[If Artificial Tears Aren't Enough. The Importance of Inflammatory Processes in Dry Eye Disease. Practical Aspects of an Anti-Inflammatory Therapy of Dry Eye Disease]. / Wenn Tränenersatzmittel nicht mehr ausreichen: die Bedeutung von Entzündungsprozessen beim Trockenen Auge. Praktische Aspekte einer antientzündlichen Therapie des Trockenen Auges.

Dry eye disease (DED) is a heterogenous disease of the ocular surface. Multiple pathogenetic factors are responsible for the disease process, but DED is generally linked to an increase in the osmolarity of the tear film and to inflammation of the ocular surface. The significance of inflammatory processes in DED is highlighted in the most recent definition of dry eye in the Dry Eye Workshop (DEWS). It is therefore critically important for the management of dry eye disease to understand the pathomechanisms and therapeutic options for the treatment of inflammatory processes. This review summarizes our current knowledge on Inflammation associated with DED and provides practical recommendations for the diagnosis and monitoring of the disease, as well as the use of currently available therapeutic options to counteract inflammation in DED.

Micro-invasive glaucoma surgery (MIGS): a review of surgical procedures using stents.

Over the last decade several novel surgical treatment options and devices for glaucoma have been developed. All these developments aim to cause as little trauma as possible to the eye, to safely, effectively, and sustainably reduce intraocular pressure (IOP), to produce reproducible results, and to be easy to adopt. The term "micro-invasive glaucoma surgery (MIGS)" was used for summarizing all these procedures. Currently MIGS is gaining more and more interest and popularity. The possible reduction of the number of glaucoma medications, the ab interno approach without damaging the conjunctival tissue, and the probably safer procedures compared to incisional surgical methods may explain the increased interest in MIGS. The use of glaucoma drainage implants for lowering IOP in difficult-to-treat patients has been established for a long time, however, a variety of new glaucoma micro-stents are being manufactured by using various materials and are available to increase aqueous outflow via different pathways. This review summarizes published results of randomized clinical studies and extensive case report series on these devices, including Schlemm's canal stents (iStent®, iStent® inject, Hydrus), suprachoroidal stents (CyPass®, iStent® Supra), and subconjunctival stents (XEN). The article summarizes the findings of published material on efficacy and safety for each of these approaches.

Preservative-free fixed combination of tafluprost 0.0015% and timolol 0.5% in patients with open-angle glaucoma and ocular hypertension: results of an open-label observational study.

BACKGROUND: Efficacy, tolerability and safety of the novel preservative-free fixed combination of tafluprost 0.0015%/timolol 0.5% (Taptiqom®) were investigated in an observational study in Germany. OBJECTIVE: To assess efficacy, tolerability and safety of the preservative-free fixed combination of tafluprost 0.0015%/timolol 0.5% in a real-life setting. METHODS: Intraocular pressure (IOP) was recorded for each eye at baseline (any previous therapy or untreated) and 4-16 weeks after changing medical treatment to or initiating treatment with the preservative-free fixed combination of tafluprost 0.0015%/timolol 0.5%. Change in IOP was evaluated over the study period for all patients and for specific pretreatment subgroups. Clinical signs such as conjunctival hyperemia and lid-parallel conjunctival folds (LIPCOF) were recorded using standardized comparative photographs. Corneal staining, subjective symptoms and local comfort were measured using a four-step scale. All adverse events were recorded. RESULTS: Among 1,157 patients enrolled, 1,075 patients were treated with the preservative-free fixed combination as the only medication at the final visit. Medical treatment was initiated in 741 patients because of an insufficient IOP-lowering effect of the prior medication. In 343 patients, medication was changed because of tolerability issues. The preservative-free fixed combination lowered IOP significantly in the subgroup of naïve patients, all subgroups with prior monotherapy and patients with prior fixed combinations: naïve patients: -8.9 mmHg, alpha- 2-agonists: -6.4 mmHg, beta-blockers: -5.7 mmHg, carbonic anhydrase inhibitors: -5.2 mmHg, prostaglandins: -4.7 mmHg, fixed-combination prostaglandins/timolol: -2.4 mmHg. At the final visit, clinical signs and subjective symptoms were improved in patients with prior medical therapy. Local comfort was rated as "very good" or "good" by 89.1% of patients at the final visit. Only few adverse events occurred during the treatment period. CONCLUSION: The preservative-free fixed combination of tafluprost 0.0015%/timolol 0.5% was effective, well tolerated and showed a good safety profile.

Preservative-free tafluprost in the treatment of naive patients with glaucoma and ocular hypertension.

PURPOSE: The study reported here investigated the efficacy, tolerability, and safety of the preservative-free prostaglandin analog tafluprost 0.0015% in treatment-naive patients. PATIENTS AND METHODS: Data were collected in two non-interventional, prospective, multicenter, observational, open-label studies of identical design that were conducted in Germany and the Czech Republic. All subjects received preservative-free tafluprost 0.0015% once daily. Intraocular pressure (IOP) levels were recorded for each eye at untreated baseline and 3 months after initiation of medical treatment. The primary outcome was change in mean IOP from baseline to month 3. In the primary open-angle glaucoma (POAG) and ocular hypertension (OH) patient subgroups, analyses were stratified by the level of baseline IOP: ≥20 to 23 mmHg versus ≥24 mmHg. In addition, responder rates and the achievement of pre-specified IOP levels at month 3 were evaluated. Local tolerance of preservative-free tafluprost was evaluated by the patients at final visit. Overall satisfaction with the medical treatment was evaluated by both patients and physicians. All adverse events were recorded. RESULTS: A total of 579 treatment-naive patients with POAG (n = 349), OH (n = 105), normal tension glaucoma (n = 71), exfoliative glaucoma (n = 27), or other glaucomas (n = 27) were included in this observational study. Mean IOP level at baseline for all patients was 23.6 ± 4.0 mmHg. Mean IOP at month 3 was 16.8 ± 2.9 mmHg (-28.8% vs baseline). At month 3, significant reductions in mean IOP (P < 0.001) were seen in all patients and all subgroups. Preservative-free tafluprost lowered mean IOP significantly in patients with POAG and OH with IOP levels ≥ 20 to 23 mmHg from 21.9 ± 1.1 mmHg at baseline to 16.5 ± 2.2 mmHg, and in the subgroup with IOP levels ≥ 24 mmHg from 26.2 ± 2.4 mmHg to 17.9 ± 2.4 mmHg. In the subgroups of patients with POAG and OH, an IOP response ≥20%, ≥30%, and ≥40% was achieved by 83.4%, 44.1%, and 12.8%, respectively. Overall, patients with higher baseline IOP values showed a better response than patients with lower baseline IOP levels. Preservative-free tafluprost was well tolerated and safe. After 3 months, 97.9% of all patients remained on therapy. CONCLUSION: In this real-world observational study, treatment with once-daily preservative-free tafluprost proved efficacious, well tolerated, and safe in treatment-naive patients.

Preservative-free tafluprost 0.0015% in the treatment of patients with glaucoma and ocular hypertension.

INTRODUCTION: The objective of this study was to evaluate efficacy, local tolerability, and safety of this first-in-class preservative-free prostaglandin preparation in patients with ocular hypertension and glaucoma. METHODS: Patients with glaucoma or ocular hypertension who required a change of medication or were naïve to treatment were included in this noninterventional and observational study. Noninterventional means that no influence was made upon the decision of the physicians to include specific patients and upon the treatment algorithm used. German law for observational studies does not allow any influence on the choice of drugs used, patient selection, masking, and comparator treatment regimens. The main aim of this observational study was to collect "real-life data" on the efficacy and safety of a new medical treatment after approval in a large patient population. Participating ophthalmologists were asked to provide anonymous patient data collected during regular visits by filling a simple data entry form. Intraocular pressure (IOP) readings were recorded at baseline (previous therapy or untreated) and 6-12 weeks after changing medical treatment to or initiating treatment with preservative-free tafluprost once daily. Changes in the IOP were evaluated over the study period for all patients as well as for specific pretreatment subgroups. Local comfort was determined using a five-point scale (very good, good, satisfactory, less satisfactory, not acceptable) before and after the change of medical treatment. All adverse events were recorded. RESULTS: Data from 2123 patients with glaucoma or ocular hypertension were considered for the final evaluation. Medication was changed in 41.1% of patients due to tolerability issues and in 25.6% of patients due to insufficient efficacy with prior medication. In all patients preservative-free tafluprost 0.0015% lowered IOP from 19.5 ± 4.4 mmHg (baseline) to 16.4 ± 2.9 mmHg after 6-12 weeks. Preservativefree tafluprost also significantly lowered the IOP in all monotherapy subgroups: treatment-naïve patients (n=440): 22.6 ± 3.9 mmHg (baseline) to 16.7 ± 2.7 mmHg (week 6-12); beta blockers (n=307): 20.3 ± 3.5 mmHg (baseline) to 16.7 ± 2.6 mmHg (week 6-12); carbonic anhydrase inhibitors (n=158): 19.0 ± 3.6 mmHg (baseline) to 16.0 ± 2.6 mmHg (week 6-12); prostaglandin analogs (PGAs; n=447): 16.8 ± 2.9 mmHg (baseline) to 15.8 ± 2.6 mmHg (week 6-12). Local comfort was rated as "very good" or "good" by 85.6% of patients at the final visit (P<0.001). Only few adverse events occurred during the treatment period: 18 patients (0.8%) discontinued medical treatment with preservative-free tafluprost due to local intolerance; six patients (0.3%) due to efficacy issues; four patients complained about systemic side effects (0.2%); and two patients preferred to use a multidose treatment regimen (0.2%). CONCLUSION: Although this study was limited by its observational design the results demonstrate that preservative-free tafluprost 0.0015% was effective, generally well tolerated, and safe in a broad and heterogeneous patient population.

Switching patients from preserved prostaglandin-analog monotherapy to preservative-free tafluprost.

PURPOSE: Efficacy, tolerability and safety of the novel preservative-free prostaglandin tafluprost 0.0015% were investigated for the treatment of patients with glaucoma or ocular hypertension in a clinical setting. PATIENTS AND METHODS: Data were collected in a non-interventional, prospective, multi-center, observational, open label study. 118 patients were treated with a prostaglandin analog (PGA) monotherapy (preserved formulations of latanoprost, travoprost or bimatoprost) prior to baseline. Intraocular pressure (IOP) readings were recorded for each eye at baseline (previous therapy), 4-6 weeks, and 12 weeks after changing medical treatment to preservative-free tafluprost once-daily. We analyzed the change in IOP over the study period for all patients as well as for a subgroup of patients with prior PGA monotherapy. Subjective symptoms and objective ocular signs were determined. Comfort was measured using a 4 step scale. All adverse events were recorded. Paired t-tests were conducted to compare IOP values at baseline to IOP values after treatment with tafluprost 0.0015%. Bowker's test of symmetry was used for statistical evaluation of changes of clinical signs (hyperemia). RESULTS: In total 118 patients were eligible for evaluation. In these patients with prior PGA monotherapy (n = 118) IOP decreased significantly from 16.2 ± 4.3 mm Hg (95% CI: 0.55) at treated baseline to 14.8 ± 3.2 mm Hg (95% CI: 0.43; P < 0.001) at final visit on tafluprost. In a subset of patients with prior latanoprost monotherapy (n = 68) mean IOP at baseline (±SD) was reduced from 16.2 ± 4.6 mm Hg (95% CI: 0.77) 14.8 ± 3.1 mm Hg at final visit (95% CI: 0.54, P < 0.001), in patients with prior travoprost monotherapy (n = 32) from 16.2 ± 4.3 mm Hg (95% CI: 1.05) to 14.9 ± 3.3 mm Hg (95% CI: 0.91; P < 0.05) and in patients with prior bimatoprost monotherapy (n = 18) from 16.4 ± 3.5 mm Hg (95% CI: 1.14) to 15.0 ± 3.3 mm Hg (95% CI: 1.14; P = 0.252). Both, objective clinical signs and subjective symptoms improved after changing medication to preservative-free tafluprost until final visit. The number of patients with moderate and severe hyperemia decreased from 51 (43.2%) at baseline to 2 (1.9%) at final visit. CONCLUSION: Preservative-free tafluprost 0.0015% was effective, well tolerated and safe. IOP was controlled effectively and ocular symptoms and clinical signs were improved after changing medication to a monotherapy with preservative-free tafluprost in patients previously treated with a preserved latanoprost, travoprost or bimatoprost monotherapy.

IOP-lowering efficacy and tolerability of preservative-free tafluprost 0.0015% among patients with ocular hypertension or glaucoma.

OBJECTIVE: Tafluprost, the first preservative-free prostaglandin analogue for topical ophthalmic use to lower IOP, was introduced in Germany in 2008. After the approval for ophthalmic use, an open-label, multicentre, observational study was conducted between October 2008 and April 2009. Major objectives of this study were to evaluate the real world efficacy, local tolerability and safety of this first in class preservative-free prostaglandin preparation in patients with ocular hypertension and glaucoma. METHODS: A total of 544 patients were treated with the preservative-free formulation of tafluprost 0.0015%. The majority of these patients had poor IOP control and/or poor local tolerance of their medication prior change of medication. The decision to change the previous therapy or to initiate treatment was made solely by the participating ophthalmologists. IOP readings were recorded at baseline before changing medication or initiating treatment in newly diagnosed patients, 4-6 weeks and 12 weeks after change of medication or initiation of treatment with preservative-free tafluprost. In addition, patient demographics, subjective symptoms (i.e. burning, foreign body sensation, itching and stinging) and objective clinical signs such as conjunctival hyperaemia were collected. Subjective symptoms were evaluated using a 4 point scale ranging from 'no symptoms', 'mild symptoms', 'moderate symptoms' to 'severe symptoms'. As a clinical sign severity of conjunctival hyperaemia was evaluated. All adverse events were collected. RESULTS: Three hundred and sixty patients were switched from monotherapy, 45 patients were naïve to treatment. A total of 139 patients were treated with fixed or non-fixed combinations prior to changing medication. In these patients preservative-free tafluprost was used either as a substitution for the fixed or non-fixed combination, as an add-on to the existing combination therapy or as one agent in a newly initiated treatment regimen. Preservative-free tafluprost provided an IOP decrease in most pre-treatment subgroups, with an overall reduction of IOP in all patients (N = 544) from 19.4 +/- 5.0 mmHg at baseline to 15.7 +/- 4.1 mmHg after 4 to 6 weeks and to 15.3 +/- 3.5 mmHg after 12 weeks. Both values were significantly lower than treated baseline IOP (p < 0.001). An IOP of

Treatment of patients with keratoconjunctivitis sicca with Optive: results of a multicenter, open-label observational study in Germany.

OBJECTIVE: To evaluate the efficacy and tolerability of Optive, a new dry eye product containing sodium carboxymethylcellulose (0.5%) and glycerol (0.9%), in patients with keratoconjunctivitis sicca (KCS). METHODS: This was a non-interventional and observational study including patients with dry eye who required a change of medication or were naïve to dry eye treatment (N = 5,277). Disease severity, tear break-up time (TBUT), tolerability, and change in clinical symptoms were recorded at baseline and at final visit (2 to 4 weeks after first treatment). RESULTS: The severity of KCS was mild in 18.6%, moderate in 59.9%, and severe in 21.5% of patients based on physicians' assessment. TBUT was measured in 4,338 patients before switching to or initiating therapy with Optive and at final visit. Baseline measurement of mean TBUT was 7.7 +/- 3.9 seconds. This value increased to 10.0 +/- 4.7 seconds at final visit. Most patients (85.4%) reported improvement in local comfort. The majority (75.1%) of patients felt an improvement in symptoms after changing their treatment. Two percent of patients reported adverse events, and 0.4% were treatment-related. CONCLUSIONS: Optive was well tolerated and improved the symptoms of dry eye after 2 to 4 weeks.

Efficacy, tolerability and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% in a broad patient population: multicenter, open-label observational study.

OBJECTIVE: To evaluate intraocular pressure (IOP)-lowering efficacy, tolerability, and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% (Ganfort) among German patients. METHODS: Multicenter, observational, open-label study of patients with primary open angle glaucoma or ocular hypertension (n = 606). As determined by participating physicians, patients had insufficient IOP control and required a medication change. They were switched to once-daily fixed-combination bimatoprost/timolol with no wash-out period. IOP was recorded at treated baseline, 4-6 weeks and 12 weeks after switching. Tolerability was measured using a 4-step scale (excellent, good, moderate, poor) and all adverse events were recorded. RESULTS: A total of 405 patients switched from monotherapy, 97 switched from other fixed combinations, and 104 switched from non-fixed combinations. Among all patients, 32.5% had used prostaglandin analog (PGA) monotherapy, 8.7% had been using a fixed combination that included a PGA, and 6.9% had been using an adjunctive combination of a PGA and a beta-blocker. Mean treated baseline IOP (+/-SD) for all patients was 20.7 +/- 3.5 mmHg. Overall, changing medication to fixed-combination bimatoprost/timolol lowered IOP to 16.6 +/- 2.7 mmHg (p < 0.001 vs. baseline) after 4-6 weeks and to 16.1 +/- 2.6 mmHg (p < 0.001) after 12 weeks; reductions of 19.8% and 22.2%, respectively. Combined bimatoprost/timolol provided an additional IOP reduction versus baseline in most subgroups based on prior treatment. At week 12, patients who had previously used a beta-blocker achieved an additional 25.8% decrease from baseline and IOP was reduced by 22.6% in former PGA monotherapy patients. At week 12, 84.6% of all eyes reached a target pressure less than or equal to 18 mmHg. Tolerability of bimatoprost/timolol was rated excellent or good by the physicians for 98.7% of patients and by 96.7% of the patients themselves. Few adverse events occurred during the treatment period. CONCLUSIONS: Although this study was limited by its observational design, our results show that the fixed combination of bimatoprost 0.03%/timolol 0.5% was effective, well tolerated, and safe in a broad patient population.

Treatment of patients with primary open-angle glaucoma with a fixed combination of brimonidine 0.2%/timolol 0.5%: multicenter, open-label, observational study in Germany.

OBJECTIVE: At the introduction of the fixed-combination of brimonidine/timolol in Germany in 2006, a non-interventional, multicenter, observational, open-label study was initiated to evaluate efficacy, tolerability, and safety of this preparation in a broad patient population. METHODS: The study population comprised patients with bilateral primary open-angle glaucoma or ocular hypertension with insufficient intraocular pressure (IOP) control who participating physicians determined required a change of medication, and who switched to exclusive use of the new fixed-combination brimonidine 0.2%/timolol 0.5%. Patient demographics and information on specific risk factors were collected. IOP readings were recorded for each eye at treated baseline (previous therapy), 4 to 6 weeks, and 12 weeks after changing to twice-daily brimonidine/timolol. Tolerability was measured using a four-step scale ranging from excellent to poor. All adverse events were recorded. RESULTS: Mean treated baseline IOP (+/-SD) for all patients (N = 861) was 20.8 +/- 3.5 mmHg. Five hundred sixty-five patients switched from monotherapy, 138 patients switched from other fixed combinations, and 158 patients had been using non-fixed combinations of up to four different active agents. The brimonidine/timolol fixed combination provided an additional IOP decrease in most pretreatment subgroups, with an overall reduction to 16.9 +/- 2.6 mmHg after 4 to 6 weeks and to 16.5 +/- 2.7 mmHg after 12 weeks. Both of these values were significantly lower than baseline IOP (p < 0.001). A target pressure of <18 mmHg was achieved in 79.5% of all eyes at week 12. Tolerability of fixed-combination brimonidine/timolol was rated excellent or good by the physicians for 97.1% of patients, and by 93.4% of the patients themselves. Few adverse events occurred during the treatment period. CONCLUSIONS: Although this study was limited by its observational design, our results show that the fixed combination of brimonidine 0.2%/timolol 0.5% was effective, well tolerated, and safe in a broad POAG patient population.

Treatment of glaucoma patients with insufficient intraocular pressure control: a survey of German ophthalmologists in private practice.

OBJECTIVE: To assess the degree to which glaucoma treatment guidelines have been incorporated into daily practices and to describe the therapeutic practices chosen for patients with insufficient intraocular pressure (IOP) control. METHODS: Ophthalmologists in private practice in Germany were surveyed to obtain information about patients who exhibited unsatisfactory progress with IOP-lowering pharmacotherapy. Using a questionnaire, physicians provided data concerning treatment difficulty, target IOP, number and type of medications used, two most recent IOP readings, and optic nerve head and visual field observations. RESULTS: Of the 853 patients analyzed, primary open-angle glaucoma was the diagnosis for 67.1%, and other diagnoses included ocular hypertension, normal tension glaucoma, and pseudoexfoliation glaucoma. Target IOP levels had been determined for 95.5% of patients, and not achieving the target pressure was identified as a treatment difficulty for 81.0% of patients. Of patients on monotherapy, beta-blockers were prescribed most often (42.3%). Of all patients, 53.3% were treated with two or more agents as either fixed or non-fixed combinations. The non-fixed combination of a prostaglandin and carbonic anhydrase inhibitor was the most frequently prescribed dual therapy (19.2%). Non-fixed prostaglandin plus beta-blocker was used by 18.0% of dual therapy patients, whereas the available fixed combination was used by 10.5%. Non-compliance was identified as a cause of unsatisfactory IOP-lowering in 26.8% of all patients. This study is limited by its descriptive, non-interventional design. CONCLUSIONS: Treatment alterations are necessary to achieve sufficient IOP control in some patients. If these patients were to take advantage of more aggressive therapies as outlined by treatment guidelines, including newer formulations and fixed combination preparations, both efficacy and compliance may be improved.