There is limited but growing evidence in the literature regarding the effectiveness of
N-acetyl-aspartyl-glutamate (NAAGA) in managing allergic conjunctivitis, particularly in
patients with concomitant tear film dysfunction. NAAGA is a neuropeptide with dual
activity as a mast cell stabilizer and anti-inflammatory agent, reducing histamine
release and mitigating inflammatory cascades such as leukotriene production and
complement activation. These mechanisms address both the allergic and inflammatory
components of ocular surface diseases. Despite its promising therapeutic potential,
studies directly comparing NAAGA to other treatments, particularly H1 receptor
antagonists like azelastine, remain scarce.
In previous studies, NAAGA has demonstrated efficacy in reducing ocular surface
inflammation, improving tear film stability, and alleviating symptoms of dry eye disease
(DED). It has been reported a significant reduction in inflammatory markers, such as
HLA-DR expression, and improvement in tear break-up time (TBUT) and Ocular Surface
Disease Index (OSDI) scores in patients treated with NAAGA. Another investigation
comparing NAAGA to cyclosporine A noted faster symptom relief and fewer adverse effects
with NAAGA, highlighting its tolerability and potential for broader application. However,
the literature lacks robust, head-to-head comparisons of NAAGA with second-generation
antihistamines, such as azelastine, in the context of allergic conjunctivitis with tear
film dysfunction.
Based on this background, this randomized, single-blind trial is designed to compare the
efficacy and safety of NAAGA (49 mg/mL) with azelastine hydrochloride (0.05%) in treating
patients with mild-to-moderate allergic conjunctivitis associated with tear film
dysfunction. Both treatments target key mechanisms of disease but differ in their primary
mode of action. NAAGA offers dual anti-inflammatory and mast cell-stabilizing effects,
while azelastine acts predominantly as an H1 receptor antagonist with additional mast
cell stabilization.
The primary objective of this study is to demonstrate that NAAGA is non-inferior to
azelastine in improving symptoms and clinical parameters of allergic conjunctivitis
associated with tear film dysfunction. Specifically, the study will evaluate changes in
the Ocular Surface Disease Index (OSDI) score over four weeks of treatment. Secondary
objectives include assessing changes in tear osmolarity, TBUT, Schirmer test results,
MMP-9 levels, and corneal staining scores, as well as patient-reported symptoms of ocular
discomfort.
This trial will include 134 patients with atopy and mild-to-moderate tear film
dysfunction, randomized to receive either NAAGA eye drops (administered four times daily)
or azelastine eye drops (administered twice daily) for four weeks. Both groups will
undergo comprehensive evaluations, including the OSDI questionnaire, tear osmolarity
testing, Schirmer I test, TBUT measurement, MMP-9 assessment, and fluorescein staining of
the ocular surface. Patient-reported discomfort will be tracked through weekly diaries.
The investigation is expected to provide critical insights into the comparative efficacy
and safety of NAAGA and azelastine in this patient population. NAAGA's dual-action
profile may offer broader therapeutic benefits, particularly in addressing
inflammation-driven tear film instability and ocular surface damage. Results from this
study could inform clinical decision-making and support the development of more targeted,
personalized treatments for patients with allergic conjunctivitis and tear film
dysfunction.