 0.05). In the 3 mm macular scan, the VD of the SCP at the fovea was significantly higher in the PCG group compared to controls (P = 0.04). In the ONH scans, there was a significantly reduced inside the disk VD in the PCG group compared to controls (P = 0.03). There was no significant difference in other macular and ONH vascular parameters between groups (P > 0.05).
CONCLUSIONS: In our study cohort, there was no difference in most of the macular and ONH vascular parameters between groups. However, the fellow eyes of PCG patients exhibited higher VD of the SCP at the fovea and reduced inside the disk VD compared with control eyes.

OBJECTIVE: We aimed to evaluate retinal nerve fiber and choroidal layer alterations in adolescents with anorexia nervosa using spectral-domain optical coherence tomography.
METHODS: Thirty patients with anorexia nervosa and 30 healthy adolescents aged 12-18 years were included in this study. Their age, sex, body mass index, anorexia nervosa type, disease duration, and spectral-domain optical coherence tomography data were recorded.
RESULTS: Central macular thickness and retinal nerve fiber layer thickness in the temporal and inferior regions were significantly lesser in patients with anorexia than in healthy controls (p<0.05). Moreover, significant choroidal thinning around the foveal and subfoveal regions in patients with anorexia was observed (p<0.05). In addition, a statistically significant relation between the increase in disease duration and the thinning of the inferior retinal nerve fiber layer was detected (p<0.05).
CONCLUSIONS: The retinal nerve fiber layer and choroidal layer thicknesses were lesser in patients with anorexia than in healthy controls. Screening for retinal indices might prevent the development of irreversible retinal pathologies in adolescents with anorexia nervosa. In addition, thinning of the retinal nerve fiber and choroidal layers could reflect structural or functional changes in the brain of adolescents with anorexia nervosa.

OBJECTIVE: The present study tested the hypothesis that repeated anti-VEGF injections are associated with reduced retinal nerve fiber layer (RNFL) and minimum rim width (MRW) of the optic nerve head.
METHODS: Sixty-six patients with a history of intravitreal injections due to neovascular age-related macular degeneration were included. RNFL and MRW were measured using optical coherence tomography (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany).
RESULTS: Mean global RNFL was 90.62 μm and both RNFL as well as MRW significantly decreased with advanced age (p = 0.005 and p = 0.019, respectively). Correlating for the number of injections, no significant impact on RNFL was found globally (p = 0.642) or in any of the sectors. In contrast, however, global MRW was significantly reduced with increasing numbers of intravitreal injections (p = 0.012). The same holds true when adjusted for the confounding factor age (RNFL p = 0.566 and MRW p = 0.023).
CONCLUSIONS: Our study shows that repeated intravitreal injections due to choroidal neovascularization seem to have a deleterious effect on MRW but not on RNFL. This suggests that MRW is a more sensitive marker than RNFL for evaluating the effect of frequent intravitreal injections on the optic nerve head since it seems to be the first structure affected.

UNASSIGNED: The aim of this study was to investigate the association between myopia and longitudinal changes in peripapillary retinal nerve fiber layer (pRNFL) thickness in type 2 diabetic patients without diabetic retinopathy (DR).
UNASSIGNED: A total of 1069 participants with a median follow-up time of 1.9 years were included in this study. The participants were categorized into four groups based on the presence of myopia (≤ -0.5 diopter [D]) and diabetes without DR, including a control group (n = 412), diabetes group (n = 416), myopia group (n = 115), and diabetes + myopia group (n = 126). Peripapillary average and sectoral RNFL measurements were obtained using 6 × 6 mm swept-source optical coherence tomography (SS-OCT) scans centered at the optic disc. The change rate of pRNFL, adjusted for age and sex, was calculated and compared among the four groups to investigate the impact of myopia and diabetes.
UNASSIGNED: The baseline estimated pRNFL thickness after adjustment for covariates was 113.7 μm, 116.2 μm, 108.0 μm, and 105.6 μm in the control, diabetes, myopia, and diabetes + myopia group, respectively (diabetes > control > myopia = diabetes + myopia, p < 0.001). The respective average pRNFL loss in the four groups was -0.48 μm/year, -1.11 μm/year, -1.23 μm/year, and -2.62 μm/year (all p < 0.01). The diabetes + myopia group exhibited a greater rate of average pRNFL reduction compared to the other groups (all p < 0.001). Multivariate analysis using a linear mixed-effects model showed that age, diabetes, axial length (AL), and baseline pRNFL thickness were significantly associated with the rate of average pRNFL reduction.
UNASSIGNED: The diabetes group showed a faster rate of average pRNFL thickness reduction compared to healthy controls, regardless of the presence of myopia. The average pRNFL thickness decreased more rapidly when diabetes and myopia were present simultaneously than in the individual diabetes or myopia group. Both diabetes and myopia were associated with accelerated pRNFL loss.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disorder. Diagnosis is challenging due to its clinical heterogeneity and the absence of definitive diagnostic tools, leading to delays averaging between 9.1 and 27 months. In vivo corneal confocal microscopy, assessing the sub-basal nerve plexus of the cornea, has been proposed as a potential biomarker for ALS. We aimed to determine whether the assessment of corneal nerves using in vivo confocal microscopy can serve as an imaging biomarker for ALS.
METHODS: A single-centre prospective case-control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria. The corneal sub-basal nerve plexus was analysed using in vivo confocal microscopy. An automated algorithm (ACCMetrics) was used to evaluate corneal parameters: nerve fibre density, nerve branch density, nerve fibre length, nerve fibre area, nerve total branch density, nerve fibre width, and nerve fractal dimension.
RESULTS: Twenty-two patients with ALS and 30 controls were included. No significant differences were found between ALS and control groups for all corneal parameters (p > 0.05). Corneal sensitivity did not differ between groups, and no correlation was identified between corneal nerve parameters and ALS disease duration, severity and rate of progression (p > 0.05).
CONCLUSIONS: The present study does not support the use of in vivo corneal confocal microscopy as an early diagnostic or prognostic tool for ALS. Further research, especially longitudinal investigations, is needed to understand any potential corneal innervation changes as ALS progresses.

OBJECTIVE: To identify specific markers indicative of macular neural and microvascular alterations in individuals with Type 2 Diabetes Mellitus (T2DM) without clinically observable retinopathy.
METHODS: Prospective cross-sectional study.
METHODS: Using the PLEX Elite 9000, all eyes underwent swept-source optical coherence tomography (SS-OCT) angiography. Quantitative analysis of acquired images compared macular neural and microvascular alterations in T2DM patients without retinopathy to age-matched controls. Precise assessments encompassed measuring the thickness of each individual retinal layer and evaluating macular vascular indices within different capillary plexuses.
RESULTS: Forty-nine T2DM patients and 51 age-matched controls participated. T2DM patients exhibited a significant reduction in the mean macular thickness of the ganglion cell-inner plexiform layer (GC-IPL) (82.5 ± 5.5 µm vs 86.2 ± 5.0 µm, P = .001) and macular retinal nerve fiber layer (RNFL) (45.8 ± 3.0 µm vs 48.1 ± 3.7 µm, P = .001). Furthermore, macular full retinal thickness was significantly lower in diabetic eyes than controls (324.9 ± 16.3 µm vs 332.8 ± 13.7 µm, P = .009). Vascular measurements revealed subtle changes in macular vascular skeleton density within the total capillary plexuses in T2DM patients (0.132 ± 0.005 vs 0.135 ± 0.005, P = .019).
CONCLUSIONS: Metrics derived from SS-OCT, particularly macular RNFL and GC-IPL thicknesses, emerged as superior indicators for the early detection of diabetic retinal disease in individuals with T2DM without clinically observable retinopathy. Further investigations are warranted to comprehensively understand the clinical implications of these findings.