Early Degeneration Research Articles

Restoring Compromised Cl- in D2 Neurons of a HD Mouse Model Rescues Motor Disability.

Huntington's disease (HD) is a progressive neurodegenerative disorder with no cure, characterized by significant neurodegeneration of striatal GABAergic medium spiny neurons (MSNs). Early stages of the disease are characterized by the loss of dopamine 2 receptor-expressing MSNs (D2 MSNs) followed by degeneration of dopamine 1 receptor-expressing MSNs (D1 MSNs), leading to aberrant basal ganglia signaling. While the early degeneration of D2 MSNs and impaired GABAergic transmission are well-documented, potassium chloride cotransporter 2 (KCC2), a key regulator of intracellular chloride (Cl-), and therefore GABAergic signaling, has not been characterized in D1 and D2 MSNs in HD. We aimed to investigate whether Cl- regulation was differentially altered in D1 and D2 MSNs and may contribute to the early degeneration of D2 MSNs in male and female symptomatic R6/2 mice. We used electrophysiology to record the reversal potential for GABAA receptors (EGABA), a read-out for the efficacy of Cl- regulation, in striatal D1 and D2 MSNs and their corresponding output structures. During the early symptomatic phase (P55-P65), Cl- impairments were observed in D2 MSNs in R6/2 mice, with no change in D1 MSNs. Cl- regulation was also dysfunctional in the globus pallidus externa, resulting in GABA-mediated excitation. When we overexpressed KCC2 in D2 MSNs using AAV-mediated delivery, we delayed the onset of motor impairments in R6/2 mice. We demonstrate that Cl- homeostasis is differentially altered in D1 and D2 MSNs and may contribute to the enhanced susceptibility of D2 MSNs during HD progression.Significance Statement Huntington's Disease is an inherited neurodegenerative disease caused by a repeat expansion in the Huntingtin gene and characterized by the sequential loss of dopamine 2 and dopamine 1 receptor-expressing medium spiny neurons (D2 and D1 MSNs) of the striatum. MSNs release GABA, which depends on proper Cl- regulation for inhibition. We asked whether Cl- homeostasis is differentially altered in D1 and D2 MSNs and their output structures, and whether this altered expression contributes to the pattern of degeneration between these two principal striatal cell types. Using electrophysiology, biochemistry, and fluorescence imaging, we determined that Cl- regulation was impaired in D2 MSNs in R6/2 mice, with no change in D1 MSNs. Cl- was also dysregulated in the globus pallidus externa resulting in excitatory GABA.

The causal effects of lifestyle, circulating, pigment, and metabolic factors on early age-related macular degeneration: a comprehensive Mendelian randomization study

PurposeEarly detection of lifestyle factors, skin and hair color, circulating parameters, and metabolic comorbidities is crucial for personalized prevention and treatment of early age-related macular degeneration (AMD). This study aimed to assess the relationships between genetically predicted comprehensive risk factors and early AMD.Methods and resultsPublicly available genome-wide association study (GWAS) data were utilized to identify genetic variants significantly associated with each trait. We applied a Bonferroni-corrected significance level of P < 0.0017. P values between 0.0017 and 0.05 were considered suggestive associations. Univariable Mendelian randomization (MR) analyses revealed that elevated serum HDL-C, lower serum TG, and decreased three circulating fatty acids levels were robust indicators of an increased risk of early AMD (all P < 0.0017), with odds ratios (ORs) and 95% confidence intervals (CIs) of 1.218 (1.140–1.303), 0.784 (0.734–0.837), 0.772 (0.698–0.855), 0.776 (0.706–0.852), and 0.877 (0.798–0.963), respectively. Additionally, the “never eat wheat products”, “age started wearing glasses”, and “skin color” were significantly associated with the risk of early AMD (both P < 0.0017), with ORs (95% CIs) of 23.853 (2.731–208.323), 1.605 (1.269–2.030) and 1.190 (1.076–1.317), respectively. Multivariable MR analysis confirmed that elevated serum HDL-C (OR = 1.187, 1.064–1.324) increased the risk of early AMD, while higher serum TG (OR = 0.838, 0.738–0.950) was associated with a significantly lower risk. Furthermore, validation results indicated that serum HDL-C 1.201 (1.101–1.310) and TG 0.795 (0.732–0.864) were significantly associated with the risk of early AMD. There were suggestive associations of smoothies, chronotype, and hair color (0.0017 < P < 0.05), but sun/UV protection, smoking, BMI, diabetes, high blood pressure, cardiovascular diseases, fresh fruit intake, fish oil/cod liver oil supplement, sleeplessness, serum C-reactive protein level, and iron level were not associated with the risk of early AMD.ConclusionsOur comprehensive MR analysis demonstrated that elevated circulating HDL-C levels increase the risk of early AMD, while TG and fatty acid levels are associated with a decreased risk. These findings provide robust evidence for improved diagnosis and personalized prevention and treatment of early AMD.

Clinical trajectories of patients with multiple sclerosis from onset and their relationship with serum neurofilament light chain levels.

Serum neurofilament light chain (sNfL) is a biomarker of neuroaxonal destruction that correlates with acute inflammation (AI) in multiple sclerosis (MS). However, in the treatment era, progression without AI is the main driver of long-term disability. sNfL may provide added value in detecting ongoing axonal damage and neurological worsening in patients without AI. We conducted a prospective three-year study on patients with a first MS relapse to evaluate the basal cut-off value predicting early increased disability unrelated to relapses. sNfL levels and AI presence were measured every 6 months during the first year and the Expanded Disability Status Scale (EDSS) was monitored until the third year. Baseline cohorts were stratified by sNfL levels, using a cut-off derived from patients without AI (absence of clinical relapses, new/enlarging T2 lesions, or gadolinium enhancement in magnetic resonance imaging) at year one. Fifty-one patients were included. A sNfL cut-off of 11 pg/mL predicted sustained neurological worsening independent of AI. Patients exceeding this threshold exhibited features of highly active MS (higher proportion of AI, oligoclonal M bands and higher EDSS). Despite AI ablation, sNfL levels persisted elevated and were significantly associated with increased EDSS at baseline and year 3. Patients with low sNfL and concurrent AI (n = 8) experienced relapses in the optic nerve, brainstem, and spinal cord topographies. sNfL elevation may detect patients with increased disability even when AI is controlled. This may reveal mechanisms associated with early axonal degeneration and help identify patients at higher risk of progression.

Influencing factors and repair advancements in rodent models of peripheral nerve regeneration.

Peripheral nerve injuries lead to severe functional impairments, with rodent models essential for studying regeneration. This review examines key factors affecting outcomes. Age-related declines, like reduced nerve fiber density and impaired axonal transport of vesicles, hinder recovery. Hormonal differences influence regeneration, with BDNF/trkB critical for testosterone and nerve growth factor for estrogen signaling pathways. Species and strain selection impact outcomes, with C57BL/6 mice and Sprague-Dawley rats exhibiting varying regenerative capacities. Injury models - crush for early regeneration, chronic constriction for neuropathic pain, stretch for traumatic elongation and transection for severe lacerations - provide insights into clinically relevant scenarios. Repair techniques, such as nerve grafts and conduits, show that autografts are the gold standard for gaps over 3cm, with success influenced by graft type and diameter. Time course analysis highlights crucial early degeneration and regeneration phases within the first month, with functional recovery stabilizing by three to six months. Early intervention optimizes regeneration by reducing scar tissue formation, while later interventions focus on remyelination. Understanding these factors is vital for designing robust preclinical studies and translating research into effective clinical treatments for peripheral nerve injuries.

SLC16A8 is a causal contributor to age-related macular degeneration risk

Age-related macular degeneration (AMD), a complex neurodegenerative disease, is a leading cause of visual impairment worldwide with a strong genetic component. Genetic studies have identified several loci, but few causal genes with functional characterization. Here we highlight multiple lines of evidence which show a causal role in AMD for SLC16A8, which encodes MCT3, a retinal pigment epithelium (RPE) specific lactate transporter. First, in an unbiased, genome-wide analysis of rare coding variants we show multiple SLC16A8 rare variants are associated with AMD risk, corroborating previous borderline significant reports from AMD rare variant studies. Second, we report a novel SLC16A8 mutation in a three-generation family with early onset macular degeneration. Finally, mis-expression in multiple model organisms shows functional and anatomic retinal consequences. This study highlights the important role for SLC16A8 and lactate regulation towards outer retina/RPE health and highlights a potential new therapeutic opportunity for the treatment of AMD.

Management of Surgical Transcatheter Aortic Valve Replacement (TAVR) Valve Explantation for Early Degeneration: A Case Report

Management of Surgical Transcatheter Aortic Valve Replacement (TAVR) Valve Explantation for Early Degeneration: A Case Report

Association between axial length and uveitis.

Multiple studies have examined the association between myopia and various ocular diseases, but there is no clinical report of the relationship between myopia and uveitis. This study aimed to elucidate the relationship between myopia and uveitis by comparing axial lengths (AL) of uveitis patients with control individuals. This study included 1052 eyes (663 patients; 288 males, 375 females; median age 56.0years) with uveitis referred to Tokyo Medical University Hospital. Controls were 738 eyes with cataract but no other ocular diseases. AL was measured by IOLMaster or conventional A-mode ultrasound system. Uveitis eyes were grouped into various types of non-infectious uveitis, infectious uveitis, and unidentified uveitis. Median AL of each uveitis group was compared with control group using Mann-Whitney U-test, and also compared with adjustment for age and sex using multiple regression analysis. Binary logistic analysis was performed to examine whether AL plays a role in the risk of developing uveitis. Of 1052 eyes, 808 eyes (76.8%) were diagnosed with non-infectious uveitis [sarcoidosis (176 eyes, 16.7%), Vogt-Koyanagi-Harada disease (122 eyes, 11.6%), Behçet's disease (130 eyes, 12.4%), and others (380 eyes, 36.1%)], 146 eyes (13.9%) with infectious uveitis, and 98 eyes (9.3%) with unidentified uveitis. Median AL in all uveitis eyes was significantly shorter than in control eyes (23.73 vs 24.31mm, p < 0.001 unadjusted), and AL remained significantly shorter in uveitis than in control after age- and sex-adjustment (p < 0.001). Median AL was significantly shorter in non-infectious uveitis (23.72mm) and in infectious uveitis (23.99mm) compared to controls (p < 0.001 and < 0.05, respectively), and was significantly shorter in non-infectious uveitis than in infectious uveitis (p < 0.05). Each millimeter decrease in AL was associated with 1.266-fold increase in unadjusted risk [odds ratio (OR), 1.266; 95% confidence interval (CI), 1.196-1.341; p < 0.001) and 1.446-fold in age- and sex-adjusted risk (OR, 1.446; 95% CI, 1.349-1.549; p < 0.001) of developing uveitis. Median AL of uveitis eyes with infectious or non-infectious etiologies was significantly shorter than that in control eyes, suggesting an increased risk of developing uveitis in eyes with shorter AL. This feature should be considered when exploring new pathogenetic mechanisms of uveitis. What is known Shorter axial length may be associated with the pathogenesis of central serous chorioretinopathy and increased risk of early age-related macular degeneration. What is new Here we assessed the relationship between myopia and uveitis by comparing axial lengths of uveitis patients. Median axial length in all uveitis eyes was significantly shorter than in control eyes, and axial length remained significantly shorter in uveitis than in control after age- and sex-adjustment. Each millimeter decrease in axial length was associated with 1.266-fold increase in unadjusted risk and 1.446-fold in age- and sex-adjusted risk of developing uveitis.

An epidemiological survey of visual impairment in rural populations aged 30 and above: the Handan Eye Study

Objective: To investigate the changes in prevalence and causes of blindness and visual impairment over six years among rural populations aged 30 and above in Yongnian County, Handan City, Hebei Province, a pilot area in northern China for blindness prevention and treatment, and to study the incidence of common blinding eye diseases. Methods: This population-based prospective cohort study included a baseline survey conducted from 2006 to 2007 using stratified cluster sampling, targeting 6 830 Han Chinese individuals aged 30 and above, with a response rate of 90.4%, and a follow-up survey conducted from 2012 to 2013 with 5 394 participants, maintaining a response rate of 85.3%. Visual impairment was defined according to World Health Organization standards as visual acuity<20/60 but ≥20/400, and blindness as visual acuity<20/400. Age-and gender-standardized prevalence rates of blindness and visual impairment, along with their 95% confidence intervals (CI), were estimated. The six-year incidence rates of primary glaucoma, age-related macular degeneration, and myopic maculopathy, along with their 95%CI, were reported. Results: At baseline, the standardized prevalence of bilateral blindness in individuals aged 30 and above was 0.6% (41/6 799) for presenting visual acuity and 0.5% (31/6 799) for best-corrected visual acuity. These rates were higher than those found in the follow-up survey, 0.5% (27/5 293) and 0.3% (17/5 276). Conversely, the standardized prevalence of bilateral visual impairment increased from 4.7% (361/6 799) and 1.0% (85/6 799) at baseline to 6.5% (355/5 293) and 1.4% (74/5 276) at follow-up, respectively. The leading cause of bilateral blindness was cataract in both baseline (13/31, 41.9%) and follow-up (7/17) surveys. Other major causes included myopic retinal degeneration (5/31, 16.1% at baseline; 2/17 at follow-up), glaucoma (3/31, 9.7% at baseline; 2/17 at follow-up), and corneal opacity (3/31, 9.7% at baseline; 2/17 at follow-up). Over six years, the incidence rates for primary glaucoma, early and late age-related macular degeneration, and myopic maculopathy in individuals aged 35 and above were 1.6% (95%CI: 1.2%-1.9%), 4.2% (95%CI: 3.8%-4.7%), 0.2% (95%CI: 0.2%-0.3%), and 0.1% (95%CI: 0.0%-0.2%), respectively. Conclusions: The prevalence of bilateral blindness in the rural population of Yongnian County, Handan City, Hebei Province, decreased over six years due to blindness prevention and treatment efforts but remained higher than in urban areas. Meanwhile, the prevalence of bilateral visual impairment increased since the baseline survey. Cataracts continued to be the primary cause of blindness, followed by myopic retinal degeneration, glaucoma, and corneal opacity.

Outer Retinal Thinning is Associated With Brain Atrophy in Early Age-Related Macular Degeneration

Both retinal changes and age-related macular degeneration (AMD) have been shown to be associated with Alzheimer's disease and related dementias (ADRD). In AMD, the outer retina is impacted significantly and early, but little is known about its association with cognition or changes in brain morphometry. This study investigates the relationship between retinal and brain morphometry in older adults with early and intermediate AMD. Cross-sectional study. Adults ≥70 years with normal, early, and intermediate AMD were recruited from Callahan Eye Hospital Clinics at the University of Alabama at Birmingham. Participants underwent cognitive testing, optical coherence tomography, and magnetic resonance imaging. Associations of retinal layer thickness with brain volume and thickness of specific brain regions were evaluated utilizing multivariable linear regression. The relevance of retinal thickness variables in brain volumetrics was quantified using least absolute shrinkage and selection operator regression models. Correlations between demographic variables, cognitive scores, and brain morphometry were evaluated. Participants with thinner outer retina had significantly smaller hippocampus (β = 0.019, P = .022), lower occipital cortex regions of interest (occipital ROIs) thickness (β = 5.68, P = .020), and lower cortical thickness in ADRD-related brain regions (β = 7.72, P = .006). People with thinner total retina had significantly lower occipital ROIs (β = 3.19, P = .009) and ADRD-related brain region (β = 3.94, P = .005) thickness. Outer retinal thickness in the outer Early Treatment of Diabetic Retinopathy Study ring was the most frequently reported retinal variable associated with brain morphometry on least absolute shrinkage and selection operator regression. Total gray matter volume showed positive correlations with education (Pearson's r = 0.30, P = .022). In older adults with normal retinal aging and early and intermediate AMD, thinner outer retina had specific associations with brain regions primarily involved in vision and cognition, such as lower hippocampal volume and lower thickness of the occipital ROIs and brain regions known to show early structural changes in dementia.

TAVR-in-TAVR for Early Degeneration of a Novel Self-Expandable Valve Dedicated to Treatment of Aortic Regurgitation.

TAVR-in-TAVR for Early Degeneration of a Novel Self-Expandable Valve Dedicated to Treatment of Aortic Regurgitation.

Short-term efficacy of photobiomodulation in early and intermediate age-related macular degeneration: the PBM4AMD study.

This independent prospective study evaluated the short-term effects and safety of photobiomodulation (PBM) in early and intermediate age-related macular degeneration. patients were treated with PBM in one eye. Functional parameters and drusen volume were measured at one (W4), three- (W12) and six-months (W24) after PBM. The study included 38 subjects who completed the PBM protocol. Two patients developed macular neovascularization during the study period. Best corrected visual acuity improved from 77.82 ± 5.83 ETDRS letters at baseline to 82.44 ± 5.67 at W12 (p < 0.01), then declined to 80.05 ± 5.79 at W24 (p < 0.01 vs. baseline). Low luminance visual acuity showed a similar pattern, improving from 61.18 ± 8.58 ETDRS letters at baseline to 66.33 ± 8.55 at W12 (p < 0.01), and decreasing to 62.05 ± 9.71 at W24 (p = 0.02). Contrast sensitivity improved at W12 (20.11 ± 9.23ETDRS letters, p < 0.01), but returned to baseline by W24 (16.45 ± 9.12, p = 0.5). Scotopic microperimetry showed a decrease in mean absolute retinal sensitivity from 9.24 ± 3.44 dB to 7.47 ± 4.41 dB at W24 (p < 0.01), while relative sensitivity decreased only at W24 (p = 0.04). Drusen volume decreased at W4 (0.018 ± 0.009 mm3, p < 0.01) and W12 (0.017 ± 0.009 mm3, p < 0.01), with a slight increase at W24 (0.019 ± 0.012 mm3, p = 0.154). PBM resulted in temporary improvements in visual function and a reduction in drusen volume, but these effects were not sustained at six months. The long-term efficacy and impact on disease progression are uncertain, necessitating further research to confirm these findings and determine optimal patient selection.

Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration.

Photobiomodulation (PBM) has become a promising approach for slowing the progression of early and intermediate dry age-related macular degeneration (dAMD) to advanced AMD. This technique uses light to penetrate tissues and activate molecules that influence biochemical reactions and cellular metabolism. This preliminary analysis is aimed at assessing the safety, tolerability, and short-term effectiveness of the EYE-LIGHT®PBM treatment device in patients with dAMD. The EYE-LIGHT® device employs two wavelengths, 590nm (yellow) and 630nm (red), in both continuous and pulsed modes. Patients over 50years of age with a diagnosis of dAMD in any AREDS (Age-Related Eye Disease Study) category were randomly assigned to either the treatment group or the sham group. The treatment plan consisted of an initial cycle of two sessions per week for 4weeks. Safety, tolerability, and compliance outcomes, along with functional and anatomical outcomes, were assessed at the end of the fourth month. This preliminary analysis included data from 76 patients (152 eyes). All patients were fully compliant with treatment sessions, and only one fifth of patients treated with PBM reported mild ocular adverse events, highlighting exceptional results in terms of tolerability and adherence. Changes in best-corrected visual acuity (BCVA) from baseline to month 4 differed significantly between the sham and PBM-treated groups, favoring the latter, with a higher proportion achieving a gain of five or more letters post-treatment (8.9% vs. 20.3%, respectively; p = 0.043). No significant differences in central subfield thickness (CST) were observed between the two groups over the 4-month period. The study also found a statistically significant disparity in mean drusen volume changes from baseline to month 4 between the groups in favor of patients treated with PBM (p = 0.013). These preliminary results indicate that PBM treatment using the EYE-LIGHT® system is safe and well tolerated among patients with dAMD. Furthermore, both functional and anatomical data support the treatment's short-term efficacy. ClinicalTrials.gov identifier NCT06046118.

OCT Changes Observed during the Progression of Early Age-Related Macular Degeneration

OCT Changes Observed during the Progression of Early Age-Related Macular Degeneration

Extent and Topography of Subretinal Drusenoid Deposits Associate With Rod-Mediated Vision in Aging and AMD: ALSTAR2 Baseline.

In AMD, rod-mediated dark adaptation (RMDA) at 5° eccentricity is slower in eyes with subretinal drusenoid deposits (SDDs) than in eyes without. Here we quantified SDD burden using supervised deep learning for comparison to vision and photoreceptor topography. In persons ≥60 years from the Alabama Study on Early Age-Related Macular Degeneration 2, normal, early AMD, and intermediate AMD eyes were classified by the AREDS nine-step system. A convolutional neural network was trained on 55°-wide near-infrared reflectance images for SDD segmentation. Trained graders annotated ground truth (SDD yes/no). Predicted and true datasets agreed (Dice coefficient, 0.92). Inference was manually proofread using optical coherence tomography. The mean SDD area (mm2) was compared among diagnostic groups (linear regression) and to vision (age-adjusted Spearman correlations). Fundus autofluorescence images were used to mask large vessels in SDD maps. In 428 eyes of 428 persons (normal, 218; early AMD, 120; intermediate AMD, 90), the mean SDD area differed by AMD severity (P < 0.0001): 0.16 ± 0.87 (normal), 2.48 ± 11.23 (early AMD), 11.97 ± 13.33 (intermediate AMD). Greater SDD area was associated with worse RMDA (r = 0.27; P < 0.0001), mesopic (r = -0.13; P = 0.02) and scotopic sensitivity (r = -0.17; P < 0.001). SDD topography peaked at 5° superior, extended beyond the Early Treatment of Diabetic Retinopathy Study grid and optic nerve, then decreased. SDD area is associated with degraded rod-mediated vision. RMDA 5° (superior retina) probes where SDD is maximal, closer to the foveal center than the rod peak at 3 to 6 mm (10.4°-20.8°) superior and the further eccentric peak of rod:cone ratio. Topographic data imply that factors in addition to rod density influence SDD formation.

Association of macular pigment optical density with plasma macular carotenoids levels and serum lipids in South Indian healthy volunteers and patients with early age-related macular degeneration.

Purpose: The objective of the present study was to investigate the relationship between macular pigment optical density (MPOD) and plasma carotenoids [(L) and (Z)] and serum lipids in South Indian young healthy volunteers and patients with early age-related macular degeneration (AMD). Methods: Two hundred and fourteen (N = 214) study participants (Healthy control group (N) = 178; Early AMD group (N) = 36) were enrolled after getting their written informed consent. The MPOD of the study participants was assessed using MPS II (Electron Technology, UK) after completing their routine ocular examination. Serum lipids were measured by the standard technique. Plasma levels of L, Z, lycopene and beta-carotene were estimated by high performance liquid chromatography with photo diode array detector. Statistical analysis used: Correlations among variables in serum, plasma and the MPOD were established using Spearman's rho correlation coefficient. Results: The overall mean MPOD in healthy control group and early AMD group were found to be 0.47 ± 0.16 (N = 178; 317 eyes) and 0.35 ± 0.22 (N = 36; 38 eyes) at 1° eccentricity respectively and were found to be statistically significant (p < 0.001). A strong positive association was found between plasma L, Z and L + Z and MPOD. Serum HDL showed a strong negative association with MPOD and other lipids showed a very weak association. MPOD was unaffected by body mass index. Conclusions: MPOD is positively associated with plasma L,Z and L + Z, adding further evidence that additional intake of L/Z may be beneficial in delaying the risk of AMD in our population.

Evidence of association between higher cardiorespiratory fitness and higher cerebral myelination in aging

Emerging evidence suggests that altered myelination is an important pathophysiologic correlate of several neurodegenerative diseases, including Alzheimer and Parkinson's diseases. Thus, improving myelin integrity may be an effective intervention to prevent and treat age-associated neurodegenerative pathologies. It has been suggested that cardiorespiratory fitness (CRF) may preserve and enhance cerebral myelination throughout the adult lifespan, but this hypothesis has not been fully tested. Among cognitively normal participants from two well-characterized studies spanning a wide age range, we assessed CRF operationalized as the maximum rate of oxygen consumption (VO2max) and myelin content defined by myelin water fraction (MWF) estimated through our advanced multicomponent relaxometry MRI method. We found significant positive correlations between VO2max and MWF across several white matter regions. Interestingly, the effect size of this association was higher in brain regions susceptible to early degeneration, including the frontal lobes and major white matter fiber tracts. Further, the interaction between age and VO2max exhibited i) a steeper positive slope in the older age group, suggesting that the association of VO2max with MWF is stronger at middle and older ages and ii) a steeper negative slope in the lower VO2max group, indicating that lower VO2max levels are associated with lower myelination with increasing age. Finally, the nonlinear pattern of myelin maturation and decline is VO2max-dependent with the higher VO2max group reaching the MWF peak at later ages. This study provides evidence of an interconnection between CRF and cerebral myelination and suggests therapeutic strategies for promoting brain health and attenuating white matter degeneration.

Alkaptonuria and Ochronotic Arthropathy: The Path to Pain-Free Mobility

This article discusses a case of ochronotic arthropathy, a manifestation of alkaptonuria. Alkaptonuria is characterized by the accumulation of homogentisic acid [HGA] in tissues, leading to a distinctive blue-black pigmentation and early joint degeneration. A 68-year-old female patient, with a history of alkaptonuria, presented with progressive hip pain and was eventually treated with an elective total hip replacement. Due to vertebral calcifications, the operation was performed under general anesthesia. Pre- and post-operative care was guided by the patient’s comorbidities and potential complications related to alkaptonuria, including potential cardiac and respiratory issues. Following surgery, the patient exhibited significant improvements in hip joint functionality. The paper also discusses the challenges in diagnosing alkaptonuria, the absence of definitive treatment, and the potential of dietary restrictions and symptomatic treatments. Moreover, it addresses surgical considerations for ochronotic arthropathy and emphasizes the role of regular calcium and vitamin D intake in maintaining bone quality. The success of the hip replacement surgery in this case suggests a potential intervention for managing ochronotic arthropathy in alkaptonuria patients.

Effect of Valuka Swedana Followed by Greeva Basti Along with Physiotherapy and Abha Guggulu in the Management of Asthigata Vata (Cervical Spondylosis)

Aging and degeneration are natural course of life, but in this modern era the advancement of technologies and busy life style contribute to the early degeneration process. Improper continuous postures, jerky movements while travelling, overuse of mobiles etc. will produce undue pressure and stress to the cervical disc and it will lead to inflammatory reaction and eventually degeneration. Cervical spondylosis caused by wear and tear phenomena in cervical spine. It is most frequently involved in the cartilage and bones of the cervical spine and causes loss of normal spine function. According to Ayurvedic perspectives cervical spondylosis can be correlated with Asthigata Vata. A female patient age 23yrs., diagnosed and non-operated case of Cervical spondylosis (19/07/2023 OPD NO.27393, IPD NO. 2150) came to Panchakarma OPD of ITRA, Jamnagar with complaints of pain at nape of neck radiating to right upper limb (Greeva Shoola) since last 5yrs along with restricted ROM of neck (Greeva Stambha) and difficulty in doing daily activities such as reading, etc. The pain aggravated in prolonged reading and morning. She was treated with Valuka Swedana for 3 days followed by Greeva Basti with Ksheera Bala Taila 14 days along with physiotherapy (isometric exercise of neck) and Abha Guggulu. Significant improvements were observed in various subjective and objective parameters after the treatment.

Bardet-Biedl syndrome improved diagnosis criteria and management: Inter European Reference Networks consensus statement and recommendations.

Four European Reference Networks (ERN-EYE, ERKNet, Endo-ERN, ERN-ITHACA) have teamed up to establish a consensus statement and recommendations for Bardet-Biedl syndrome (BBS). BBS is an autosomal recessive ciliopathy with at least 26 genes identified to date. The clinical manifestations are pleiotropic, can be observed in utero and will progress with age. Genetic testing has progressively improved in the last years prompting for a revision of the diagnostic criteria taking into account clinical Primary and Secondary features, as well as positive or negative molecular diagnosis. This consensus statement also emphasizes on initial diagnosis, monitoring and lifelong follow-up, and symptomatic care that can be provided to patients and family members according to the involved care professionals. For paediatricians, developmental anomalies can be at the forefront for diagnosis (such as polydactyly) but can require specific care, such as for associated neuro developmental disorders. For ophthalmology, the early onset retinal degeneration requires ad hoc functional and imaging technologies and specific care for severe visual impairment. For endocrinology, among other manifestations, early onset obesity and its complications has benefited from better evaluation of eating behaviour problems, improved lifestyle programs, and from novel pharmacological therapies. Kidney and urinary track involvements warrants lifespan attention, as chronic kidney failure can occur and early management might improve outcome. This consensus recommends revised diagnostic criteria for BBS that will ensure certainty of diagnosis, giving robust grounds for genetic counselling as well as in the perspective of future trials for innovative therapies.

Retinal Sensitivity in Macular Subfields and Their Association with Contrast Sensitivity in Early and Intermediate Age-Related Macular Degeneration.

The objective of this study was to evaluate retinal sensitivity in subfields and its association with the novel quantitative contrast sensitivity function (qCSF) in patients with early age-related macular degeneration (eAMD), in patients with intermediate AMD (iAMD), and in healthy controls. In this prospective longitudinal study, retinal sensitivity of a customized 24-point grid was assessed by microperimetry Macular Integrity Assessment (MAIA, CenterVue, Padova, Italy) and divided into different subfields. The Multiple Contrast Vision Meter (Adaptive Sensory Technology, San Diego, CA, USA) was used for qCSF testing. Linear models were used to test the association of functional metrics with variables of interest. 92 study eyes from 92 participants were analyzed (13 eAMD, 31 iAMD, and 48 controls). Microperimetry subfield comparison showed significant differences (p &lt; 0.0001) in the control group between superior and inferior hemifield as well as between central and peripheral subfields. For eAMD, significant differences were found between central and peripheral subfields (p &lt; 0.001) and specific subfields (p &lt; 0.05) and finally for iAMD between specific quadrants (p &lt; 0.05) and specific squares (p &lt; 0.05). Significant associations of retinal sensitivity with qCSF metrics were found for the area underneath the logarithmic contrast sensitivity function, contrast acuity and for the contrast sensitivity at specific spatial frequencies. This study showed significant differences in the evaluated retinal sensitivity subfields, providing localized natural history data for retinal sensitivity in healthy controls and patients with eAMD and iAMD.