Role of fixed-combination brinzolamide 1%/timolol 0.5% in the treatment of elevated intraocular pressure in open-angle glaucoma and ocular hypertension

Brinzolamide 1%/timolol 0.5% is a new fixed-combination for the treatment of open-angle glaucoma or ocular hypertension. Brinzolamide/timolol has a favorable safety profile, with an incidence of ocular burning and stinging <5%. Published data show that brinzolamide 1%/timolol 0.5% and dorzolamide 2%/timolol 0.5% have similar efficacies for lowering intraocular pressure (IOP). There is some evidence that brinzolamide/timolol may be more comfortable. Although patients receiving brinzolamide/timolol may experience more blurred vision on instillation, some data show a preference for brinzolamide/timolol over dorzolamide/timolol. Although available data to assess the role of brinzolamide/timolol in daily clinical practice are still limited, these first results suggest the agent to be a reasonable alternative for patients who do not reach target IOP with monotherapy

Baerveldt implant for secondary glaucoma due to iris melanoma

Annelie N Tan1, Juliette GMM Hoevenaars1, Carroll AB Webers1, Bertil Damato2, Henny JM Beckers11University Eye Clinic, Maastricht, The Netherlands; 2Ocular Oncology Service Royal Liverpool University Hospital, Liverpool, United KingdomBackground: Proton beam therapy (PBT) is effective in the treatment of iris melanoma. Reported complications after PBT are radiation-induced cataract and raised intraocular pressure (IOP). Filtering glaucoma surgery has generally been avoided because of fears of seeding.Case report: A 37-year-old man presented with a self-discovered, pigmented lesion on his right iris. Four years later, the pigmented lesion was diagnosed as an iris melanoma, because of documented growth. The patient was treated with PBT but developed secondary glaucoma one month later. The IOP could not be controlled despite maximal medical therapy and selective laser trabeculoplasty (SLT). Finally, Baerveldt implant surgery was performed, resulting in an IOP lowering to 10 mmHg and stabilization of the glaucomatous visual field loss.Conclusion: Our case demonstrates that Baerveldt implant surgery is a reasonable therapy for glaucoma following successful radiotherapy of iris melanoma.Keywords: iris melanoma, proton beam therapy, secondary glaucoma, Baerveldt implant surger

Understanding the clinical and molecular basis of thyroid orbitopathy:a review of recent evidence

Thyroid eye disease (TED) is an autoimmune orbital inflammatory disease which ranges from mild to severe. Tissue remodeling, fibrosis and fat proliferation cause changes in the orbital tissues which can affect esthetics and visual function. In its severe form, it is sight threatening, debilitating, and disfiguring and may lead to social stigma, the embarrassment about which has an impact on the quality of life of those affected and the family members. The pathogenesis of TED, which is influenced by genetic, immunological, and environmental factors, is complex and not fully elucidated. However, it remains unknown what factors determine the severity of the disease. Recent research has revealed a number of diagnostic and prognostic biomarkers of this disease. In this overview of TED, we focus on new insights and perspectives regarding biological agents that may provide a basis for new treatment modalities.</p

Effect of combined water drinking test and dark room provocative testing in Caucasian eyes with narrow angles

Purpose: To assess the usefulness of water drinking test and dark room provocative testing (WDT + DRPT) in current clinical practice by evaluating input parameters from Swept-source Optical Coherence Tomography (SS-OCT) images, and to determine if clinical factors like axial length, central endothelial cell count (CECC) and retinal nerve fibre layer thickness (RNFL) thickness are associated with a positive WDT + DRPT. Methods: SS-OCT examination was performed in consecutive subjects presenting as new patients in the outpatient clinic aged > 40 years. If at least one eye met the inclusion criteria (anterior chamber angles <20° and anterior chamber depth < 2.5 mm on SS-OCT), subjects were included in this study and WDT + DRPT was carried out. The eye with the smallest angle was analysed. The difference in parameters between eyes with a positive (≥8 mmHg) and negative (<8 mmHg) increase in intraocular pressure (IOP) after WDT + DRPT were statistically analysed. Second, the correlation between IOP increase after WDT + DRPT and anterior chamber angle parameters (RNFL thickness, CECC and axial length) was studied. Results: A total of 95 subjects with a mean age of 64 years were included. There was an association between IOP increase after WDT + DRPT and anterior chamber angle characteristics, however this was not of clinical significance. No positive results after WDT + DRPT were found in patients with anterior chamber angles ≥ 20°. Conclusions: The present findings indicate that this combined provocative test has no definite correlative or predictive value in angle closure disease. Further, the test is not useful in predicting early diagnosis or possible CECC or RNFL loss

Mapping mRNA Expression of Glaucoma Genes in the Healthy Mouse Eye

Purpose/Aim: Many genes have been associated with primary open-angle glaucoma (POAG). Knowing exactly where they are expressed in the eye helps to unravel POAG pathology and to select optimal targets for intervention. We investigated whether RNA in situ hybridization (RNA-ISH) is a convenient technique to obtain detailed pan-ocular expression data of these genes. We tested this for four diverse candidate POAG genes, selected because of unclear ocular distribution (F5 and Dusp1) and relevance for potential new therapies (Tnf, Tgfβr3). Optn, a POAG gene with well-known ocular expression pattern served as control. Methods: We made a list of candidate glaucoma genes reported in genetic studies. A table of their ocular expression at the tissue level was compiled using publicly available microarray data (the ocular tissue database). To add cellular detail we performed RNA-ISH for Optn, Tnf, Tgfβr3, F5, and Dusp1 on eyes of healthy, 2-month-old, pigmented, and albino mice. Results: Expression of the Optn control matched with published immunohistochemistry data. Ocular expression of Tnf was generally low, with patches of higher Tnf expression, superficially in the corneal epithelium. F5 had a restricted expression pattern with high expression in the nonpigmented ciliary body epithelium and moderate expression in the peripapillary region. Tgfβr3 and Dusp1 showed ubiquitous expression. Conclusions: RNA-ISH is a suitable technique to determine the ocular expression pattern of POAG genes, adding meaningful cellular detail to existing microarray expression data. For instance, the high expression of F5 in the nonpigmented ciliary body epithelium suggests a role of this gene in aqueous humor dynamics and intraocular pressure. In addition, the ubiquitous expression of Tgfβr3 has implications for designing TGF-β-related glaucoma therapies, with respect to side effects. Creating pan-ocular expression maps of POAG genes with RNA-ISH will help to identify POAG pathways in speci

Aqueous humor proteome of primary open angle glaucoma: A combined dataset of mass spectrometry studies

Analysis of the proteins of the aqueous humor can help to elucidate the complex pathogenesis of primary open angle glaucoma. Thanks to advances in liquid chromatography tandem mass spectrometry (LC-MS/MS) it is now possible to identify hundreds of proteins in individual aqueous humor samples without the need to pool samples. We performed a systematic literature search to find publications that performed LC-MS/MS on aqueous humor samples of glaucoma patients and of non-glaucomatous controls. Of the seven publications that we found, we obtained the raw data of three publications. These three studies used glaucoma patients that were clinically similar (i.e. undergoing glaucoma filtration surgery) which prompted us to reanalyse and combine their data. Raw data of each study were analysed separately with the latest version of MaxQuant (version v1.6.11.0). Outcome files were exported to Microsoft Excel. Samples belonging to the same patient were averaged to obtain peptide expression values per individual. We compared the overlap of identified proteins using the VLOOKUP function of Excel and a publicly available Venn diagram software. For the peptide sequences that can belong to multiple proteins (usually of the same protein family), we initially included all possibly identified proteins. This ensured that we would not miss a potential overlap between the studies due to differences in identified peptide counts. Next, of those peptides of which we compared multiple proteins, only one unique protein was included in our analysis i.e. either the protein overlapping bet