Current and emerging fixed combination therapies in glaucoma: a safety and tolerability review.

INTRODUCTION: Fixed dose combinations (FCs) represent a potentially valuable treatment strategy in glaucoma management. Fixed combinations not only improve adherence by reducing the medication burden, but also decrease the total amount of potentially deleterious preservatives an eye is exposed to. AREAS COVERED: We provide a critical review of selected evidence on both the safety and tolerability of presently available and emerging glaucoma FCs. There is convincing short-term safety and tolerability evidence on intraocular pressure (IOP)-lowering FCs compared to that of monotherapies and, to a lesser degree, to that of concomitant, equivalent combination therapies. In contrast, there is a scarcity of trials evaluating the long-term efficacy and safety of glaucoma FCs and no conclusive data on the reduction of adverse events with FCs. EXPERT OPINION: It is vital for clinicians to carefully weigh the efficacy, safety, tolerability, and adherence of IOP-lowering FCs. Given the number of currently available and emerging FC therapy options in glaucoma, as well as the complexities of incorporating them in the various combination therapy regimens, successful stepwise therapy remains often elusive.

Optical coherence tomography analysis of filtering blebs after long-term, functioning trabeculectomy and XEN® stent implant.

PURPOSE: The purpose of this study was to use Triton® SweptSource OCT to evaluate the morphology of blebs formed when eyes are treated with XEN® implants and to compare these with the blebs in successfully functioning eyes after trabeculectomy (TB) and with eyes of healthy controls. METHODS: A cross-sectional, observational study. We analyzed 25 eyes, 15 after TB and 10 with XEN® implants, comparing them with 23 healthy eyes (controls). We evaluated the conjunctival morphology of the eyes using AS-OCT. The main parameters evaluated were bleb height, sub-epithelial fibrosis, epithelial thickness, and changes in intraocular pressure (IOP). RESULTS: We found that the filtering blebs formed in eyes in which a XEN® stent was implanted were significantly flatter (bleb height 417 ± 183 µm) than the blebs formed in TB eyes (bleb height 618 ± 256 µm, p < 0.05). Moreover, sub-epithelial fibrosis did not develop in any of the blebs produced by the XEN stent, whereas some fibrosis was evident in 40% of the blebs that formed after TB (p < 0.05). The epithelium was thicker when the XEN implant was used (65 ± 18.5 µm) than when eyes underwent TB (60 ± 17.7 µm), and it was thicker than in control eyes (51 ± 9.7 µm, p < 0.05). Moreover, the decrease in the IOP induced by the XEN® stent (- 8.5 ± 5.3 mmHg) was similar to that produced by TB (- 8.8 ± 5.2 mmHg, p > 0.05). CONCLUSIONS: Filtering blebs obtained after the introduction of a XEN® stent were morphologically distinct to those produced by TB, and they are more similar to the healthy conjunctiva.

Outcomes of Trabeculectomy and Phacotrabeculectomy With Collagen Matrix Implant (Ologen) and Low-dose Mitomycin C: 2-Year Follow-up.

PURPOSE: The purpose of this article is to analyze the results achieved in lowering intraocular pressure (IOP) after trabeculectomy or combined surgery (phacotrabeculectomy) with low-dose mitomycin C (MMC) using the Ologen Collagen Matrix (Ologen CM) implant. MATERIALS AND METHODS: This retrospective study included 58 eyes from 47 consecutive patients with glaucoma who underwent filtering surgery alone or combined with cataract surgery. The study group included 29 eyes that underwent trabeculectomy (14 eyes) or phacotrabeculectomy (15 eyes) with low-dose MMC (0.1 mg/mL×1 min) and subconjunctival Ologen CM implant at the end of surgery. The control group included 29 eyes, 12 that underwent trabeculectomy and 17 that underwent phacotrabeculectomy, with the same MMC dose but without the collagen matrix implant. All surgical procedures were performed by the same surgeon. The follow-up period for the patients was 2 years. RESULTS: We found statistically significant differences between the 2 groups in the age of the patients (P=0.02). We found no statistically significant differences in the baseline IOP (P=0.37) or preoperative IOP (P=0.5), nor in the visual field damage measured with mean deviation (P=0.2). The number of hypotensive medications used preoperatively was higher in the study group (P=0.0001). At 1 and 2 years after surgery, we only found statistically significant differences in favor of the study group in patients who underwent phacotrabeculectomy (P=0.0008 and 0.02, respectivily). CONCLUSION: The Ologen CM implant can be considered as an adjunct to MMC in patients undergoing filtering surgery combined with phacoemulsification to improve postoperative IOP results over the long term.

Effect of topical prostaglandin analogues on corneal hysteresis.

PURPOSE: To evaluate possible changes in corneal hysteresis (CH) after topical treatment with a prostaglandin analogue in medication-naïve eyes. METHODS: This was a prospective, observational cohort study. Sixty-eight eyes of 68 patients were prospectively included who were newly diagnosed with primary open-angle glaucoma or ocular hypertension in our institution. All patients were treatment-naïve. Patients were evaluated at baseline and after 6 months of treatment with latanoprost in the eye with the lower intraocular pressure (IOP) measured by Goldmann applanation tonometry (GAT). The ocular response analyzer was used to measure CH. RESULTS: CH increased significantly (p = 0.0001) from 8.96 ± 2.3 mmHg to 9.79 ± 1.97 mmHg, and this increase was correlated significantly (p = 0.0001, r = 0.64, r(2) = 0.41) with the basal CH. We identified a weak but significant (r(2) = 0.06, p = 0.01) relationship between the basal CH and the drug-induced reduction of the GAT IOP. Nevertheless, the increase in the drug-induced CH was not correlated with the decrease in the GAT IOP. CONCLUSION: Treatment with latanoprost increases CH. The CH increase was not correlated with the drug-induced decrease in the GAT IOP, which suggested a direct effect of latanoprost on the viscoelastic corneal properties.

Haem oxygenase-1 down-regulates high mobility group box 1 and matrix metalloproteinases in osteoarthritic synoviocytes.

OBJECTIVES: Activation of osteoarthritic synoviocytes by pro-inflammatory cytokines results in the release of biochemical mediators such as MMPs and high mobility group box 1 (HMGB1). Extracellular HMGB1 can play an important role in joint diseases as a mediator of synovitis. We have shown previously that haem oxygenase-1 (HO-1) exerts protective effects during inflammatory responses. In this study, we have examined whether HO-1 induction would be an effective strategy to control MMP and HMGB1 production in osteoarthritic synoviocytes. METHODS: Osteoarthritic synoviocytes were obtained by digestion with collagenase and cultured until third passage. HO-1 was induced by cobalt protoporphyrin IX (CoPP). Lentiviral HO-1 vector (LV-HO-1) was also used for HO-1 overexpression. HO-1 gene silencing was achieved by using a specific small interfering RNA. Gene expression was analysed by quantitative PCR and protein expression by western blot, ELISA and IF. MMP activity was studied by fluorometric procedures. RESULTS: Induction of HO-1 by CoPP in the presence of IL-1beta decreased the expression of MMP-1 and -3, and MMP activity. IL-1beta stimulation of synoviocytes increased HMGB1 expression, its translocation into the cytoplasm and secretion. HO-1 induction exerted inhibitory effects on these processes. The consequences of HO-1 induction were counteracted by HO-1 gene silencing, whereas transfection with LV-HO-1 confirmed the effects of pharmacological HO-1 induction. CONCLUSIONS: We have provided direct evidence that HO-1 down-regulates MMP-1, -3 and HMGB1 in osteoarthritic synoviocytes. HO-1 may be a potential strategy to control inflammatory and degradative processes in the progression of OA.