A Pilot Study to Evaluate Genipin in Staphylococcus aureus and Pseudomonas aeruginosa Keratitis Models: Modulation of Pro-Inflammatory Cytokines and Matrix Metalloproteinases.

Infectious keratitis is a vision-threatening microbial infection. The increasing antimicrobial resistance and the fact that severe cases often evolve into corneal perforation necessitate the development of alternative therapeutics for effective medical management. Genipin, a natural crosslinker, was recently shown to exert antimicrobial effects in an ex vivo model of microbial keratitis, highlighting its potential to serve as a novel treatment for infectious keratitis. This study aimed to evaluate the antimicrobial and anti-inflammatory effects of genipin in an in vivo model of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) keratitis. Clinical scores, confocal microscopy, plate count, and histology were carried out to evaluate the severity of keratitis. To assess the effect of genipin on inflammation, the gene expression of pro- and anti-inflammatory factors, including matrix metalloproteinases (MMPs), were evaluated. Genipin treatment alleviated the severity of bacterial keratitis by reducing bacterial load and repressing neutrophil infiltration. The expression of interleukin 1B (IL1B), interleukin 6 (IL6), interleukin 8 (IL8), interleukin 15 (IL15), tumor necrosis factor-α (TNF-α), and interferon γ (IFNγ), as well as MMP2 and MMP9, were significantly reduced in genipin-treated corneas. Genipin promoted corneal proteolysis and host resistance to S. aureus and P. aeruginosa infection by suppressing inflammatory cell infiltration, regulating inflammatory mediators, and downregulating the expression of MMP2 and MMP9.

Novel treatments for dry eye syndrome.

Dry eye syndrome (DES) is a prevalent and multifactorial disease that leads to a self-perpetuating cycle of inflammation and damage to the ocular surface. This results in symptoms such as redness, burning, and blurred vision, which can negatively affect a patient's quality of life. While treatments are available to manage DES, they only temporarily relieve symptoms. Furthermore, long-term use of certain medications can cause harm to the ocular surface. Therefore, there is a need for safer and effective treatments for DES. This review highlights the latest advancements in DES therapy, providing valuable insights into ongoing efforts to improve patient outcomes.

Descemet Membrane Endothelial Keratoplasty as Treatment for Late-Onset Interface Fluid Syndrome After Laser In Situ Keratomileusis.

PURPOSE: We herein present Descemet membrane endothelial keratoplasty (DMEK) as an effective surgical means of treatment for the management of interface fluid syndrome (IFS) in a series of cases with distant history of laser in situ keratomileusis (LASIK). METHODS: Three cases from a single institution were included. All patients had documented IFS in the setting of history of LASIK. All 3 patients underwent DMEK for the treatment of IFS. Visual acuity, clinical findings, pachymetry, endothelial cell count, and anterior segment optical coherence tomography were recorded. RESULTS: We describe 3 cases of late-onset IFS that developed in eyes many years after LASIK (ranging from 15 to 31 years). All 3 patients had clinically significant corneal edema and evidence of poor endothelial function at the time of IFS diagnosis. DMEK was subsequently performed in each case. All 3 eyes showed resolution of corneal edema and improvement in best-corrected visual acuity after DMEK. CONCLUSIONS: DMEK can provide successful visual and anatomical recovery in patients who have had previous LASIK and experience late-onset IFS due to endothelial cell dysfunction.

Effect of Anterior Chamber Air on Central Corneal Thickness in Human Donor Eyes.

PURPOSE: The purpose of this study was to describe the effects of intracameral air on corneal edema. METHODS: A laboratory investigation was performed on human donor corneas. Baseline pachymetry measurements through anterior segment optical coherence tomography and endothelial cell density were obtained for all corneas. Each pair of corneas was separated and randomly assigned to undergo air injection or Optisol-GS into a BIONIKO artificial anterior chamber for 5 minutes at physiologic intraocular pressure confirmed by digital palpation. Photographs were obtained immediately on connection of the cornea to the artificial anterior chamber and on completion of the 5 minutes of treatment, with anterior chamber air being exchanged for Optisol-GS. Pretreatment and posttreatment photographs were obtained. Immediately after treatment, pachymetry was again obtained on all corneas. Pachymetry data underwent statistical analysis. RESULTS: Corneal pachymetry improved from 690.5 ± 126.6 to 576.1 ± 87.2 µm, yielding a 114.4 ± 50.4 µm improvement of pachymetry in the group with air injected into the anterior chamber. This was a significant improvement of pachymetry when compared with the group with Optisol-GS injected into the anterior chamber, which showed an improvement from 662.3 ± 126.5 to 613.5 ± 108.0 µm, yielding an improvement of 48.8 ± 34.3 µm. CONCLUSIONS: Injection of air into the anterior chamber leads to a significant decrease in corneal pachymetry. We thereby propose that injecting air intracamerally is an effective intraoperative intervention when visualization is negatively affected by corneal edema.

Genipin in an Ex Vivo Corneal Model of Bacterial and Fungal Keratitis.

Purpose: To determine whether genipin (a natural crosslinker) could reduce the colonization and proliferation of bacteria and fungi in an ex vivo model of corneal infection. Methods: This study, using an ex vivo model of bacterial and fungal keratitis, investigated the antimicrobial efficacy of genipin crosslinking. Excised corneoscleral buttons were wounded by scalpel incision and subsequently infected with Staphylococcus aureus, Pseudomonas aeruginosa, or Candida albicans. After inoculation, corneas were treated with genipin for 24 hours at 37°C. Histologic examinations were carried out, and the number of viable colony-forming units (CFU)/cornea was determined. Results: Genipin exerts bactericidal action against S. aureus and P. aeruginosa, as well as fungicidal action against C. albicans and significantly reduced the CFU compared to contralateral eyes that received saline treatment (P < 0.05). Conclusions: These data identify genipin as a novel ocular antimicrobial agent that has the potential to be incorporated into the therapeutic armamentarium against microbial keratitis. Translational Relevance: This study provided evidence for the antimicrobial and antifungal properties of genipin as an alternative crosslinker that could be used in the management of infectious keratitis.