Ten-year outcomes of congenital cataract surgery performed within the first 6 months of life.

PURPOSE: In the spectrum of pediatric cataract, genuine congenital cataract poses challenges and has a poorer prognosis than developmental cataract. We investigated the long-term outcomes of congenital cataract surgery performed within the first 6 months of life. SETTING: Eleven ophthalmic surgical sites in Japan. METHODS: Medical charts were retrospectively reviewed for 216 eyes of 121 patients. The age at surgery was 2.9 ± 1.7 months, with follow-up duration 13.0 ± 2.3 years. The cohort consisted of 83 cases with bilateral aphakia, 12 with bilateral pseudophakia, 20 with unilateral aphakia, and 6 with unilateral pseudophakia. RESULTS: Surgical intervention within the critical period of visual system development (10 weeks for bilateral and 6 weeks for unilateral cases) led to significantly better final visual acuity than surgery conducted after this timeframe. The incidence of secondary glaucoma was similar between groups, while the occurrence of visual axis opacification was more frequent with earlier surgery. A forward stepwise multiple regression analysis revealed that the final visual acuity was significantly associated with laterality of cataract (better outcomes in bilateral cases), phakic status (with pseudophakia outperforming aphakia), presence of systemic and ocular comorbidities, and development of secondary glaucoma. Secondary glaucoma was significantly more prevalent in aphakic eyes than pseudophakic eyes. CONCLUSIONS: In patients with genuine congenital cataract, surgery within the critical period of visual development results in better final visual acuity, albeit with an increased risk of visual axis opacification. The use of intraocular lens with sophisticated surgical techniques shows promise even in congenital cataract surgery.

Characterization of the visually impaired patients with diabetes mellitus in Japan.

AIMS/INTRODUCTION: To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan. MATERIALS AND METHODS: Visually impaired patients with diabetes mellitus in Japan were divided into blind and low-vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups. RESULTS: Among 408 visually impaired persons (blind group: 257, low-vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low-vision groups, respectively. CONCLUSIONS: In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention.

N6-methyladenosine methylation in ophthalmic diseases: From mechanisms to potential applications.

N6-methyladenosine (m6A) modification, as the most common modification method in eukaryotes, is widely involved in numerous physiological and pathological processes, such as embryonic development, malignancy, immune regulation, and premature aging. Under pathological conditions of ocular diseases, changes in m6A modification and its metabolism can be detected in aqueous and vitreous humor. At the same time, an increasing number of studies showed that m6A modification is involved in the normal development of eye structures and the occurrence and progress of many ophthalmic diseases, especially ocular neovascular diseases, such as diabetic retinopathy, age-related macular degeneration, and melanoma. In this review, we summarized the latest progress regarding m6A modification in ophthalmic diseases, changes in m6A modification-related enzymes in various pathological states and their upstream and downstream regulatory networks, provided new prospects for m6A modification in ophthalmic diseases and new ideas for clinical diagnosis and treatment.

Clinical features of 26 cases of COVID-19-associated conjunctivitis.

PURPOSE: To explore the clinical features of COVID-19-associated conjunctivitis with the objective of preventing the spread of infection. STUDY DESIGN: Retrospective cohort study. METHODS: From March 2020 to March 2021, we retrospectively reviewed 26 (9.8%) consecutive COVID-19 patients with conjunctivitis among 282 COVID-19 cases admitted to our hospital. Clinical symptoms, onset date of conjunctivitis, time to patient recovery, and eye drop intervention were investigated. In addition, risk factors for developing conjunctivitis were statistically examined among 206 inpatients available for within 5 days of the onset. A multivariate analysis of conjunctivitis risk factors was performed. RESULTS: Among the 282 COVID-19 patients, 4 (1.4%) had conjunctival hyperemia as the primary symptom. The median time of onset was 4 days after the COVID-19 onset. Hyperemia was observed in all cases, but other ocular symptoms were rare. The median duration of hyperemia was 3 days. A multiple logistic regression analysis revealed that a young age (p=0.005) and current smoking habit (p=0.027) were independent risk factors for conjunctivitis after COVID-19. CONCLUSIONS: COVID-19-associated conjunctivitis is rare in the elderly and strongly associated with a history of smoking. It often occurs in the early stages of infection, and while hyperemia is recognized as a clinical symptom, other ocular symptoms are rare or non-existent. Many cases recover within a short time.

Long-term surgical outcomes of pediatric cataract-multivariate analysis of prognostic factors.

We assessed the 10-year postoperative outcomes of pediatric cataract patients who underwent surgery at the age of 6 years or younger. A retrospective review of medical charts was conducted for 457 eyes of 277 patients, with the age at surgery averaging 1.3 ± 1.5 years (mean ± SD) and the follow-up duration averaging 12.8 ± 2.4 years (ranging from 10 to 17 years). The cohort included 250 eyes of 125 cases with bilateral aphakia (age at surgery 0.5 ± 0.8 years), 110 eyes of 55 cases with bilateral pseudophakia (1.9 ± 1.6 years), 42 cases with unilateral aphakia (1.1 ± 1.3 years), and 55 cases with unilateral pseudophakia (2.6 ± 1.7). A forward stepwise multiple regression analysis revealed that the best-corrected visual acuity at the final visit was significantly associated with laterality of cataract (with bilateral cases showing better results compared to unilateral cases), presence of systemic comorbidities, presence of ocular comorbidities, development of glaucoma, and phakic status (with better results in the pseudophakia group than the aphakia group). The age at surgery did not significantly affect visual acuity outcomes. A multiple logistic regression analysis demonstrated that the incidence of secondary glaucoma was significantly linked to younger age at surgery, phakic status (higher in aphakic than pseudophakic eyes), and presence of systemic comorbidities. In conclusion, after pediatric cataract surgery, final visual acuity was better in patients with bilateral cataracts, those treated with an intraocular lens, and cases without systemic or ocular comorbidities and secondary glaucoma. The development of secondary glaucoma was linked to younger age at surgery, aphakic status, and presence of systemic comorbidities.

Decreased Elastic Modulus of Knee Articular Cartilage Based on New Macroscopic Methods Accurately Represents Early Histological Findings of Degeneration.

OBJECTIVE: Ex vivo nanoindentation measurement has reported that elastic modulus decreases as cartilage degenerates, but no method has been established to macroscopically evaluate mechanical properties in vivo. The objective of this study was to evaluate the elastic modulus of knee joint cartilage based on macroscopic methods and to compare it with gross and histological findings of degeneration. DESIGN: Osteochondral sections were taken from 50 knees with osteoarthritis (average age, 75 years) undergoing total knee arthroplasty. The elastic modulus of the cartilage was measured with a specialized elasticity tester. Gross findings were recorded as International Cartilage Repair Society (ICRS) grade. Histological findings were graded as Mankin score and microscopic cartilage thickness measurement. RESULTS: In ICRS grades 0 to 2 knees with normal to moderate cartilage abnormalities, the elastic modulus of cartilage decreased significantly as cartilage degeneration progressed. The elastic modulus of cartilage was 12.2 ± 3.8 N/mm for ICRS grade 0, 6.3 ± 2.6 N/mm for ICRS grade 1, and 3.8 ± 2.4 N/mm for ICRS grade 2. Similarly, elastic modulus was correlated with Mankin score (r = -0.51, P < 0.001). Multiple regression analyses showed that increased Mankin score is the most relevant factor associated with decreased elastic modulus of the cartilage (t-value, -4.53; P < 0.001), followed by increased histological thickness of the cartilage (t-value, -3.15; P = 0.002). CONCLUSIONS: Mechanical properties of damaged knee cartilage assessed with new macroscopic methods are strongly correlated with histological findings. The method has potential to become a nondestructive diagnostic modality for early cartilage damage in the clinical setting.

Progress and prospects of gene therapy in ophthalmology from 2000 to 2022: A bibliometric analysis.

Background: Gene therapy is a treatment approach at the genetic level, which brings great advances in many diseases and develops rapidly in recent years. Currently, its mechanism of action is mainly through the replacement of missing or defective genes, or the reduction of harmful gene products. However, the application of gene therapy in ophthalmology remains limited. Methods: A total of 1143 articles and reviews published in the field of ocular gene therapies were found in the Web of Science Core Collection database and used for the bibliometric analysis. CiteSpace was mainly applied to the network analysis of countries, institutions, keywords, and dual-map overlay of journals. The visual analysis of authors, journals, and references was used by VOSviewer. The geographical distribution of publications was conducted by R language. Results: The annual publications are increasing in general. Currently, the USA and the UK are two main sources of publications in this field. Switzerland, Denmark, and Finland are the top 3 countries that establish the most cooperation and exchanges with other countries or regions. The most cited and co-cited journal in this field is Investigative Ophthalmology & Visual Science. Gene therapy studies for eye diseases are mainly focused on retinal dysfunctions by the analysis of references, keywords, and counting of original research, including Leber's congenital amaurosis and retinitis pigmentosa. Conclusion: This study used bibliometrics to analyze overall characteristics and put forward prospects for the future in the field of gene therapy in ophthalmology. Ocular diseases, especially hereditary retinal diseases, will be the major focus of gene therapy in the future.

Exosomal non-coding RNAs in angiogenesis: Functions, mechanisms and potential clinical applications.

Exosomes are extracellular vesicles that can be produced by most cells. Exosomes act as important intermediaries in intercellular communication, and participate in a variety of biological activities between cells. Non-coding RNAs (ncRNAs) usually refer to RNAs that do not encode proteins. Although ncRNAs have no protein-coding capacity, they are able to regulate gene expression at multiple levels. Angiogenesis is the formation of new blood vessels from pre-existing vessels, which is an important physiological process. However, abnormal angiogenesis could induce many diseases such as atherosclerosis, diabetic retinopathy and cancer. Many studies have shown that ncRNAs can stably exist in exosomes and play a wide range of physiological and pathological roles including regulation of angiogenesis. In brief, some specific ncRNAs can be enriched in exosomes secreted by cells and absorbed by recipient cells through the exosome pathway, thus activating relevant signaling pathways in target cells and playing a role in regulating angiogenesis. In this review, we describe the physiological and pathological functions of exosomal ncRNAs in angiogenesis, summarize their role in angiogenesis-related diseases, and illustrate potential clinical applications like novel drug therapy strategies and diagnostic markers in exosome research as inspiration for future investigations.

The influence of Bouba- and Kiki-like shape on perceived taste of chocolate pieces.

In this paper, we present the findings of a study investigating the impact of shape on the taste perception of chocolate. Previous research has explored the influence of various sensory information on taste perception, but there has been little focus on the effect of food shape being eaten on taste perception. To explore this, we focused on the Bouba-Kiki effect, illustrating an interaction between shape and several modalities, and investigated the effect of Bouba- and Kiki-shaped (rounded and angular) foods eaten on taste perception. We utilized a 3D food printer to produce four different shapes of chocolate pieces based on the Bouba-Kiki. Participants tasted each piece and completed a chocolate flavor questionnaire. With Bayesian analysis, we determined that the Bouba-shaped chocolate pieces were perceived as sweeter than the Kiki-shaped ones, supporting earlier studies on crossmodal correspondences between shape and taste perception. However, there were no significant differences in ratings of other tastes, such as sourness and bitterness. Our research indicates that shape can affect taste perception during consumption and suggests that 3D food printers offer an opportunity to design specific shapes that influence taste experiences.

Modification of the therapist's facial expressions using virtual reality technology during the treatment of social anxiety disorder: a case series.

Exposure therapy is a mainstream of treatment for social anxiety disorder (SAD). However, effort and time are required to recreate interpersonal situations that produce moderate anxiety. On the other hand, virtual reality exposure therapy can easily control anxiety-inducing conditions and allow for graduated exposure. However, artificial intelligence and animations that speak as naturally as actual humans are not yet practical, adding to the limitations of these treatments. The authors propose the use of a virtual reality technology that can transform facial expressions into smiling or sad faces in real time and display them on a monitor, potentially solving the above-mentioned problems associated with virtual reality animations. This feasibility study was conducted to determine whether this system can be safely applied to the treatment of SAD patients. A total of four SAD patients received 16 exposure therapy sessions led by an experienced therapist over a monitor; throughout the sessions, the facial expressions of the therapist were modified using software to display expressions ranging from smiling to sad on the monitor that was being viewed by the patient. Client satisfaction, treatment alliance, and symptom assessments were then conducted. Although one patient dropped out of the study, treatment satisfaction and treatment alliance were scored high in all the cases. In two of the four cases, the improvement in symptoms was sustained over time. Exposure therapy in which the interviewer's facial expressions are modified to induce appropriate levels of anxiety in the patient can be safely used for the treatment of SAD patients and may be effective for some patients.

Identification and clinical significance of tsRNAs and miRNAs in PBMCs of treatment-requiring retinopathy of prematurity.

The aim of the study is to reveal the expression profiling and clinical significance of peripheral blood mononuclear cell (PBMC) tRNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) of premature infants with treatment-requiring retinopathy of prematurity (ROP). Significantly altered tsRNAs and miRNAs were screened using small RNA sequencing. RT-qPCR was used to verify the altered RNAs identified by small RNA transcriptomics. The target genes, their enriched functions, and possibly involved signaling pathways were identified by bioinformatics analyses. According to the small RNA sequencing, 125 tsRNAs and 205 miRNAs were significantly altered in PBMCs obtained from infants with treatment-requiring ROP compared with the premature controls without retinopathy. We preliminarily validated the significant alterations of 6 tsRNAs and 9 miRNAs. The target genes for those tsRNAs were enriched for cellular macromolecule metabolic process, intracellular anatomical structure, transcription regulatory region nucleic acid binding, and Th17 cell differentiation; those of the altered miRNAs were enriched for the developmental process, cell junction, DNA-binding transcription activator activity, and FoxO signaling pathway. By verification with the extended sample size, we identified tsRNAs and miRNAs that could be potential biomarkers with clinical values. The study recognized the alterations and clinical significance of changed tsRNA/miRNA profiles in PBMCs from premature infants with ROP. These significantly altered tsRNAs and miRNAs might be useful as potential diagnostic biomarkers and molecular targets for treatment-requiring ROP.

Decrease in Ocular Blood Flow Thirty Minutes After Intravitreal Injections of Brolucizumab and Aflibercept for Neovascular Age-Related Macular Degeneration.

Purpose: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents such as brolucizumab and aflibercept are used widely to treat neovascular age-related macular degeneration (nAMD); however; they may theoretically affect the ocular blood flow. We investigated the short-term changes in the ocular blood flow between eyes with nAMD treated with intravitreal brolucizumab injections (IVBr) and intravitreal aflibercept injections (IVA). Methods: This study included 21 eyes of 21 Japanese patients with nAMD treated with either IVBr or IVA at Kurume University Hospital from April 2021 through June 2022. The rates of ocular blood flow at the optic nerve head (ONH mean blur rate [MBR]-vessel) and at the choroid (CHOR MBR) were analyzed before and 30 minutes after injections using laser speckle flowgraphy. Results: In the IVBr-treated group, the ONH MBR-vessel and CHOR MBR rates decreased significantly by 10.6% and 16.9% from baseline to 30 minutes after IVBr, respectively. In the IVA-treated group, ONH MBR-vessel and CHOR MBR rates decreased significantly by 9.4% and 6.1% from baseline to 30 minutes after IVA, respectively. There was no significant difference in the rates of decrease in the ONH MBR-vessel or CHOR MBR between the IVBr-treated and IVA-treated groups. Conclusion: Intravitreal injections of brolucizumab and aflibercept in eyes with nAMD cause significant decreases in ocular blood flow at the ONH and the choroid 30 minutes after injection. The rate of decrease in ocular blood flow was not significant between the eyes treated with brolucizumab and aflibercept. However, 3 of 10 eyes treated with brolucizumab but none of 11 eyes treated with aflibercept had more than a 30% decrease in the ocular blood flow at the choroid 30 minutes after injection.

Presenting Morphing Shape Illusion: Enhanced Sense of Morphing Virtual Object With Weight Shifting VR Controller by Computational Perception Model.

The haptic sensation is crucial for virtual reality, as it gives the presence of objects in a virtual world and thus gives a greater sense of immersion. To provide a sense of the shape of handheld objects, a haptic device that changes weight distribution is proposed. It is known that the visual feedback enhances the haptic sensation of shape, and it is also known that it does for morphing shape as well. Our previous publication presented a perception model for the static shape of a virtual object. In this article, we extend the model to produce a plausible sense of the morphing shape of handheld objects. Our stochastic model predicts the proper weight actuation for the weight-shifting haptic device, which users can plausibly feel while reducing hardware effort. We evaluated our perception model and resulted in the model accuracy average of 8.1% error. Using this perception model, the amount of weight actuation at 75% probability of plausibility is reduced up to 37%.

m6A modifications of circular RNAs in ischemia-induced retinal neovascularization.

Ischemia-induced pathological neovascularization in the retina is a leading cause of blindness in various age groups. The purpose of the current study was to identify the involvement of circular RNAs (circRNAs) methylated by N6-methyladenosine (m6A), and predict their potential roles in oxygen-induced retinopathy (OIR) in mice. Methylation assessment via microarray analysis indicated that 88 circRNAs were differentially modified by m6A methylation, including 56 hyper-methylated circRNAs and 32 hypo-methylated circRNAs. Gene ontology enrichment analysis predicted that the enriched host genes of the hyper-methylated circRNAs were involved in cellular process, cellular anatomical entity, and protein binding. Host genes of the hypo-methylated circRNAs were enriched in the regulation of cellular biosynthetic process, the nucleus, and binding. According to the Kyoto Encyclopedia of Genes and Genomes analysis, those host genes were involved in the pathways of selenocompound metabolism, salivary secretion, and lysine degradation. MeRIP-qPCR verified significant alterations in m6A methylation levels of mmu_circRNA_33363, mmu_circRNA_002816, and mmu_circRNA_009692. In conclusion, the study revealed the m6A modification alterations in OIR retinas, and the findings above shed light on the potential roles of m6A methylation in circRNA regulatory functions in the pathogenesis of ischemia-induced pathological retinal neovascularization.

Reduced Size of Telangiectatic Capillaries After Intravitreal Injection of Anti-Vascular Endothelial Growth Factor Agents in Diabetic Macular Edema.

Purpose: Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents reduces microaneurysms in patients with diabetic macular edema (DME). However, residual anti-VEGF-resistant telangiectatic capillaries (TelCaps) have been reported. In this study, we investigated changes in the size of TelCaps after intravitreal injection of anti-VEGF agents in DME. Patients and Methods: Indocyanine green angiography (IA) and optical coherence tomography were performed before and 3 months after the intravitreal injection of anti-VEGF agents (pro re nata regimen after three monthly loading doses) in 12 eyes of 12 patients (7 males and 5 females, mean age 65.2 ± 8.8 years) with DME. The number and size of TelCaps within a 6-mm diameter macular region of the edema were measured using optical coherence tomography B-scan images overlaid on IA images. Results: There were significant reductions in the number and size of TelCaps between the baseline and 3 months after anti-VEGF agent administration (P < 0.05 and P < 0.0001, respectively). The maximum corrected visual acuity (logMAR visual acuity) and the central macular thickness after anti-VEGF therapy were significantly improved (P < 0.01 and P < 0.02, respectively). The TelCaps remaining after loading three consecutive anti-VEGF agents had a significantly larger mean size at baseline than the TelCaps that resolved after the treatment (P < 0.03). Conclusion: Our study demonstrated that intravitreal injection of anti-VEGF agents could reduce TelCap size in patients with DME. We propose that larger-sized TelCaps detected by IA might be useful predictors of refractory DME, which could thus be principal targets of laser photocoagulation.

Risk Factors for Legal Blindness in 237 Japanese Patients with Exogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST.

PURPOSE: We investigated potential risk factors for visual prognosis in Japanese patients with exogenous endophthalmitis. METHODS: In this retrospective observational multicenter cohort study, risk factors for legal blindness at 12 weeks after treatment initiation were evaluated based on patient characteristics, initial BCVA, causative events, pathogens, ocular symptoms, duration from symptom onset to initial treatment, and selected treatments. RESULTS: Overall, 23.1% of eyes developed legal blindness. The six risk factors for legal blindness were presence of eye pain, pathogen identification, poor BCVA at the initial visit, longer duration from symptom onset to initial treatment, type of causative event, and type of causative pathogen. Regarding the type of causative pathogen, coagulase-negative staphylococci was associated with a better visual impairment outcome. CONCLUSION: Exogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatment, as well as other advances in medical knowledge and technology.

ACCELERATED PROGRESSION OF DIABETIC RETINOPATHY IN A PATIENT WITH ACQUIRED LIPODYSTROPHY AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION.

PURPOSE: To report a case of bilateral proliferative diabetic retinopathy and lipemia retinalis in a patient with acquired lipodystrophy. METHODS: A retrospective case report. RESULTS: A 23-year-old woman with a diagnosis of acquired lipodystrophy was referred for ophthalmic evaluation. She had been diagnosed with acute lymphocytic leukemia at the age of 3 years and undergone hematopoietic stem cell transplantation. Best-corrected visual acuity was 20/20 in both eyes; however, funduscopy revealed bilateral diabetic retinopathy and lipemia retinalis, neither of which was apparent 2 years earlier. She had a glycated hemoglobin level of 9.6% and a triglyceride level of 7,394 mg/dL with creamy appearance of serum. Fluorescein angiography showed bilateral neovascularization. CONCLUSION: Accelerated progression of diabetic retinopathy in this case seemed to be associated with the onset of lipemia retinalis. We encourage continued ophthalmologic monitoring of patients who underwent hematopoietic stem cell transplantation in childhood for possible accelerated course of diabetic retinopathy.

Risk Factors for Legal Blindness in 77 Japanese Patients with Endogenous Endophthalmitis: A Multicenter Cohort Study from J-CREST.

PURPOSE: We investigated potential predictive factors for visual prognosis in Japanese patients with endogenous endophthalmitis. DESIGN: Retrospective observational multicenter cohort study. METHODS: We examined the characteristics of 77 Japanese patients with endogenous endophthalmitis and performed statistical analyses of these real-world data. The primary endpoint was the identification of factors associated with visual prognosis. We examined differences between patients in the better vision and legal blindness groups at 12 weeks after treatment initiation. RESULTS: The five risk factors for visual impairment at 12 weeks after treatment initiation were presence of pressure injuries, severe clinical symptoms (presence of eye pain and ciliary injection), pathogen identification, and poor best-corrected visual acuity at baseline. Staphylococcus aureus and fungus were associated with a better visual impairment outcome. CONCLUSIONS: Endogenous endophthalmitis remains a severe ocular infection; however, it can be managed with rapid treatments, as well as other advances in medical knowledge and technology.

Larger bone marrow lesion volume before medial open-wedge high tibial osteotomy correlates with better improvement of clinical scores in patients with knee osteoarthritis.

PURPOSE: This study evaluated the clinical outcomes of medial open-wedge high tibial osteotomy (MOWHTO) and bone marrow lesion (BML) scores and volumes. The hypotheses were that quantitative BML volume is more associated with clinical outcomes of MOWHTO than qualitative BML evaluations, and pre-operative BML volume is associated with the improvement of clinical outcomes. METHODS: Patients who underwent MOWHTO were retrospectively enrolled. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was recorded before the initial surgery and at plate removal surgery. Using pre-operative short-time inversion recovery magnetic resonance imaging, BMLs were evaluated using three qualitative scores, reflecting the maximum length, proportion, and intensity of BML. For quantification, BMLs of the femur and tibia were separately defined as lesions with a threshold greater than the mean signal intensity plus two standard deviations, using the corresponding lateral condyles as controls. The association between the KOOS scales and BML scores/volume was evaluated using Spearman's correlation coefficient. Multivariate linear regression analyses for post-operative KOOS scales were performed using the tibial BML volume as one of the four independent variables. RESULTS: The final analysis included 40 MOWHTO cases. Two qualitative BML scores correlated only with pre-operative KOOS sports. Femoral and tibial BML volumes were correlated with post-operative KOOS QOL (ρ = 0.40, p = 0.01) and sports (ρ = 0.36, p = 0.02), respectively. Tibial BML volume was significantly correlated with all five delta KOOS scales (ρ = 0.39-0.51, p = 0.01-0.001), however, femoral BML volume was only correlated with delta KOOS QOL (ρ = 0.41, p = 0.01). In multivariate analyses, tibial BML volume was a significant positive predictor for every post-operative KOOS scale, while post-operative % mechanical axis was also a positive significant variable, except post-operative KOOS pain. CONCLUSION: Tibial BML volume was positively correlated with one post-operative KOOS scale and all delta KOOS scales. A larger pre-operative tibial BML and appropriate alignment correction were associated with a better post-operative KOOS scales. Pre-operative large BML had no negative influence on post-operative clinical outcomes; hence, surgeons need not hesitate to perform MOWHTO in patients with large BMLs in the medial condyles. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

Knee Alignment Correction by High Tibial Osteotomy Reduces Symptoms and Synovial Inflammation in Knee Osteoarthritis Accompanied by Macrophage Phenotypic Change From M1 to M2.

OBJECTIVE: This study aimed to determine whether alignment correction by high tibial osteotomy (HTO) can change the biologic intraarticular microenvironment of osteoarthritic (OA) knees. METHODS: Synovial tissue (ST) and fluid (SF) were collected from the affected knees of 31 OA patients during initial HTO and plate removal surgeries. Changes in gene expression in ST were investigated by microarray and real-time polymerase chain reaction (PCR). ST specimens were also evaluated histologically using synovitis scores and immunofluorescence staining to determine macrophage polarity. Cytokines and chemokines in SF were analyzed by enzyme-linked immunosorbent assays. The mechanism of macrophage polarization was investigated in human peripheral blood mononuclear cell-derived macrophages and fibroblast-like synoviocytes (FLS) stimulated with cartilage fragments. We also evaluated Spearman correlations between Knee Injury and Osteoarthritis Outcome scores (KOOS) and macrophage-related gene expression. RESULTS: The microarray results indicated down-regulated inflammatory genes and pathways. Real-time PCR determined that genes expressing proinflammatory IL1B and IL6 were down-regulated and M2 macrophage-related IL1RA, IL10, CCL18, and CD206 were up-regulated. Histologic findings revealed attenuated synovitis scores and a shift from M1 to M2 macrophages. Interleukin-1ß (IL-1ß) concentrations in SF decreased after HTO. Cartilage fragments were responsible for M1 macrophage polarization and proinflammatory gene and protein expression in macrophages, whereas cartilage fragments up-regulated only IL-6 protein in FLS. Postoperative KOOS positively correlated with the expression of the M2-related genes CCL18 and CD206. CONCLUSION: Correction of lower limb alignment with HTO attenuated synovial inflammation and changed macrophage polarization from M1 to M2, suggesting an improved intraarticular environment in knee OA.