Ocular Disease as a Comorbidity of Atopic Dermatitis
Main Article Content
Keywords
ocular, comorbidities, atopic dermatitis, adverse effects, biologics
Abstract
A variety of ocular disorders are commonly encountered in individuals affected by atopic dermatitis (AD). In addition to commonly observed ocular surface disease (OSD), other comorbid eye disorders seen inherently with AD include infections, keratoconjunctivitis, cataracts, and keratoconus. Some ocular diseases are recognized as potential adverse effects of therapies used to treat AD, especially topical and systemic corticosteroids, and biologic agents that inhibit interleukins (IL) 4 and/or 13. The latter includes dupilumab (IL-4/IL-13), tralokinumab (IL-13), and lebrikizumab (IL-13), all of which may be associated with OSD. This article serves to provide a thorough review of ocular diseases that are comorbidities of AD and/or occur in association with therapies used to treat AD.
References
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9. Achten, R. E. et al. Ocular surface disease is common in moderate-to-severe atopic dermatitis patients. Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol. 52, 801–805 (2022).
10. Valeille, A. et al. Comprehensive Ophthalmological Evaluation in Atopic Dermatitis. Dermatol. Basel Switz. 240, 434–442 (2024).
11. Achten, R. et al. Dupilumab‐associated ocular surface disease in atopic dermatitis patients: Clinical characteristics, ophthalmic treatment response and conjunctival goblet cell analysis. Allergy 78, 2266–2276 (2023).
12. Bielory, L. Immunobiologicals and ocular surface disease. Curr. Opin. Allergy Clin. Immunol. 22, 314–318 (2022).
13. Feser, A., Plaza, T., Vogelgsang, L. & Mahler, V. Periorbital dermatitis-a recalcitrant disease: causes and differential diagnoses. Br. J. Dermatol. 159, 858–863 (2008).
14. Achten, R. et al. Ocular surface disease in moderate-to-severe atopic dermatitis patients and the effect of biological therapy. Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol. 54, 241–252 (2024).
15. Craig, J. P. et al. TFOS DEWS II Definition and Classification Report. Ocul. Surf. 15, 276–283 (2017).
16. Bielory, B. & Bielory, L. Atopic Dermatitis and Keratoconjunctivitis. Immunol. Allergy Clin. North Am. 30, 323–336 (2010).
17. Guglielmetti, S., Dart, J. K. & Calder, V. Atopic keratoconjunctivitis and atopic dermatitis. Curr. Opin. Allergy Clin. Immunol. 10, 478–485 (2010).
18. Yamamoto, K. et al. Recent trends of ocular complications in patients with atopic dermatitis. Jpn. J. Ophthalmol. 63, 410–416 (2019).
19. Leonardi, A., Righetti, G., Giovannini, G., De Marchi, V. & Occhiuto, M. Diagnostic criteria of chronic conjunctivitis: atopic keratoconjunctivitis and vernal keratoconjunctivitis. Curr. Opin. Allergy Clin. Immunol. 23, 390–396 (2023).
20. Patel, N., Venkateswaran, N., Wang, Z. & Galor, A. Ocular involvement in atopic disease: a review. Curr. Opin. Ophthalmol. 29, 576–581 (2018).
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22. Shi, V. Y. et al. Practical management of ocular surface disease in patients with atopic dermatitis, with a focus on conjunctivitis: A review. J. Am. Acad. Dermatol. 89, 309–315 (2023).
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24. Kaur, K. & Gurnani, B. Vernal Keratoconjunctivitis. in (StatPearls Publishing, Treasure Island (FL), 2024).
25. Feizi, S. et al. Management of corneal complications in vernal keratoconjunctivitis: A review. Ocul. Surf. 19, 282–289 (2021).
26. Ali, A. et al. Management of vernal keratoconjunctivitis: Navigating a changing treatment landscape. Surv. Ophthalmol. 69, 265–278 (2024).
27. Pietruszyńska, M. et al. Ophthalmic manifestations of atopic dermatitis. Postepy Dermatol. Alergol. 37, 174–179 (2020).
28. Santodomingo-Rubido, J. et al. Keratoconus: An updated review. Contact Lens Anterior Eye 45, 101559 (2022).
29. Haeck, I. M., Rouwen, T. J., Timmer-de Mik, L., De Bruin-Weller, M. S. & Bruijnzeel-Koomen, C. A. Topical corticosteroids in atopic dermatitis and the risk of glaucoma and cataracts. J. Am. Acad. Dermatol. 64, 275–281 (2011).
30. Bair, B., Dodd, J., Heidelberg, K. & Krach, K. Cataracts in Atopic Dermatitis: A Case Presentation and Review of the Literature. Arch. Dermatol. 147, 585 (2011).
31. Beck, K. M., Seitzman, G. D., Yang, E. J., Sanchez, I. M. & Liao, W. Ocular Co-Morbidities of Atopic Dermatitis. Part I: Associated Ocular Diseases. Am. J. Clin. Dermatol. 20, 797–805 (2019).
32. Sahni, D., Darley, C. R. & Hawk, J. L. M. Glaucoma induced by periorbital topical steroid use - a rare complication. Clin. Exp. Dermatol. 29, 617–619 (2004).
33. Luan, X., Cui, X., Fan, L., Wang, Z. & Luo, D. No Evidence of Causal Association Between Atopic Dermatitis and Primary Open-Angle Glaucoma: A Bidirectional Two-Sample Mendelian Randomization Study. Dermatitis® 35, 508–512 (2024).
34. Sasoh, M. et al. Incidence of retinal detachment associated with atopic dermatitis in Japan: review of cases from 1992 to 2011. Clin. Ophthalmol. 1129 (2015) doi:10.2147/OPTH.S85020.
35. Lee, Y. et al. Characteristics of retinal detachment associated with atopic dermatitis. BMC Ophthalmol. 21, 359 (2021).
36. Wang, V., Boguniewicz, J., Boguniewicz, M. & Ong, P. Y. The infectious complications of atopic dermatitis. Ann. Allergy Asthma Immunol. Off. Publ. Am. Coll. Allergy Asthma Immunol. 126, 3–12 (2021).
37. Prabriputaloong, T. et al. Atopic Disease and Herpes Simplex Eye Disease: A Population-Based Case-Control Study. Am. J. Ophthalmol. 142, 745-749.e2 (2006).
38. Rezende, R. A. et al. Comparative Study of Ocular Herpes Simplex Virus in Patients With and Without Self-Reported Atopy. Am. J. Ophthalmol. 141, 1120-1125.e1 (2006).
39. Borkar, D. S. et al. Association Between Atopy and Herpetic Eye Disease: Results From the Pacific Ocular Inflammation Study. JAMA Ophthalmol. 132, 326 (2014).
40. Beck, K. M., Seitzman, G. D., Yang, E. J., Sanchez, I. M. & Liao, W. Ocular Co-Morbidities of Atopic Dermatitis. Part II: Ocular Disease Secondary to Treatments. Am. J. Clin. Dermatol. 20, 807–815 (2019).
41. Fachler, T., Shreberk-Hassidim, R. & Molho-Pessach, V. Dupilumab-induced ocular surface disease: A systematic review. J. Am. Acad. Dermatol. 86, 486–487 (2022).
42. Silverberg, J. I. et al. Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. N. Engl. J. Med. 388, 1080–1091 (2023).
43. Wollenberg, A. et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br. J. Dermatol. 184, 437–449 (2021).
44. Chu, A. W. L. et al. Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials. J. Allergy Clin. Immunol. 152, 1470–1492 (2023).
45. Adam, D. N. et al. Expert consensus on the systemic treatment of atopic dermatitis in special populations. J. Eur. Acad. Dermatol. Venereol. JEADV 37, 1135–1148 (2023).
46. Renfro, L. & Snow, J. S. Ocular Effects of Topical and Systemic Steroids. Dermatol. Clin. 10, 505–512 (1992).
47. Touhouche, A. T. et al. Incidence and risk factors for dupilumab associated ocular adverse events: a real‐life prospective study. J. Eur. Acad. Dermatol. Venereol. 35, 172–179 (2021).
48. Ardern-Jones, M. R. et al. An expert consensus on managing dupilumab-related ocular surface disorders in people with atopic dermatitis 2024. Br. J. Dermatol. ljae344 (2024) doi:10.1093/bjd/ljae344.
49. Thyssen, J. P. et al. Management of Ocular Manifestations of Atopic Dermatitis: A Consensus Meeting Using a Modified Delphi Process. Acta Derm. Venereol. 100, adv00264 (2020).
50. Shim, S., Kim, J. S., Yee, J. & Gwak, H. S. A risk-scoring system to predict dupilumab-associated ocular surface disease in patients with atopic dermatitis. Front. Pharmacol. 15, 1425550 (2024).
51. Achten, R. et al. Long-term follow-up and treatment outcomes of conjunctivitis during dupilumab treatment in patients with moderate-to-severe atopic dermatitis. J. Allergy Clin. Immunol. Pract. 9, 1389-1392.e2 (2021).
52. Calabrese, G. et al. Dupilumab and conjunctivitis: a case series of twenty patients. J. Eur. Acad. Dermatol. Venereol. JEADV 35, e612–e614 (2021).
53. Beck, L. A. et al. Dupilumab Provides Acceptable Safety and Sustained Efficacy for up to 4 Years in an Open-Label Study of Adults with Moderate-to-Severe Atopic Dermatitis. Am. J. Clin. Dermatol. 23, 393–408 (2022).
54. Licata, G. et al. Efficacy and safeness of tralokinumab in patients with atopic dermatitis who developed conjunctivitis under dupilumab: A case series. J. Eur. Acad. Dermatol. Venereol. 37, (2023).
55. Shi, V. Y. et al. Phase 3 efficacy and safety of abrocitinib in adults with moderate-to-severe atopic dermatitis after switching from dupilumab (JADE EXTEND). J. Am. Acad. Dermatol. 87, 351–358 (2022).
2. Chiesa Fuxench, Z. C. et al. Atopic Dermatitis in America Study: A Cross-Sectional Study Examining the Prevalence and Disease Burden of Atopic Dermatitis in the US Adult Population. J. Invest. Dermatol. 139, 583–590 (2019).
3. Thyssen, J. P., Halling, A.-S., Schmid-Grendelmeier, P., Guttman-Yassky, E. & Silverberg, J. I. Comorbidities of atopic dermatitis—what does the evidence say? J. Allergy Clin. Immunol. 151, 1155–1162 (2023).
4. Mocanu, M. et al. Atopic Dermatitis-Beyond the Skin. Diagn. Basel Switz. 11, 1553 (2021).
5. Eichenfield, L. F. et al. Current guidelines for the evaluation and management of atopic dermatitis: A comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines. J. Allergy Clin. Immunol. 139, S49–S57 (2017).
6. Narla, S. & Silverberg, J. I. Association between atopic dermatitis and autoimmune disorders in US adults and children: A cross-sectional study. J. Am. Acad. Dermatol. 80, 382–389 (2019).
7. Brunner, P. M. et al. Increasing comorbidities suggest that atopic dermatitis is a systemic disorder. J. Invest. Dermatol. 137, 18–25 (2017).
8. Carmi, E. et al. Ocular complications of atopic dermatitis in children. Acta Derm. Venereol. 86, 515–517 (2006).
9. Achten, R. E. et al. Ocular surface disease is common in moderate-to-severe atopic dermatitis patients. Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol. 52, 801–805 (2022).
10. Valeille, A. et al. Comprehensive Ophthalmological Evaluation in Atopic Dermatitis. Dermatol. Basel Switz. 240, 434–442 (2024).
11. Achten, R. et al. Dupilumab‐associated ocular surface disease in atopic dermatitis patients: Clinical characteristics, ophthalmic treatment response and conjunctival goblet cell analysis. Allergy 78, 2266–2276 (2023).
12. Bielory, L. Immunobiologicals and ocular surface disease. Curr. Opin. Allergy Clin. Immunol. 22, 314–318 (2022).
13. Feser, A., Plaza, T., Vogelgsang, L. & Mahler, V. Periorbital dermatitis-a recalcitrant disease: causes and differential diagnoses. Br. J. Dermatol. 159, 858–863 (2008).
14. Achten, R. et al. Ocular surface disease in moderate-to-severe atopic dermatitis patients and the effect of biological therapy. Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol. 54, 241–252 (2024).
15. Craig, J. P. et al. TFOS DEWS II Definition and Classification Report. Ocul. Surf. 15, 276–283 (2017).
16. Bielory, B. & Bielory, L. Atopic Dermatitis and Keratoconjunctivitis. Immunol. Allergy Clin. North Am. 30, 323–336 (2010).
17. Guglielmetti, S., Dart, J. K. & Calder, V. Atopic keratoconjunctivitis and atopic dermatitis. Curr. Opin. Allergy Clin. Immunol. 10, 478–485 (2010).
18. Yamamoto, K. et al. Recent trends of ocular complications in patients with atopic dermatitis. Jpn. J. Ophthalmol. 63, 410–416 (2019).
19. Leonardi, A., Righetti, G., Giovannini, G., De Marchi, V. & Occhiuto, M. Diagnostic criteria of chronic conjunctivitis: atopic keratoconjunctivitis and vernal keratoconjunctivitis. Curr. Opin. Allergy Clin. Immunol. 23, 390–396 (2023).
20. Patel, N., Venkateswaran, N., Wang, Z. & Galor, A. Ocular involvement in atopic disease: a review. Curr. Opin. Ophthalmol. 29, 576–581 (2018).
21. Hsu, J. I., Pflugfelder, S. C. & Kim, S. J. Ocular complications of atopic dermatitis. Cutis 104, 189–193 (2019).
22. Shi, V. Y. et al. Practical management of ocular surface disease in patients with atopic dermatitis, with a focus on conjunctivitis: A review. J. Am. Acad. Dermatol. 89, 309–315 (2023).
23. Larsen, A. C. & Rasmussen, M. L. R. A Patient-Centered Approach to Vernal Keratoconjunctivitis (VKC): A Podcast. Ophthalmol. Ther. 13, 1061–1069 (2024).
24. Kaur, K. & Gurnani, B. Vernal Keratoconjunctivitis. in (StatPearls Publishing, Treasure Island (FL), 2024).
25. Feizi, S. et al. Management of corneal complications in vernal keratoconjunctivitis: A review. Ocul. Surf. 19, 282–289 (2021).
26. Ali, A. et al. Management of vernal keratoconjunctivitis: Navigating a changing treatment landscape. Surv. Ophthalmol. 69, 265–278 (2024).
27. Pietruszyńska, M. et al. Ophthalmic manifestations of atopic dermatitis. Postepy Dermatol. Alergol. 37, 174–179 (2020).
28. Santodomingo-Rubido, J. et al. Keratoconus: An updated review. Contact Lens Anterior Eye 45, 101559 (2022).
29. Haeck, I. M., Rouwen, T. J., Timmer-de Mik, L., De Bruin-Weller, M. S. & Bruijnzeel-Koomen, C. A. Topical corticosteroids in atopic dermatitis and the risk of glaucoma and cataracts. J. Am. Acad. Dermatol. 64, 275–281 (2011).
30. Bair, B., Dodd, J., Heidelberg, K. & Krach, K. Cataracts in Atopic Dermatitis: A Case Presentation and Review of the Literature. Arch. Dermatol. 147, 585 (2011).
31. Beck, K. M., Seitzman, G. D., Yang, E. J., Sanchez, I. M. & Liao, W. Ocular Co-Morbidities of Atopic Dermatitis. Part I: Associated Ocular Diseases. Am. J. Clin. Dermatol. 20, 797–805 (2019).
32. Sahni, D., Darley, C. R. & Hawk, J. L. M. Glaucoma induced by periorbital topical steroid use - a rare complication. Clin. Exp. Dermatol. 29, 617–619 (2004).
33. Luan, X., Cui, X., Fan, L., Wang, Z. & Luo, D. No Evidence of Causal Association Between Atopic Dermatitis and Primary Open-Angle Glaucoma: A Bidirectional Two-Sample Mendelian Randomization Study. Dermatitis® 35, 508–512 (2024).
34. Sasoh, M. et al. Incidence of retinal detachment associated with atopic dermatitis in Japan: review of cases from 1992 to 2011. Clin. Ophthalmol. 1129 (2015) doi:10.2147/OPTH.S85020.
35. Lee, Y. et al. Characteristics of retinal detachment associated with atopic dermatitis. BMC Ophthalmol. 21, 359 (2021).
36. Wang, V., Boguniewicz, J., Boguniewicz, M. & Ong, P. Y. The infectious complications of atopic dermatitis. Ann. Allergy Asthma Immunol. Off. Publ. Am. Coll. Allergy Asthma Immunol. 126, 3–12 (2021).
37. Prabriputaloong, T. et al. Atopic Disease and Herpes Simplex Eye Disease: A Population-Based Case-Control Study. Am. J. Ophthalmol. 142, 745-749.e2 (2006).
38. Rezende, R. A. et al. Comparative Study of Ocular Herpes Simplex Virus in Patients With and Without Self-Reported Atopy. Am. J. Ophthalmol. 141, 1120-1125.e1 (2006).
39. Borkar, D. S. et al. Association Between Atopy and Herpetic Eye Disease: Results From the Pacific Ocular Inflammation Study. JAMA Ophthalmol. 132, 326 (2014).
40. Beck, K. M., Seitzman, G. D., Yang, E. J., Sanchez, I. M. & Liao, W. Ocular Co-Morbidities of Atopic Dermatitis. Part II: Ocular Disease Secondary to Treatments. Am. J. Clin. Dermatol. 20, 807–815 (2019).
41. Fachler, T., Shreberk-Hassidim, R. & Molho-Pessach, V. Dupilumab-induced ocular surface disease: A systematic review. J. Am. Acad. Dermatol. 86, 486–487 (2022).
42. Silverberg, J. I. et al. Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis. N. Engl. J. Med. 388, 1080–1091 (2023).
43. Wollenberg, A. et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br. J. Dermatol. 184, 437–449 (2021).
44. Chu, A. W. L. et al. Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials. J. Allergy Clin. Immunol. 152, 1470–1492 (2023).
45. Adam, D. N. et al. Expert consensus on the systemic treatment of atopic dermatitis in special populations. J. Eur. Acad. Dermatol. Venereol. JEADV 37, 1135–1148 (2023).
46. Renfro, L. & Snow, J. S. Ocular Effects of Topical and Systemic Steroids. Dermatol. Clin. 10, 505–512 (1992).
47. Touhouche, A. T. et al. Incidence and risk factors for dupilumab associated ocular adverse events: a real‐life prospective study. J. Eur. Acad. Dermatol. Venereol. 35, 172–179 (2021).
48. Ardern-Jones, M. R. et al. An expert consensus on managing dupilumab-related ocular surface disorders in people with atopic dermatitis 2024. Br. J. Dermatol. ljae344 (2024) doi:10.1093/bjd/ljae344.
49. Thyssen, J. P. et al. Management of Ocular Manifestations of Atopic Dermatitis: A Consensus Meeting Using a Modified Delphi Process. Acta Derm. Venereol. 100, adv00264 (2020).
50. Shim, S., Kim, J. S., Yee, J. & Gwak, H. S. A risk-scoring system to predict dupilumab-associated ocular surface disease in patients with atopic dermatitis. Front. Pharmacol. 15, 1425550 (2024).
51. Achten, R. et al. Long-term follow-up and treatment outcomes of conjunctivitis during dupilumab treatment in patients with moderate-to-severe atopic dermatitis. J. Allergy Clin. Immunol. Pract. 9, 1389-1392.e2 (2021).
52. Calabrese, G. et al. Dupilumab and conjunctivitis: a case series of twenty patients. J. Eur. Acad. Dermatol. Venereol. JEADV 35, e612–e614 (2021).
53. Beck, L. A. et al. Dupilumab Provides Acceptable Safety and Sustained Efficacy for up to 4 Years in an Open-Label Study of Adults with Moderate-to-Severe Atopic Dermatitis. Am. J. Clin. Dermatol. 23, 393–408 (2022).
54. Licata, G. et al. Efficacy and safeness of tralokinumab in patients with atopic dermatitis who developed conjunctivitis under dupilumab: A case series. J. Eur. Acad. Dermatol. Venereol. 37, (2023).
55. Shi, V. Y. et al. Phase 3 efficacy and safety of abrocitinib in adults with moderate-to-severe atopic dermatitis after switching from dupilumab (JADE EXTEND). J. Am. Acad. Dermatol. 87, 351–358 (2022).
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Mar 17, 2025
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[1]
Tottori, K., Tottori, D. and Del Rosso, J. 2025. Ocular Disease as a Comorbidity of Atopic Dermatitis. SKIN The Journal of Cutaneous Medicine. 9, 2 (Mar. 2025), 2162–2174. DOI:https://doi.org/10.25251/skin.9.2.2.
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