Potential application of traditional Chinese medicine in age-related macular degeneration-focusing on mitophagy.

Retinal pigment epithelial cell and neuroretinal damage in age-related macular degeneration (AMD) can lead to serious visual impairments and blindness. Studies have shown that mitophagy, a highly specialized cellular degradation system, is implicated in the pathogenesis of AMD. Mitophagy selectively eliminates impaired or non-functioning mitochondria via several pathways, such as the phosphatase and tensin homolog-induced kinase 1/Parkin, BCL2-interacting protein 3 and NIP3-like protein X, FUN14 domain-containing 1, and AMP-activated protein kinase pathways. This has a major impact on the maintenance of mitochondrial homeostasis. Therefore, the regulation of mitophagy could be a promising therapeutic strategy for AMD. Traditional Chinese medicine (TCM) uses natural products that could potentially prevent and treat various diseases, such as AMD. This review aims to summarize recent findings on mitophagy regulation pathways and the latest progress in AMD treatment targeting mitophagy, emphasizing methods involving TCM.

Exosomes from umbilical cord mesenchymal stem cells ameliorate intervertebral disc degeneration via repairing mitochondrial dysfunction.

Background: Reactive oxygen species (ROS), predominantly generated by mitochondria, play a crucial role in the pathogenesis of intervertebral disc degeneration (IVDD). Reduction of ROS levels may be an effective strategy to delay IVDD. In this study, we assessed whether umbilical cord mesenchymal stem cell-exosomes (UCMSC-exos) can be used to treat IVDD by suppressing ROS production caused by mitochondrial dysfunction. Materials and methods: Human UCMSC-exos were isolated and identified. Nucleus pulposus cells (NPCs) were stimulated with H2O2 in the presence or absence of exosomes. Then, 4D label free quantitative (4D-LFQ) proteomics were used to analyze the differentially expressed (DE) proteins. Mitochondrial membrane potential (MMP), mitochondrial ROS and protein levels were determined via immunofluorescence staining, flow cytometry and western blotting respectively. Additionally, high-throughput sequencing was performed to identify the DE miRNAs in NPCs. Finally, therapeutic effects of UCMSC-exos were investigated in a puncture-induced IVDD rat model. Degenerative grades of rat IVDs were assessed using magnetic resonance imaging and histochemical staining. Results: UCMSC-exos effectively improved the viability of NPCs and restored the expression of the extracellular matrix (ECM) proteins, collagen type II alpha-1 (COL2A1) and matrix metalloproteinase-13 induced by H2O2. Additionally, UCMSC-exos not only reduced the total intracellular ROS and mitochondrial superoxide levels, but also increased MMP in pathological NPCs. 4D-LFQ proteomics and western blotting further revealed that UCMSC-exos up-regulated the levels of the mitochondrial protein, mitochondrial transcription factor A (TFAM), in H2O2-induced NPCs. High-throughput sequencing and qRT-PCR uncovered that UCMSC-exos down-regulated the levels of miR-194-5p, a potential negative regulator of TFAM, induced by H2O2. Finally, in vivo results showed that UCMSC-exos injection improved the histopathological structure and enhanced the expression levels of COL2A1 and TFAM in the rat IVDD model. Conclusions: Our findings suggest that UCMSC-exos promote ECM synthesis, relieve mitochondrial oxidative stress, and attenuate mitochondrial dysfunction in vitro and in vivo, thereby effectively treating IVDD. The translational potential of this article: This study provides solid experimental data support for the therapeutic effects of UCMSC-exos on IVDD, suggesting that UCMSC-exos will be a promising nanotherapy for IVDD.

Bacterial identification in herniated intervertebral discs: a prospective cohort study.

BACKGROUND CONTEXT: Reports of Cutibacterium acnes isolated in cultures of intervertebral disc samples suggest it as possibly responsible for inflammatory conditions causing Modic changes on spinal magnetic resonance imaging (MRI). PURPOSE: Our objective was to investigate the prevalence of C. acnes in samples of intervertebral disc of patients with lumbar disc herniation; to investigate prognostic factors and the relationship of Modic changes with infection one year after microdiscectomy. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: In this single-center study, patients consecutively operated on for disc herniation had samples of the disc, multifidus muscle and ligamentum flavum (as an indication of contamination) extracted for culture. OUTCOME MEASURES: Age, sex, alcohol and tobacco consumption, body mass index; function, pain, and Modic chances in MRI before surgery and MRI one year later; rate of disc, muscle and ligament infection (primary outcome); diabetes and corticoid use (confoundings). METHODS: The protruded disc, muscle and ligament samples were sent for culture analysis in up to 30 minutes. A subsample of 17 patients underwent next-generation sequencing (NGS) molecular analysis too. We performed descriptive analysis and comparison of groups of patients with and without infection or contamination using Student's t, Mann-Whitney, chi-square, or Fisher's exact tests as appropriate, and pre- and post-surgical comparisons with the Wilcoxon test. RESULTS: From January 2018 to September 2019, 112 patients underwent open lumbar microdiscectomy, 67 (59.8%) men. Cultures showed 7 (6.3%) positive cases in the disc (2 with C. acnes), 3 (2.7%) in the ligament, and 12 (10, 7%) in muscle. No evidence of a difference in Modic alterations pre- or post-operatively was found between patients with and without positive culture one year after surgery. No association was found between culture positivity and functional or pain differences either. NGS results were all negative for C. acnes. CONCLUSIONS: We identified infective bacterial presence in the herniated disc in less than 2% of patients with disc herniation. C. acnes was not identified in any disc microbiome analysis. No significant association was observed between positivity for tissue infection and any clinical prognostic factor.

Pachy-Reticular Pseudodrusen.

PURPOSE: To characterize the features of a peculiar association between reticular pseudodrusen (RPD) and pachychoroid (namely "pachy-RPD") and to compare them with eyes affected by RPD and normal/leptochoroid. DESIGN: Observational, retrospective, case-control study. PARTICIPANTS: Among a cohort of intermediate age-related macular degeneration (AMD) population, we selected eyes with RPD and pachychoroid (i.e. choroidal thickness > 250 µm). A control group of RPD eyes but without pachychoroid (i.e. a choroidal < 250 µm) was included. METHODS: Number and stages of RPD were evaluated in each ETDRS subfield. Furthermore, choroidal perfusion was investigated using choroidal vascularity index (CVI), and choriocapillaris perfusion density (PD) on structural optical coherence tomography (OCT) and OCT-Angiography. MAIN OUTCOME MEASURES: Description of the multimodal imaging features of pachy-RPD and differences with RPD associated with normal/leptochoroid. RESULTS: Among 111 RPD eyes, 37 were included in the pachy-RPD group and 74 in the control group. Pachy-RPD patients were significantly younger than patients with RPD and normal/leptochoroid (mean age 75±16 and 82±7-year-old, respectively)(p=0.002). Total RPD number was comparable between the two groups (p=0.220). However, pachy-RPD eyes showed a significantly higher number of stage 1 RPD in comparison to the controls (p<0.001), and a lower number of stage 3 (p<0.001) and stage 4 RPD (p=0.052). The CVI and choriocapillaris PD were greater in pachy-RPD than in the control group (p<0.001 and p=0.010, respectively). CONCLUSIONS: Pachy-RPD are characterized by a different distribution of RPD stages (i.e. more early stages and lower advanced stages) in comparison to RPD in normal/leptochoroid. Furthermore, pachy-RPD eyes showed greater perfusion indexes of the choroid. These features suggest that the presence of pachychoroid could be a "protective" factor in the RPD evolution to the advanced AMD forms.

Automated, IMU-based spine angle estimation and IMU location identification for telerehabilitation.

BACKGROUND: Telerehabilitation is a promising avenue for improving patient outcomes and expanding accessibility. However, there is currently no spine-related assessment for telerehabilitation that covers multiple exercises. METHODS: We propose a wearable system with two inertial measurement units (IMUs) to identify IMU locations and estimate spine angles for ten commonly prescribed spinal degeneration rehabilitation exercises (supine chin tuck head lift rotation, dead bug unilateral isometric hold, pilates saw, catcow full spine, wall angel, quadruped neck flexion/extension, adductor open book, side plank hip dip, bird dog hip spinal flexion, and windmill single leg). Twelve healthy subjects performed these spine-related exercises, and wearable IMU data were collected for spine angle estimation and IMU location identification. RESULTS: Results demonstrated average mean absolute spinal angle estimation errors of 2.59 ∘ and average classification accuracy of 92.97%. The proposed system effectively identified IMU locations and assessed spine-related rehabilitation exercises while demonstrating robustness to individual differences and exercise variations. CONCLUSION: This inexpensive, convenient, and user-friendly approach to spine degeneration rehabilitation could potentially be implemented at home or provide remote assessment, offering a promising avenue to enhance patient outcomes and improve accessibility for spine-related rehabilitation. TRIAL REGISTRATION:  No. E2021013P in Shanghai Jiao Tong University.

A cohort study of 19 patients with gyrate atrophy of the choroid and retina (GACR).

PURPOSE: Gyrate atrophy of the choroid and retina (GACR) is an autosomal recessive inherited metabolic disorder (IMD) characterised by progressive retinal degeneration, leading to severe visual impairment. The rapid developments in ophthalmic genetic therapies warrant knowledge on clinical phenotype of eligible diseases such as GACR to define future therapeutic parameters in clinical trials. METHODS: Retrospective chart analysis was performed in nineteen patients. Data were analysed using IBM SPSS Statistics version 28.0.1.1. RESULTS: Nineteen patients were included with a mean age of 32.6 years (range 8-58). Mean age at onset of ophthalmic symptoms was 7.9 years (range 3-16). Median logMAR of visual acuity at inclusion was 0.26 (range -0.18-3.00). Mean age at cataract surgery was 28.8 years (n = 11 patients). Mean spherical equivalent of the refractive error was -8.96 (range -20.87 to -2.25). Cystoid maculopathy was present in 68% of patients, with a loss of integrity of the foveal ellipsoid zone (EZ) in 24/38 eyes. Of the 14 patients treated with dietary protein restriction, the four patients who started the diet before age 10 showed most benefit. CONCLUSION: This study demonstrates the severe ophthalmic disease course associated with GACR, as well as possible benefit of early dietary treatment. In addition to visual loss, patients experience severe myopia, early-onset cataract, and CME. There is a loss of foveal EZ integrity at a young age, emphasising the need for early diagnosis enabling current and future therapeutic interventions.

Remyelination-oriented clemastine treatment attenuates neuropathies of optic nerve and retina in glaucoma.

As one of the top causes of blindness worldwide, glaucoma leads to diverse optic neuropathies such as degeneration of retinal ganglion cells (RGCs). It is widely accepted that the level of intraocular pressure (IOP) is a major risk factor in human glaucoma, and reduction of IOP level is the principally most well-known method to prevent cell death of RGCs. However, clinical studies show that lowering IOP fails to prevent RGC degeneration in the progression of glaucoma. Thus, a comprehensive understanding of glaucoma pathological process is required for developing new therapeutic strategies. In this study, we provide functional and histological evidence showing that optic nerve defects occurred before retina damage in an ocular hypertension glaucoma mouse model, in which oligodendroglial lineage cells were responsible for the subsequent neuropathology. By treatment with clemastine, an Food and Drug Administration (FDA)-approved first-generation antihistamine medicine, we demonstrate that the optic nerve and retina damages were attenuated via promoting oligodendrocyte precursor cell (OPC) differentiation and enhancing remyelination. Taken together, our results reveal the timeline of the optic neuropathies in glaucoma and highlight the potential role of oligodendroglial lineage cells playing in its treatment. Clemastine may be used in future clinical applications for demyelination-associated glaucoma.

Risk of post-injection endophthalmitis peaks within the first three injections of anti-vascular endothelial growth factor therapy: A nationwide registry-based study.

PURPOSE: To report the incidence of post-injection endophthalmitis (PIE) and the cumulative risk associated with repeated injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: We employed nationwide registries in Denmark to include all individuals aged ≥40 years who received at least one intravitreal anti-VEGF injection in 2007-2022. Our primary endpoint PIE was identified using specific diagnostic codes for endophthalmitis and procedure codes for vitreous biopsy within 10 days prior to and 120 days post-injection. Patients were stratified according to the underlying diagnoses for which they received the treatment. The relative risk (RR) for PIE was calculated between groups based on the number of injections received by the patients. RESULTS: We identified 60 825 patients who received intravitreal anti-VEGF treatment during study time, with a median age of 77.2 years and females constituting 58.1%. We identified 232 cases of PIE after 1 051 549 injections during follow-up, resulting in an incidence of 0.022% [95% CI 0.019%-0.025%]. Despite a linear growth in annual anti-VEGF use, the incidence remained stable at 0.020% [95% CI 0.017%-0.023%] from 2013 to 2022. Compared to patients receiving 1-3 injections, RR for patients receiving 4-20, 21-40, and >40 injections were 0.46 [95% CI 0.34-0.63], 0.32 [95% CI 0.21-0.50], and 0.54 [95% CI 0.36-0.81], respectively. Findings were similar across the different diagnoses. CONCLUSIONS: Based on 16 years of nationwide registry data, this study identified a low and stable incidence of PIE. Notably, the highest risk of endophthalmitis was within the first three anti-VEGF injections.

Vascular Endothelial Growth Factor C and D Signaling Pathways as Potential Targets for the Treatment of Neovascular Age-Related Macular Degeneration: A Narrative Review.

The development of treatments targeting the vascular endothelial growth factor (VEGF) signaling pathways have traditionally been firstly investigated in oncology and then advanced into retinal disease indications. Members of the VEGF family of endogenous ligands and their respective receptors play a central role in vasculogenesis and angiogenesis during both development and physiological homeostasis. They can also play a pathogenic role in cancer and retinal diseases. Therapeutic approaches have mostly focused on targeting VEGF-A signaling; however, research has shown that VEGF-C and VEGF-D signaling pathways are also important to the disease pathogenesis of tumors and retinal diseases. This review highlights the important therapeutic advances and the remaining unmet need for improved therapies targeting additional mechanisms beyond VEGF-A. Additionally, it provides an overview of alternative VEGF-C and VEGF-D signaling involvement in both health and disease, highlighting their key contributions in the multifactorial pathophysiology of retinal disease including neovascular age-related macular degeneration (nAMD). Strategies for targeting VEGF-C/-D signaling pathways will also be reviewed, with an emphasis on agents currently being developed for the treatment of nAMD.

RPE melanin and its influence on the progression of AMD.

OBJECTIVE: The aim of this review article is to summarize the latest findings and current understanding of the origin of melanin in the retinal pigment epithelium (RPE), its function within the RPE, its role in the pathogenesis of age-related macular degeneration (AMD), its effect on retinal development, and its potential therapeutic benefit in the treatment of AMD. METHODS: A comprehensive search of peer-reviewed journals was conducted using various combinations of key terms such as "melanin," "retinal pigment epithelium" or "RPE," "age-related macular degeneration" or AMD," "lipofuscin," "oxidative stress," and "albinism." Databases searched include PubMed, Scopus, Science Direct, and Google Scholar. 147 papers published between the years of 1957 and 2023 were considered with an emphasis on recent findings. SUMMARY OF FINDINGS: AMD is thought to result from chronic oxidative stress within the RPE that results in cellular dysfunction, metabolic dysregulation, inflammation, and lipofuscin accumulation. Melanin functions as a photoscreener, free radical scavenger, and metal cation binding reservoir within the RPE. RPE melanin does not regenerate, and it undergoes degradation over time in response to chronic light exposure and oxidative stress. RPE melanin is important for retinal development and RPE function, and in the aging eye, melanin loss is associated with increased lipid peroxidation, inflammation, and the accumulation of toxic oxidized cellular products. Therefore, melanin-based treatments may serve to preserve RPE and retinal function in AMD. CONCLUSIONS: The pathogenesis of AMD is not fully understood, but RPE dysfunction and melanin loss in response to chronic oxidative stress and inflammation are thought to be primary drivers of the disease. Due to melanin's antioxidative effects, melanin-based nanotechnology represents a promising avenue for the treatment of AMD.

Attenuating intervertebral disc degeneration through spermidine-delivery nanoplatform based on polydopamine for persistent regulation of oxidative stress.

As one of the most widespread musculoskeletal diseases worldwide, intervertebral disc degeneration (IVDD) remains an intractable clinical problem. Currently, oxidative stress has been widely considered as a significant risk factor in the IVDD pathological changes, and targeting oxidative stress injury to improve the harsh microenvironment may provide a novel and promising strategy for disc repair. It is evident that spermidine (SPD) has the ability to attenuate oxidative stress across several disease models. However, limited research exists regarding its impact on oxidative stress within the intervertebral disc. Moreover, enhancing the local utilization rate of SPD holds great significance in IVDD management. This study aimed to develop an intelligent biodegradable mesoporous polydopamine (PDA) nanoplatform for sustained release of SPD. The obtained PDA nanoparticles with spherical morphology and mesoporous structure released loaded-therapeutic molecules under low pH and H2O2. Combined treatment with SPD loaded into PDA nanoparticles (SPD/PDA) resulted in better therapeutic potential than those with SPD alone on oxidative stress injury. Furthermore, both SPD and SPD/PDA could induce anti-inflammatory M2 macrophage polarization. Upon injection into degenerative IVDs, the SPD/PDA group achieved a good repair efficacy with a long-term therapeutic effect. These findings indicated that the synergized use of SPD with responsive drug delivery nanocarriers may steadily scavenge reactive oxygen species and provide an effective approach toward the treatment of IVDD.

Biomechanical Predictors of Sacroiliac Joint Uptake on SPECT/CT.

OBJECTIVE: Single Photon Emission Computed Tomography/ Computed Tomography (SPECT/CT) is an emerging imaging modality that identifies sites of heightened bone metabolism in response to increased stresses. The relationship between sacroiliac joint (SI) radiotracer uptake and anatomic biomechanical parameters is poorly understood. METHODS: Adult patients with SPECT/CT scans performed at our institution between 2021-2023 for the workup of low back pain were included. Patient charts were reviewed for demographic factors, including age, gender, and prior thoracolumbar fusion history. Biomechanical spinopelvic parameters were measured from standing scoliosis x-rays. SPECT/CT scans were reviewed for uptake at the SI joint. Patients were stratified into two cohorts; patients with SI uptake greater than iliac crest uptake were designated "hot," whereas those with less or equal uptake were labeled "cold." RESULTS: 160 patients met inclusion criteria. Patients were slightly more male (55%) with average age 55 ± 14.9 years. 68 patients (43%) had evidence of increased SI activity. Interrater reliability showed substantial agreement (kappa = 0.62). The hot cohort demonstrated greater pelvic incidence (54.8 ± 14.0° vs. 51.0 ± 11.0°, p = 0.031) and pelvic tilt (20.8 ± 9.5° vs. 18.4 ± 8.6°, p =0.047) compared to the cold cohort. Patients were otherwise similar between cohorts (p >0.05). CONCLUSIONS: Increased pelvic incidence and pelvic tilt angles are associated with SPECT/CT uptake at the SIJ, which may reflect altered biomechanics at the spinopelvic junction. SPECT/CT may be a valuable tool to assess SI degeneration. Future studies are warranted to better characterize the clinical applications of these findings.

The current insights of mitochondrial hormesis in the occurrence and treatment of bone and cartilage degeneration.

It is widely acknowledged that aging, mitochondrial dysfunction, and cellular phenotypic abnormalities are intricately associated with the degeneration of bone and cartilage. Consequently, gaining a comprehensive understanding of the regulatory patterns governing mitochondrial function and its underlying mechanisms holds promise for mitigating the progression of osteoarthritis, intervertebral disc degeneration, and osteoporosis. Mitochondrial hormesis, referred to as mitohormesis, represents a cellular adaptive stress response mechanism wherein mitochondria restore homeostasis and augment resistance capabilities against stimuli by generating reactive oxygen species (ROS), orchestrating unfolded protein reactions (UPRmt), inducing mitochondrial-derived peptides (MDP), instigating mitochondrial dynamic changes, and activating mitophagy, all prompted by low doses of stressors. The varying nature, intensity, and duration of stimulus sources elicit divergent degrees of mitochondrial stress responses, subsequently activating one or more signaling pathways to initiate mitohormesis. This review focuses specifically on the effector molecules and regulatory networks associated with mitohormesis, while also scrutinizing extant mechanisms of mitochondrial dysfunction contributing to bone and cartilage degeneration through oxidative stress damage. Additionally, it underscores the potential of mechanical stimulation, intermittent dietary restrictions, hypoxic preconditioning, and low-dose toxic compounds to trigger mitohormesis, thereby alleviating bone and cartilage degeneration.

Ulnocarpal Abutment Syndrome With Triquetrum Degeneration.

We present the case of a 47-year-old patient with a congenital positive ulnar variance and elucidate its effects on nearby structures in relation to ulnocarpal abutment syndrome (UAS). While magnetic resonance imaging (MRI) helped to identify soft tissue changes in the wrist, the use of an arthrogram, in this case, allowed for a more comprehensive and detailed analysis of the ligaments and soft tissues. Image findings included a complex degenerative tear of the disc of the triangular fibrocartilage (TFCC), a degenerated triquetrum, and partial tears of the scapholunate and lunotriquetral ligaments. Mild dorsal angulation of the lunate was noted, representing dorsal intercalated segmental instability (DISI), suggesting scapholunate ligament injury. Palmar classification was utilized to classify the extent of the TFCC injury as Type IIE. This case shines a light on the presentation of UAS in a patient that was not the usual demographic affected by this pathology, as well as their UAS affecting the triquetrum rather than the more commonly associated lunate.

Clinical Characteristics and Progression of Pachychoroid and Conventional Geographic Atrophy.

Purpose: To elucidate the clinical characteristics and progression rates of pachychoroid and conventional geographic atrophy (GA). Design: Retrospective, multicenter, observational study. Participants: A total of 173 eyes from 173 patients (38 eyes with pachychoroid GA and 135 with conventional GA) from 6 university hospitals in Japan were included. All patients were Japanese, aged ≥50 years and with fundus autofluorescence images having analyzable image quality. A total of 101 eyes (22 with pachychoroid GA and 79 with conventional GA) were included in the follow-up group. Methods: The studied eyes were classified as having pachychoroid or conventional GA; the former was diagnosed if the eye had features of pachychoroid and no drusen. The GA area was semiautomatically measured on fundus autofluorescence images, and the GA progression rate was calculated for the follow-up group. Multivariable linear regression analysis was used to determine whether the rate of GA progression was associated with GA subtype. Main Outcome Measures: Clinical characteristics and progression rates of pachychoroid and conventional GA. Results: The pachychoroid GA group was significantly younger (70.3 vs. 78.7 years; P < 0.001), more male-dominant (89.5 vs. 55.6%; P < 0.001), and had better best-corrected visual acuity (0.15 vs. 0.40 in logarithm of the minimum angle of resolution; P = 0.002), thicker choroid (312.4 vs. 161.6 µm; P < 0.001), higher rate of unifocal GA type (94.7 vs. 49.6%; P < 0.001), and smaller GA area (0.59 vs. 3.76 mm2;P < 0.001) than the conventional GA group. In the follow-up group, the mean GA progression rate (square-root transformation) was significantly lower in the pachychoroid GA group than in the conventional GA group (0.11 vs. 0.27 mm/year; P < 0.001). Conclusions: Demographic and ocular characteristics differed between GA subtypes. The progression rate of pachychoroid GA, adjusted for age and baseline GA area, was significantly lower than that of conventional GA. Japanese patients with conventional GA showed characteristics and progression rates similar to those in White populations. Some characteristics of GA in Japanese population differ from those in Waucasian populations, which may be due to the inclusion of pachychoroid GA. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Do the Clinical and Radiological Features of Knees with Mucoid Degeneration of the Anterior Cruciate Ligament Differ According to Knee Osteoarthritis Status?

Background: The etiology and pathology of mucoid degeneration of the anterior cruciate ligament (MD-ACL) remain poorly understood. MD-ACL may be associated with knee osteoarthritis (OA) or a mechanism other than OA. This study evaluated the radiological differences between knees with MD-ACL and those with a normal ACL and compared the clinical and radiological features of knees with MD-ACL according to the knee OA status. Methods: This retrospective study compared the radiological features of the intercondylar notch width index (NWI) and posterior tibial slope (PTS) of 67 MD-ACL patients (MD group) and 67 age-, sex-, and OA grade-matched patients with a normal ACL (control group). During the subgroup analysis, MD-ACL patients were divided into the non-OA subgroup (n = 41) and OA subgroup (n = 26). The pain location and characteristics of the knee, PTS, and NWI were compared between these subgroups. Results: Compared to the control group, the MD group had a lower NWI (0.26 ± 0.03 vs. 0.28 ± 0.01, p < 0.001) and a larger PTS (11.3° ± 3.0° vs. 9.2° ± 2.5°, p < 0.001). During the subgroup analysis, the most common pain locations were the posterior and medial aspects of the knee in the non-OA subgroup (43.9%) and OA subgroup (53.8%), respectively. Pain on terminal flexion was the most common pain characteristic in both subgroups (non-OA subgroup, 73.1%; OA subgroup, 53.8%). The PTS was not different between subgroups (11.7° ± 3.2° in the non-OA subgroup vs. 10.6° ± 2.7° in the OA subgroup; p = 0.159). However, the non-OA subgroup had a lower NWI than the OA subgroup (0.25 ± 0.03 vs. 0.28 ± 0.02, p = 0.001). Conclusions: Patients with MD-ACL had a lower NWI and a larger PTS than patients with a normal ACL. Furthermore, the clinical and radiological features of MD-ACL differed according to the knee OA status. A narrow intercondylar notch may be more closely associated with the development of MD-ACL without OA.

Real-World Outcomes of Faricimab Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.

Purpose: The purpose of this study was to assess preliminary real-world outcomes in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) treated with intravitreal faricimab. Patients and Methods: This was a retrospective, observational consecutive-case real-world study of patients with nAMD or DME initiated on intravitreal faricimab between November 2022 and April 2023. Treatment-naïve patients and patients previously treated with alternate anti-vascular endothelial growth factor (anti-VEGF) agents were initiated on an intended treatment plan of four monthly faricimab injections as a loading regime. Efficacy was assessed across four treatment groups. Primary outcomes assessed for both cohorts were changes in best corrected visual acuity (BCVA) and central subfield thickness (CST) on optical coherence tomography (OCT). Secondary outcomes were alterations in OCT-defined structural features. Results: From 127 patients, 146 eyes received at least one dose of faricimab. Mean BCVA, measured in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, from baseline to fifth visit increased from: 59.0±12.8 to 62.2±14.3 in treatment-naïve nAMD; 61.1±17.6 to 63.5±14.8 in previously-treated nAMD; 61.1±13.0 to 72.8±11.5 in treatment-naïve DME; and 60.8±14.6 to 63.3±15.6 in previously-treated DME. Mean CST reduced in all four treatment groups between initiation to final loading dose, from: 442.8±172.0µm to 305.2±117.0µm (p<0.0001) in treatment-naïve nAMD; 355.2±115.1µm to 297.9±92.54µm (p<0.0001) in previously-treated nAMD; 465.8±109.1µm to 343.1±100.3µm (p<0.0001) in treatment-naïve DME; and 492.5±133.1µm to 388.5±131.4µm (p<0.0001) in previously-treated DME. Conclusion: Real-world outcomes showed some improvement in BCVA and CST for nAMD and DME following faricimab administration, including in patients previously treated with other anti-VEGF agents. Further work involving larger cohorts over longer periods is required to determine whether improvement is maintained, and if intervals can be extended to match those observed in clinical trials.

Real-World Outcomes of a Loading Phase with Intravitreal Faricimab in Neovascular Age-Related Macular Degeneration (n-AMD) and Diabetic Macular Edema (DME).

INTRODUCTION: The aims of this work were to evaluate the real-world efficacy and safety of a loading dose of intravitreal faricimab in eyes with active neovascular age-related macular degeneration (n-AMD) or diabetic macular edema (DME) and to analyze the treatment outcome in relation to specific biomarkers. METHODS: Patients with active n-AMD or DME, treated with four monthly intravitreal injections of faricimab, were enrolled in this retrospective, uncontrolled study. Best-corrected visual acuity (BCVA), central subfield thickness (CST), presence of retinal fluid (RF) on optical coherence tomography (OCT), and adverse events were assessed at baseline and at weeks 4, 8, 12, and 16. Predefined biomarkers were evaluated at baseline (BL) and at last visit. RESULTS: Sixteen eyes of 15 patients with n-AMD (n-AMD group) and 15 eyes of 12 patients with DME (DME group) were included. Mean (± standard deviation) logarithm of minimum angle of resolution (logMAR) BL BCVA changed from 0.68 (± 0.43) to 0.53 (± 0.36; P = 0.13) and from 0.51 (± 0.34) to 0.32 (± 0.24; P: 0.048) at week 16 in n-AMD and DME group, respectively. A statistically significant mean CST reduction was reported in both groups at last visit (n-AMD: - 166.5 µm; P = 0.0009/DME: - 110.8 µm; P = 0.0086). Seventy-five and 33% of eyes with n-AMD and DME respectively achieved complete RF resolution at last visit. Subfoveal inner and outer retinal damage correlated with a lower final BCVA in n-AMD group. The presence of large (> 100 µm) juxtafoveal microaneurysms (MAs) was significantly correlated with a higher chance of residual fluid in eyes with DME. CONCLUSIONS: Both n-AMD and DME groups achieved satisfactory anatomical results after a loading-dose of intravitreal faricimab. BCVA improvement might be hampered by pre-existing retinal damage in eyes with n-AMD. Large, juxtafoveal MAs might represent a hallmark of a slower anatomical response to the treatment in eyes with DME.

Polyphenols as Potential Antioxidants for the Treatment of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is a common musculoskeletal system disease, which is one of the most important causes of low back pain. Despite the high prevalence of IDD, current treatments are limited to relieving symptoms, and there are no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative stress, the result of an imbalance between the production of reactive oxygen species (ROS) and clearance by the antioxidant defense system, plays an important role in the progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production, which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review, we discussed the antioxidant effects of polyphenols and their regulatory role in different molecular pathways associated with the pathogenesis of IDD, as well as the limitations and future prospects of polyphenols as a potential treatment of IDD.