Keeping track of time: An interaction of mossy fibers and climbing fibers.

Precisely tracking time over second-long timescales is important for accurate anticipation and consequential actions, yet the neurobiological underpinnings remain unknown. In this issue of Neuron, Garcia-Garcia and colleagues1 show that computations in the cerebellum resulting from interactions between the mossy fiber and climbing fiber pathways contribute to long-interval learning during operant conditioning.

A cross-sectional study on the impact of hemodialysis duration on retinal nerve fiber layer thinning in hemodialysis patients.

This study aimed to investigate the relationship between hemodialysis duration (HDD) and retinal nerve fiber layer (RNFL) thickness. A total of 60 patients receiving maintenance hemodialysis and 67 healthy controls were analyzed. Spectral domain optical coherence tomography (SD-OCT) was employed to measure annular RNFL thicknesses. The hemodialysis group exhibited reduced temporal and inferior RNFL thicknesses relative to the control group. In hemodialysis patients, the inferior RNFL thickness was negatively correlated with HDD and positively correlated with intraocular pressure (IOP). Moreover, IOP was positively correlated with HDD. Mediation analysis showed that the negative correlation between HDD and inferior RNFL thickness was mediated by IOP. In conclusion, hemodialysis leads to temporal and inferior RNFL thinning, and the thickness reduction is proportional to hemodialysis duration. However, such changes are not induced by an increase in IOP.

Peripheral Ganglion Cell Complex Thickness and Retinal Microvasculature in Myopia Using Wide-Field Swept-Source OCT.

Purpose: This study aims to investigate the impact of axial elongation on ganglion cell complex thickness (GCCT) and retinal capillary density (CD) using wide-field swept-source optical coherence tomography angiography. Methods: A retrospective cross-sectional analysis was conducted involving 506 eyes. Fovea-centered scans were obtained to assess the subregional GCCT and capillary density across the whole retina, the superficial capillary plexus (SCP), and deep capillary plexus (DCP) among three groups: normal control, high myopia (HM) eyes with axial length < 28 mm, and HM eyes with axial length > 28 mm. Regional variations (central vs. peripheral, quadrants difference [superior, inferior, nasal, and temporal]) were analyzed. Results: In HM eyes with axial length > 28 mm, GCCT and retinal CD exhibit a general decline in most regions (P < 0.05). In HM eyes with axial length < 28 mm, significant reductions were observed specifically in peripheral regions, as in the GCCT beyond the 3 × 3 mm2 area and CD in the 9-12 mm whole retina, 9-12 mm superior SCP, and 6-12 mm DCP (P < 0.05). Maximum GCCT and retinal CD reduction with axial elongation was observed in subregions beyond 6 × 6  mm2. Conclusions: GCCT beyond the 3 × 3 mm2 area and peripheral retinal CD beyond the 6 × 6  mm2 area were more susceptible to axial elongation and are thereby deserving of particular attention. Translational Relevance: It is necessary to evaluate different regions during the clinical assessment of the effect of myopia on the fundus and pay close attention to the peripheral retina.

Effect of magnification error and axial length on circumpapillary capillary density and retinal nerve fiber layer thickness.

This study aimed to evaluate the effect of magnification error and axial length (AL) on circumpapillary capillary density (cpCD) and circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in healthy eyes. Seventy-two healthy eyes of 72 subjects with AL 24.7 ± 1.5 mm (range: 20.9-28.0 mm) were enrolled in this retrospective cross-sectional study and underwent optical coherence tomography angiography scanning. Magnification corrected measurement areas were obtained using AL upon which corrected cpCD, cpRNFLT values were determined. Relationships between AL and the percentage difference between corrected and uncorrected values (ΔcpCD, ΔcpRNFLT) as well as the effect of AL on magnification corrected cpCD, cpRNFLT were evaluated. ΔcpCD significantly increased with AL in the global, inferior nasal and superior nasal sectors (all p < 0.001). ΔcpRNFLT significantly increased with AL in global and all sectors (all p < 0.001) and the correlations were significantly stronger than that of ΔcpCD-AL in all sectors (all p < 0.001). Corrected cpCD did not associate with AL while corrected cpRNFLT demonstrated a significant positive association with AL in the global (p = 0.005) and temporal sector (p < 0.001). Magnification error led to a significant underestimation of cpCD in eyes with longer AL although its underestimation and the effect of AL was smaller in comparison to that of cpRNFLT.

Clinical follow-up investigation on thickness changes in the peripapillary retinal nerve fibre layer of patients with Leber hereditary optic neuropathy.

BACKGROUND: To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients. METHODS: Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery. RESULTS: This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months. CONCLUSION: The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase.

Detecting Visual Field Worsening From Optic Nerve Head and Macular Optical Coherence Tomography Thickness Measurements.

Purpose: Compare the use of optic disc and macular optical coherence tomography measurements to predict glaucomatous visual field (VF) worsening. Methods: Machine learning and statistical models were trained on 924 eyes (924 patients) with circumpapillary retinal nerve fiber layer (cp-RNFL) or ganglion cell inner plexiform layer (GC-IPL) thickness measurements. The probability of 24-2 VF worsening was predicted using both trend-based and event-based progression definitions of VF worsening. Additionally, the cp-RNFL and GC-IPL predictions were combined to produce a combined prediction. A held-out test set of 617 eyes was used to calculate the area under the curve (AUC) to compare cp-RNFL, GC-IPL, and combined predictions. Results: The AUCs for cp-RNFL, GC-IPL, and combined predictions with the statistical and machine learning models were 0.72, 0.69, 0.73, and 0.78, 0.75, 0.81, respectively, when using trend-based analysis as ground truth. The differences in performance between the cp-RNFL, GC-IPL, and combined predictions were not statistically significant. AUCs were highest in glaucoma suspects using cp-RNFL predictions and highest in moderate/advanced glaucoma using GC-IPL predictions. The AUCs for the statistical and machine learning models were 0.63, 0.68, 0.69, and 0.72, 0.69, 0.73, respectively, when using event-based analysis. AUCs decreased with increasing disease severity for all predictions. Conclusions: cp-RNFL and GC-IPL similarly predicted VF worsening overall, but cp-RNFL performed best in early glaucoma stages and GC-IPL in later stages. Combining both did not enhance detection significantly. Translational Relevance: cp-RNFL best predicted trend-based 24-2 VF progression in early-stage disease, while GC-IPL best predicted progression in late-stage disease. Combining both features led to minimal improvement in predicting progression.

Can the diameter of nerve fibers be effectively utilized to enhance the accuracy of determining the length of the aganglionic segment compared to intraoperative biopsy in patients with Hirschsprung's disease?

OBJECTIVE: The aim of this study is to investigate the accuracy of utilizing neural fiber trunk diameter in accurately diagnosing the length of the aganglionic segment in patients definitively diagnosed with Hirschsprung's disease. RESULTS: In this study, 40 patients (19 males, 21 females; mean age 2.5 ± 2.2646 years) were assessed for Hirschsprung's disease. Constipation was the main symptom (75%), followed by abdominal issues. All underwent contrast enema and rectal suction biopsy for diagnosis, followed by surgery (predominantly Soave and Swensen techniques). Majority (85%) had rectosigmoid involvement. Neural fiber diameter was measured, with 52.5% ≤40 µm and 47.5% >40 µm. Statistical analysis showed 40% sensitivity(CI:95%) and 47% specificity(CI:95%) with a cutoff of 40.5 µm. Cohen's kappa index for aganglionic segment size was 0.7.

Tracing nerve fibers with volume electron microscopy to quantitatively analyze brain connectivity.

The highly complex structure of the brain requires an approach that can unravel its connectivity. Using volume electron microscopy and a dedicated software we can trace and measure all nerve fibers present within different samples of brain tissue. With this software tool, individual dendrites and axons are traced, obtaining a simplified "skeleton" of each fiber, which is linked to its corresponding synaptic contacts. The result is an intricate meshwork of axons and dendrites interconnected by a cloud of synaptic junctions. To test this methodology, we apply it to the stratum radiatum of the hippocampus and layers 1 and 3 of the somatosensory cortex of the mouse. We find that nerve fibers are densely packed in the neuropil, reaching up to 9 kilometers per cubic mm. We obtain the number of synapses, the number and lengths of dendrites and axons, the linear densities of synapses established by dendrites and axons, and their location on dendritic spines and shafts. The quantitative data obtained through this method enable us to identify subtle traits and differences in the synaptic organization of the samples, which might have been overlooked in a qualitative analysis.

Retinal imaging with hand-held optical coherence tomography in older people with or without postoperative delirium after hip fracture surgery: A feasibility study.

INTRODUCTION: Postoperative delirium in older people may result from the interaction between intrinsic brain vulnerability (e.g. neurodegeneration) and precipitating factors (e.g. surgery induced cytokines). Intrinsic brain vulnerability may be overt (e.g. Alzheimer's disease) or preclinical. In cognitively intact older people presenting for surgery, identification of preclinical neurodegeneration using bedside tools could aid postoperative delirium risk stratification. Thinning of the circumpapillary retinal nerve fibre layer thickness is associated with neurodegenerative disorders e.g. Alzheimer's disease. We propose that thinning of the retinal nerve fibre layer may be present some older people with postoperative delirium due to preclinical neurodegeneration, albeit to a lesser extent than in overt dementia. OBJECTIVES: The primary objective: Feasibility of acquiring usable retinal images with the hand-held optical coherence device, at the bedside of older, hip fracture surgery patients. Secondary objective: Comparison of the circumpapillary retinal nerve fibre layer thickness between people who did/did not have postoperative delirium. Proportion of exclusions due to retinal pathology. METHOD: Feasibility study involving 30, cognitively intact, older people recovering from hip fracture surgery. Retinal images were obtained using the hand-held optical coherence tomography device at the participants' bedside. Imaging was deferred in participants who had postoperative delirium. RESULTS: Retinal images that could be assessed for circumpapillary retinal nerve fibre layer thickness were obtained in 26 participants (22 no postoperative delirium, 4 postoperative delirium). The mean circumpapillary retinal nerve fibre layer thickness was lower in the participants who had postoperative delirium compared to those who did not experience postoperative delirium (Mean (95% CI) of 76.50 (62.60-90.40) vs 89.19 (85.41-92.97) respectively). CONCLUSION: Retinal imaging at the patient's bedside, using hand-held OCT is feasible. Our data suggests that the circumpapillary retinal nerve fibre layer may be thinner in older people who experience postoperative delirium compared to those who do not. Further studies are required.

A phase 2a study investigating the effects of ritlecitinib on brainstem auditory evoked potentials and intraepidermal nerve fiber histology in adults with alopecia areata.

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.

Wide-Field Optical Coherence Tomography Imaging Improves Rate of Change Detection in Progressing Glaucomatous Eyes Compared With Standard-Field Imaging.

Purpose: To compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images. Methods: Forty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube scans centered on the fovea. Visual field progression was defined as guided progression analysis likely progression and/or a significant (P < 0.01) mean deviation slope of less than -1.0 dB/year. Mixed effects models were used to compare rates of change. Highly myopic eyes were included. Results: Thirty glaucomatous eyes were classified as progressing. In eyes with glaucoma, mean global rate of change was -1.22 µm/year (P < 0.001) using SWF images and -0.83 µm/year (P = 0.003) using ONH cube scans. Rate of change was significantly greater in eyes with progressing glaucoma compared with eyes with nonprogressing glaucoma (-1.51 µm/year vs. -1.24 µm/year; P = 0.002) using SWF images and was similar using ONH cube scans (P = 0.27). Conclusions: In this cohort that includes eyes with and without high axial myopia, the mean rate of retinal nerve fiber layer thinning measured using SWF images was faster in eyes with progressing glaucoma than in eyes with nonprogressing glaucoma. Wide-field OCT images including the ONH and macula can be effective for monitoring glaucomatous progression in patients with and without high myopia.

Comparative analysis of changes in retinal layer thickness following femtosecond laser-assisted cataract surgery and conventional cataract surgery.

BACKGROUND: To investigate the influence of femtosecond laser-assisted cataract surgery (FLACS) on macula by examining changes in retinal layers after FLACS and to compare these changes with those after conventional cataract surgery (CCS). METHODS: This study included 113 unrelated Korean patients with age-related cataract who underwent CCS or FLACS in Severance Hospital between September 2019 and July 2021. Optical coherence tomography was performed before and 1 month after surgery. The total retinal layer (TRL) was separated into the inner retinal layer (IRL) and outer retinal layer (ORL); moreover, the IRL was subdivided into the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer (INL), outer plexiform layer, and outer nuclear layer. We performed between-group comparisons of the postoperative thickness in each retinal layer and the postoperative differences in retinal thickness. The average retinal thickness of the four inner macular ring quadrants was used for comparative analysis. RESULTS: Compared with the CCS group, the FLACS group exhibited a thicker ORL (P = 0.004) and a thinner INL (P = 0.007) after surgery. All retinal layer thickness values showed significant postoperative changes regardless of the type of surgery (P < 0.05). The postoperative increase in TRL and IRL thickness was significantly smaller in the FLACS group than in the CCS group (P = 0.027, P = 0.012). CONCLUSIONS: The 1-month postoperative retinal changes were less pronounced in the FLACS group than in the CCS group.

Comparative Analysis of Retinal Structural and Angiographic Parameters in Diabetic Patients, Alzheimer's Disease Patients, and Healthy Controls: An OCT-Based Study.

Objective: This study aimed to investigate the potential connections between Alzheimer's Disease (AD) and diabetes. Methods: This is a cross-sectional study in which AD and diabetes patients sent by the Psychiatry and Diabetes Departments for ophthalmological screening were observed for inclusion/exclusion criteria. Patients were divided into two comparison groups. The first group (n=3) consisted of the age-matched normal and diabetic patient of the stage 3 AD disease participant. The second group (n=3) was for the stage 5 AD patient with diabetes and normal age-matched controls. Each patient underwent a full ophthalmological examination and SS-OCT (Swept Source-Ocular Computer Tomography) for retinal evaluation. Results: A total of 6 patients (12 eyes) were obtained, three men and three women. In the early AD group, the patient with diabetes showed lower macular thickness compared to other groups. In the nasal-inferior (NI) and temporal-superior (TS) ganglion cell layer (GCL), the AD patient showed statistically significant lower values compared to the other patients. In the moderately severe AD group, we found that the AD patient had lower retinal nerve fiber layer (RNFL) thickness on the temporal side compared to the rest of the patients and both the AD patient and diabetes patient showed lower RNFL thickness in the nasal-superior (NS) quadrant. Also, the foveal avascular zone (FAZ) area was statistically significantly lower for both the diabetes and AD patients compared to the healthy control. Conclusions: In conclusion, distinct retinal findings associated with AD and diabetes in young and elderly patients were revealed in our study. The clinical implications and potential interplay between these conditions need to be elucidated by further research. Abbreviations: AD = Alzheimer's Disease, SS-OCT = Swept Source - Ocular Computer Tomography, GCL = Ganglion cell layer, RNFL = Retinal nerve fiber layer, FAZ = foveal avascular zone.

Correlation of pre-operative and post-operative retinal nerve fibre layer thickness with visual outcome following decompression of pituitary macroadenoma.

OBJECTIVE: To (i) correlate preoperative retinal nerve fibre layer (RNFL) thickness with visual parameters in patients with pituitary macroadenomas. (ii) study the predictive role of preoperative RNFL in visual outcome following surgery for pituitary macroadenomas (iii) correlate change in postoperative RNFL thickness (RNFLT) with visual outcome. METHODS: Preoperative and post-operative RNFL thickness of thirty-three consecutive patients operated for pituitary macro adenoma between June 2022 and May 2023 were measured using Optical Coherence Tomography (OCT) and compared with standard visual examination findings and Magnetic Resonance Imaging (MRI) measurements. RESULTS: A total of 66 eyes of 33 patients who underwent surgical excision of pituitary macro adenoma between June 2022 and May 2023 were studied. The mean age in years of the study group was 44.36 ± 13.77 and both sexes were equally represented (Male: Female = 16:17). RNFL thinning predominantly involved the temporal (51.21+/-15.19 µm) followed by nasal quadrants (62.67+/- 17.03 µm) and correlated well with the visual field (VF) deficit (p <0.001). Patients with severe disc pallor had extremely thin RNFL (less than 67 +/- 8.68 µm). Patients with moderate to severe visual acuity (VA) deficits had significantly thinner RNFLs (65.08±7.09) compared to patients with normal to mild impairment in vision. (83.185±1.2) (p<0.05). RNFL values were significantly thinner for patients with Wilson Grade C, D and E tumours (66.13 ±12.19 µm) compared to those in Grade A and B (77.67±22.12 µm). The mean preop RNFL of patients who showed post-operative improvement in vision was 87.025± 15.02 µm, of patients in whom vision remained static was 74.58 ±18.31 µm. The mean VA (Decimal) increased from a minimum of 0.60 at the pre-operative timepoint to a maximum of 0.68 at the post-operative timepoint. (Wilcoxon Test: V = 42.5, p = <0.001). The mean RNFLT (µm) increased from 77.14 µm at the pre-operative timepoint to 83.77 µm at the post-operative timepoint. (Wilcoxon Test: V = 218.0, p = <0.001). The mean change of RNFL in patients in whom vision improved was 3.6 µm and the mean change of RNFL in patients in whom vision remained static was 9.51 µm. Absence of postoperative visual improvement was noted despite postoperative RNFL thickness improvement in eyes which showed significant preoperative thinning of the nasal (<65 µm) and temporal (<52µm) quadrants. CONCLUSION: RNFL thinning corelates directly with visual acuity, visual field, and optic disc pallor. Patients with pituitary adenoma have preferential thinning of temporal and nasal quadrants. Visual outcome is better in patients with preserved RNFLT of values more than 82 +/- 5 µm. Reversal of RNFL thinning postoperatively need not necessarily correlate with visual improvement especially in patients who showed significant preoperative thinning of nasal and temporal quadrants.

Independent Effects of Blood Pressure on Intraocular Pressure and Retinal Ganglion Cell Degeneration: A Mendelian Randomization Study.

Purpose: To investigate the causal effect of elevated blood pressure on primary open-angle glaucoma (POAG) and POAG endophenotypes. Methods: Two-sample Mendelian randomization (MR) was performed to investigate the causal effect of elevated systolic blood pressure (SBP) (N = 757,601) and diastolic blood pressure (DBP) (N = 757,601) on intraocular pressure (IOP) (N = 139,555), macular retinal nerve fiber layer (mRNFL) thickness (N = 33,129), ganglion cell complex (GCC) thickness (N = 33,129), vertical cup-to-disc ratio (VCDR) (N = 111,724), and POAG liability (Ncases = 16,677, Ncontrols = 199,580). The primary analysis was conducted using the inverse-variance weighted approach. Sensitivity analyses were performed to investigate robustness to horizontal pleiotropy, winner's curse, and collider bias. Multivariable MR was performed to investigate whether any effect of blood pressure on retinal ganglion cell degeneration was mediated through increased IOP. Results: Increased genetically predicted SBP and DBP associated with an increase in IOP (0.17 mm Hg [95% CI = 0.11 to 0.24] per 10 mm Hg higher SBP, P = 5.18 × 10-7, and 0.17 mm Hg [95% CI = 0.05 to 0.28 mm Hg] per 10 mm Hg higher DBP, P = 0.004). Increased genetically predicted SBP associated with a thinner GCC (0.04 µm [95% CI = -0.07 to -0.01 µm], P = 0.018) and a thinner mRNFL (0.04 µm [95% CI = -0.07 to -0.01 µm], P = 0.004), an effect that arises independently of IOP according to our mediation analysis. Neither SBP nor DBP associated with VCDR or POAG liability. Conclusions: These findings support a causal effect of elevated blood pressure on retinal ganglion cell degeneration that does not require intermediary changes in IOP. Targeted blood pressure control may help preserve vision by lowering IOP and, independently, by preventing retinal ganglion cell degeneration, including in individuals with a normal IOP.

Linking physiology and demographics, non-ocular pathology and pharmaceutical drug use to standard OCT measures of the inner retina: The PPP project.

PURPOSE: To assess the associations between physiology and demographics, non-ocular pathology and pharmaceutical drug use against peri-papillary retinal nerve fibre layer thickness (pRNFL T) and other optical coherence tomography (OCT) inner retinal measures in normal, healthy eyes. METHODS: A retrospective, cross-sectional study of 705 consecutive participants with bilateral normal, healthy optic nerves and maculae. PRNFL Ts, vertical cup/disc ratio (CDR), cup volume and macular ganglion cell layer-inner plexiform layer (GCL-IPL) Ts were extracted from Cirrus OCT scans, then regressed against predictor variables of participants' physiology and demographics (eye laterality, refraction, intraocular pressure [IOP], age, sex, race/ethnicity, etc.) and non-ocular pathology and pharmaceutical drug use according to the World Health Organisation classifications. Associations were assessed for statistical significance (p < 0.05) and clinical significance (|ß| > 95% limits of agreement for repeated measures). RESULTS: A multitude of non-ocular pathology and pharmaceutical drug use were statistically and clinically significantly associated with deviations in standard OCT inner retinal measures, exceeding the magnitude of other factors such as age, IOP and race/ethnicity. Thinner inner retina and larger optic nerve cup measures were linked to use of systemic corticosteroids, sex hormones/modulators, presence of vasomotor/allergic rhinitis and other diseases and drugs (up to -29.3 [-49.88, -8.72] µm pRNFL T, 0.31 [0.07, 0.54] vertical CDR, 0.29 [0.03, 0.54] mm3 cup volume and -10.18 [-16.62, -3.74] µm macular GCL-IPL T; all p < 0.05). Thicker inner retina and smaller optic nerve cup measures were diffusely associated with use of antineoplastic agents, presence of liver or urinary diseases and other diseases and drugs (up to 67.12 [64.92, 69.31] µm pRNFL T, -0.31 [-0.53, -0.09] vertical CDR, -0.06 [-0.11, 0] mm3 cup volume and 28.84 [14.51, 43.17] µm macular GCL-IPL T; all p < 0.05). CONCLUSION: There are a multitude of systemic diseases and drugs associated with altered OCT inner retinal measures, with magnitudes far exceeding those of other factors such as age, IOP and race/ethnicity. These systemic factors should at least be considered during OCT assessments to ensure precise interpretation of normal versus pathological inner retinal health.

Assessment of neuropathy subtypes in type 1 diabetes.

INTRODUCTION: Diabetic polyneuropathy (DPN), a common complication of diabetes, can manifest as small, large, or mixed fiber neuropathy (SFN, LFN, and MFN, respectively), depending on the type of fibers involved. Despite evidence indicating small fiber involvement prior to large fiber involvement in type 1 diabetes mellitus (T1DM)-associated DPN, no evidence has been produced to determine the more prevalent subtype. We aim to determine the more prevalent type of nerve fiber damage-SFN, LFN, and MFN-in T1DM-associated DPN, both with and without pain. RESEARCH DESIGN AND METHODS: In this cross-sectional study, participants (n=216) were divided into controls; T1DM; T1DM with non-painful DPN (NP-DPN); and T1DM with painful DPN (P-DPN). DPN was further subgrouped based on neuropathy severity. The more prevalent type of fiber damage was determined applying small and large fiber-specific tests and three diagnostic models: model 1 (≥1 abnormal test); model 2 (≥2 abnormal tests); and model 3 (≥3 abnormal tests). RESULTS: MFN showed the highest prevalence in T1DM-associated DPN. No differences in neuropathy subtype were found between NP-DPN and P-DPN. DPN, with prevalent SFN plateaus between models 2 and 3. All models showed increased prevalence of MFN according to DPN severity. Model 3 showed increased DPN with prevalent LFN in early neuropathy. DPN with prevalent SFN demonstrated a similar, but non-significant pattern. CONCLUSIONS: DPN primarily manifests as MFN in T1DM, with no differentiation between NP-DPN and P-DPN. Additionally, we propose model 2 as an initial criterion for diagnosing DPN with a more prevalent SFN subtype in T1DM. Lastly, the study suggests that in mild stages of DPN, one type of nerve fiber (either small or large) is more susceptible to damage.

Retinal sublayer analysis in juvenile systemic lupus erythematosus without lupus retinopathy.

INTRODUCTION: We aimed to analyze the thicknesses of the retinal sublayer and peripapillary retinal nerve fiber layer (pRNFL) in patients with juvenile systemic lupus erythematosus (JSLE) without lupus retinopathy. METHODS: Thirty-six patients with JSLE (36 eyes) and 30 control subjects (30 eyes) were included retrospectively. Demographic data, disease duration, and clinical manifestations were recorded. Optical coherence tomography was used to examine the macula and optic disc. The thicknesses of the retina, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), and pRNFL were measured. The correlation between the thickness of retina and disease duration, erythrocyte sedimentation rate (ESR) were investigated. RESULTS: The retinal thicknesses of I3 and T3 were thinner in the JSLE group than in the control group (P = 0.019, P = 0.043, respectively). The thicknesses of the I3 and S6 sectors of the GCL decreased significantly (P = 0.013, and P = 0.022, respectively). The thickness of the S6 sector of the IPL was reduced in the JSLE group compared with the control group (P = 0.047). The JSLE group showed significant decrease in the thickness of the central sector of the ONL (P = 0.034). No statistically significant differences in INL, OPL, RPE, and pRNFL thicknesses were found. The retinal thicknesses of I3 (r = -0.386, P = 0.020) and T3 (r = -0.384, P = 0.021) presented negative associations with ESR, but had no significant correlations with disease duration. CONCLUSIONS: Retinal thinning was observed in patients with JSLE without lupus retinopathy, and this change was more pronounced in the inner layer. Key Points • Retinal thinning occurs in JSLE patients without lupus retinopathy. • Changes in retinal thicknesses are related to the ESR.

Analysis of macular thickness and peripapillary retinal nerve fiber layer thickness in various ABO and Rh blood groups.

PURPOSE: To determine the association between ABO and Rh blood groups with retinal structural indices including macular thickness and peripapillary retinal nerve fiber layer (RNFL) thickness. METHODS: This cross-sectional study was conducted using convenience sampling in a tertiary referral eye hospital in Tehran, Iran. Study participants were referred to the hospital laboratory to test their blood group. Ocular examinations were performed including measurement of visual acuity, auto-refraction, subjective refraction, and slit-lamp biomicroscopy. Retinal imaging was carried out using Spectral-domain OCT under dilated papillary conditions. RESULTS: Three hundred and twenty-eight individuals were recruited in this study. Of these, 219 (60.7%) were female and the mean age of the participants was 63.29 ± 5.57 years (range: 56 to 83 years). According to the multiple linear regression model, the global peripapillary RNFL thickness [coefficient: -3.05 (95% CI: -5.30 to -0.74); P = 0.010] and peripapillary RNFL thickness in the superior [coefficient: -4.65 (95% CI: -8.40 to -0.89), P < 0.001] and inferior [coefficient: -4.00 (95% CI: -7.81 to -0.19); P = 0.040] quadrants were significantly thinner in individuals with blood type B compared to those with other ABO blood groups. The average [coefficient: 12.69 (95% CI: 4.12-21.64); P = 0.004) and central [coefficient: 16.21 (95%: 6.44-25.97); P = 0.001) macular thicknesses were significantly thicker in AB group compared to other blood groups. The average macular thickness was significantly thinner in Rh + compared to the Rh- group [coefficient: -8.33 (95% CI: -15.4 to -1.25); P = 0.021]. CONCLUSION: Retinal structural indices may be related to blood groups implying a genetic linkage. Considering the lack of consistency among various studies, larger trials are needed to explore the effect of ABO and Rh grouping on peripapillary RNFL and macular thicknesses.