- Pedram Hamrah, MD
Pedram Hamrah, MD
- New England Eye Center/Tufts Medical Center
- Tufts University School of Medicine
- Reza Dana, MD, MPH, MSc
Reza Dana, MD, MPH, MSc
- Claes Dohlman Professor of Ophthalmology
- Harvard Medical School
- Section Editors
- Bruce S Bochner, MD
Bruce S Bochner, MD
- Editor-in-Chief — Allergy and Immunology
- Section Editor — Adult Allergy; Asthma
- Samuel M Feinberg Professor of Medicine
- Northwestern University Feinberg School of Medicine
- Robert A Wood, MD
Robert A Wood, MD
- Editor-in-Chief — Allergy and Immunology
- Section Editor — Pediatric Allergy
- Professor of Pediatrics
- Johns Hopkins University School of Medicine
There are five main types of ocular allergy: seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and giant papillary conjunctivitis (GPC). VKC and AKC are chronic, bilateral, and severe forms of allergic inflammation affecting the ocular surface. These two relatively uncommon types of allergic eye disease can cause severe damage to the ocular surface, leading to corneal scarring and vision loss if not treated properly (this occurs more commonly with AKC than VKC). Type I hypersensitivity reactions are important in these diseases, although they are not the only pathophysiologic mechanism. VKC is reviewed in this topic. AKC is discussed separately. (See "Atopic keratoconjunctivitis".)
GPC is an inflammatory disorder that represents a reaction to lid movement over a foreign substance, such as contact lenses. Toxic conjunctivitis is not allergic in nature, but it is frequently confused with allergic ocular disease. It develops with protracted use of topical medications, mostly due to preservatives. GPC and toxic conjunctivitis are discussed in detail separately. (See "Giant papillary conjunctivitis" and "Toxic conjunctivitis".)
Seasonal and perennial allergic conjunctivitis, the most common forms of ocular allergy, are also discussed separately. (See "Allergic conjunctivitis: Clinical manifestations and diagnosis".)
VKC most commonly occurs in boys living in warm, dry, subtropical climates, such as the Mediterranean, the Middle East, Central and West Africa, South America, and Asian countries, such as Japan, Thailand, and India . The limbal form of VKC is seen most often in dark-skinned individuals from Africa and India. VKC is generally rare in cooler climates, such as Northern Europe and the temperate areas of North America. In the past, prevalence in these regions has been approximately 0.03 percent of the population. As an example, prevalence for Western Europe was 3.2 in 10,000, whereas a higher prevalence ranging from 2.4 to 27.8 in 10,000 was seen in Italy, a country with a Mediterranean climate . However, the prevalence in cooler regions has increased, probably due to immigration of individuals from susceptible populations .
Males are more commonly affected than females. In one series, the male-to-female ratio was 3.2:1 in patients <20 years of age but was nearly equal in older patients . Age at onset is generally before 10 years, with the earliest reported onset at five months of age , although VKC can infrequently occur in adults. Patients usually "outgrow" the disease with the onset of puberty.
- Kumar S. Vernal keratoconjunctivitis: a major review. Acta Ophthalmol 2009; 87:133.
- Bremond-Gignac D, Donadieu J, Leonardi A, et al. Prevalence of vernal keratoconjunctivitis: a rare disease? Br J Ophthalmol 2008; 92:1097.
- Montan PG, Ekström K, Hedlin G, et al. Vernal keratoconjunctivitis in a Stockholm ophthalmic centre--epidemiological, functional, and immunologic investigations. Acta Ophthalmol Scand 1999; 77:559.
- Bonini S, Bonini S, Lambiase A, et al. Vernal keratoconjunctivitis revisited: a case series of 195 patients with long-term followup. Ophthalmology 2000; 107:1157.
- Ukponmwan CU. Vernal keratoconjunctivitis in Nigerians: 109 consecutive cases. Trop Doct 2003; 33:242.
- Lambiase A, Minchiotti S, Leonardi A, et al. Prospective, multicenter demographic and epidemiological study on vernal keratoconjunctivitis: a glimpse of ocular surface in Italian population. Ophthalmic Epidemiol 2009; 16:38.
- Tesse R, Spadavecchia L, Fanelli P, et al. New insights into childhood Vernal keratoconjunctivitis-associated factors. Pediatr Allergy Immunol 2012; 23:682.
- Tuft SJ, Dart JK, Kemeny M. Limbal vernal keratoconjunctivitis: clinical characteristics and immunoglobulin E expression compared with palpebral vernal. Eye (Lond) 1989; 3 ( Pt 4):420.
- Leonardi A. Vernal keratoconjunctivitis: pathogenesis and treatment. Prog Retin Eye Res 2002; 21:319.
- Mantelli F, Lambiase A, Bonini S. A simple and rapid diagnostic algorithm for the detection of ocular allergic diseases. Curr Opin Allergy Clin Immunol 2009; 9:471.
- Offiah I, Calder VL. Immune mechanisms in allergic eye diseases: what is new? Curr Opin Allergy Clin Immunol 2009; 9:477.
- Mumcuoglu YK, Zavaro A, Samra Z, Lazarowitz Z. House dust mites and vernal keratoconjunctivitis. Ophthalmologica 1988; 196:175.
- Fujishima H, Saito I, Takeuchi T, Tsubota K. Immunological characteristics of patients with vernal keratoconjunctivitis. Jpn J Ophthalmol 2002; 46:244.
- Bonini S, Bonini S, Schiavone M, et al. Conjunctival hyperresponsiveness to ocular histamine challenge in patients with vernal conjunctivitis. J Allergy Clin Immunol 1992; 89:103.
- Pucci N, Novembre E, Lombardi E, et al. Long eyelashes in a case series of 93 children with vernal keratoconjunctivitis. Pediatrics 2005; 115:e86.
- Abelson MB, Baird RS, Allansmith MR. Tear histamine levels in vernal conjunctivitis and other ocular inflammations. Ophthalmology 1980; 87:812.
- Leonardi A, Fregona IA, Plebani M, et al. Th1- and Th2-type cytokines in chronic ocular allergy. Graefes Arch Clin Exp Ophthalmol 2006; 244:1240.
- Leonardi A, Curnow SJ, Zhan H, Calder VL. Multiple cytokines in human tear specimens in seasonal and chronic allergic eye disease and in conjunctival fibroblast cultures. Clin Exp Allergy 2006; 36:777.
- Leonardi A, Abatangelo G, Cortivo R, Secchi AG. Collagen types I and III in giant papillae of vernal keratoconjunctivitis. Br J Ophthalmol 1995; 79:482.
- Leonardi A, Di Stefano A, Vicari C, et al. Histamine H4 receptors in normal conjunctiva and in vernal keratoconjunctivitis. Allergy 2011; 66:1360.
- Abu El-Asrar AM, Al-Mansouri S, Tabbara KF, et al. Immunopathogenesis of conjunctival remodelling in vernal keratoconjunctivitis. Eye (Lond) 2006; 20:71.
- Bonini S, Sacchetti M, Mantelli F, Lambiase A. Clinical grading of vernal keratoconjunctivitis. Curr Opin Allergy Clin Immunol 2007; 7:436.
- Sacchetti M, Lambiase A, Mantelli F, et al. Tailored approach to the treatment of vernal keratoconjunctivitis. Ophthalmology 2010; 117:1294.
- Kumar S, Gupta N, Vivian AJ. Modern approach to managing vernal keratoconjunctivitis. Curr Allergy Asthma Rep 2010; 10:155.
- Abelson MB. Evaluation of olopatadine, a new ophthalmic antiallergic agent with dual activity, using the conjunctival allergen challenge model. Ann Allergy Asthma Immunol 1998; 81:211.
- Abelson MB, Spitalny L. Combined analysis of two studies using the conjunctival allergen challenge model to evaluate olopatadine hydrochloride, a new ophthalmic antiallergic agent with dual activity. Am J Ophthalmol 1998; 125:797.
- Berdy GJ, Stoppel JO, Epstein AB. Comparison of the clinical efficacy and tolerability of olopatadine hydrochloride 0.1% ophthalmic solution and loteprednol etabonate 0.2% ophthalmic suspension in the conjunctival allergen challenge model. Clin Ther 2002; 24:918.
- Spangler DL, Bensch G, Berdy GJ. Evaluation of the efficacy of olopatadine hydrochloride 0.1% ophthalmic solution and azelastine hydrochloride 0.05% ophthalmic solution in the conjunctival allergen challenge model. Clin Ther 2001; 23:1272.
- Uchio E. Treatment of allergic conjunctivitis with olopatadine hydrochloride eye drops. Clin Ophthalmol 2008; 2:525.
- Corum I, Yeniad B, Bilgin LK, Ilhan R. Efficiency of olopatadine hydrochloride 0.1% in the treatment of vernal keratoconjunctivitis and goblet cell density. J Ocul Pharmacol Ther 2005; 21:400.
- Abelson MB, Weston JH. Antihistamines. In: Clinical ophthalmic pharmacology, Lamberts DW, Potter DE (Eds), Little Brown, Boston 1987.
- Abelson MB, Gomes P, Crampton HJ, et al. Efficacy and tolerability of ophthalmic epinastine assessed using the conjunctival antigen challenge model in patients with a history of allergic conjunctivitis. Clin Ther 2004; 26:35.
- Gous P, Ropo A. A comparative trial of the safety and efficacy of 0.1 percent pemirolast potassium ophthalmic solution dosed twice or four times a day in patients with seasonal allergic conjunctivitis. J Ocul Pharmacol Ther 2004; 20:139.
- Crampton HJ. Comparison of ketotifen fumarate ophthalmic solution alone, desloratadine alone, and their combination for inhibition of the signs and symptoms of seasonal allergic rhinoconjunctivitis in the conjunctival allergen challenge model: a double-masked, placebo- and active-controlled trial. Clin Ther 2003; 25:1975.
- Hida WT, Nogueira DC, Schaefer A, et al. [Comparative study between 0.025% ketotifen fumarate and 0.1% olopatadine hydrochloride in the treatment of vernal keratoconjunctivitis]. Arq Bras Oftalmol 2006; 69:851.
- Foster CS. Evaluation of topical cromolyn sodium in the treatment of vernal keratoconjunctivitis. Ophthalmology 1988; 95:194.
- Tabbara KF, al-Kharashi SA. Efficacy of nedocromil 2% versus fluorometholone 0.1%: a randomised, double masked trial comparing the effects on severe vernal keratoconjunctivitis. Br J Ophthalmol 1999; 83:180.
- Bonini S, Lambiase A, Matricardi P, et al. Atopic and vernal keratoconjunctivitis: a model for studying atopic disease. Curr Probl Dermatol 1999; 28:88.
- Avunduk AM, Avunduk MC, Kapicioglu Z, et al. Mechanisms and comparison of anti-allergic efficacy of topical lodoxamide and cromolyn sodium treatment in vernal keratoconjunctivitis. Ophthalmology 2000; 107:1333.
- Leonardi A, Borghesan F, Avarello A, et al. Effect of lodoxamide and disodium cromoglycate on tear eosinophil cationic protein in vernal keratoconjunctivitis. Br J Ophthalmol 1997; 81:23.
- Mantelli F, Santos MS, Petitti T, et al. Systematic review and meta-analysis of randomised clinical trials on topical treatments for vernal keratoconjunctivitis. Br J Ophthalmol 2007; 91:1656.
- Alexander M. Comparative therapeutic studies with Tilavist. Allergy 1995; 50:23.
- Kosrirukvongs P, Vichyanond P, Wongsawad W. Vernal keratoconjunctivitis in Thailand. Asian Pac J Allergy Immunol 2003; 21:25.
- Bonini S, Coassin M, Aronni S, Lambiase A. Vernal keratoconjunctivitis. Eye (Lond) 2004; 18:345.
- López-Piedrahita E, Sánchez-Caraballo JM, Ramírez-Girado RH, Cardona-Villa R. [Effectiveness of allergen immunotherapy in patients with vernal keratoconjuctivitis]. Rev Alerg Mex 2013; 60:11.
- Miyazaki D, Tominaga T, Kakimaru-Hasegawa A, et al. Therapeutic effects of tacrolimus ointment for refractory ocular surface inflammatory diseases. Ophthalmology 2008; 115:988.
- Vichyanond P, Tantimongkolsuk C, Dumrongkigchaiporn P, et al. Vernal keratoconjunctivitis: Result of a novel therapy with 0.1% topical ophthalmic FK-506 ointment. J Allergy Clin Immunol 2004; 113:355.
- Bleik JH, Tabbara KF. Topical cyclosporine in vernal keratoconjunctivitis. Ophthalmology 1991; 98:1679.
- Pucci N, Novembre E, Cianferoni A, et al. Efficacy and safety of cyclosporine eyedrops in vernal keratoconjunctivitis. Ann Allergy Asthma Immunol 2002; 89:298.
- Secchi AG, Tognon MS, Leonardi A. Topical use of cyclosporine in the treatment of vernal keratoconjunctivitis. Am J Ophthalmol 1990; 110:641.
- Holland EJ, Olsen TW, Ketcham JM, et al. Topical cyclosporin A in the treatment of anterior segment inflammatory disease. Cornea 1993; 12:413.
- Tomida I, Schlote T, Bräuning J, et al. [Cyclosporin A 2% eyedrops in therapy of atopic and vernal keratoconjunctivitis]. Ophthalmologe 2002; 99:761.
- Avunduk AM, Avunduk MC, Erdöl H, et al. Cyclosporine effects on clinical findings and impression cytology specimens in severe vernal keratoconjunctivitis. Ophthalmologica 2001; 215:290.
- Keklikci U, Soker SI, Sakalar YB, et al. Efficacy of topical cyclosporin A 0.05% in conjunctival impression cytology specimens and clinical findings of severe vernal keratoconjunctivitis in children. Jpn J Ophthalmol 2008; 52:357.
- Daniell M, Constantinou M, Vu HT, Taylor HR. Randomised controlled trial of topical ciclosporin A in steroid dependent allergic conjunctivitis. Br J Ophthalmol 2006; 90:461.
- Tesse R, Spadavecchia L, Fanelli P, et al. Treatment of severe vernal keratoconjunctivitis with 1% topical cyclosporine in an Italian cohort of 197 children. Pediatr Allergy Immunol 2010; 21:330.
- Lambiase A, Leonardi A, Sacchetti M, et al. Topical cyclosporine prevents seasonal recurrences of vernal keratoconjunctivitis in a randomized, double-masked, controlled 2-year study. J Allergy Clin Immunol 2011; 128:896.
- Pucci N, Caputo R, di Grande L, et al. Tacrolimus vs. cyclosporine eyedrops in severe cyclosporine-resistant vernal keratoconjunctivitis: A randomized, comparative, double-blind, crossover study. Pediatr Allergy Immunol 2015; 26:256.
- Gedik S, Akova YA, Gür S. Secondary bacterial keratitis associated with shield ulcer caused by vernal conjunctivitis. Cornea 2006; 25:974.
- Ozbek Z, Burakgazi AZ, Rapuano CJ. Rapid healing of vernal shield ulcer after surgical debridement: A case report. Cornea 2006; 25:472.
- Solomon A, Zamir E, Levartovsky S, Frucht-Pery J. Surgical management of corneal plaques in vernal keratoconjunctivitis: a clinicopathologic study. Cornea 2004; 23:608.
- Cetinkaya A, Akova YA, Dursun D, Pelit A. Topical cyclosporine in the management of shield ulcers. Cornea 2004; 23:194.
- Sharma A, Gupta R, Ram J, Gupta A. Topical ketorolac 0.5% solution for the treatment of vernal keratoconjunctivitis. Indian J Ophthalmol 1997; 45:177.
- Kosrirukvongs P, Luengchaichawange C. Topical cyclosporine 0.5 per cent and preservative-free ketorolac tromethamine 0.5 per cent in vernal keratoconjunctivitis. J Med Assoc Thai 2004; 87:190.
- Uchio E, Itoh Y, Kadonosono K. Topical bromfenac sodium for long-term management of vernal keratoconjunctivitis. Ophthalmologica 2007; 221:153.
- D'Angelo G, Lambiase A, Cortes M, et al. Preservative-free diclofenac sodium 0.1% for vernal keratoconjunctivitis. Graefes Arch Clin Exp Ophthalmol 2003; 241:192.
- Sud RN, Greval RS, Bajwa RS. Topical flurbiprofen therapy in vernal keratoconjunctivitis. Indian J Med Sci 1995; 49:205.
- Gupta S, Khurana AK, Ahluwalia BK, Gupta NC. Topical indomethacin for vernal keratoconjunctivitis. Acta Ophthalmol (Copenh) 1991; 69:95.
- Occasi F, Duse M, Nebbioso M, et al. Vernal keratoconjunctivitis treated with omalizumab: A case series. Pediatr Allergy Immunol 2017; 28:503.
- Sanchez J, Cardona R. An option in vernal keratoconjunctivitis? Allergol Immunopathol (Madr) 2012; 40:19.
- de Klerk TA, Sharma V, Arkwright PD, Biswas S. Severe vernal keratoconjunctivitis successfully treated with subcutaneous omalizumab. J AAPOS 2013; 17:305.
- Occasi F, Zicari AM, Petrarca L, et al. Vernal Keratoconjunctivitis and immune-mediated diseases: One unique way to symptom control? Pediatr Allergy Immunol 2015; 26:289.
- Heffler E, Picardi G, Liuzzo MT, et al. Omalizumab Treatment of Vernal Keratoconjunctivitis. JAMA Ophthalmol 2016; 134:461.
- CLINICAL MANIFESTATIONS
- DIFFERENTIAL DIAGNOSIS
- Basic eye care and avoidance of triggers
- Initial topical therapy
- Add-on initial therapy for moderate to severe disease
- Treatment of refractory disease
- - Topical corticosteroids
- - Allergen immunotherapy
- - Calcineurin inhibitors
- Topical cyclosporine
- Topical tacrolimus
- Systemic cyclosporine
- Treatment for subsequent seasons
- Treatment of corneal shield ulcers
- Additional agents
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS