Peripheral Ulcerative Keratitis: Clinical Characteristics, Differential Diagnoses and Therapeutic Concepts

Abstract

Peripheral ulcerative keratitis (PUK) is an inflammatory disease of the peripheral cornea, which may frequently be associated with several rare, but potentially life-threatening systemic diseases. The inflammatory pathogenesis of PUK results from humoral and cell-mediated inflammation. The diagnosis is usually based on the typical clinical findings and always requires detailed diagnostic testing to identify a potential systemic underlying disease. Treatment includes topical and systemic immunosuppressive and immunomodulatory therapeutic strategies and, in the event of impending or existing perforation, also various surgical interventions. PUK is a potentially blinding disease that initially affects the periphery, but, if left untreated, can lead to destruction of the entire cornea. Interdisciplinary diagnostic testing and therapy are crucial to preserve vision in the affected patients and reduce morbidity and mortality. The following article provides an overview of the pathophysiology, clinical findings, possible underlying systemic diseases, relevant differential diagnoses and therapeutic strategies.

Keywords

keratitis - peripheral ulcerative keratitis - PUK

Publication History

Received: 22 November 2023

Accepted: 14 March 2024

Article published online:
22 May 2024

• References/Literatur

• 1 Sura AA, McCallum RM. Peripheral ulcerative keratitis due to systemic diseases. Curr Opin Ophthalmol 2022; 33: 543-550 DOI: 10.1097/ICU.0000000000000895.
• 2 Gupta Y, Kishore A, Kumari P. et al. Peripheral ulcerative keratitis. Surv Ophthalmol 2021; 66: 977-998 DOI: 10.1016/j.survophthal.2021.02.013.
• 3 Fu L, Jones S. Peripheral Ulcerative Keratitis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023
• 4 McKibbin M, Isaacs JD, Morrell AJ. Incidence of corneal melting in association with systemic disease in the Yorkshire Region, 1995–7. Br J Ophthalmol 1999; 83: 941-943 DOI: 10.1136/bjo.83.8.941.
• 5 Sainz de la Maza M, Foster CS, Jabbur NS. et al. Ocular characteristics and disease associations in scleritis-associated peripheral keratopathy. Arch Ophthalmol 2002; 120: 15-19 DOI: 10.1001/archopht.120.1.15.
• 6 Timlin HM, Hall HN, Foot B. et al. Corneal perforation from peripheral ulcerative keratopathy in patients with rheumatoid arthritis: epidemiological findings of the British Ophthalmological Surveillance Unit. Br J Ophthalmol 2018; 102: 1298-1302 DOI: 10.1136/bjophthalmol-2017-310671.
• 7 Sangwan VS, Zafirakis P, Foster CS. Moorenʼs ulcer: current concepts in management. Indian J Ophthalmol 1997; 45: 7-17
• 8 Tauber J, Sainz de la Maza M, Hoang-Xuan T. et al. An analysis of therapeutic decision making regarding immunosuppressive chemotherapy for peripheral ulcerative keratitis. Cornea 1990; 9: 66-73
• 9 Zhou HY, Cao Y, Wu J. et al. Role of corneal collagen fibrils in corneal disorders and related pathological conditions. Int J Ophthalmol 2017; 10: 803-811 DOI: 10.18240/ijo.2017.05.24.
• 10 Al-Aqaba MA, Dhillon VK, Mohammed I. et al. Corneal nerves in health and disease. Prog Retin Eye Res 2019; 73: 100762 DOI: 10.1016/j.preteyeres.2019.05.003.
• 11 Müller LJ, Marfurt CF, Kruse F. et al. Corneal nerves: structure, contents and function. Exp Eye Res 2003; 76: 521-542 DOI: 10.1016/s0014-4835(03)00050-2.
• 12 Yamagami S, Ebihara N, Usui T. et al. Bone marrow-derived cells in normal human corneal stroma. Arch Ophthalmol 2006; 124: 62-69 DOI: 10.1001/archopht.124.1.62.
• 13 Wolf J, Kammrath Betancor P, Maier P. et al. Transcriptional Profiling Provides New Insights into Organ Culture-Induced Changes in Human Donor Corneas. Int J Mol Sci 2022; 23: 14507 DOI: 10.3390/ijms232314507.
• 14 EyeWiki, American Academy of Ophthalmology. Peripheral Ulcerative Keratitis. Im Internet (Stand: 16.10.2023): https://eyewiki.aao.org/Peripheral_Ulcerative_Keratitis
• 15 Riley GP, Harrall RL, Watson PG. et al. Collagenase (MMP-1) and TIMP-1 in destructive corneal disease associated with rheumatoid arthritis. Eye (Lond) 1995; 9: 703-718 DOI: 10.1038/eye.1995.182.
• 16 Rosman Z, Shoenfeld Y, Zandman-Goddard G. Biologic therapy for autoimmune diseases: an update. BMC Med 2013; 11: 88 DOI: 10.1186/1741-7015-11-88.
• 17 Karampatakis V, Konidaris V, Michailidou M. et al. Peripheral corneal ulceration associated with rheumatoid arthritis. Am J Case Rep 2013; 14: 318-321 DOI: 10.12659/AJCR.883998.
• 18 Hsieh JL, Shiau AL, Lee CH. et al. CD8+ T cell-induced expression of tissue inhibitor of metalloproteinses-1 exacerbated osteoarthritis. Int J Mol Sci 2013; 14: 19951-19970 DOI: 10.3390/ijms141019951.
• 19 Sharma N, Sinha G, Shekhar H. et al. Demographic profile, clinical features and outcome of peripheral ulcerative keratitis: a prospective study. Br J Ophthalmol 2015; 99: 1503-1508 DOI: 10.1136/bjophthalmol-2014-306008.
• 20 Brown SI, Mondino BJ. Therapy of Moorenʼs ulcer. Am J Ophthalmol 1984; 98: 1-6 DOI: 10.1016/0002-9394(84)90179-x.
• 21 Gomes BF, Santhiago MR. Biology of peripheral ulcerative keratitis. Exp Eye Res 2021; 204: 108458 DOI: 10.1016/j.exer.2021.108458.
• 22 Ashar JN, Mathur A, Sangwan VS. Immunosuppression for Moorenʼs ulcer: evaluation of the stepladder approach–topical, oral and intravenous immunosuppressive agents. Br J Ophthalmol 2013; 97: 1391-1394 DOI: 10.1136/bjophthalmol-2012-302627.
• 23 Cao Y, Zhang W, Wu J. et al. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment. J Ophthalmol 2017; 2017: 7298026 DOI: 10.1155/2017/7298026.
• 24 Dominguez-Casas LC, Sánchez-Bilbao L, Calvo-Río V. et al. Biologic therapy in severe and refractory peripheral ulcerative keratitis (PUK). Multicenter study of 34 patients. Semin Arthritis Rheum 2020; 50: 608-615 DOI: 10.1016/j.semarthrit.2020.03.023.
• 25 Clarke D, Sartor L, Do V. et al. Biologics in peripheral ulcerative keratitis. Semin Arthritis Rheum 2023; 63: 152269 DOI: 10.1016/j.semarthrit.2023.152269.
• 26 Hardy S, Hashemi K, Catanese M. et al. Necrotising Scleritis and Peripheral Ulcerative Keratitis Associated with Rheumatoid Arthritis Treated with Rituximab. Klin Monbl Augenheilkd 2017; 234: 567-570 DOI: 10.1055/s-0042-121315.
• 27 Guillevin L, Pagnoux C, Karras A. et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med 2014; 371: 1771-1780 DOI: 10.1056/NEJMoa1404231.
• 28 Fiehn C, Holle J, Iking-Konert C. et al. [S2e guideline: treatment of rheumatoid arthritis with disease-modifying drugs]. Z Rheumatol 2018; 77: 35-53 DOI: 10.1007/s00393-018-0481-y.
• 29 Schirmer JH, Moosig F. [S1 guidelines on diagnostics and treatment of ANCA-associated vasculitis]. Z Rheumatol 2017; 76: 75-76 DOI: 10.1007/s00393-017-0393-2.
• 30 Schirmer JH, Aries PM, de Groot K. et al. [S1 guidelines Diagnostics and treatment of ANCA-associated vasculitis]. Z Rheumatol 2017; 76: 77-104 DOI: 10.1007/s00393-017-0394-1.
• 31 Lal I, Shivanagari SB, Ali MH. et al. Efficacy of conjunctival resection with cyanoacrylate glue application in preventing recurrences of Moorenʼs ulcer. Br J Ophthalmol 2016; 100: 971-975 DOI: 10.1136/bjophthalmol-2015-307350.
• 32 Eberwein P, Reinhard T. [Current and future therapeutic options in limbal stem cell insufficiency]. Klin Monbl Augenheilkd 2012; 229: 1178-1184 DOI: 10.1055/s-0032-1315286.
• 33 Spelsberg H, Sundmacher R. [Amniotic membrane transplantation and high-dose systemic cyclosporin A (Sandimmun optoral) for Moorenʼs ulcer]. Klin Monbl Augenheilkd 2007; 224: 135-139 DOI: 10.1055/s-2006-927400.
• 34 Wiedenmann CJ, Böhringer D, Maier P. et al. Indications, techniques, and graft survival of mini and corneo-scleral tectonic keratoplasties: A retrospective single-center case series. PLoS One 2023; 18: e0289601 DOI: 10.1371/journal.pone.0289601.