Petr Kolář

Treatment of exudative age-related macular degeneration with a designed ankyrin repeat protein that binds vascular endothelial growth factor: a phase I/II study.

PURPOSE To evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD). DESIGN Phase I/II, open-label, multicenter, dose-escalation study. METHODS Patients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response. RESULTS Altogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for ≥4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16. CONCLUSIONS A single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. Larger-scale studies are warranted to confirm these observations.

Influence of climatic factors on the low yields of spring barley and winter wheat in Southern Moravia (Czech Republic) during the 1961–2007 period

The paper aims to study the variability of spring barley and winter wheat yields, the most important crops in the Czech Republic, with respect to the variability of weather and climatic factors. Yields of both crops have been studied for 13 districts in Southern Moravia for the 1961–2007 period. From detrended series of spring barley and winter wheat yields, years with very low (lower than the mean minus a 2.5-multiple of the standard deviation) and extremely low (interval given by the mean minus a 1.5- and 2.5-multiple of the standard deviation) yields were selected. Years in which at least one of the districts had extremely low/very low yields were further analyzed. From 10 such years selected separately for spring barley and winter wheat, six of them agreed for both crops. Extreme years were studied using NUTS4-level yield data with respect to temperature, precipitation, the self-calibrated Palmer Drought Severity Index (scPDSI), snow cover, frost patterns, and the onset and duration of select phenophases. Extremely/very low barley yields in 1993, 2000, and 2007 were related to high April–June (AMJ) temperatures, low AMJ precipitation totals, and negative AMJ scPDSI (indicating drought) with an earlier onset of flowering and full ripeness and shorter intervals from tillering to flowering and from flowering to full ripeness compared to the entire 1961–2007 mean. As for extremely/very low winter wheat yields, in addition to the previously mentioned factors, winter patterns also played an important role, particularly the occurrence of severe frosts with a coinciding lack of snow cover and a long-lasting snow cover (in highlands), indicating that low yields are the result of not only one unfavorable factor but a combination of several of them.

CD36 gene is associated with intraocular pressure elevation after intravitreal application of anti-VEGF agents in patients with age-related macular degeneration: Implications for the safety of the therapy

ABSTRACT Background: The wet form of age-related macular degeneration (AMD) is characterized by pathological vascularization of the outer retinal layers. The condition responds to treatment with antibodies against vascular endothelial growth factor (VEGF), but the patients receiving such anti-VEGF therapy sometimes show undesirable acute short-term increases in the intraocular pressure (IOP). The cause of this adverse effect is unknown, and here, we are testing a hypothesis that it is related to CD36 gene polymorphisms. Materials and Methods: A group of 134 patients with AMD were given three therapeutic doses of anti-VEGF antibody (ranibizumab) at monthly intervals. Their IOP was measured immediately before and 30 min after each injection. Patients’ DNA was analyzed, and the changes in IOP were matched against seven polymorphisms of the CD36 gene. Results: Three polymorphisms were found to be associated with increases in IOP: rs1049673 (p = 0.006), rs3211931 (p = 0.01), and rs1761667 (p = 0.043) at the time of the third injection only. Pronounced elevations (IOP > 25 mmHg) were associated with rs1049673 polymorphism: GC genotype (p < 0.01) and CC genotype (p < 0.05); both increasing the risk 2.6-fold, the presence of C-allele conferring a 1.5-fold greater risk and with rs3211931 polymorphism: AG genotype (p < 0.01) and GG genotype (p < 0.05); increasing the risk 2.6-fold (AG) and 2.7-fold (GG). Conclusions: CD36 receptor may be involved in mediating the effects of VEGF on IOP. The findings will help to identify the patients at risk of acutely elevated IOP following the anti-VEGF therapy.

Cost and effectiveness of therapy for wet age-related macular degeneration in routine clinical practice.

Purpose: Evaluation of the cost and effectiveness of therapy for patients with the wet form of age-related macular degeneration (AMD) in routine clinical practice. Methods: A retrospective multicentre evaluation of changes in the best-corrected visual acuity in applied kinds of therapy and a comparison with the cost of individual therapeutic procedures. Results: An overall total of 788 eyes of 763 patients with an average age of 73.2 ± 8.6 years was evaluated for a 1-year minimum period. In the ranibizumab and pegaptanib therapy groups, a reduction of 1.3 letters (p = 0.303) and 1.4 letters (p = 0.197) was found, respectively. In the group of photodynamic therapy (PDT) with verteporfin, a reduction of 5.2 letters was achieved (p < 0.001). Under the conditions of routine practice in the Czech Republic, the annual cost is highest (EUR 5,467.63/patient) in patients with pegaptanib therapy. The annual cost in patients with ranibizumab therapy is lower by EUR 1,220.16. The cost is nearly half (EUR 2,783.65) in the group treated with PDT with verteporfin. Conclusion: An initiation of AMD therapy by ranibizumab is cost-effective as compared to pegaptanib. Both ranibizumab and pegaptanib are significantly more efficient as compared to PDT with verteporfin. Therapy with ranibizumab and pegaptanib, as compared to PDT with verteporfin, prevents the loss of 1 line of vision on the ETDRS chart for EUR 1,225.98 and 2,286.18, respectively.

Prognostic Factors of Early Morphological Response to Treatment with Ranibizumab in Patients with Wet Age-Related Macular Degeneration

Aim. To assess the significance of age, gender, baseline best corrected visual acuity, baseline macula thickness, and type and size of choroidal neovascularization in early morphological therapeutic response to ranibizumab treatment in patients with the wet form of age-related macular degeneration. Methods. From 09/2008 to 06/2013 we evaluated 1153 newly diagnosed, treatment-naïve patients treated with ranibizumab. Based on the morphological findings in the macula following the initial 3 injections of ranibizumab, the patients were divided into two groups based on active and inactive choroidal neovascularization. Results. After the initial 3 injections of ranibizumab, we examined the sample of 841 eyes with active CNV and 312 eyes with inactive CNV. In the inactive group, we found a statistically higher proportion of occult CNV (P < 0.001) and lower incidence of CNV greater than 5DA (P < 0.001) compared with the active group. We found no statistically significant difference in age, gender, baseline best corrected visual acuity, or baseline macula thickness between the inactive and active groups. Conclusion. Occult CNV and CNV smaller than 5DA are optimistic factors for a better morphological therapeutic response at the beginning of ranibizumab treatment.