Real-World Effectiveness, Tolerability and Safety of Cyclosporine A 0.1% Cationic Emulsion in Severe Keratitis and Dry Eye Treatment.

INTRODUCTION: The PERSPECTIVE study evaluated, in routine clinical practice, the effectiveness, tolerability and safety of cyclosporine A (CsA) 0.1% cationic emulsion (CE) in controlling severe keratitis in adults with dry eye who remained insufficiently controlled despite artificial tear (AT) use. METHODS: A prospective, multicenter, observational study was conducted at 44 ophthalmology clinics across Finland, Germany, Norway, Sweden and the UK. Adults treated with ATs for severe keratitis and dry eye received CsA 0.1% CE therapy (1 drop in both eyes at bedtime) and were followed up at weeks 4, 12 and 24 and at month 12. Primary endpoint was mean [standard deviation (SD)] change from baseline in corneal fluorescein staining (CFS; Oxford Grade Scale) at month 12 following CsA 0.1% CE initiation. Secondary endpoints examined ocular sign and symptom severity and adverse events (AEs). RESULTS: The full analysis set included 472 adults (75.9% female). Mean (SD) age was 61.9 (15.41) years. Mean (SD) CFS score was significantly reduced from baseline [2.56 (1.10)] at month 12 [1.10 (SD 1.13); P < 0.0001]. CFS score reductions were statistically significant from week 4, with further incremental decreases reported at study visits through month 12 (P < 0.0001). Severity of eyelid and conjunctival erythema was significantly reduced from baseline at week 4 and maintained through month 12 (P < 0.001). Tear film breakup time increased significantly from baseline at all study visits through month 12 (P < 0.001). Ocular symptom severity was significantly reduced from baseline at all study visits through month 12 (P < 0.001). Overall, 101 treatment-related AEs were reported. Most were mild/moderate (83.6%) and resolved by month 12 (73.3%). CONCLUSIONS: In routine clinical practice, CsA 0.1% CE provided statistically significant reductions in dry eye signs and symptoms. Improvements were seen at week 4 and maintained over 12 months. Treatment tolerability was good and consistent with previous CsA 0.1% CE clinical studies. TRIAL REGISTRATION: EU PAS register number: EUPAS 22376.

The role of benzalkonium chloride in the occurrence of punctate keratitis: a meta-analysis of randomized, controlled clinical trials.

BACKGROUND: Benzalkonium chloride (BAK), the most commonly used preservative in topical ophthalmic solutions, has undergone considerable criticism in recent years, principally based on in vitro and in vivo studies. Relevance to the clinical setting has not been confirmed. OBJECTIVE: To determine whether administration of twice the amount of BAK was associated with an increased incidence of punctate keratitis in long-term, double-masked trials comparing latanoprost ophthalmic solution and vehicle with timolol ophthalmic solution in patients with glaucoma or ocular hypertension. METHODS: A meta-analysis of the double-masked phases of 7 prospective, controlled clinical trials compared the incidence of punctate keratitis among patients assigned to treatment with latanoprost or timolol. In all studies, the amount of BAK administered daily in the latanoprost arms was approximately twice the amount used in the timolol arms. All reports of punctate keratitis either as a finding or an adverse event were included. A fixed-effect model was used because the heterogeneity was small and not statistically significant. Sensitivity analyses were conducted. Funnel plots were provided to address potential publication bias. RESULTS: Of the 1694 patients enrolled in the double-masked portion of the trials (latanoprost, n = 892; timolol, n = 802), the overall incidence of punctate keratitis was 6.3% (106/1694). The incidence in latanoprost-treated patients was 6.5% and in timolol-treated patients was 6.0%. The risk difference for punctate keratitis of latanoprost versus timolol was 0.005 (95% CI -0.011 to 0.020; p = 0.574), and the risk ratio of latanoprost versus timolol was 1.084 (95% CI 0.739 to 1.589; p = 0.680). CONCLUSIONS: These results indicate that BAK does not produce significant corneal toxicity in the vast majority of patients with glaucoma or ocular hypertension at the concentrations used in these studies.

Developments in ocular allergy.

PURPOSE OF REVIEW: The goal of this article is to evaluate developments in the knowledge of inflammatory mechanisms and treatments of ocular allergy. RECENT FINDINGS: Research developments in ocular allergy summarized in this article include the following findings: (1) ocular epithelial cells play a role in inflammation; (2) respiratory syncytial virus is a pathogen in allergic conjunctivitis; (3) transglutaminase inhibitors reverse allergic related inflammation; (4) eosinophils and neutrophils both play a role in ocular allergy; (5) eotaxin-1 and eotaxin-2 play a role in eosinophilic recruitment; and (6) loteprednol etabonate, desonide phosphate, and cyclosporine have been shown to be effective and safe in the treatment of ocular allergy. SUMMARY: This article summarizes the research conducted for each of the above recent findings and outlines their clinical applications.

Modulation of IL-8 and RANTES release in human conjunctival epithelial cells: primary cells and cell line compared and contrasted.

PURPOSE: Recent research indicates that epithelial cells of the ocular surface can contribute to the allergic reaction by the release of inflammatory and/or chemotactic mediators. In this study, the role of two inflammatory mediators, previously identified in the tear film of ocular allergy subjects, TNF-alpha and IFN-gamma, were evaluated for their effect on the release of two chemotactic mediators, IL-8 and RANTES, from cultured human conjunctival epithelial cells. METHODS: Human conjunctival epithelial cells (primary cells or HC0597 cell line) were grown to confluence and stimulated with various concentrations of TNF-alpha, IFN-gamma, or a combination of both. Supernatants were collected at 6, 24, and 48 hours and stored frozen for subsequent ELISA analyses of RANTES and IL-8. RESULTS: RANTES and IL-8 release from HC0597 cells was stimulated in a dose- and time-dependent manner following treatment with TNF-alpha. However, only RANTES release was modulated by IFN-gamma treatment. Treatment of HC0597 cells with both TNF-alpha and IFN-gamma resulted in a synergistic increase in the release of RANTES. This synergistic effect was confirmed using primary cultures of human conjunctival epithelial cells. CONCLUSIONS: Stimulation of conjunctival epithelium with proinflammatory mediators, TNF-alpha and/or IFN-gamma, generated the release of the chemotactic factors IL-8 and RANTES, which could act to prolong inflammation. These two chemokines may prolong inflammation by recruiting eosinophils to the ocular surface. This is the first study to compare chemokine release in a cell line and primary cells; similar chemokine release after mediator stimulation was demonstrated, indicating that the two cell types are phenotypically similar.

Spectrum of ocular allergy.

PURPOSE OF REVIEW: To elaborate and review the immunologic spectrum of the five basic types of ocular allergy. RECENT FINDINGS: Perennial allergic conjunctivitis (PAC) appears to be an extension of seasonal allergic conjunctivitis (SAC) based on the similarity of clinical symptoms and the immune mechanism involved. T helper type 2 (TH2)-type cytokines, increased ratio of TH1/TH2 cytokines and increased statement of adhesion molecules all appear to play an integral role in the inflammatory process of SAC and PAC. Vernal keratoconjunctivitis (VKC), which is a pediatric disease, differs from SAC and PAC by its more severe and chronic nature. Increased numbers of T cells, eosinophils (along with the products of degranulation), chemokines and their receptors may contribute to the more serious symptoms of VKC. Atopic keratoconjunctivitis (AKC) is similar to VKC by the increased concentration of cytokines involved (i.e. interleukin-4 and -5). Despite clinical similarities with VKC, the presence of atopic dermatitis, along with some differences in clinical signs, make AKC a separate entity, which is sometimes referred to as an adult variant of VKC. Giant papillary conjunctivitis has similar cell involvement as VKC and AKC. However, giant papillary conjunctivitis differs from VKC and AKC by the clinical signs present (i.e. the presence of giant papillae) and the necessary concurrent contact lens wear. SUMMARY: The important differences and similarities observed in these five types of allergic diseases might help to better treat the patients affected with these disorders.