Vernal keratoconjunctivitis: state of art and update on treatment

Giulia  Brindisi; Bianca Cinicola; Caterina  Anania; Giovanna  De Castro; Marcella  Nebbioso; Michele  Miraglia del Giudice; Amelia Licari; Carlo Caffarelli; Maria  De Filippo; Fabio Cardinale; Marzia  Duse; Anna Maria  Zicari

doi:10.23750/abm.v92iS7.12419

Vernal keratoconjunctivitis: state of art and update on treatment

Authors

Giulia Brindisi Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy
Bianca Cinicola Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy
Caterina Anania Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy
Giovanna De Castro Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy
Marcella Nebbioso Department of Sense Organs, Sapienza University, Rome, Italy
Michele Miraglia del Giudice Department of Woman, Child and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
Amelia Licari Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy; Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy
Carlo Caffarelli Pediatric Clinic, Department of Medicine and Surgery, Unversity of Parma, Parma, Italy
Maria De Filippo Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy; Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy
Fabio Cardinale Department of Pediatrics, Giovanni XXIII Pediatric Hospital, University of Bari, Bari, Italy
Marzia Duse Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy
Anna Maria Zicari Department of Pediatrics, Giovanni XXIII Pediatric Hospital, University of Bari, Bari, Italy

DOI: https://doi.org/10.23750/abm.v92iS7.12419

Keywords:

Vernal keratocongiuntivitis, children, therapy, omalizumab, cyclosporine A

Abstract

Vernal keratocongiuntivitis (VKC) is a chronic inflammatory disease affecting the ocular conjunctiva and cornea. It is a rare and underestimated pathology, whose missed or delayed diagnosis can lead to the development of serious ocular complications. Moreover, despite VKC symptoms are well known, they can overlap and be mistaken with allergic conjunctivitis. In fact, diagnostic criteria and severity grading are not standardized yet. The pathogenesis of VKC is still controversial and it is difficult to identify a single mechanism underlying the chronic ocular inflammation. Different studies hypothesized both allergies and autoimmune diseases and also oxidative stress contribute significantly to the origin of the disease. However, the unclear pathogenesis and the lack of specific disease biomarkers make treatment a challenge. The standard therapy includes antihistamines, anti-inflammatory and immunosuppressant drugs and novel therapies are currently under investigation. However, considering treatment guidelines and recommendations are not well defined yet, therapy should be personalized on the clinical features of the patient. This paper provides an overview of the VKC and updates on the challenges that need to be addressed in the future to improve the management of the patient with this disease and improve his quality of life.

References

- Leonardi A, Busca F, Motterle L, et al. Case series of 406 vernal keratoconjunctivitis patients: a demographic and epidemi- ological study. Acta Ophthalmol Scand 2006;84: 406–410.

- Ghiglioni DG, Zicari AM, Parisi GF, et al. Vernal keratoconjunctivitis: An update. Eur J Ophthalmol 2021 May 31:11206721211022153. doi: 10.1177/11206721211022153. Epub ahead of print. PMID: 34058899.

- Zicari AM, Capata G, Nebbioso M, et al. Vernal keratoconjunctivitis: an update focused on clinical grading system. Ital J Pediatr 2019;45:64.

- Player U, Leonardi A. Keratoconjunctivitis vernalis. Ophthalmology 2015;112:177–92.

- Yorston D and Gang P. Corneal grafting: what eye care workers need to know. Community Eye Health 2009;22:44–45.

- Jeng BH, Whitcher JP, Margolis TP. Pseudogerontoxon. Clin Exp Ophthalmol 2004;32:433–434.

- Vichyanond P, Parham P, Pleyer U, et al. Vernal kerato- conjunctivitis: a severe allergic eye disease with remodeling changes. Pediatr Allergy Immunol 2014;25:314–322.

- Zicari AM, Zicari A, Nebbioso M, et al. High-mobility group box-1 (HMGB-1) and serum soluble receptor for advanced glycation end products (sRAGE) in children affected by vernal keratoconjunctivitis. Pediatr Allergy Immunol 2014;25:57-63.

- Ge Y, Huang M and Yao YM. Autophagy and proinflammatory cytokines: interactions and clinical implications. Cytokine Growth Factor Rev 2018;43:38–46.

- Zicari AM, Nebbioso M, Lollobrigida V, et al. Vernal keratoconjunctivitis: atopy and autoimmunity. Eur Rev Med Pharmacol Sci 2013;17:1419-1423.

- Occasi F, Zicari AM, Petrarca L, Nebbioso M, Salvatori G, Duse M. Vernal Keratoconjunctivitis and immune-mediated diseases: One unique way to symptom control? Pediatr Allergy Immunol 2015;26:289-291.

- Zicari AM, Mora B, Lollobrigida V, et al. Immunogenetic investigation in vernal keratoconjunctivitis. Pediatr Allergy Immunol 2014;25:508-10.

- Zicari AM, Brindisi G, De Castro G, Lollobrigida V, Nebbioso M, Duse M. Is oxidative stress involved in vernal keratoconjunctivitis? Results from a pilot study in children. Pediatr Allergy Immunol 2020;31 Suppl 26:52-56.

- Leonardi A, Borghesan F, Faggian D, Depaoli M, Secchi AG, Plebani M. Tear and serum soluble leukocyte. Am J Ophtalmol 2000;129:151–8.

- Leonardi A, Sathe S, Bortolotti M, Beaton A, Sack R. Cytokines, matrix metalloproteases, angiogenic and growth factors in tears of normal subjects and vernal keratoconjunctivitis patients. Allergy 2009;64:710-7.

- Bruschi G, Ghiglioni DG, Osnaghi S, et al. Role of ocular cytology in vernal keratoconjunctivitis. Immun Inflamm Dis 2020;8:3–7.

- Gelardi M, Iannuzzi L, Quaranta N. Nasal cytology: practical aspects and clinical relevance. Clin Exp Allergy 2016;46:785–792.

- Esposito S, Fior G, Mori A, et al. An update on the therapeutic approach to vernal keratoconjunctivitis. Paediatr Drugs 2016;18:347–355.

- Leonardi A, Lazzarini D, La Gloria Valerio A, Scalora T, Fregona I. Corneal staining patterns in vernal keratoconjunctivitis: the new VKC-CLEK scoring scale. Br J Ophthalmol 2018;102:1448–1453.

- Spadavecchia L, Fanelli P, Tesse R, et al. Efficacy of 1.25 and 1% topical cyclosporine in the treatment of severe vernal keratoconjunctivitis in childhood. Pediatr Allergy Immunol 2006;17:527–532.

- Gokhale NS. Systematic approach to managing vernal keratoconjunctivitis in clinical practice: severity grading system and a treatment algorithm. Indian J Ophthalmol 2016;64:145–148.

- Bonini S, Sacchetti M, Mantelli F, Lambiase A. Clinical grading of vernal keratoconjunctivitis. Curr Opin Allergy Clin Immunol 2007;7:436–441.

- Shoji J, Inada N, Sawa M. Evaluation of novel scoring system named 5-5-5 exacerbation grading scale for allergic conjunctivitis disease. Allergol Int 2009;58:591–597.

- Bron AJ, Evans VE, Smith JA. Grading of corneal and conjunctival staining in the context of other dry eye tests. Cornea 2003;22:640–650;

- Bron AJ, Argüeso P, Irkec M, et al. Clinical staining of the ocular surface: mechanisms and interpretations. Prog Retin Eye Res 2015;44:36–61.

- Pucci N, Novembre E, Cianferoni A, et al. Efficacy and safety of cyclosporine eyedrops in vernal keratoconjunctivitis. Ann Allergy Asthma Immunol 2002;89:298–303.

- Leonardi A, Borghesan F, Faggian D, Depaoli M, Secchi AG, Plebani M. Tear and serum soluble leukocyte. Am J Ophtalmol 2000;129:151–8.

- Guidera AC, Luchs JI, Udell IJ. Keratitis, ulceration, and perforation associated with topical nonsteroidal anti-inflammatory drugs. Ophthalmology 2001;108:936-44.

- Rasmussen MLR, Schou MG, Bach-Holm D, et al. Comparative efficacy of medical treatments for vernal keratoconjunctivitis in children and young adults: a systematic review with network meta-analyses. Acta Ophthalmol. 2021 Mar 28. doi: 10.1111/aos.14858. Epub ahead of print.

- Nebbioso M, Sacchetti M, Bianchi G, et al. Tear ferning test and pathological effects on ocular surface before and after topical cyclosporine in vernal keratoconjunctivitis patients. J Ophthalmol 2018;2018:1061276.

- Occasi F, Duse M, Nebbioso M, et al. Vernal keratoconjunctivitis treated with omalizumab: A case series. Pediatr Allergy Immunol 2017;28:503–5.

- Manti S, Parisi GF, Papale M, Marseglia GL, Licari A, Leonardi S. Clinical efficacy and safety of omalizumab in conventional treatment-resistant vernal keratoconjunctivitis: Our experience and literature review. Immun Inflamm Dis 2021;9:3-7.