Background: Usher syndrome (USH), the most common cause of combined deaf-blindness, is a genetically and phenotypically heterogeneous disorder characterized by congenital hearing impairment and progressive vision loss due to rod-cone dystrophy. Although the original classification in three subtypes (USH I, USH II, and USH III) is still valid, recent findings have changed and widened perspectives in its classification, genotype–phenotype correlations, and management strategies: Objective: This study aims to provide new insights into the classification of Usher syndrome, explore the genotype-phenotype correlations, and review current and emerging management strategies. Methods: A comprehensive literature review has been conducted, incorporating data from clinical studies, genetic databases, and patient registries. Results: Recent studies have led to the identification of several novel pathogenic variants in the USH genes, leading to refined subclassifications of Usher syndrome. Interactions between different genes being part of the network of this ciliopathy have been investigated and new mechanisms unveiled. Significant correlations were found between certain genotypes and the presentation of both auditory and visual phenotypes. For instance, pathogenic variants in the MYO7A gene (USH1B) were generally associated with more severe hearing impairment and earlier onset of retinal dystrophy, if compared to other USH genes-related forms. Other genes, such as USH1G, traditionally considered as causing a specific subtype, can display phenotypic heterogeneity in some patients. Conclusions: This review provides insights into a better understanding of Usher syndrome that considers recent findings regarding its genetic causes and clinical features. Precise genotype–phenotype correlations can lead to better genetic counselling, more precise characterization of the natural history of the condition, and a personalized and effective management approach. Recent progress has been made in research into gene-specific therapies that appear promising for improving the quality of life for individuals affected by Usher syndrome.

Primary open angle glaucoma (POAG) is defined as a “genetically complex trait”, where modifying factors act on a genetic predisposing background. For the majority of glaucomatous conditions, DNA variants are not sufficient to explain pathogenesis. Some genes are clearly underlying the more “Mendelian” forms, while a growing number of related polymorphisms in other genes have been identified in recent years. Environmental, dietary, or biological factors are known to influence the development of the condition, but interactions between these factors and the genetic background are poorly understood. Several studies conducted in recent years have led to evidence that epigenetics, that is, changes in the pattern of gene expression without any changes in the DNA sequence, appear to be the missing link. Different epigenetic mechanisms have been proven to lead to glaucomatous changes in the eye, principally DNA methylation, post-translational histone modification, and RNA-associated gene regulation by non-coding RNAs. The aim of this work is to define the principal epigenetic actors in glaucoma pathogenesis. The identification of such mechanisms could potentially lead to new perspectives on therapeutic strategies.

Pericytes, specialized mural cells surrounding microvessels, play a crucial role in maintaining vascular homeostasis and function across various organs, including the eye. These versatile cells regulate blood flow, support the integrity of the blood–retinal barrier, and contribute to angiogenesis. Recent advancements in molecular and cellular biology have revealed the heterogeneity of pericytes and their critical involvement in ocular physiology and pathology. This review provides a comprehensive analysis of pericyte functions in ocular health and their implications in diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, and retinal vein occlusion. Pericyte dysfunction is implicated in vascular instability, neurovascular coupling failure, inflammation, and pathological neovascularization, contributing to vision-threatening disorders. The review further explores recent findings on pericyte-targeted therapies, including pharmacological agents, gene therapy, and cell-based approaches, aiming to restore pericyte function and preserve ocular health.

Background: In systemic sclerosis (SSc) patients, dry eye syndrome (DES) is the most frequent ocular feature. The aim of this study was to investigate ocular DES-related SSc patients and to establish any correlation with the severity of the disease. Methods: Retrospectively, data from 60 patients with SSc underwent ophthalmic examination, where non-invasive film tear break-up time (NIF-TBUT), tear film lipid layer thickness (LLT), anesthetic-free Schirmer test I, tear osmolarity measurement (TearLab System), and modified Rodnan skin score (mRSS) data were collected. The visual analog scale (VAS) and Symptom Assessment in Dry Eye (SANDE) methods were utilized. The results were correlated with mRSS and the duration of SSc. Results: Severe DES occurred in 84% of cases, and was more severe in women. The eyelids were involved in 86.6%, secondary to meibomian gland disease (MGD). A direct correlation was found between the tear osmolarity (mean 328.51 ± 23.8 SD) and skin score (mRSS) (r = 0.79; p < 0.01). Significantly reduced NIF-TBUT, LLT, and Schirmer test I values were observed in the case of severe skin involvement. Conclusions: SSc patients show lipid tear dysfunction related to the severity and duration of the disease due to inflammation and the subsequent atrophy of the meibomian glands.

Background/Objectives: Optic neuropathies are a category of illnesses that ultimately cause damage to the optic nerve, leading to vision impairment and possible blindness. Disorders such as dominant optic atrophy (DOA), Leber hereditary optic neuropathy (LHON), and glaucoma demonstrate intricate genetic foundations and varied phenotypic manifestations. This narrative review study seeks to consolidate existing knowledge on the genetic and molecular mechanisms underlying ocular neuropathies, examine genotype-phenotype correlations, and assess novel therapeutic options to improve diagnostic and treatment methodologies. Methods: A systematic literature review was performed in October 2024, utilizing PubMed, Medline, the Cochrane Library, and ClinicalTrials.gov. Search terms encompassed “optic neuropathy”, “genetic variants”, “LHON”, “DOA”, “glaucoma”, and “molecular therapies”. Studies were chosen according to established inclusion criteria, concentrating on the genetic and molecular dimensions of optic neuropathies and their therapeutic ramifications. Results: The results indicate that DOA and LHON are mostly associated with the mitochondrial dysfunction resulting from pathogenic variants in nuclear genes, mainly OPA1, and mitochondrial DNA (mtDNA) genes, respectively. Glaucoma, especially its intricate variants, is linked to variants in genes like MYOC, OPTN, and TBK1. Molecular mechanisms, such as oxidative stress and inflammatory modulation, are pivotal in disease progression. Innovative therapeutics, including gene therapy, RNA-based treatments, and antioxidants such as idebenone, exhibit promise for alleviating optic nerve damage and safeguarding vision. Conclusions: Genetic and molecular investigations have markedly enhanced our comprehension of ocular neuropathies. The amalgamation of genetic and phenotypic data is essential for customized medical strategies. Additional research is required to enhance therapeutic strategies and fill the gaps in our understanding of the underlying pathophysiology. This interdisciplinary approach shows potential for enhancing patient outcomes in ocular neuropathies.

Background and Objectives: Dry eye disease (DED) affects 5–50% of the global population and deeply influences everyday life activities. This study compared the efficacy, tolerability, and safety of novel Respilac artificial tears containing lipidure and hypromellose (HPMC) with the widely used Nextal artificial tears, which are also HPMC-based, for the treatment of moderate DED in contact lenses (CL) wearers. Materials and Methods: In a prospective, single-center, randomized investigation, 30 patients aged ≥18 years, diagnosed with moderate DED, and wearing CL were randomly assigned to the Respilac (n = 15) or Nextal group (n = 15). Patients self-administrated one drop of Respilac or Nextal in both eyes three times daily for 21 days. Changes in the endpoint (visual analogue scale (VAS) score for ocular tolerability, symptom assessment in dry eye (SANDE) score, non-invasive first break-up time (NIF-BUT) results, tear analysis value, meibography results, and CL tolerability results were assessed, comparing treatment groups and time-point evaluations. Adverse events (AEs) were also recorded and evaluated. Results: VAS scores decreased with time (p < 0.001) in both groups, showing no statistically significant difference among them (p = 0.13). Improvements were also detected from screening to end-of-treatment, which were indicated by the SANDE scores for severity and frequency (p < 0.001) and by tear analysis results (p < 0.001) with no observed difference between the Nextal and Respilac arms. NIF-BUT, meibography, and CL tolerability values were shown to be non-significantly affected by treatment and time. There were no AEs detected in this study cohort. Conclusions: Respilac was confirmed to be effective, safe, and well-tolerated. Lipidure-based ophthalmic solution was shown not to be inferior to the currently used Nextal, however, showing improvements in DED symptoms. Within the existing literature, our study is one of the first to report that MPC plus HPMC-containing eye drops are an effective option for the treatment of moderate dry eye disease and desiccation damage prevention in contact lens wearers.