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

Abstract

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 patient's 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.

Early nonreactivity in the conjunctival provocation test predicts beneficial outcome of sublingual immunotherapy

“…There were also placebo-treated patients who did not react to conjunctival challenge after 4 weeks of treatment. This effect was already described by Gloistein et al [ 31 ]. They found that repeated conjunctival provocation may have a hyposensitizing effect.…”

Clinical trials in allergen immunotherapy: current concepts and future needs

“…However, the type of challenge must be chosen to match the study population's profile; for example, we consider that children are less likely to cooperate during CPTs than during NPTs. Whenever possible, an allergic reaction during a challenge (eg, redness of the conjunctiva in a CPT) should be documented objectively and/or digitally in a format that is compatible with (semi)automated processing (ie, digital photography) …”

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

“…4a). Recently, Gloistein et al [35] have provided a hypothesis that repeated CPTs may cause a local desensitization of the conjunctiva but emphasized that more pilot studies are warranted to confirm this. Another possible explanation for this discrepancy could be that by V3, patients had become accustomed to the symptoms occurring after CPT differently and were less troubled by them as the total score (Table 1) largely consisted of purely subjective descriptions provided by the patient.…”