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The human microbiota refers to a large variety of microorganisms (bacteria, viruses, and fungi) that live in different human body sites, including the gut, oral cavity, skin, and eyes. In particular, the presence of an ocular surface microbiota with a crucial role in maintaining ocular surface homeostasis by preventing colonization from pathogen species has been recently demonstrated. Moreover, recent studies underline a potential association between gut microbiota (GM) and ocular health. In this respect, some evidence supports the existence of a gut–eye axis involved in the pathogenesis of several ocular diseases, including age-related macular degeneration, uveitis, diabetic retinopathy, dry eye, and glaucoma. Therefore, understanding the link between the GM and these ocular disorders might be useful for the development of new therapeutic approaches, such as probiotics, prebiotics, symbiotics, or faecal microbiota transplantation through which the GM could be modulated, thus allowing better management of these diseases.

The term ocular microbiota refers to all types of commensal and pathogenic microorganisms present on or in the eye. The ocular surface is continuously exposed to the environment and harbors various commensals. Commensal microbes have been demonstrated to regulate host metabolism, development of immune system, and host defense against pathogen invasion. An unbalanced microbiota could lead to pathogenic microbial overgrowth and cause local or systemic inflammation. The specific antigens that irritate the deleterious immune responses in various inflammatory eye diseases remain obscure, while recent evidence implies a microbial etiology of these illnesses. The purpose of this review is to provide an overview of the literature on ocular microbiota and the role of commensal microbes in several eye diseases. In addition, this review will also discuss the interaction between microbial pathogens and host factors involved in intraocular inflammation, and evaluate therapeutic potential of targeting ocular microbiota to treat intraocular inflammation.

Background The visual organ plays a crucial role in sensing environmental information. However, its mucosal surfaces are constantly exposed to selective pressures from aquatic or airborne pathogens and microbial communities. Although few studies have characterized the conjunctival-associated lymphoid tissue (CALT) in the ocular mucosa (OM) of birds and mammals, little is known regarding the evolutionary origins and functions of immune defense and microbiota homeostasis of the OM in the early vertebrates. Results Our study characterized the structure of the OM microbial ecosystem in rainbow trout (Oncorhynchus mykiss ) and confirmed for the first time the presence of a diffuse mucosal-associated lymphoid tissue (MALT) in fish OM. Moreover, the microbial communities residing on the ocular mucosal surface contribute to shaping its immune environment. Interestingly, following IHNV infection, we observed robust immune responses, significant tissue damage, and microbial dysbiosis in the trout OM, particularly in the fornix conjunctiva (FC), which is characterized by the increase of pathobionts and a reduction of beneficial taxa in the relative abundance in OM. Critically, we identified a significant correlation between viral-induced immune responses and microbiome homeostasis in the OM, underscoring its key role in mucosal immunity and microbiota homeostasis. Conclusions Our findings suggest that immune defense and microbiota homeostasis in OM occurred concurrently in early vertebrate species, shedding light on the coevolution between microbiota and mucosal immunity. 1WNPLmNTzstteMxSNP_LzT Video Abstract

A healthy ocular surface is inhabited by microorganisms that constitute the ocular microbiome. The core of the ocular microbiome is still a subject of debate. Numerous culture-dependent and gene sequencing studies have revealed the composition of the ocular microbiome. There was a confirmed correlation between the ocular microbiome and ocular surface homeostasis as well as between ocular dysbiosis and pathologies such as blepharitis, microbial keratitis, and conjunctivitis. However, the role of the ocular microbiome in the pathogenesis and treatment of ocular surface diseases remains unclear. This article reviews available data on the ocular microbiome and microbiota, their role in maintaining ocular homeostasis, and the impact of dysbiosis on several ophthalmic disorders. Moreover, we aimed to discuss potential treatment targets within the ocular microbiota.

This pilot study characterized the tear microbiota profile in patients with primary open-angle glaucoma (POAG) and compared it with healthy controls. Tear samples from 22 participants (10 POAG patients and 12 matched controls) were analyzed using 16 S rRNA gene sequencing. While no significant differences were found in alpha diversity, beta diversity analyses revealed distinct microbial community structures between groups, with POAG patients exhibiting a more homogeneous and less diverse microbiota. Three phyla—Fusobacteriota, Planctomycetota, and Synergistota—were significantly more abundant in the glaucoma group ( p  < 0.0001), and 23 bacterial genera showed differential abundance. Additionally, preserved eye drops appeared to modulate microbial composition, with specific alterations observed in several genera. These findings support the hypothesis of ocular dysbiosis associated with POAG, potentially linked to inflammatory and immunological mechanisms. The study suggests that microbiota-based interventions, such as probiotics or postbiotics, may offer complementary therapeutic strategies, and highlights the need for longitudinal studies with larger sample sizes to validate these preliminary results.

Moxifloxacin is a fourth-generation fluoroquinolone antibiotic available for ophthalmic use. It inhibits two enzymes involved in bacterial DNA synthesis, covering Gram-positive and Gram-negative pathogens. This spectrum allows for the formulation of self-preserving bottle solutions, while its interesting pharmacological profile is distinguished by efficacy at low tissue concentrations and by an infrequent dose regimen due to its long duration on ocular tissues. This enhances patient compliance, promoting its use in children. The human eye hosts several microorganisms; this collection is called the ocular microbiota, which protects the ocular surface, assuring homeostasis. When choosing an antibiotic, it is appropriate to consider its influence on microbiota. A short dose regimen is preferred to minimize the impact of the drug. Moxifloxacin eyedrops represent an effective and safe tool to manage and prevent ocular infections. As healthcare providers face the complexity of the ocular microbiota and microbial resistance daily, the informed use of moxifloxacin is necessary to preserve its efficacy in the future. In this regard, it is well known that moxifloxacin has a lower capacity to induce resistance (an optimal WPC and MPC) compared to other quinolones, but much still needs to be explored regarding the impact that fluoroquinolones could have on the ocular microbiota.

Traditionally used to combat infections, systemic effects of antibiotics are increasingly recognized in the context of absorption through unconventional routes. One such as the ocular surface. This review tackles the bidirectional liver–eye axis, highlighting how trace antibiotic residues from environmental and therapeutic sources affect the tear film, disturb ocular microbiota, and impact liver metabolism. It engages in anatomical pathways, microbial regulation, pharmacokinetics, and systemic immune responses. Additionally, this review discusses forensic uses and new therapeutic strategies, stressing the importance of integrated environmental monitoring and precision medicine to tackle nonmedicinal antibiotic exposure. Due to the absence of results from a systematic literature review, a narrative literature review was undertaken instead. More than 100 studies discussing mechanistic, clinical, and experimental insights were reviewed, with 98 of those studies being documented as source literature. The findings demonstrate that antibiotics may penetrate and be absorbed through the ocular surface, cause modifications of the hepatic first-pass metabolism, and change the activity of cytochrome P450. Correlations were documented between the various liver function biomarkers and the ocular tear film, as well as the thickness of the retinal pigment epithelium. The dysbiosis of eye microbiota may be an indicator of systemic inflammation associated with immune dysregulation. Restoring microbial homeostasis and addressing systemic dysregulation are novel therapeutic approaches, including the use of probiotics, nanoparticle scavengers, and CRISPR. The eye is a sensory organ and a metabolically active organ. Systemically, the eye can affect the liver through the ocular surface and the antibiotics through the liver–eye axis. To protect the systemic health of the individual and the lensed metabolically active eye, the eye and liver must be viewed as a sentinel of systemic balance. Novel therapies will be necessary with the added need for environmental monitoring.

The advent of multidrug resistance among pathogenic bacteria is devastating the worth of antibiotics and changing the way of their administration, as well as the approach to use new or old drugs. The crisis of antimicrobial resistance is also due to the unavailability of newer drugs, attributable to exigent regulatory requirements and reduced financial inducements. The emerging resistance to antibiotics worldwide has led to renewed interest in old drugs that have fallen into disuse because of toxic side effects. Thus, comprehensive efforts are needed to minimize the pace of resistance by studying emergent microorganisms and optimize the use of old antimicrobial agents able to maintain their profile of susceptibility. Chloramphenicol is experiencing its renaissance because it is widely used in the treatment and prevention of superficial eye infections due to its broad spectrum of activity and other useful antimicrobial peculiarities, such as the antibiofilm properties. Concerns have been raised in the past for the risk of aplastic anemia when chloramphenicol is given intravenously. Chloramphenicol seems suitable to be used as topical eye formulation for the limited rate of resistance compared to fluoroquinolones, for its scarce induction of bacterial resistance and antibiofilm activity, and for the hypothetical low impact on ocular microbiota disturbance. Further in-vitro and in vivo studies on pharmacodynamics properties of ocular formulation of chloramphenicol, as well as its real impact against biofilm and the ocular microbiota, need to be better addressed in the near future.

Objectives: This study aims to assess the presence of pathogenic microorganisms in the corneal epithelial layer of keratoconus patients. Methods: DNA was extracted from corneal epithelial samples procured from ten individual keratoconus eyes and three healthy controls. Metagenomic next-generation sequencing (mNGS) was performed to detect ocular microbiota using an agnostic approach. Results: Metagenomic sequencing revealed a low microbial read count in corneal epithelial samples derived from both keratoconus eyes (average: 530) and controls (average: 622) without a statistically significant difference (p = 0.29). Proteobacteria were the predominant phylum in both keratoconus and control samples (relative abundance: 72% versus 79%, respectively). Conclusions: The overall low microbial read count and the lack of difference in the relative abundance of different microbial species between keratoconus and control samples do not support the hypothesis that a chronic corneal infection is implicated in the pathogenesis of keratoconus. These findings do not rule out the possibility that an acute infection may be involved in the disease process as an initiating event.

The study highlights the importance of considering these factors for studying microbiomes of sparsely colonized sites such as the ocular surface for better reliability of data and provides potential sources of bias in analyzing microbial composition of low abundance on the ocular surface. By exploring the mechanism of early perforation and thinning of cornea with P. aeruginosa infection after PM10 exposure, they report that PM10 exposure worsens the defense mechanism by oxidative stress, inflammation, and susceptibility to infection, and SKQ1 protects by reversing the adverse effects of PM10 via mitochondria-targeted antioxidant effects. Alenezi et al. demonstrate differential expression of genes in corneal infections in their study to understand the pathogenic mechanism of microbial keratitis, particularly the overreactive immune response to infection that causes corneal scarring and vision loss. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.