Purpose: To report early safety and efficacy of Descemet stripping only (DSO) supplemented with ripasudil. Methods: A pre-post clinical trial with a historical control group for time to heal and cell count parameters. The study received ethics approval and was conducted with oversight of a data safety monitoring board. All enrolled patients had a superior endothelial cell count of >1000 cells/mm2 and were symptomatic from the presence of central guttata degrading vision and/or producing glare. DSO was carried out with a peeling technique and not combined with any other intervention. Ripasudil 0.4% was applied topically from day 1 postoperatively at a dose of 6 times/d until corneal clearance. Cases with relapse of edema were permitted to restart on ripasudil at a reduced dose of 2 drops/d for a further 2 weeks. Stopping rules with progression to a corneal graft were established. Baseline ocular and systemic investigations were carried out and repeated at varying intervals to monitor for local and systemic adverse events. Results: Twenty-three eyes of 23 patients met the inclusion criteria and underwent DSO. Twenty-two of 23 eyes achieved corneal clearance at a mean time of 4.1 weeks. In all patients achieving clearance, improvement in vision was recorded. Improvement in mean uncorrected visual acuity was 0.20 Logarithm of the minimum angle of resolution (LogMar), and improvement in mean best spectacle corrected visual acuity was 0.156 LogMar. One patient failed to clear and underwent Descemet membrane endothelial keratoplasty at week 12. Twenty-one of 22 patients achieving corneal clearance expressed satisfaction with the procedure. The commonest systemic side effect of topical ripasudil was gastrointestinal upset (24%), and the commonest local side effect was ocular irritation (43%). No patient experienced a serious adverse event in the course of the trial. Thirty-nine percent of patients experienced a relapse of edema on ceasing ripasudil, with clearance again on recommencing. Conclusions: This trial of DSO supplemented with ripasudil included local and systemic safety analysis. We judge that this treatment option is emerging as a reliable intervention for select patients with Fuchs' Endothelial Corneal Dystrophy (FECD) with an acceptable safety profile. The observation of relapse edema is strong evidence of a drug effect. The longevity of these results remains unknown.

Purpose: Chronic topical treatment for glaucoma may lead to Ocular Surface Disease (OSD). This study aimed to evaluate: (1) the prevalence of OSD in glaucoma patients under topical treatment, quantifying symptoms and objective ocular surface parameters and (2) the impact of ocular surface treatment on OSD and IOP control. Methods: Patients with primary open angle or primary angle closure glaucoma under topical treatment for at least 6 months were enrolled in the study. Patients underwent symptom screening with the ocular surface disease index (OSDI) questionnaire, assessment of objective ocular surface parameters, ocular surface staining and Schirmer test. A treatment for OSD with eyelid hygiene, fluorometholone acetate 0.1%, preservative-free lubricants, free-acid supplementation and oral tetracyclin derivate was started, and the same evaluation was performed. Results: In our sample (n=19), 73.68% of the patients reported severe symptoms of dry eye disease, with OSDI scores higher than 33 at baseline. Tear film instability was found in 50% of patients, while 23.53% had severe meibomian gland abnormalities. Fluorescein and lissamine green stainings were abnormal in 88.24% and 82.35% of patients, respectively. After ocular surface treatment, statistically significant improvement was found in bestcorrected visual acuity (p=0.0003), OSDI score (p<0.0001), bulbar redness (p=0.0196) and fluorescein staining (p<0.0001.) Mean IOP following OSD treatment reduced −1.59 mmHg from baseline in the left eye (p=0.0510). Conclusion: The prevalence of OSD signs and symptoms was high in glaucoma patients under medical treatment. Short-term OSD treatment may improve ocular surface disease and IOP control, with no need to discontinue glaucoma medications.

Pterygium is a common ocular surface condition frequently associated with irritative symptoms. The precise identity of its critical triggers as well as the hierarchical relationship between all the elements involved in the pathogenesis of this disease are not yet elucidated. Meta-analysis of gene expression studies represents a novel strategy capable of identifying key pathogenic mediators and therapeutic targets in complex diseases. Samples from nine patients were collected during surgery after photo documentation and clinical characterization of pterygia. Gene expression experiments were performed using Human Clariom D Assay gene chip. Differential gene expression analysis between active and atrophic pterygia was performed using limma package after adjusting variables by age. In addition, a meta-analysis was performed including recent gene expression studies available at the Gene Expression Omnibus public repository. Two databases including samples from adults with pterygium and controls fulfilled our inclusion criteria. Meta-analysis was performed using the Rank Production algorithm of the RankProd package. Gene set analysis was performed using ClueGO and the transcription factor regulatory network prediction was performed using appropriate bioinformatics tools. Finally, miRNA-mRNA regulatory network was reconstructed using up-regulated genes identified in the gene set analysis from the meta-analysis and their interacting miRNAs from the Brazilian cohort expression data. The meta-analysis identified 154 up-regulated and 58 down-regulated genes. A gene set analysis with the top up-regulated genes evidenced an overrepresentation of pathways associated with remodeling of extracellular matrix. Other pathways represented in the network included formation of cornified envelopes and unsaturated fatty acid metabolic processes. The miRNA-mRNA target prediction network, also reconstructed based on the set of up-regulated genes presented in the gene ontology and biological pathways network, showed that 17 target genes were negatively correlated with their interacting miRNAs from the Brazilian cohort expression data. Once again, the main identified cluster involved extracellular matrix remodeling mechanisms, while the second cluster involved formation of cornified envelope, establishment of skin barrier and unsaturated fatty acid metabolic process. Differential expression comparing active pterygium with atrophic pterygium using data generated from the Brazilian cohort identified differentially expressed genes between the two forms of presentation of this condition. Our results reveal differentially expressed genes not only in pterygium, but also in active pterygium when compared to the atrophic ones. New insights in relation to pterygium’s pathophysiology are suggested.

was a previous consultant of Kowa India Private Limited, manufacturers of Ripasudil; the other authors have no conflicts of interest to disclose. Use of ripasudil for corneal hydrops is an off-label use of the medication.

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