Anatoli Astvatsatourov

Ultra-short-course booster is effective in recurrent grass pollen-induced allergic rhinoconjunctivitis

A relevant proportion of allergic rhinoconjunctivitis (ARC) patients experience recurrent symptoms after successfully completing allergen immunotherapy (AIT). This prospective, controlled, noninterventional study used internationally standardized instruments to determine the clinical effects of a preseasonal, ultra‐short‐course booster AIT on clinical outcome parameters.

Digitally Analyzed Conjunctival Redness: Does Repeated Conjunctival Provocation Intrinsically Cause Local Desensitization of the Eye?

Background: Allergic reactions in patients with seasonal or perennial rhinoconjunctivitis mediated by airborne allergens can be effectively assessed with the conjunctival provocation test (CPT). The CPT is a fast and easy diagnostic procedure that challenges the ocular mucosa with instillations of allergen solutions into the conjunctival region. This paper aimed to investigate the possible influence of repeated diagnostic CPT procedures on the patients clinical presentation, i.e. to analyze desensitization effects caused by diagnostic solutions and to show the reproducibility of CPT results. Methods: Treatment progress in 120 placebo-treated patients from 2 immunotherapeutic dose-finding studies was estimated and documented, as based on the CPT which was applied at 4 visits with intervals of 4, 8 and 16 weeks. High-resolution digital photos collected as part of the CPT documentation were analyzed by an external observer and by digital analysis software to determine conjunctival redness, completely independent of the subjectivity of investigators and patients. Results: Two extremal scenarios of the redness changes were considered after provocation with 10,000 standard quality units/ml. A maximal decrease of about 3% (t test: p = 0.0002; U test: p = 0.001) and a minimal decrease of about 1% (t test: p = 0.254; U test: p = 0.431) were found. Conclusions: The observed decrease in conjunctival hyperemia can be explained by local desensitization or by placebo effect. Due to the setup of both studies considered, we could not ascertain how these factors influence the decrease in redness. In order to attribute the observed effects to local conjunctival desensitization with certainty, further pilot studies are needed.

Automatic conjunctival provocation test combining Hough circle transform and self-calibrated color measurements

Computer-aided diagnosis is developed for assessment of allergic rhinitis/rhinoconjunctivitis measuring the relative redness of sclera under application of allergen solution. Images of the patients eye are taken using a commercial digital camera. The iris is robustly localized using a gradient-based Hough circle transform. From the center of the pupil, the region of interest within the sclera is extracted using geometric anatomy-based apriori information. The red color pixels are extracted thresholding in the hue, saturation and value color space. Then, redness is measured by taking mean of saturation projected into zero hue. Evaluation is performed with 98 images taken from 14 subjects, 8 responders and 6 non-responders, which were classified according to an experienced otorhinolaryngologist. Provocation is performed with 100, 1,000 and 10,000 AU/ml allergic solution and normalized to control images without provocation. The evaluation yields relative redness of 1.01, 1.05, 1.30 and 0.95, 1.00, 0.96 for responders and non-responders, respectively. Variations in redness measurements were analyzed according to alteration of parameters of the image processing chain proving stability and robustness of our approach. The results indicate that the method improves visual inspection and may be suitable as reliable surrogate endpoint in controlled clinical trials.

A randomized, double-blind, placebo-controlled, dose-finding trial with Lolium perenne peptide immunotherapy

A novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up‐dosing phase has been developed to treat grass pollen–induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety.

Lolium perenne peptide immunotherapy is well tolerated and elicits a protective B-cell response in seasonal allergic rhinitis patients

Systemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short‐course treatment with adjuvant‐free Lolium perenne peptides (LPP) following a 6‐week dose‐escalation protocol.

Reliability of a New Symptom Score in a Titrated Quantitative Conjunctival Provocation Test Supported by an Objective Photodocumentation

Background: Allergen provocation tests are useful methods for proving the clinical relevance of an allergen-specific sensitization. Among these methods, the conjunctival provocation test (CPT) represents an easy-to-use tool. However, its readout parameters have not yet been internationally standardized or validated. Photodocumentation has been shown as a good option for objectifying a CPT reaction, supporting the local investigator assessment. Based on test-retest reliability of the score and an objective digital photoanalysis of the conjunctival redness, this study aimed to prove the reproducibility of a new CPT scoring system for use in clinical trials (ClinicalTrials.gov identifier: NCT02690740). Methods: A titrated quantitative CPT was conducted outside of the pollen season in a final cohort of 23 adult patients with birch or grass pollen-induced allergic rhinoconjunctivitis. Conjunctival symptoms were analyzed using a standardized symptom score. Conjunctival redness was also evaluated by an external observer and correlated with a digital photoanalysis using MATLAB software. Results: A test-retest correlation of 0.6 (p < 0.01) was found for the symptom score results. Likewise, a correlation of 0.65 (p < 0.01) was observed in the digital photoanalysis. The total symptom score showed a decrease in the mean value of 0.48 score points in the retest. Conclusions: This study reveals both a valuable test-retest correlation of the proposed score as well as a good correlation of eye redness with the (objective) photodocumentation. Based on our results, we can recommend the use of this scoring system as a valuable clinical protocol for future clinical trials.

Contents Vol. 168, 2015

Founded 1950 by D. Harley, P. Kallós, W. Löffler and F.W. Wittich Continued by E.A. Brown (1952–1954), W. Kaufman (1955–1967), F. Hahn (1961–1972), H.C. Goodman (1963–1975), R.R.A. Coombs (1955–1984), Z. Trnka (1972–1987), P. Kallós (1950–1988), G.B. West (1959–1991), J. Bienenstock (1990–1991), L.Å. Hanson (1981–1991), K. Kano (1982–1991), F. Milgrom (1965–1991), K. Rother (1982–1991), G. Wick (1991–1997), B. Grubeck-Loebenstein (1991–1997), D. Kraft (1998–2002) Official Journal of the

Automatic Conjunctival Provocation Test Using Hough Transform of Extended Canny Edge Maps

Computer-aided diagnosis is developed for assessment of allergic rhinitis/rhinoconjunctivitis measuring the relative redness of sclera under application of allergen solution. The patient’s eye images are taken from commercial digital camera. The iris is robustly localized using a gradient-based Hough circle transform. From the center of the pupil, the region of interest within the sclera is extracted using geometric anatomybased a-priori information. The red color pixels are extracted thresholding in the hue, saturation and value color space. Then, redness is measured by taking mean of saturation projected into zero hue. Evaluation is performed with 92 images taken from 13 subjects, 8 responders and 5 non-responders, which were classified according to an experienced otorhinolaryngologist. Provocation is performed with 100, 1,000 and 10,000 AU/ml allergic solution and normalized to control images without provocation. The evaluation yields redness of 1.14, 1.30, 1.60 and 1.04, 1.12, 1.11 for responders and non-responders, respectively. This indicates that our method is suitable as reliable endpoint in controlled clinical trials.