Allergic conjunctival diseases (ACDs) are inflammatory diseases of the conjunctiva and cornea caused predominantly by the IgE-mediated immediate hypersensitivity response. Allergic conjunctival diseases include allergic conjunctivitis, vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and giant papillary conjunctivitis. In clinical practice of ACDs, an ocular allergy test using biomarker measurement is a crucial examination technique for diagnosing, evaluating severity, and determining the efficacy of medical treatment. The ocular allergy test includes the tear test for evaluating the concentration of biomarkers in tears and an ocular surface test for assessing the expression levels of messenger ribonucleic acid (mRNA) biomarkers on the ocular surface. The clinical usefulness of several biomarkers has been demonstrated in patients with ACDs; specifically, eosinophil cationic protein and eotaxin-2 as eosinophilic inflammation biomarkers; interleukin-4 and thymus and activation regulated chemokine (CCL17/TARC) as Th2 inflammation biomarkers; eotaxin, tumor necrosis factor-alpha and soluble IL-6 receptor as giant papillae biomarkers; and osteopontin and periostin as allergic inflammation and remodeling biomarkers. Furthermore, the ocular allergy test, quantitative evaluation methods using biomarkers have allowed for better understanding of the immunological and pathophysiological mechanisms of ACDs. Therefore, the search for a biomarker is important to make an ocular allergy test useful. In previous ocular allergy tests, the biomarkers for allergic inflammation in patients with chronic ACDs including VKC and AKC were substantial. However, the selection of biomarkers associated with the early phase reaction of immediate hypersensitivity and innate immunity responses needs to be addressed in future investigations.

Allergic conjunctival disease (ACD) is an inflammatory disease of the conjunctiva that is mainly caused by type I hypersensitivity response to allergens and accompanied by subjective symptoms and other findings induced by antigens. ACD is classified as allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. This article summarizes the third edition of the Japanese guidelines for allergic conjunctival diseases published in 2021 and outlines the diagnosis, pathogenesis, and treatment of ACD. Since the introduction of immunosuppressive eye drops, the treatment strategies for severe ACDs have significantly changed. To clarify the recommended standard treatment protocols for ACD, the advantages and disadvantages of these treatments were assessed using clinical questions, with a focus on the use of steroids and immunosuppressive drugs. This knowledge will assist healthcare providers and patients in taking an active role in medical decision making.

Purpose: This study investigated the clinical usefulness of a multiple tear cytokine/chemokine test by simultaneously determining tear levels of CC chemokine ligand 17 (CCL17)/thymus and activation-regulated chemokine (TARC), CCL24/eotaxin-2, and interleukin-16 (IL-16) for assessing acute and chronic allergic inflammation in allergic conjunctival disorders (ACDs). Subjects and Methods: This study included 37 patients with ACD and 11 healthy adults (controls). Patients with ACDs were divided into the following three groups; patients with allergic conjunctivitis (AC group, n = 17), patients with atopic keratoconjunctivitis (AKC group, n = 6), and patients with vernal keratoconjunctivitis (VKC group, n = 14). Tear samples were collected using the Schirmer I method with a filter paper. Tear levels of CCL17/TARC, CCL24/eotaxin-2, and IL-16 were determined by performing a magnetic bead assay (tear cytokine/chemokine test). Tear levels of eosinophil cationic protein (ECP) were determined by performing enzyme immunoassay. In patients with AC, clinical scores of objective findings and results of the tear cytokine/chemokine test at baseline were compared with those at 7 days after treatment with the histamine H₁ receptor antagonist (epinastine) ophthalmic solution. Results: Tear positive rates of CCL17/TARC, CCL24/eotaxin-2, and IL-16 were higher in patients with AC, AKC, and VKC compared with controls. Tear levels of CCL17/TARC, CCL24/eotaxin-2, and IL-16 in patients with AKC and VKC were significantly higher than those in patients with AC. Moreover, tear levels of IL-16 in patients with AC that showed improvement of their clinical score by treatment with epinastine ophthalmic solution decreased significantly after 7 days of the treatment compared with those at baseline. In patients with AKC and VKC, a significant correlation was observed between the tear levels of CCL24/eotaxin-2 and ECP. Conclusion: Simultaneous measurement of the tear levels of CCL17/TARC, CCL24/eotaxin-2, and IL-16 may be a useful test for assessing acute and chronic allergic inflammation in ACDs.

Purpose/Aim: This study evaluated the efficacy of topical 0.1% tacrolimus ophthalmic suspension for treating chronic allergic conjunctival disease with and without atopic dermatitis. Materials and Methods: This study was conducted as a prospective observational post-market survey. Our large-scale study protocol was accepted by the Pharmaceuticals and Medical Devices Agency in Japan and included patients who were prescribed topical tacrolimus for the treatment of chronic allergic conjunctival disease from May 2008 to Aug 2010 in Japan. Topical tacrolimus was instilled 2 times daily for 6 months. The primary endpoint was the change from baseline in papillae-limbus-cornea clinical signs score (based on the presence of papillae, giant papillae, Trantas’ dots, limbal swelling, and corneal epithelial signs). Remission rate following topical tacrolimus treatment was investigated using generalized estimating equations. Results: A total of 1821 subjects were included in the analyses. Six months into treatment, 83.0% and 87.7% of subjects with and without atopic dermatitis, respectively, were in remission (based on the papillae-limbus-cornea grading score). Topical tacrolimus treatment was equally effective in improving papillae-limbus-cornea grading scores from baseline in both study groups after 6 months of treatment. Additionally, the odds ratio for remission increased over time. The concomitant use of topical steroids improved papillae-limbus-cornea grading scores, including papillary signs with a statistically significant, but low odds ratio. Conclusion: Tacrolimus ophthalmic suspension is useful for treating chronic allergic conjunctival disease with and without atopic dermatitis. Clinical response to local tacrolimus therapy is dependent upon treatment duration.

Patients with atopic dermatitis have a predisposition to Staphylococcus aureus and a Herpes simplex virus infection. The treatment of atopic diseases with steroid and immunosuppressive agents induces opportunistic infection. However, there is a concern regarding visual prognosis in patients with atopic keratoconjunctivitis (AKC) complicated with infectious keratitis. We report an unusual case of an atopic shield ulcer with Kocuria keratitis. A 51-year-old Japanese man presented with a 14-day history of eye pain and visual loss in his left eye. At the initial examination, a shield ulcer was observed in the upper-central cornea of the left eye, and the conjunctiva in both eyes had a velvety appearance due to papillary formation, as well as hyperemia and swelling in the palpebral area. The shield ulcer showed white stromal opacification in the marginal zone with a coral-like appearance. Samples were obtained by corneal scraping, and Kocuria sp. was identified by microbiological examination including culture and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The 16S rRNA gene sequence analysis was performed using isolated Kocuria strain from the patient. The obtained DNA sequence showed 99% homology with Kocuria koreensis. The combination of corneal scraping and instillation of cefmenoxime antibiotic ophthalmic solution was considered useful for the treatment of Kocuria keratitis. Clinicians should be aware of Kocuria keratitis as a corneal complication of AKC, and that rapid diagnosis of Kocuria keratitis may improve visual prognosis.

Purpose: We investigated ocular surface microbiota dysbiosis in patients with refractory allergic conjunctival diseases (ACDs; stratified into mild and severe groups) treated with topical tacrolimus. Methods: Patients (n = 21) with refractory ACDs (including vernal and atopic keratoconjunctivitis) actively treated with topical tacrolimus and 6 healthy controls were evaluated. Based on clinical scores and expression of specific cytokines on the ocular surface, patients with ACDs were divided into mild and severe groups using cluster analysis. The microbial composition of tear specimens collected from patients with mild and severe ACD and control subjects using the Schirmer test paper was determined through next-generation 16S rRNA sequencing analysis. Results: Compared with healthy controls, patients with ACDs exhibited significantly decreased ocular surface microbiota α-diversity. Ocular surface microbiota mainly comprised members of the phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria in all groups. The relative abundance of ocular surface microbiota in patients with ACDs was increased for phylum Firmicutes and decreased for phylum Proteobacteria (compared with control subjects). The genera Blautia (vs. mild ACD group) and Morganella (vs. control group) exhibited significantly increased abundance only in the severe ACD group. Conclusions: The ocular surface microbiota in patients with severe ACD exhibited decreased diversity and exacerbation of dysbiosis compared with that in patients with mild ACD and control subjects. Patients with mild refractory ACD also exhibited decreased diversity of these microbiota. These alterations in microbiota indicated a change in the ocular surface of patients with refractory ACD (be it because of disease pathogenesis or topical immunomodulatory treatment).