Allergic conjunctivitis

Japanese: アレルギー性結膜炎

What kind of disease is it?

●Main symptoms and progression This is a disease in which an allergic reaction to certain substances occurs in the conjunctiva of the eye.
The initial symptoms are itchy eyes and eyelids. The itching causes people to rub their eyes, which can lead to conjunctival congestion and pain. As the condition worsens, symptoms include swelling of the eyelids, a jelly-like discharge from the conjunctiva, constant tears, and a gritty foreign body sensation.
In addition to this, symptoms of allergic rhinitis such as runny nose and constant sneezing may also occur. This is particularly common in people with atopic constitutions or those who already have allergic diseases such as bronchial asthma.

●Causes of the disease and how symptoms developSubstances that cause allergies are called allergens (antigens). Typical allergens in allergic conjunctivitis include pollen, house dust, dust mites, pet hair, chemicals, food, and fibers.
Depending on the allergen, symptoms may only appear during certain seasons, which is called seasonal allergic conjunctivitis (hay fever), while symptoms that appear all year round are called perennial allergic conjunctivitis.

EBM checks on common treatments and care

[Treatment and care] Identify the allergen causing the problem [Evaluation] ☆☆
[Evaluation points] The treatment of allergic conjunctivitis is based on identifying and removing the allergen, so this is naturally considered necessary. (1)(2)

■ Avoid allergens as much as possible [Treatment and care] Carefully vacuum up house dust and mites [Rating] ☆☆☆
[Evaluation Points] Clinical studies have shown that there is a strong correlation between house dust and mites and allergic conjunctivitis. Removing these allergens is necessary to alleviate the symptoms of allergic conjunctivitis. (1)(2)

[Treatment and care] Futons are disinfected in sunlight and then vacuumed. [Rating] ☆☆☆
[Evaluation Points] Clinical studies have shown that bedding and allergic conjunctivitis are related. Since bedding and bedding are ideal habitats for mites, it is effective to disinfect them by exposing them to sunlight and to remove dead mites and dust that serves as food with a vacuum cleaner. (1)(2)

[Treatment and care] Wear glasses and a mask to protect against pollen. [Rating] ☆☆☆
[Evaluation points] Clinical studies have shown that protecting the eyes from allergens with glasses or other items is effective in improving the symptoms of allergic conjunctivitis. (2)

[Treatment and care] Brush off pollen from clothes when outside the house. [Rating] ☆☆
[Treatment and care] Gargling and washing the face [Rating] ☆☆
[Evaluation points] Although there are no clinical studies showing that these methods relieve the symptoms of allergic conjunctivitis, they are supported by the experience and opinion of experts.

[Treatment and care] Avoid stress and be careful not to get too little sleep or get too tired. [Rating] ☆☆☆
[Evaluation Points] Clinical studies have shown that there is a relationship between stressful events (death in the family, interpersonal conflicts, etc.) and allergic conjunctivitis. It is best to avoid stress if possible. (4)

[Treatment and care] In the case of seasonal allergies, preventive eye drops containing antihistamines or antiallergic drugs should be started before symptoms appear. [Rating] ☆☆☆☆☆
[Evaluation Points] Highly reliable clinical studies have shown that eye symptoms improved in approximately 90% of patients when eye drops containing levocabastine hydrochloride were used for 8 weeks starting just before the pollen season. It has also been shown to be as effective as oral antihistamines, with no changes in side effects. It is said to be particularly effective when the pollen count is high. (5)
Similar results have been observed with sodium cromoglycate and ibudilast. (3)(8)(9)

[Treatment and care] If symptoms are severe, corticosteroid eye drops and anti-allergy medications are used in combination for a limited period of time. [Rating] ☆☆
[Evaluation Points] Several highly reliable clinical studies have confirmed that corticosteroid eye drops can relieve acute symptoms of allergic conjunctivitis (itchiness, redness, etc.). At the same time, it has been reported that side effects from long-term use (increased intraocular pressure, cataracts, etc.) can be problematic. However, after two weeks of use, almost no side effects were observed, and symptoms were relieved in about one week, so short-term use is preferable. (6)(8)(10)

[Treatment and care] Immunosuppressants [Rating] ☆☆☆
[Evaluation Points] It is expected to be as effective as or more effective than corticosteroid eye drops. In particular, high-quality clinical studies have confirmed that tacrolimus hydrate is effective even in severe cases of steroid resistance where steroids are not effective. (11)-(16)

Checking commonly used drugs with EBM

Antihistamine eye drops [Drug name] Livostin (levocabastine hydrochloride) (5)
[Rating] ☆☆☆☆☆
[Drug name] Zaditen (Ketotifen fumarate) (6)
[Rating] ☆☆☆☆☆
[Drug name] Patanol (Olopatadine hydrochloride) (6)(7)
[Rating] ☆☆☆☆☆
[Evaluation Points] The effectiveness of these drugs has been confirmed by highly reliable clinical studies. In the case of seasonal allergies caused by pollen, it has been reported that approximately 90% of patients have seen improvement in symptoms when levocabastine hydrochloride is used for 8 weeks starting just before pollen dispersion. Ketotifen fumarate has been reported to be effective in over 80% of patients for symptoms such as itchy, bloodshot, and watery eyes.

Antiallergic eye drops [Name of drug] Intal (sodium cromoglycate) (8)
[Rating] ☆☆☆☆☆
[Drug name] Alegisal (Pemirolast potassium) (17)
[Rating] ☆☆☆☆☆
[Drug name] Ketas (Ibudilast) (5) (18)
[Rating] ☆☆☆
[Drug name] Rizaben (Tranilast)
[Rating] ☆☆
[Evaluation Points] The effectiveness of sodium cromoglycate has been confirmed by highly reliable clinical studies, but it is considered to be slightly less effective than levocabastine hydrochloride in terms of symptom relief. The preventive effect of pemirolast potassium against seasonal allergic conjunctivitis has been confirmed by highly reliable clinical studies. Clinical studies have also shown that ibudilast relieves symptoms such as congestion. Additionally, there are no clinical studies showing the effectiveness of tranilast, but it is supported by expert opinion and experience.

Corticosteroid eye drops [Drug name] Flumetholone (Fluorometholone) (10)
[Rating] ☆☆
[Evaluation points] The effectiveness of fluorometholone has not been confirmed by clinical studies, but the effectiveness of a similar drug, hydrocortisone, has been confirmed by clinical studies. It should be used with caution, paying attention to the possibility of side effects (increased intraocular pressure, cataracts).

Immunosuppressant eye drops [Drug name] Papilloc (cyclosporine) (11)-(15)
[Rating] ☆☆☆
[Drug name] Talimus (tacrolimus hydrate) (16)
[Rating] ☆☆☆
[Evaluation points] It is recommended for moderate to severe cases where anti-allergic eye drops alone are not effective enough.

Overall, it is currently the most reliable treatment <br /> The basis of treatment is to identify and remove the allergen The basis of treatment for allergic conjunctivitis is to identify and remove the allergen. If the allergen is house dust or mites, symptoms can be controlled by improving the environment by cleaning the home and disinfecting bedding with sunlight, and removing the allergen.
If pollen is an allergen, protecting your eyes with glasses or other items can help improve symptoms.
There are also reports that stress can worsen symptoms, so it is best to avoid stress if possible.

Beware of side effects of corticosteroids There are many types of drugs that have been proven to be effective in relieving symptoms. One drug that is sure to have an immediate effect is the corticosteroid flumetholone (fluorometholone), but it can cause side effects (increased intraocular pressure, cataracts), so it is safer to use antihistamines and antiallergic drugs such as Livostin (levocabastine hydrochloride), Zaditen (ketotifen fumarate), and Patanol (olopatadine hydrochloride).
If the symptoms are not too severe and it is okay to wait a little longer for the effects to take effect, it is recommended to use Intal (sodium cromoglycate) or Alegysal (pemirolast potassium).
If nasal allergies (allergic rhinitis) are also present, oral antiallergy medication may be used.

Use immunosuppressant eye drops in moderate to severe cases For patients with moderate to severe seasonal allergic conjunctivitis for whom antihistamine or antiallergic eye drops alone are ineffective, it is recommended that immunosuppressant eye drops be administered in addition. For severe patients whose symptoms do not improve with these two drugs, the addition of corticosteroid eye drops for a short period of time should be considered.

(1)Bilkhu PS, Wolffsohn JS, Naroo SA. A review of non-pharmacological and pharmacological management of seasonal and perennial allergic conjunctivitis.Cont Lens Anterior Eye. 2012 Feb;35(1):9-16.
(2) Japan Ophthalmological Society, Etsuko Takamura. Guidelines for the Treatment of Allergic Conjunctival Disease (2nd Edition). Chapter 6: Prevention: Self-care Chapter 7: Medical Care. Japanese Journal of Ophthalmology. 114:829-870, 2010.
(3) Takamura E. [Guidelines for the clinical management of allergic conjunctival disease (2nd edition): the point of the management with using eye drops]. Arerugi. 2014 Sep;63(8):1103-9.
(4)Kilpelainen M, Koskenvuo M, Helenius H, et al. Stressful life events promote the manifestation of asthma and atopic diseases. ClinExp Allergy. 2002;32:256-263.
(5)Sohoel P, Freng BA, Kramer J, et al. Topical levocabastine compared with orally administered terfenadine for the prophylaxis and treatment of seasonal rhinoconjunctivitis. J Allergy ClinImmunol. 1993;92:73-81.
(6)Uchio E. Treatment of allergic conjunctivitis with olopatadine hydrochloride eye drops. ClinOphthalmol. 2008 Sep;2(3):525-31.
(7)Mortemousque B, Bourcier T, Khairallah M, et al. Ketotifen Study Group. Comparison of preservative-free ketotifen fumarate and preserved olopatadine hydrochloride eye drops in the treatment of moderate to severe seasonal allergic conjunctivitis. J Fr Ophtalmol. 2014 Jan;37(1):1-8.
(8)Juniper EF, Guyatt GH, Ferrie PJ, et al. Sodium cromoglycate eye drops:Regular versus “as needed” use in the treatment of seasonal allergic conjunctivitis. J Allergy ClinImmunol. 94: 36-43, 1994.
(9) Ebihara, N. Effect of topical ibudilast prophylactic treatment in seasonal allergic conjunctivitis. Atarashii Ophthalmology. 20:259-262, 2003.
(10)Leonardi A, Papa V, Milazzo G, et al. Efficacy and safety of desonide phosphate for the treatment of allergic conjunctivitis. Cornea. 2002;21:476-481.429-434.
(11)Bertelmann E, Pleyer U. Immunomodulatory therapy in ophthalmology-is there a place for topical application? Ophthalmologica. 218:359-367, 2004.
(12)Cetinkaya A, Akova YA, Dursun D, et al. Topical cyclosporine in the management of shield ulcers. Cornea. 23:194-200, 2004.
(13)Pucci N, Novembre E, Lombardi E, et al. Long eyelashes in a case series of 93 children with vernal keratoconjunctivitis. Pediatrics. 115:e 86-91, 2005.
(14)Strong B, Farley W, Stern ME, Pflugfelder SC. Topical cyclosporine inhibits conjunctival epithelial apoptosis in experimental murine keratoconjuncti- vitis sicca. Cornea. 24:80-85, 2005.
(15) Ebihara, Nobuyuki. Treatment of vernal conjunctivitis with immunosuppressive eye drops. Japanese Ophthalmology. 80:1155-1159, 2009.
(16)Fukushima A, Ohashi Y, Ebihara N, et al. Therapeutic effects of 0.1% tacrolimus eye drops for refractory allergic ocular diseases with proliferative lesions or corneal involvement. Br J Ophthalmol. 2014 Aug;98(8):1023-7.
(17)Fujishima H, Fukagawa K, Tanaka M, et al. The effect of a combined therapy with a histamine H1 antagonist and a chemical mediator release inhibitor on allergic conjunctivitis.Ophthalmologica. 2008;222(4):232-9.
(18)Sakuma K, Toshida H, Honda R, et al. Effects of topical application of ibudilast for seasonal allergic conjunctivitis in patients wearing soft contact lenses. Eye Contact Lens. 2009 Sep;35(5):251-4.

Source: "EBM: A book that explains correct treatment" Information about the book "EBM: A book that explains correct treatment"

Japanese:

どんな病気でしょうか?

●おもな症状と経過
　ある特定の物質に過敏に反応するアレルギー反応が、目の結膜(けつまく)でおきる病気です。
　初期症状としては目やまぶたがかゆくなります。かゆくてたまらず目をこすることが多くなるので、結膜の充血や痛みもでてきます。悪化するとまぶたが腫(は)れ、結膜にゼリー状の目やにがでたり、涙が止まらなくなったり、ごろごろとした異物感などの症状がおきたりします。
　またこれに加えて、鼻水やくしゃみが止まらないといったアレルギー性鼻炎の症状が伴うこともあります。とくにアトピー体質の人や、もともと気管支喘息(ぜんそく)などアレルギー性の病気をもっている人などに多くみられます。

●病気の原因や症状がおこってくるしくみ
　アレルギーを引きおこす物質をアレルゲン（抗原）といいますが、アレルギー性結膜炎における代表的なアレルゲンには、花粉、ハウスダスト、ダニ、ペットの毛、化学物質、食べもの、繊維(せんい)などがあります。
　アレルゲンによっては特定の季節にしか症状が現れず、これを季節性アレルギー性結膜炎（花粉性結膜炎）といい、1年中症状があるものは通年性アレルギー性結膜炎と呼ばれます。

よく行われている治療とケアをEBMでチェック

［治療とケア］原因となっているアレルゲン物質を特定する
［評価］☆☆
［評価のポイント］　アレルギー性結膜炎の治療は、アレルゲン物質の特定と除去が基本ですから、当然必要と考えられます。(1)(2)

■アレルゲン物質をできるだけ避けるようにする
［治療とケア］ハウスダスト、ダニはていねいに掃除機で吸い取る
［評価］☆☆☆
［評価のポイント］　ハウスダストやダニとアレルギー性結膜炎は強い関連があるという臨床研究があります。これらのアレルゲン物質を取り除くことはアレルギー性結膜炎の症状をやわらげるために必要とされています。(1)(2)

［治療とケア］布団は日光消毒し、その後掃除機をかける
［評価］☆☆☆
［評価のポイント］　布団とアレルギー性結膜炎は関連があるという臨床研究があります。布団などの寝具はダニの格好の住み家ですから、よく日光にあてて消毒し、掃除機でダニの死骸やえさとなるほこりを取り除くことは有効な方法です。(1)(2)

［治療とケア］花粉に対しては眼鏡やマスクをする
［評価］☆☆☆
［評価のポイント］　眼鏡などで目をアレルゲンから保護することは、アレルギー性結膜炎の症状改善に効果があるという臨床研究があります。(2)

［治療とケア］衣服についた花粉は家の外でよく払う
［評価］☆☆
［治療とケア］うがいや洗顔をする
［評価］☆☆
［評価のポイント］　これらの方法がアレルギー性結膜炎の症状を緩和(かんわ)するという臨床研究は見あたりませんが、専門家の経験と意見から支持されています。

［治療とケア］ストレスを避け、睡眠不足や過労に注意する
［評価］☆☆☆
［評価のポイント］　ストレスを強く感じるできごと（家族の死、人間関係の対立など）とアレルギー性結膜炎は関連があるという臨床研究があります。避けることができるストレスは回避したほうがいいでしょう。(4)

［治療とケア］季節性の場合は、症状がでる前から予防的に抗ヒスタミン薬や抗アレルギー薬の点眼を始める
［評価］☆☆☆☆☆
［評価のポイント］　非常に信頼性の高い臨床研究で、点眼用のレボカバスチン塩酸塩は、流行の季節の直前から始めて8週間用いることで約90パーセントの患者さんで目の症状が改善されたと報告されています。また、抗ヒスタミン薬の内服薬と同程度の効果があり、副作用は変わらないことが示されています。とくに花粉の量が多いときほど効果があるとしています。(5)
　クロモグリク酸ナトリウムやイブジラストでも同様の結果が確認されています。(3)(8)(9)

［治療とケア］症状が重い場合は、期間を限って副腎皮質(ふくじんひしつ)ステロイド薬の点眼液と抗アレルギー薬を併用する
［評価］☆☆
［評価のポイント］　いくつかの非常に信頼性の高い臨床研究によって副腎皮質ステロイド薬の点眼液はアレルギー性結膜炎の急性期の症状（かゆみ、充血など）を緩和することが確認されています。同時に、長期使用による副作用（眼圧上昇、白内障など）が問題となると報告しています。2週間の使用では副作用はほとんど認められず、約1週間で症状が緩和されたとしていますので、短期使用が望ましいでしょう。(6)(8)(10)

［治療とケア］免疫抑制薬
［評価］☆☆☆
［評価のポイント］　副腎皮質ステロイド点眼薬と同等またはそれ以上の効果が期待されています。なかでもタクロリムス水和物は、ステロイドが効きにくいステロイド抵抗性の重症例でも効果が得られることが質の高い臨床研究で確認されています。(11)～(16)

よく使われている薬をEBMでチェック

抗ヒスタミン薬点眼用
［薬名］リボスチン（レボカバスチン塩酸塩）(5)
［評価］☆☆☆☆☆
［薬名］ザジテン（ケトチフェンフマル酸塩）(6)
［評価］☆☆☆☆☆
［薬名］パタノール（オロパタジン塩酸塩）(6)(7)
［評価］☆☆☆☆☆
［評価のポイント］　これらの薬は非常に信頼性の高い臨床研究によって効果が確認されています。花粉をアレルゲンとする季節性の場合、レボカバスチン塩酸塩を花粉飛散の直前から8週間用いると、約90パーセントの患者さんで症状の改善が認められたとしています。ケトチフェンフマル酸塩では目のかゆみ、充血、涙目などの症状に対して80パーセント以上の人で効果があったとしています。

抗アレルギー薬点眼用
［薬名］インタール（クロモグリク酸ナトリウム）(8)
［評価］☆☆☆☆☆
［薬名］アレギサール（ペミロラストカリウム）(17)
［評価］☆☆☆☆☆
［薬名］ケタス（イブジラスト）(5)(18)
［評価］☆☆☆
［薬名］リザベン（トラニラスト）
［評価］☆☆
［評価のポイント］　クロモグリク酸ナトリウムは、非常に信頼性の高い臨床研究によって効果が確認されていますが、症状緩和に関して、レボカバスチン塩酸塩に比べやや効果が弱いとされています。ペミロラストカリウムは、非常に信頼性の高い臨床研究によって季節性のアレルギー性結膜炎に対する予防効果が確認されています。イブジラストによっても充血などの症状が緩和されたことが臨床研究によって示されています。また、トラニラストの効果を示す臨床研究は見あたりませんが、専門家の意見や経験から支持されています。

副腎皮質ステロイド薬点眼用
［薬名］フルメトロン（フルオロメトロン）(10)
［評価］☆☆
［評価のポイント］　フロオロメトロンの効果は臨床研究によって確かめられていませんが、類似薬であるヒドロコルチゾンは臨床研究によって効果が確認されています。副作用（眼圧の上昇、白内障）の可能性に注意し慎重に用いる必要があります。

免疫抑制薬点眼用
［薬名］パピロック（シクロスポリン）(11)～(15)
［評価］☆☆☆
［薬名］タリムス（タクロリムス水和物）(16)
［評価］☆☆☆
［評価のポイント］　抗アレルギー薬点眼用だけで効果が不十分な、中等症以上の症例に対して推奨されています。

総合的に見て現在もっとも確かな治療法
治療の基本はアレルゲン物質の特定と除去
　アレルギー性結膜炎の治療の基本は、アレルゲン物質を特定することと除去することです。ハウスダストやダニなどがアレルゲンの場合は、住居の掃除や寝具の日光消毒などによって環境を整備し、アレルゲン物質を取り除くことで症状をコントロールすることができます。
　花粉がアレルゲンであれば、眼鏡などで目を保護することは症状改善に効果があります。
　また、ストレスによって症状が悪化するという報告もみられますから、避けることができるストレスは回避したほうがよいでしょう。

副腎皮質ステロイド薬は副作用に注意
　症状を緩和するのに有効なことが実証されている薬は何種類もあります。確実に、しかもすぐに効果がでる薬としては、副腎皮質ステロイド薬のフルメトロン（フルオロメトロン）がありますが、副作用（眼圧の上昇、白内障）の可能性もありますので、リボスチン（レボカバスチン塩酸塩）、ザジテン（ケトチフェンフマル酸塩）やパタノール（オロパタジン塩酸塩）などの抗ヒスタミン薬や抗アレルギー薬のほうが安心して使えると思います。
　症状がそれほど強くなく、効果がでるまでに少し時間がかかってもよい場合にはインタール（クロモグリク酸ナトリウム）やアレギサール（ペミロラストカリウム）の使用が勧められます。
　鼻アレルギー（アレルギー性鼻炎）を合併している場合には、経口の抗アレルギー薬を用いることもあります。

中等症以上の場合には免疫抑制薬点眼用を使用する
　抗ヒスタミン薬や抗アレルギー薬の点眼用だけで効果が不十分である中等症以上の季節性アレルギー性結膜炎の患者さんに対しては、免疫抑制薬点眼用を追加投与することが推奨されます。2剤で症状の改善がみられない重症の患者さんに対しては、さらに短期間の副腎皮質ステロイド薬点眼用の追加が検討されます。

(1)Bilkhu PS, Wolffsohn JS, Naroo SA. A review of non-pharmacological and pharmacological management of seasonal and perennial allergic conjunctivitis.Cont Lens Anterior Eye. 2012 Feb;35(1):9-16.
(2)日本眼科学会,高村悦子.　アレルギー性結膜疾患診療ガイドライン（第2版）.第6章　予防：セルフケア　第7章　メディカルケア．日眼学誌.114:829-870,2010.
(3)Takamura E．[Guidelines for the clinical management of allergic conjunctival disease (2nd edition): the point of the management with using eye drops].　Arerugi. 2014 Sep;63(8):1103-9.
(4)Kilpelainen M, Koskenvuo M, Helenius H, et al. Stressful life events promote the manifestation of asthma and atopic diseases. ClinExp Allergy. 2002;32:256-263.
(5)Sohoel P, Freng BA, Kramer J, et al. Topical levocabastine compared with orally administered terfenadine for the prophylaxis and treatment of seasonal rhinoconjunctivitis. J Allergy ClinImmunol. 1993;92:73-81.
(6)Uchio E.　Treatment of allergic conjunctivitis with olopatadine hydrochloride eye drops.　ClinOphthalmol. 2008 Sep;2(3):525-31.
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