Japanese guidelines for allergic conjunctival diseases 2017.

The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease (Second Edition) revised in 2010. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs.

Steroid-Sparing Effect of 0.1% Tacrolimus Eye Drop for Treatment of Shield Ulcer and Corneal Epitheliopathy in Refractory Allergic Ocular Diseases.

PURPOSE: To evaluate the effects of 0.1% topical tacrolimus alone or in combination with steroids for the treatment of shield ulcers and corneal epitheliopathy in patients with refractory allergic ocular diseases. DESIGN: Open cohort study. PARTICIPANTS: Patients with refractory allergic conjunctivitis epitheliopathy, shield ulcers, or corneal plaques (N = 791). METHODS: The 791 patients were treated with topical tacrolimus alone or in combination with topical or oral steroids. The effectiveness of the treatments was determined by a corneal epitheliopathy score during the 3-month follow-up period. The clinical signs were rated on a 4-grade scale. Corneal epitheliopathy with no corneal staining was graded as 0, and shield ulcers or plaques were graded as 3, the highest grade. The effects of tacrolimus with and without topical steroids on the epitheliopathy scores were assessed after adjustments for the severity of the clinical signs and characteristics. MAIN OUTCOME MEASURES: Changes in the corneal epitheliopathy score. RESULTS: Adjusted mean epitheliopathy score at the baseline was 1.73 (95% confidence interval [CI], 1.65-1.81) for patients treated with tacrolimus alone, and this was significantly reduced by -0.93 at 1 month. The reduction of the score by topical and oral steroids was -0.02 for fluorometholone, 0.02 for betamethasone, and -0.02 for oral steroids, and these reductions were not significant compared with the reduction effect of topical tacrolimus alone at -0.93. The 238 patients with shield ulcer (score 3) were analyzed with adjustments, and the mean epitheliopathy score at 1 month was reduced to 1.38 with tacrolimus alone (95% CI, 1.24-1.51), 1.41 (95% CI, 1.26-1.56) with adjuvant fluorometholone, and 1.46 (95% CI, 1.32-1.61) with adjuvant betamethasone. No significant difference was observed in the adjunctive topical steroids. The presence of severe palpebral conjunctival symptoms, including giant papillae, was a significant resisting factor for topical tacrolimus. CONCLUSIONS: The significant effects of topical tacrolimus alone on shield ulcers and corneal epitheliopathy suggest that it may be used without the need for steroids.

Therapeutic effects of 0.1% tacrolimus eye drops for refractory allergic ocular diseases with proliferative lesion or corneal involvement.

BACKGROUND: The objective of this study was to investigate the efficacy of topical 0.1% tacrolimus in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement. METHODS: This prospective observational study included 1436 patients with refractory allergic conjunctivitis whose condition had responded poorly to conventional antiallergic drugs and/or topical steroids and/or topical cyclosporine. All patients received tacrolimus eye drops twice daily during the study period. Ten clinical signs and six clinical symptoms were rated on a four-grade scale. The primary endpoint was the change from baseline in total clinical signs and symptoms score at the last observation or following 6 months of treatment. RESULTS: Total signs and symptoms score significantly decreased after 1 month of treatment (p<0.001). Giant papillae and corneal lesions were also reduced by tacrolimus eye drop use (p<0.001). The drug proved effective in patients whose condition did not respond well to topical cyclosporine therapy. About 50% of all patients using topical steroids were weaned. The most common adverse reaction was a transient burning sensation (3.20%). CONCLUSIONS: Tacrolimus eye drops are highly effective in treating refractory allergic conjunctivitis with proliferative lesions and/or corneal involvement, and may reduce or replace topical steroid use. TRIAL REGISTRATION NUMBER: UMIN 000008640.

Blood level of tacrolimus in patients with severe allergic conjunctivitis treated by 0.1% tacrolimus ophthalmic suspension.

BACKGROUND: To estimate the efficacy and safety of 0.1% tacrolimus ophthalmic suspension based on the blood level of tacrolimus in patients with severe allergic conjunctivitis. METHODS: Fifty-two patients in whom topical anti-allergic agents had been ineffective were treated with 0.1% tacrolimus ophthalmic suspension twice daily for 12 weeks. Adverse drug reactions were monitored, as well as ocular symptoms and signs. The blood concentration of tacrolimus was measured before the initiation of treatment and 4 and 12 weeks later. RESULTS: About 75% of the patients without concomitant using of tacrolimus ointment had blood levels of tacrolimus below the detection limit of the assay (0.5ng/mL). On the other hand, 71% (week 4) and 57% (week 12) of patients with concomitant using of tacrolimus ointment had blood levels above the detection limit of the assay. However, the maximum blood concentration was less than 2ng/mL. Adverse drug reactions occurred in 16 patients. These were disorders of the eye such as warmness, irritation, and a burning sensation. However, all of the patients could continue treatment with tacrolimus for 12 weeks. There were no serious adverse events such as increased intraocular pressure or ocular infection during the study. All symptoms and signs improved over time. CONCLUSIONS: The good safety profile of 0.1% tacrolimus ophthalmic suspension based on the low blood concentration of tacrolimus, coupled with demonstrated efficacy, make it an important tool for treating severe allergic conjunctivitis.

[A prospective, observational, all-prescribed-patients study of cyclosporine 0.1% ophthalmic solution in the treatment of vernal keratoconjunctivitis].

PURPOSE: To evaluate the effectiveness and safety of topical cyclosporine 0.1% in patients with vernal keratoconjunctivitis (VKC). METHODS: All patients who were prescribed topical cyclosporine 0.1% during the 2 year period after market launch were registered and followed up for 6 months. We assessed the severity of 6 subjective ocular symptoms, such as itching and 10 objective signs, such as giant papillae in the tarsal conjunctiva. RESULTS: All scores for symptoms and signs in 2597 patients with VKC significantly decreased throughout a 6-month follow-up. For total symptoms scores, mean changes from baseline at 1, 3, and 6 months were -4.0, -4.8, and -5.1, respectively. Total sign scores were -4.6, -6.1, and -6.5, respectively. Thirty percent of topical steroid users were able to discontinue the steroids within 3 months. Adverse drug reactions (ADRs) were found in 7.44% of patients, the most common ADR being eye irritation. Ocular infections were observed in 1.44% of patients. During long-term use of topical cyclosporine 0.1%, there was no increase in the incidence of ADR and no late-onset ADRs. CONCLUSIONS: Topical cyclosporine 0.1% is an effective and safe treatment for VKC over the long term, provided care is exercised to avoid the occurrence of infection.

Japanese guideline for allergic conjunctival diseases.

The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease (Second Edition) revised in 2010. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the above mentioned drugs.

A randomized, placebo-controlled clinical trial of tacrolimus ophthalmic suspension 0.1% in severe allergic conjunctivitis.

AIMS: To examine the efficacy of tacrolimus ophthalmic suspension 0.1% in treating severe allergic conjunctivitis. METHODS: This was a multicenter, randomized, double-masked, placebo-controlled clinical trial. Fifty-six patients with severe allergic conjunctivitis in whom topical antiallergic agents and corticosteroids had been ineffective were randomized to tacrolimus or placebo treatment. Patients were treated either with tacrolimus or placebo twice-daily for 4 weeks. Severity of objective signs in palpebral and bulbar conjunctiva, limbus, and corneal involvement was assessed using 4 grades. Seven subjective symptoms were evaluated by visual analog scale (VAS) assessment. The primary efficacy endpoint was change in the total score of objective signs at the end of treatment. The secondary efficacy endpoints included change in the score for each objective sign and change in the VAS for each subjective symptom. Safety was assessed based on the severity and the incidence of adverse events. RESULTS: Mean change from baseline in total score for objective signs was significantly greater in the tacrolimus (-5.6 + or - 5.1) than in the placebo group (-0.1 + or - 4.5; P < 0.001). Tacrolimus significantly improved giant papillae (P = 0.001) and corneal involvement (P = 0.005). Five subjective symptoms (itching, discharge, hyperemia, lacrimation, and foreign body sensation) were significantly better in the tacrolimus than in the placebo group. The most frequent treatment-related adverse event in the tacrolimus group was mild ocular irritation upon topical instillation, which was well-tolerated. CONCLUSION: Tacrolimus ophthalmic suspension 0.1% is effective in treating severe allergic conjunctivitis.

A large prospective observational study of novel cyclosporine 0.1% aqueous ophthalmic solution in the treatment of severe allergic conjunctivitis.

PURPOSE: To evaluate the effectiveness and safety of a novel cyclosporine 0.1% aqueous ophthalmic solution in a large population with vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). METHODS: A prospective observational postmarketing study was initiated in Japan. A total of 594 patients with VKC or AKC were started on this drug within 1 year after market launch (January 2006) and completed a 6-month follow-up. These patients were observed clinically, and subjective ocular symptoms (itching, discharge, tearing, photophobia, foreign body sensation, and pain), objective signs (hyperemia, swelling, follicle, papillae, and giant papillae for the tarsal conjunctiva; hyperemia and edema for the bulbar conjunctiva; Trantas dots and swelling for the limbus; and corneal involvement), and adverse events were recorded. RESULTS: All scores for symptoms and signs significantly decreased from Month 1 through Month 6 of treatment in both VKC and AKC. Median total symptom scores at baseline, Month 1, and Month 6 were 6, 2, and 1, respectively, for VKC, and 7, 3, and 2, respectively, for AKC. Similarly, median total sign scores were 12, 7, and 5, respectively, for VKC, and 14, 10, and 7, respectively, for AKC. The percentage of patients able to complete topical cyclosporine 0.1% therapy within 6 months due to alleviation of symptoms was higher for VKC (44.4%) than for AKC (21.9%). In both VKC and AKC, approximately 30% of steroid users were able to discontinue topical steroids. Adverse drug reactions (ADRs) were found in 12.0% of patients, and the most common ADR was eye irritation (4.4%). Infectious corneal complications were observed in five AKC patients, including two cases of bacterial corneal ulcer and three cases of herpetic keratitis; all of these patients were concomitantly using topical steroids. CONCLUSIONS: Topical cyclosporine 0.1% is an effective and safe treatment for VKC and AKC.

Comparison of efficacy of bromfenac sodium 0.1% ophthalmic solution and fluorometholone 0.02% ophthalmic suspension for the treatment of allergic conjunctivitis.

AIMS: Bromfenac sodium (BF) 0.1% was compared with fluorometholone (FML) 0.02% for the treatment of seasonal allergic conjunctivitis when concomitantly used with disodium cromoglycate (DSCG) 2.0%. METHODS: Eighty-six patients with seasonal allergic conjunctivitis were treated with DSCG four times a day, and BF was concomitantly administered twice a day in one eye and FML was administered four times a day in the contralateral eye for 1 week. Ocular signs were scored on a four-graded severity. Patients recorded symptoms using visual analog scale. Patients were asked which concomitant treatment was more suitable for them and scored global evaluation. RESULTS: All subjective symptom scores were decreased in both concomitant treatment groups compared with baseline (P < 0.05). Objective signs were significantly improved with the concomitant use of BF or FML with DSCG (P < 0.05). Neither symptoms nor signs differed significantly between the concomitant use of BF and FML. Fifteen patients selected BF and 29 patients selected FML as the more preferred concomitant eye drops, 42 patients judged no difference in efficacy between the groups. No significant difference was observed in patient's global evaluation between the groups. CONCLUSIONS: Bromfenac sodium for allergic conjunctivitis was effective, with efficacy equivalent to that of FML when used with DSCG.

The effect of a combined therapy with a histamine H1 antagonist and a chemical mediator release inhibitor on allergic conjunctivitis.

PURPOSE: To evaluate the efficacy of a combined therapy with levocabastine hydrochloride ophthalmic suspension and pemirolast potassium ophthalmic solution compared to single therapy with levocabastine hydrochloride ophthalmic suspension alone. METHODS: Thirty-two allergic conjunctivitis patients were randomized to combined-treatment (n = 15) or single-treatment groups (n = 17). The improvement of subjective symptoms as well as objective findings were evaluated. RESULTS: The degree of improvement was significantly higher in the combined-treatment group for lacrimation (p = 0.008) among the subjective symptoms, for conjunctival edema (p = 0.030), eyelid edema (p = 0.032) and conjunctival papilla formation(p = 0.040) among the objective findings. CONCLUSIONS: Both objective assessments and subjective symptoms of allergic conjunctivitis showed the greatest improvements when patients were treated with combined therapy as compared to single-agent therapy. The enhanced benefits of combined therapy may result from these agents having different mechanisms of action.

The early efficacy of topical levocabastine in patients with allergic conjunctivitis.

BACKGROUND: We investigated the early efficacy of topical levocabastine, an H(1) histamine-receptor antagonist, in improving the clinical symptoms of allergic conjunctivitis. METHODS: Thirty-six patients with allergic conjunctivitis were enrolled. One drop of levocabastine was instilled in one eye and one drop of artificial tears in the contralateral eye. Clinical examinations were performed before, and 15 and 30 minutes after instillation. Symptoms of itching and signs of injection were assessed at each time point. RESULTS: Both levocabastine and artificial tears resulted in a statistically significant reduction in ocular itching. However, levocabastine was significantly more effective. CONCLUSIONS: Although artificial tears had a positive effect in reducing symptoms of allergic conjunctivitis, by the washing out of allergens, levocabastine was more effective than artificial tears in controlling acute symptoms of allergic conjunctivitis, demonstrating that the selective H1 histamine-receptor antagonist action of levocabastine is rapidly effective in a clinical setting.

Endogenous endophthalmitis and disseminated intravascular coagulation complicating a Klebsiella pneumoniae perirenal abscess in a patient with type 2 diabetes.

We describe a 56-year-old woman with type 2 diabetes complicated by a Klebsiella pneumoniae perirenal abscess. The patient further developed incipient diabetic ketoacidosis, disseminated intravascular coagulation, and endogenous endophthalmitis. Occurrence of the latter as a metastatic infection from perirenal abscess caused by this organism is very rare, and we know of no previously reported patient with the additional occurrence of disseminated intravascular coagulation. Since prompt intravitreal antibiotic administration is needed, physicians should be aware of these rare but severe complications of K pneumoniae infection, especially in patients with poorly controlled diabetes.

Unusual neutrophil infiltration under the soft contact lens in a patient with Behçet's disease.

BACKGROUND: Behçet's disease (BD) characterized by multisystemic disorders has many kinds of ocular involvement. We report one case of BD with unusual neutrophil infiltration under a soft contact lens (SCL). CASE: A 31-year-old woman diagnosed as having BD exhibited bilateral recurrent phlyctenular keratitis and finally developed corneal perforation in the cornea of her right eye. OBSERVATIONS: A therapeutic SCL was immediately fitted on the right cornea as a bandage and another SCL on the left, as prophylaxis. White gelatinous membrane suddenly appeared between the bandage SCL and the cornea in the left eye. After peeling off this gelatinous membrane from the cornea, we examined it after hematoxylin-eosin staining. We also measured the levels of interleukin-8 (IL-8) both in the tears of the patient and on the surface of the SCL. A great amount of neutrophils had infiltrated into this gelatinous membrane. Laboratory data showed a marked increase of IL-8 levels both on the SCL and in the reflex tears (right SCL, 4980 pg/mL; left SCL, 6810 pg/mL. Reflex tears: right, 2080 pg/mL; left, 2170 pg/mL). CONCLUSION: This case emphasizes the association between the IL-8 level and the disease activity in BD, and provides additional evidence that a BD attack can be induced on the ocular surface under certain conditions.

Evaluation of pulse corticosteroid therapy for vogt-koyanagi-harada disease assessed by optical coherence tomography.

PURPOSE: To evaluate the rapid effects of pulse corticosteroid therapy on the serous retinal detachment found at the acute phase of Vogt-Koyanagi-Harada disease. DESIGN: Interventional case series. METHODS: Nine Japanese patients determined to be at the acute phase of Vogt-Koyanagi-Harada disease with serous retinal detachment were treated with pulse corticosteroid therapy. Optical coherence tomography was used to follow the resolution of the retinal detachment. RESULTS: Optical coherence tomography images showed a marked decrease in the retinal detachment immediately after the first intravenous injection of corticosteroid and subsequent resolution. CONCLUSION: The rapid improvement of serous retinal detachment associated with Vogt-Koyanagi-Harada disease following pulse corticosteroid therapy supports an early therapeutic mechanism related to improved permeability of capillaries and permeability of the blood-retinal barrier rather than an anti-inflammatory or immunosuppressive action.