Результаты поиска

Madras motor neuron disease (MMND): clinical description and survival pattern of 116 patients from Southern India seen over 36 years (1971-2007).

Madras motor neuron disease (MMND), MMND variant (MMNDV) and Familial MMND (FMMND) have a unique geographic distribution predominantly reported from Southern India. The characteristic features are onset in young, weakness and wasting of limbs, multiple lower cranial nerve palsies and sensorineural hearing loss. We describe the clinical features and survival pattern in 116 patients with Sporadic MMND, MMND variant and FMMND. A retrospective review of patients' medical records for clinical manifestations, electromyography, imaging, audiological and histopathology findings was performed. Over 36

Metabolic Analysis of Human Retinal Pigment Epithelium and Choroid Tissue in Aging and Macular Degeneration.

Age-related macular degeneration is a common ocular disease that causes vision loss in the elderly, with a complex set of risk factors and p … retina. Levels of 215 metabolites were determined in young donors, AMD donors (early/intermediate, geographic atrophy, and neovascularization) and age-matched controls. The largest number of metabolite differences were observed between young and healthy aged controls, as opposed to between aged controls and any stage of AMD. Two notable metabolites found to be incr …

Cell-penetrating asymmetric siRNA targeting MyD88 suppresses inflammasome-driven ocular degeneration and angiogenesis.

Chronic inflammation mediated by innate immune signaling contributes to retinal degeneration, pathological angiogenesis, and ocular surface … stribution and sustained MyD88 knockdown in mice and rabbits. In sodium iodate- and Alu RNA-induced geographic atrophy models, OLX10212 preserved retinal architecture and electroretinographic function while suppressing NLRP3-associated transcripts, consistent with the inhibition of inflammasome signaling. A single intravitreal dose reduced lesion volume in laser-ind …

Breach and restoration of retinal immune privilege: barrier failure, innate dysregulation, and adaptive autoimmunity.

The retina preserves vision by tightly regulating inflammation ("immune privilege") via blood-retinal barriers, neuroglial checkpoints, and … nterventional human evidence supports immunity as a therapeutic target: complement inhibition slows geographic atrophy; anti-VEGF reduces leak; intravitreal corticosteroids suppress inflammatory edema; and anti-TNF/IL-6R improve refractory NIU. Emerging strategies aim at privilege restoration-reinforcing myeloid checkpoints, tempering inflammasomes, and exploring to …

A comprehensive review of structure-function correlations in age-related macular degeneration: Contributions of microperimetry.

Age-related macular degeneration (AMD) is a leading cause of visual impairment and irreversible blindness worldwide. High-resolution imaging … hyperreflective foci, the integrity and thickness of various retinal layers, the junctional zone of geographic atrophy, exudative features of neovascular AMD, choriocapillaris flow deficits, and diverse patterns of autofluorescence, among numerous other relevant structural markers. By offering a deeper understanding of the structure-function correlations in disease …

Long-Term Follow-Up of Dry Age-Related Macular Degeneration Patients.

PURPOSE: To assess the progression rate from dry age-related macular degeneration (dAMD) to advanced AMD and possible risk factors. METHODS … ed AMD, with 25 eyes (33.78%) developing neovascular AMD (nAMD) and 22 eyes (29.72%) progressing to geographic atrophy (GA). Patients progressing to advanced AMD were older (77.8 ± 6.5 vs. 73.8 ± 9.5, P = 0.03). A higher incidence of open-angle glaucoma (OAG) was noted in progressing eyes (32.5% vs. 8.8%, P = 0.01), along with thinner baseline central macular thickn …

Development of a fit-for-purpose semi-homogeneous competitive ELISA for total PEG quantitation in a PEGylated molecule.

AIM: The therapeutic effectiveness of a drug could be significantly enhanced by prolonging its retention time. Polyethylene glycosylation (PEGylation) technology is a method to increase the half-life of protein therapeutics. PEGylated anti-Factor D Fab (PEG-aFD) was developed as a potential therapeutic, targeting factor D to reduce the frequency of intravitreal injections in patients with geographic atrophy. To support a GLP Toxicology study, there was a need to develop a PEG assay to measure total PEG concentration. RESULT: PEG-aFD consists of Fabs conjugated to a multi-arm PEG molecule, whi…

Two Siblings with LRPPRC Mutation: Mitochondrial Complex IV Deficiency: Case Report.

INTRODUCTION: Mitochondrial diseases caused by mutations in the LRPPRC gene are rare and lead to multisystemic dysfunction. We report two siblings from consanguineous Iraqi parents, both harboring a rare homozygous deletion in LRPPRC (c.2726_2728del; p.Lys909del), previously reported in one other patient. These cases contribute to the expanding phenotypic and geographic spectrum of LRPPRC-related mitochondrial disease. CASE PRESENTATION: The younger sibling, a 9-year-old girl, presented with severe growth retardation, global developmental delay, hypotonia, spastic ataxic gait, and lactic acid

Clinical and Genetic Findings in an Autosomal Dominant Optic Atrophy-Compatible Phenotype Harboring an OPA1 Variant: A Case Report.

We report a case of an 18-year-old Hispanic male patient with clinical features consistent with autosomal dominant optic atrophy (ADOA), including bilateral optic disc pallor, childhood color deficits, and visual field loss. The patient reported one year of progressive blurry vision; best-corrected visual acuity was measured at 20/30 in the right eye (OD) and 20/60 in the left eye (OS). Multimodal imaging revealed the expected structure-function pattern, with spectral-domain OCT demonstrating predominant retinal nerve fiber layer (RNFL) thinning and a preserved macular contour. Meanwhile, Hump

Ассоциации адаптивной иммунной системы и связанной с возрастом базовой дегенерации.

В последние годы адаптивная иммунная система получила значительное внимание в связи с ее потенциальной ролью в возрастной дегенерации (AMD). Ортологовые подходы, включая модели клеток и животных, а также экспериментальные клинические испытания, проложили путь к пониманию частотности, изменений и взаимодействия популяций Т клеток в сетчатке. Интересно, что понятия участия адаптивной иммунной системы в АМД также получили поддержку благодаря недавним исследованиям различных нейродегенеративных и хронических низкосортных заболеваний, включая множественный склероз, болезнь Паркинсона или артериоскл

Совпадение в аннотации оригинала
In recent years, the adaptive immune system has gained a significant amount of attention due to its potential role in age-related macular de … lammatory process involving T cell biology. Using a murine model relevant to the pathophysiology of geographic atrophy, we have demonstrated that specific populations of memory T cells are recruited to the retina prior to neurodegeneration. The investigation of these retinas at later degenerative stages revealed the presence of activated cytotoxic T cells at the inj …

Ophthalmic Use of Targeted Biologics in the Management of Intraocular Diseases: Current and Emerging Therapies.

BACKGROUND: Monoclonal antibodies (mAbs) have demonstrated substantial potential in the treatment of intraocular diseases. This review aimed … infectious uveitis. Complement system-targeted therapies like pegcetacoplan offered new options for geographic atrophy. Anti-VEGF antibodies showed potential in managing retinopathy of prematurity (ROP). However, challenges persist, including high costs, potential drug resistance, and limited long-term safety data in certain scenarios. CONCLUSIONS: Monoclonal antib …

Adeno-associated virus serotype 9 antibody seroprevalence for patients in the United States with spinal muscular atrophy.

Onasemnogene abeparvovec is a recombinant adeno-associated virus serotype 9 (AAV9) vector-based gene therapy for spinal muscular atrophy (SMA). Patients with elevated titers of anti-AAV9 antibodies (AAV9-Ab) should not receive onasemnogene abeparvovec because of potential safety and efficacy implications. We conducted a retrospective study to describe the seroprevalence of anti-AAV9 binding antibodies for pediatric patients with SMA in the United States. At initial testing, 13.0% (115 of 882) of patients (mean [SD] age, 26.29 [33.66] weeks) had elevated AAV9-Ab titers. The prevalence of elevat

Linear Diagnostic Procedure Elicited by Clinical Genetics and Validated by mRNA Analysis in Neuronal Ceroid Lipofuscinosis 7 Associated with a Novel Non-Canonical Splice Site Variant in MFSD8.

Neuronal ceroid lipofuscinoses (CNL) are lysosomal storage diseases that represent the most common cause of dementia in children. To date, 13 autosomal recessive (AR) and 1 autosomal dominant (AD) gene have been characterized. Biallelic variants in MFSD8 cause CLN7 type, with nearly 50 pathogenic variants, mainly truncating and missense, reported so far. Splice site variants require functional validation. We detected a novel homozygous non-canonical splice-site variant in MFSD8 in a 5-year-old girl who presented with progressive neurocognitive impairment and microcephaly. The diagnostic proced

Three-Month Safety and Efficacy Outcomes for the Smaller-Incision New-Generation Implantable Miniature Telescope (SING IMT™).

The smaller-incision new-generation implantable miniature telescope (SING IMT™) is the second generation of the IMT™, a telescope prosthesis that is indicated for monocular implantation in patients with stable vision impairment caused by bilateral central scotomas associated with end-stage Age-related macular degeneration (AMD). This non-comparative retrospective study is the first and largest single-surgeon case series to evaluate the short-term (3 months) safety and efficacy of the device in patients with disciform scars or geographic atrophy at baseline. The main outcome measures included b…

Ageing fundus degenerations of Macaca fascicularis on multi-modal imaging and histopathology: Similarities and differences compared to human.

To characterize the ageing fundus degenerations in Macaca fascicularis, we used multimodal imaging including color fundus photograph, spectr … atchy hyperautoflurescence, and the absence of subretinal drusenoid deposit, basal laminar deposit, geographic atrophy or choroidal neovascularization. Same with human, hard drusen, soft drusen, atherosclerosis, tessellated retina, staining of vessels in peripheral choroid on late-phase ICGA, and peripheral hard drusen were detected. HE and IF staining suggested the …

A SYSTEMATIC REVIEW OF DEEP LEARNING APPLICATIONS FOR OPTICAL COHERENCE TOMOGRAPHY IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To survey the current literature regarding applications of deep learning to optical coherence tomography in age-related macular degeneration (AMD). METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review was conducted from January 1, 2000, to May 9, 2021, using PubMed and EMBASE databases. Original research investigations that applied deep learning to optical coherence tomography in patients with AMD or features of AMD (choroidal neovascularization, geographic atrophy, and drusen) were included. Summary statements, data set characteristics, and…

AMD Genomics: Non-Coding RNAs as Biomarkers and Therapeutic Targets.

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease that is the world's leading cause of blindness in the agin … have recently shown promising results in phase 3 clinical trials, in terms of slowing the growth of geographic atrophy, an advanced form of AMD. Interestingly, both drugs appear to be associated with an increased incidence of wet AMD, another advanced form of the disease, and will require frequent intravitreal injections. Certainly, there remains a need for other th …

Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Meta-Analysis.

Although complement inhibition has emerged as a possible therapeutic strategy for age-related macular degeneration (AMD), there is not a clear consensus regarding what aspects of the complement pathway are dysregulated in AMD and when this occurs relative to disease stage. We recently published a systematic review describing systemic complement activation profiles in patients with early/intermediate AMD or geographic atrophy (GA) compared to non-AMD controls. Here, we sought to meta-analyze these results to estimate the magnitude of complement dysregulation in AMD using restricted maximum like…

Neuroprotection for Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Early to intermediate AMD is characterized by the accumulation of lipid- and protein-rich drusen. Late stages of the disease are characterized by the development of choroidal neovascularization, termed "exudative" or "neovascular AMD," or retinal pigment epithelium (RPE) cell and photoreceptor death, termed "geographic atrophy" (GA) in advanced nonexudative AMD. Although we have effective treatments for exudative AMD in the form of anti-VEGF agents, they have no role for patients with GA. Neuroprotection strategi…

Clinical and genetic characterization of limb girdle muscular dystrophy R7 telethonin-related patients from three unrelated Chinese families.

Limb girdle muscular dystrophy LGMD R7 telethonin-related is a rare autosomal recessive muscle disorder characterized by proximal muscle weakness of pelvic and shoulder girdles. Mutation in TCAP is responsible for LGMD R7, and the disease has a wide geographic distribution in diverse populations, but genotype-phenotype relationships remain unclear. We collected 5 LGMD R7 patients from three unrelated Chinese families. The average onset age was 16 ± 1.41; the initial symptoms included progressive proximal muscle weakness in limbs, difficulty in fast running, and asymmetric muscle atrophy in cal