Survival by first-line therapy and prognostic group among men with metastatic castration-resistant prostate cancer.

INTRODUCTION: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with prognoses varying from months to years at time of castration-resistant diagnosis. Optimal first-line therapy for those with different prognoses is unknown. METHODS: We conducted a retrospective cohort study of men in a national healthcare delivery system receiving first-line therapy for mCRPC (abiraterone, enzalutamide, docetaxel, or ketoconazole) from 2010 to 2017, with follow-up through 2019. Using commonly drawn prognostic labs at start of mCRPC therapy (hemoglobin, albumin, and alkaline phosphatase), we categorized men into favorable, intermediate, or poor prognostic groups depending on whether they had none, one to two, or all three laboratory values worse than designated laboratory cutoffs. We used Kaplan-Meier methods to examine prostate specific antigen (PSA) progression-free and overall survival (OS) according to prognostic group and first-line therapy, and multivariable cox regression to determine variables associated with survival outcomes. RESULTS: Among 4135 patients, median PSA progression-free survival (PFS) was 6.9 months (95% confidence interval [CI] 6.6-7.3), and median OS 18.8 months (95% CI 18.0-19.6), ranging from 5.7 months (95% CI 4.8-7.0) in the poor prognosis group to 31.3 months (95% CI 29.7-32.9) in the favorable group. OS was similar regardless of initial treatment received for favorable and intermediate groups, but worse for those in the poor prognostic group who received ketoconazole (adjusted hazard ratio 2.07, 95% CI 1.2-3.6). PSA PFS was worse for those who received ketoconazole compared to abiraterone across all prognostic groups (favorable HR 1.76, 95% CI 1.34-2.31; intermediate HR 1.78, 95% CI 1.41-2.25; poor HR 8.01, 95% CI 2.93-21.9). CONCLUSION: Commonly drawn labs at mCRPC treatment start may aid in predicting survival and response to therapies, potentially informing discussions with care teams. First-line treatment selection impacts disease progression for all men with mCRPC regardless of prognostic group, but impacted OS only for men with poor prognosis at treatment start.

Oral microbiome, periodontal disease and systemic bone-related diseases in the era of homeostatic medicine.

BACKGROUND: Homeostasis is a state of self-regulation and dynamic equilibrium, maintaining the good physiological functions of each system in living organisms. In the oral cavity, the interaction between the host and the oral microbiome forms oral microbial homeostasis. Physiological bone remodeling and renewal can occur under the maintenance of oral microbial homeostasis. The imbalance of bone homeostasis is a key mechanism leading to the occurrence of systemic bone-related diseases. Considering the importance of oral microbial homeostasis in the maintenance of bone homeostasis, it still lacks a complete understanding of the relationship between oral microbiome, periodontal disease and systemic bone-related diseases. AIM OF REVIEW: This review focuses on the homeostatic changes, pathogenic routes and potential mechanisms in the oral microbiome in periodontal disease and systemic bone-related diseases such as rheumatoid arthritis, osteoarthritis, osteoporosis and osteomyelitis. Additionally, this review discusses oral microbiome-based diagnostic approaches and explores probiotics, mesenchymal stem cells, and oral microbiome transplantation as promising treatment strategies. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review highlights the association between oral microbial homeostasis imbalance and systemic bone-related diseases, and highlights the possibility of remodeling oral microbial homeostasis for the prevention and treatment of systemic bone-related diseases.

Advances in spatial multi-omics in tumors.

Single-cell techniques have convincingly demonstrated that tumor tissue usually contains multiple genetically defined cell subclones with different gene mutation sets as well as various transcriptional profiles, but the spatial heterogeneity of the microenvironment and the macrobiological characteristics of the tumor ecosystem have not been described. For the past few years, spatial multi-omics technologies have revealed the cellular interactions, microenvironment, and even systemic tumor-host interactions in the tumor ecosystem at the spatial level, which can not only improve classical therapies such as surgery, radiotherapy, and chemotherapy but also promote the development of emerging targeted therapies in immunotherapy. Here, we review some emerging spatial omics techniques in cancer research and therapeutic applications and propose prospects for their future development.

Bi-functional CpG-STAT3 decoy oligonucleotide triggers multilineage differentiation of acute myeloid leukemia in mice.

Acute myeloid leukemia (AML) cells resist differentiation stimuli despite high expression of innate immune receptors, such as Toll-like receptor 9 (TLR9). We previously demonstrated that targeting Signal Transducer and Activator of Transcription 3 (STAT3) using TLR9-targeted decoy oligodeoxynucleotide (CpG-STAT3d) increases immunogenicity of human and mouse AML cells. Here, we elucidated molecular mechanisms of inv(16) AML reprogramming driven by STAT3-inhibition/TLR9-activation in vivo. At the transcriptional levels, AML cells isolated from mice after intravenous administration of CpG-STAT3d or leukemia-targeted Stat3 silencing and TLR9 co-stimulation, displayed similar upregulation of myeloid cell differentiation (Irf8, Cebpa, Itgam) and antigen-presentation (Ciita, Il12a, B2m)-related genes with concomitant reduction of leukemia-promoting Runx1. Single-cell transcriptomics revealed that CpG-STAT3d induced multilineage differentiation of AML cells into monocytes/macrophages, erythroblastic and B cell subsets. As shown by an inducible Irf8 silencing in vivo, IRF8 upregulation was critical for monocyte-macrophage differentiation of leukemic cells. TLR9-driven AML cell reprogramming was likely enabled by downregulation of STAT3-controlled methylation regulators, such as DNMT1 and DNMT3. In fact, the combination of DNA methyl transferase (DNMT) inhibition using azacitidine with CpG oligonucleotides alone mimicked CpG-STAT3d effects, resulting in AML cell differentiation, T cell activation, and systemic leukemia regression. These findings highlight immunotherapeutic potential of bi-functional oligonucleotides to unleash TLR9-driven differentiation of leukemic cells by concurrent STAT3 and/or DNMT inhibition.

Pulmonary hypertension and the potential of 'drug' repurposing: A case for African medicinal plants.

Abstract: Pulmonary hypertension (PH) is a haemodynamic disorder in which elevated blood pressure in the pulmonary circulation is caused by abnormal vascular tone. Despite advances in treatment, PH mortality remains high, and drug repurposing has been proposed as a mitigating approach. This article reviews the studies that have investigated drug repurposing as a viable option for PH. We provide an overview of PH and highlight pharmaceutical drugs with repurposing potential, based on limited evidence of their mechanisms of action. Moreover, studies have demonstrated the benefits of medicinal plants in PH, most of which are of Indian or Asian origin. Africa is a rich source of many medicinal plants that have been scientifically proven to counteract myriad pathologies. When perusing these studies, one will notice that some African medicinal plants can counteract the molecular pathways (e.g. proliferation, vasoconstriction, inflammation, oxidative stress and mitochondrial dysfunction) that are also involved in the pathogenesis of PH. We review the actions of these plants with actions applicable to PH and highlight that they could be repurposed as adjunct PH therapies. However, these plants have either never been tested in PH, or there is little evidence of their actions against PH. We therefore encourage caution, as more research is needed to study these plants further in experimental models of PH while acknowledging that the outcomes of such proof of-concept studies may not always yield promising findings. Regardless, this article aims to stimulate future research that could make timely contributions to the field. Study synopsis: What the study adds. Pulmonary hypertension (PH) remains a fatal disease, and 80% of the patients live in developing countries where resources are scarce and specialised therapies are often unavailable. Drug repurposing is a viable option to try to improve treatment outcomes.Implications of the findings. We propose that another form of 'drug' repurposing is the use of medicinal plants, many of which have demonstrated benefits against pathological processes that are also key in PH, e.g. apoptosis, tumour-like growth of cells, proliferation, oxidative stress and mitochondrial dysfunction.

Established and Emerging Nucleic Acid Therapies for Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is a genetic disease that leads to elevated low-density lipoprotein cholesterol levels and risk of coronary heart disease. Current therapeutic options for FH remain relatively limited and only partially effective in both lowering low-density lipoprotein cholesterol and modifying coronary heart disease risk. The unique characteristics of nucleic acid therapies to target the underlying cause of the disease can offer solutions unachievable with conventional medications. DNA- and RNA-based therapeutics have the potential to transform the care of patients with FH. Recent advances are overcoming obstacles to clinical translation of nucleic acid-based medications, including greater stability of the formulations as well as site-specific delivery, making gene-based therapy for FH an alternative approach for treatment of FH.

Emerging and alternative strategies for the treatment of nontuberculous mycobacterial infections.

INTRODUCTION: Nontuberculous mycobacteria (NTM) infections have emerged as a significant clinical challenge due to their intrinsic multidrug resistance and the limited efficacy of existing treatments. These infections are becoming increasingly prevalent, with a need for new and effective therapeutic strategies. AREAS COVERED: This review addresses several key aspects of NTM infections: i) pathogenesis and epidemiology; ii) the limitations and challenges of current treatment options; iii) emerging and alternative therapeutic strategies; iv) advanced drug delivery systems such as nanoparticles and efflux pump inhibitors; v) innovative antibacterial alternatives like antimicrobial peptides, bacteriophage therapy, and phytochemicals; and vi) other potential treatment modalities such as inhaled nitric oxide, small molecules, surgical debridement, phototherapy, and immunomodulatory therapy. EXPERT OPINION: Personalized medicine, advanced drug delivery systems, and alternative therapies hold promise for the future of NTM treatment. Early and accurate identification of NTM species, enabled by improved diagnostic methods, is critical for tailoring treatment regimens. Emerging therapies show promise against drug-resistant NTM strains, but overcoming barriers like clinical trials, regulatory hurdles, and high production costs is crucial. Continued research and innovation are essential to improve treatment efficacy and patient outcomes.

Synthetic RIG-I agonist-mediated cancer immunotherapy synergizes with MAP kinase inhibition against BRAF-mutated melanoma.

The implementation of targeted molecular therapies and immunotherapy in melanoma vastly improved the therapeutic outcome in patients with limited efficacy of surgical intervention. Nevertheless, a large fraction of patients with melanoma still remain refractory or acquire resistance to these new forms of treatment, illustrating a need for improvement. Here, we report that the clinically relevant combination of mitogen-activated protein (MAP) kinase pathway inhibitors dabrafenib and trametinib synergize with RIG-I agonist-induced immunotherapy to kill BRAF-mutated human and mouse melanoma cells. Kinase inhibition did not compromise the agonist-induced innate immune response of the RIG-I pathway in host immune cells. In a melanoma transplantation mouse model, the triple therapy outperformed individual therapies. Our study suggests that agonist-induced activation of RIG-I with its synthetic ligand 3pRNA could vastly improve tumor control in a substantial fraction of patients with melanoma receiving MAP kinase inhibitors.

Unlocking insights: Navigating COVID-19 challenges and Emulating future pandemic Resilience strategies with strengthening natural immunity.

The original COVID-19 vaccines, developed against SARS-CoV-2, initially mitigated hospitalizations. Bivalent vaccine boosters were used widely during 2022-23, but the outbreaks persisted. Despite this, hospitalizations, mortality, and outbreaks involving dominant mutants like Alpha and Delta increased during winters when the population's vitamin D levels were at their lowest. Notably, 75 % of human immune cell/system functions, including post-vaccination adaptive immunity, rely on adequate circulatory vitamin D levels. Consequently, hypovitaminosis compromises innate and adaptive immune responses, heightening susceptibility to infections and complications. COVID-19 vaccines primarily target SARS-CoV-2 Spike proteins, thus offering only a limited protection through antibodies. mRNA vaccines, such as those for COVID-19, fail to generate secretory/mucosal immunity-like IgG responses, rendering them ineffective in halting viral spread. Additionally, mutations in the SARS-CoV-2 binding domain reduce immune recognition by vaccine-derived antibodies, leading to immune evasion by mutant viruses like Omicron variants. Meanwhile, the repeated administration of bivalent boosters intended to enhance efficacy resulted in the immunoparesis of recipients. As a result, relying solely on vaccines for outbreak prevention, it became less effective. Dominant variants exhibit increased affinity to angiotensin-converting enzyme receptor-2, enhancing infectivity but reducing virulence. Meanwhile, spike protein-related viral mutations do not impact the potency of widely available, repurposed early therapies, like vitamin D and ivermectin. With the re-emergence of COVID-19 and impending coronaviral pandemics, regulators and health organizations should proactively consider approval and strategic use of cost-effective adjunct therapies mentioned above to counter the loss of vaccine efficacy against emerging variants and novel coronaviruses and eliminate vaccine- and anti-viral agents-related serious adverse effects. Timely implementation of these strategies could reduce morbidity, mortality, and healthcare costs and provide a rational approach to address future epidemics and pandemics. This perspective critically reviews relevant literature, providing insights, justifications, and viewpoints into how the scientific community and health authorities can leverage this knowledge cost-effectively.

Methicillin-resistant Staphylococcus pseudintermedius: epidemiological changes, antibiotic resistance, and alternative therapeutic strategies.

Staphylococcus pseudintermedius is a major opportunistic bacterial pathogen that belongs to the skin and mucosal microbiota of the dog. Since its global emergence around 2006, multidrug - methicillin-resistant S. pseudintermedius (MRSP) clones have become endemic worldwide. MRSP strains pose a significant threat to animal health and make antimicrobial therapy difficult due to their typical multidrug resistance phenotypes. The difficulty to treat MRSP infections using the current antimicrobials licensed for veterinary use has intensified research efforts to develop new treatment strategies and alternative anti-infective approaches to conventional antimicrobial therapy. The present narrative review outlines the latest changes in the epidemiology of MRSP with focus on the geographical distribution variability and antimicrobial resistance profiles in the main MRSP lineages. It also provides an overview of the effectiveness of currently available antimicrobials and the status of anti-infective alternatives to conventional antimicrobials.Recent studies have reported notable changes in the population structure of MRSP, with the emergence of new epidemic lineages, such as ST258, ST123, ST496, and ST551 in European countries and ST45, ST181, ST258, ST496 in non-European countries, which partly or totally replaced those that were initially prevalent, such as ST71 in Europe and ST68 in the US. Due to methicillin resistance often associated with the resistance to a broader number of antimicrobials, treating canine MRSP skin infection is challenging. Several alternative or supplementary treatment options to conventional antibiotics, especially for topical treatment, such as a novel water-soluble hydroxypyridinone-containing iron-chelating 9 kDa polymer (DIBI), antimicrobial peptides (AMPs), nanoparticles, and bacteriophages seem to be particularly interesting from a clinical perspective.

Antihistamine and COVID-19 outcomes in outpatients.

The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic on March 11, 2020. Since then, researchers have been investigating the efficacy and side effects of its medication, up until now. From the viewpoint of Persian medicine, some medications such as antihistamines may cause retention of secretions and lead to exacerbation and spread of the disease in the body. There are studies with conflicting results regarding the effectiveness of antihistamines in COVID-19. Systematic reviews found a lack of data on beneficial effect of antihistamine-decongestant-analgesic combinations for the common cold and a limited short-term effect of antihistamines on severity of overall symptoms. This prospective cohort study was designed to investigate the relationship between the use of antihistamines and the severity of COVID-19 symptoms. Three hundred patients with a diagnosis of COVID-19 participated in the study in Shiraz, Iran from December 4, 2021 until January 24, 2022. The interviews were conducted via phone call by a single interviewer. Patients were followed weekly for 4 weeks. We collected information by using a data collection form, containing demographic information, underlying disease, COVID-19 symptoms, treatment methods, medications, and a list of antihistamines and herbs that might have been used. Generalized estimating equations were applied to assess the relationship between the severity of COVID-19 and the use of antihistamines, taking into account potential confounding factors such as time and herbal consumption. The difference in the severity of COVID-19 disease in antihistamine users compared to nonusers was not significant in 4 weeks despite the higher baseline severity in nonusers. The comparison of two groups of antihistamine users and nonusers showed that there was a significant difference (p = 0.001) regarding the use of herbal medicines.

Infectious Disease Prophylaxis During and After Immunosuppressive Therapy.

Immune-mediated renal diseases are a diverse group of disorders caused by antibody, complement, or cell-mediated autosensitization. Although these diseases predispose to infection on their own, a growing array of traditional and newer, more targeted immunosuppressant medications are used to treat these diseases. By understanding their mechanisms of action and the infections associated with suppression of each arm of the immune system, nephrologists can better anticipate these risks and effectively prevent and recognize opportunistic infections. Focusing specifically on nonkidney transplant recipients, this review discusses the infections that can be associated with each of the commonly used immunosuppressants by nephrologists and suggest interventions to prevent infectious complications in patients with immune-mediated renal disease.

Overcoming treatment resistance in cholangiocarcinoma: current strategies, challenges, and prospects.

Significant advancements in our understanding and clinical treatment of cholangiocarcinoma (CCA) have been achieved over the past 5 years. Groundbreaking studies have illuminated the immune landscape and pathological characteristics of the tumor microenvironment in CCA. The development of immune- and metabolism-based classification systems has enabled a nuanced exploration of the tumor microenvironment and the origins of CCA, facilitating a detailed understanding of tumor progression modulation. Despite these insights, targeted therapies have not yet yielded satisfactory clinical results, highlighting the urgent need for innovative therapeutic strategies. This review delineates the complexity and heterogeneity of CCA, examines the current landscape of therapeutic strategies and clinical trials, and delves into the resistance mechanisms underlying targeted therapies. Finally, from a single-cell and spatial transcriptomic perspective, we address the challenge of therapy resistance, discussing emerging mechanisms and potential strategies to overcome this barrier and enhance treatment efficacy.

Successful Treatment of Sperm DNA Fragmentation Through Ayurveda Rasayana Therapy: A Case Study.

Background: Sperm DNA fragmentation (SDF) can affect fertilization rate and embryo development, making it a useful measure for assessing male fertility. Available evidence supports the association between high sperm DNA fragmentation and poor outcomes, with regard to natural conception. Several treatment options are being adopted with varying degrees of success. Some of the commonly used treatment options are the intake of oral antioxidants, varicocele repair, and techniques like micro-manipulation-based sperm selection and use of testicular sperm for intracytoplasmic sperm injection. Case Presentation: Studies have shown that around 29% of couples depend on complementary and alternative medicine (CAM) modality for the treatment of infertility. However, there is a lack of substantial evidence regarding its efficacy in treating various aspects of infertility in couples. The current case report is about a 44 year-old male patient with infertility, who has a known diagnosis of sex chromosome abnormalities. Meanwhile, the SDF study reports indicated the presence of chromosomal abnormalities. This patient was treated exclusively with Ayurveda therapy aimed towards qualitative improvement in reproductive tissues (Shukra Dhatu as per Ayurveda). Patient was assessed periodically for changes in chromosomal abnormality. After four months of treatment, the evaluations demonstrated the presence of completely normal chromosomes. Conclusion: This case study indicates the potential of Ayurveda therapy in treating cases of male infertility caused by DNA fragmentation. Furthermore, observations and systematically designed clinical trials are warranted to establish a stronger level of evidence before making further clinical recommendations.

Representation of women in clinical trials supporting FDA-approval of contemporary cancer therapies.

Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well-represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA-drug-reviews, we identified all pivotal (phase II and III) non-sex specific trials supporting FDA-approval of anticancer drugs (1998-2018). Observed-enrollment-rates were compared to expected-population-rates derived from concurrent US-National-Cancer-Institute's Surveillance-Epidemiology-and-End-Results (SEER) reported rates and US-Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation-to-prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex-specific analysis of efficacy and/or safety, irrespective of treatment-arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune-based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p < .01). Altogether, women were under-represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight-average PPR of 0.91 (relative difference: -9.1%, p < .01). Women were most under-represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR = .81) cancer trials. Sex-based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p = .96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA-approved cancer drugs, women were frequently under-represented and sex-specific-efficacy and safety-outcomes were commonly not reported.

Serum Biomarkers to Dynamically Predict the Risk of Cardiovascular Events in Patients under Oncologic Therapy. A Multicenter Observational Study.

Background: Serum biomarkers have been investigated as predictive risk factors for cancer-related cardiovascular (CV) risk, but their analysis is limited to their baseline level rather than their overtime change. Besides historically validated causal factors, inflammatory and oxidative stress (OS) related markers seem to be correlated to CV events but this association needs to be further explored. We conducted an observational study to determine the predictive role of the longitudinal changes of commonly used and OS-related biomarkers during the cancer treatment period. Methods: Patients undergoing anticancer therapies, either aged 75+ years old or younger with an increased CV risk according to European Society of Cardiology guidelines, were enrolled. We assessed the predictive value of biomarkers for the onset of CV events at baseline and during therapy using Cox model, Subpopulation Treatment-Effect Pattern Plot (STEPP) method and repeated measures analysis of longitudinal data. Results: From April 2018 to August 2021, 182 subjects were enrolled, of whom 168 were evaluable. Twenty-eight CV events were recorded after a median follow up of 9.2 months (Interquartile range, IQR: 5.1-14.7). Fibrinogen and troponin levels were independent risk factors for CV events. Specifically, patients with higher than the median levels of fibrinogen and troponin at baseline had higher risk compared with patients with values below the medians, hazard ratio (HR) = 3.95, 95% CI, 1.25-12.45 and HR = 2.48, 0.67-9.25, respectively. STEPP analysis applied to Cox model showed that cumulative event-free survival at 18 and 24 months worsened almost linearly as median values of fibrinogen increased. Repeated measure analysis showed an increase over time of D-Dimer (p-interaction event*time = 0.08), systolic (p = 0.07) and diastolic (p = 0.05) blood pressure and a decrease of left ventricular ejection fraction (p = 0.15) for subjects who experienced a CV event. Conclusions: Higher levels of fibrinogen and troponin at baseline and an increase over time of D-Dimer and blood pressure are associated to a higher risk of CV events in patients undergoing anticancer therapies. The role of OS in fibrinogen increase and the longitudinal monitoring of D-dimer and blood pressure levels should be further assessed.

Advances in the Treatment of Pediatric Low-Grade Gliomas.

PURPOSE OF REVIEW: Pediatric low-grade gliomas (pLGGs) often result in significant long-term morbidities despite high overall survival rates. This review aims to consolidate the current understanding of pLGG biology and molecular features and provide an overview of current and emerging treatment strategies. RECENT FINDINGS: Surgical resection remains a primary treatment modality, supplemented by chemotherapy and radiotherapy in specific cases. However, recent advances have elucidated the molecular underpinnings of pLGGs, revealing key genetic abnormalities such as BRAF fusions and mutations and the involvement of the RAS/MAPK and mTOR pathways. Novel targeted therapies, including MEK, BRAF and pan-RAF inhibitors, have shown promise in clinical trials, demonstrating significant efficacy and manageable toxicity. Understanding of pLGGs has significantly improved, leading to more personalized treatment approaches. Targeted therapies have emerged as effective alternatives, potentially reducing long-term toxicities. Future research should focus on optimizing therapy sequences, understanding long-term impacts, and ensuring global accessibility to advanced treatments.

Non-exudative choroidal and macular neovascularizations: An overview.

Non-exudative choroidal and/or macular neovascularizations (NV) represent nowadays a common finding in different retinal disorders. The introduction of non-invasive techniques such as structural optical coherence tomography (OCT) and OCT angiography (OCTA) allowed for easy detection and follow-up of non-exudative NVs. Recognized as a distinct entity, these lesions demonstrate a high variability in terms of pathophysiology, morphology, and prognostic implications. In the absence of a consensus regarding correct classification of subtypes of non-exudative NVs, accurate management through strict follow-up strategies and prompt treatment is required. In this review we offer a comprehensive overview of the non-exudative NV spectrum in various retinal diseases aiming to provide a deeper insight into this clinical entity.