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Mooren's ulcer

January 01, 1970

Mooren's ulcer is a rare idiopathic ocular disorder that may lead to blindness due to progressive destruction of the peripheral cornea. Although the etiology of Mooren's ulcer is poorly understood, recent evidence suggests that the pathogenesis of this disease appears to be the result of an autoimmune process directed against molecules expressed in the corneal stroma.[1]

Mooren's ulcer is also defined as a special and the most common type of peripheral ulcerative keratitis (PUK).

Signs and symptoms edit

Symptoms of Mooren's ulcer can include:[1]

  • Pain in the affected eye(s)
  • Redness of the affected eye(s)
  • Progressive ulceration of the cornea
  • Blurred vision
  • Photophobia
  • Tearing

Some epidemiological studies have noted that men tend to be affected more than women.[2][3]

Classification edit

The most commonly used classification was proposed by Watson in 1997. He divided the disease into three types based on the clinical picture:[4]

  • Unilateral Mooren's ulceration is characterized by extremely painful progressive ulceration of the cornea in one eye. This form is more common in elderly patients.
  • Bilateral aggressive Mooren's ulceration which is observed more often in young patients and progresses along the entire circumference, then captures the central area of the cornea.
  • Bilateral indolent Mooren's ulceration (BIM) usually occurs in middle-aged patients and manifested by a progressive peripheral corneal guttering in both eyes.

Risk factors edit

Several risk factors affecting the development of Mooren's ulcer have been suggested.[citation needed]

Corneal trauma edit

Previous ocular trauma or infection can cause disruption of the corneal integrity resulting in the expression of tissue-specific antigens that are normally hidden from the immune system. It may lead to an increased risk of a sensitization to corneal antigens and an autoimmune reaction against antigens expressed in corneal tissues.

HLA association edit

Like most autoimmune diseases, Mooren's ulcer is thought to be associated with specific HLA haplotypes. In some studies, HLA-DR17 and HLA-DQ2 have been found in increased frequencies in affected patients compared to healthy controls. These results propose a possible association between HLA and Mooren's ulcer.[5]

Pathology edit

The precise pathophysiological mechanism of Mooren's ulcer remains unclear, but most data suggest that both cell-mediated immunity and humoral immunity are involved in the pathogenesis of the disease.[6]

Reduces numbers of suppressor T cells have been found in peripheral blood from patients with Mooren's ulcer. This deficit in systematic immunoregulatory mechanism may lead to loss of a control over autoreactive T and B cells and contributes to disease pathogenesis.[7]

Immunohistochemical studies in patients suffered from Mooren's ulcer showed massive infiltration of multiple types of inflammatory cells in the conjunctival tissue.

The cell types in the inflammatory lesion includes CD4+ and CD8+ T-lymphocytes, B-lymphocytes, macrophages, a small amount of neutrophils was also observed in the conjunctiva from patients with Mooren's ulcer.[6][8][9]

In addition, circulating IgG antibodies with specificity for corneal and conjunctival antigens have been isolated from patients with Mooren’s ulcer.[10] Gottsch and colleagues have suggested that calgranulin C, a protein expressed in the corneal stroma, may be a possible main target for autoimmune response causing Mooren’s ulcer.[11]

Also, significantly increased expression levels of adhesion and co-stimulatory molecules have been found in ocular tissues affected by Mooren's ulcer compared to healthy eyes. Upregulation of adhesion molecules allows leukocyte migration into inflamed tissues. Co-stimulatory molecules may contribute to sustained local immune activation. Therefore, blockage of these molecules suppose to be a protentional therapeutic strategy for suppressing the inflammatory progression.[9]

Elevated levels of proteases and collagenases which damage the corneal stroma have also been found in affected conjunctival tissues.[12]

Diagnosis edit

In view of rarity and limited knowledge of the etiology of Mooren’s ulcer, the diagnosis of the disease is complicated. The absence of any systematic disorders which can lead to peripheral corneal ulceration supports the diagnosis of Mooren’s ulcer. To diagnose Mooren’s ulcer, it is necessary to rule out other forms of non-infectious peripheral ulcerative keratitis.[3]

Treatment edit

Medical treatment edit

Topical corticosteroids are usually used as first line of therapy. Severe cases require administration of systemic immunosuppressive agents. The more commonly used drugs are cyclosporine A, methotrexate and cyclophosphamide.

Several case reports showed that biological agents, such as anti-tumor necrosis factor alpha (anti-TNF) or monoclonal antibodies against CD20, also can be used as an effective treatment of progressive Mooren’s ulceration.[13][14]

Surgical treatment edit

If patients do not respond to medication, surgical intervention must be performed. Conjunctival excision has been shown to be an effective method. The principle of this surgery is based on the removal of unhealthy limbal conjunctiva adjacent to the ulcer. slow down the disease progression due to eliminating the local source of inflammatory cells, mediators and enzymes which cause the tissue damage.[15]

Another surgical treatment option which has been successfully used as a treatment for Mooren’s ulcer is Amniotic Membrane Transplantation (AMT). This method consists of applying a piece of amniotic membrane to the ocular surface. Amniotic membrane patches are prepared from placental tissues from women who had a planned cesarean sections. AMT appears to be a useful therapy which results with stabilization of the ulcer progression and corneal epithelial defect healing.[16] It is most likely, that amniotic membrane used as an ocular graft stop the inflammation process because of the expression of immunoregulatory molecules, including Fas ligand and HLA–G antigens. In addition, the amniotic membrane contains a large number of collagens, growth factors and protease inhibitors which can promote healing and reconstruction of the conjunctival epithelium.[17]

Other surgical interventions such as lamellar keratectomy, keratoepithelioplasty and corneal transplantation have also been reported as effective treatment options for Mooren’s ulcer.

References edit

  1. ^ a b Zelefsky, Joseph R; Srinivasan, Muthiah; Cunningham, Emmett T (August 2011). "Mooren's ulcer". Expert Review of Ophthalmology. 6 (4): 461–467. doi:10.1586/eop.11.46. ISSN 1746-9899. S2CID 29415711.
  2. ^ Dong, Yanling; Zhang, Yangyang; Xie, Lixin; Ren, Jianmei (February 2017). "Risk Factors, Clinical Features, and Treatment Outcomes of Recurrent Mooren Ulcers in China". Cornea. 36 (2): 202–209. doi:10.1097/ico.0000000000001084. ISSN 0277-3740. PMID 28060068. S2CID 13508732.
  3. ^ a b Srinivasan, M.; Zegans, M. E; Zelefsky, J. R; Kundu, A.; Lietman, T.; Whitcher, J. P; Cunningham, E. T (2006-10-11). "Clinical characteristics of Mooren's ulcer in South India". British Journal of Ophthalmology. 91 (5): 570–575. doi:10.1136/bjo.2006.105452. ISSN 0007-1161. PMC 1954782. PMID 17035269.
  4. ^ Watson, P G (May 1997). "Management of Mooren's ulceration". Eye. 11 (3): 349–356. doi:10.1038/eye.1997.74. ISSN 0950-222X. PMID 9373475. S2CID 12163492.
  5. ^ Taylor, Craig J.; Smith, Sheila I.; Morgan, Catherine H.; Stephenson, Susan F.; Key, Tim; Srinivasan, M.; Cunningham, Emmett; Watson, Peter G. (2000-01-01). "HLA and Mooren's ulceration". British Journal of Ophthalmology. 84 (1): 72–75. doi:10.1136/bjo.84.1.72. ISSN 0007-1161. PMC 1723219. PMID 10611103.
  6. ^ a b Lee, Hyun Ju; Kim, Mee Kum; Wee, Won Ryang; Oh, Joo Youn (September 2015). "Interplay of Immune Cells in Mooren Ulcer". Cornea. 34 (9): 1164–1167. doi:10.1097/ICO.0000000000000471. ISSN 0277-3740. PMID 25970436. S2CID 30578961.
  7. ^ Murray, P. I.; Rahi, A. H. (March 1984). "Pathogenesis of Mooren's ulcer: some new concepts". The British Journal of Ophthalmology. 68 (3): 182–187. doi:10.1136/bjo.68.3.182. ISSN 0007-1161. PMC 1040283. PMID 6230102.
  8. ^ Shinomiya, Katsuhiko; Ueta, Mayumi; Sotozono, Chie; Inatomi, Tsutomu; Yokoi, Norihiko; Koizumi, Noriko; Kinoshita, Shigeru (2013-03-01). "Immunohistochemical analysis of inflammatory limbal conjunctiva adjacent to Mooren's ulcer". British Journal of Ophthalmology. 97 (3): 362–366. doi:10.1136/bjophthalmol-2012-302631. ISSN 0007-1161. PMID 23292924. S2CID 7491218.
  9. ^ a b Kafkala, Chrysanthi; Choi, John; Zafirakis, Panayotis; Baltatzis, Stefanos; Livir-Rallatos, Charalampos; Rojas, Blanca; Foster, C. Stephen (July 2006). "Mooren Ulcer: An Immunopathologic Study". Cornea. 25 (6): 667–673. doi:10.1097/01.ico.0000214216.75496.7e. ISSN 0277-3740. PMID 17077658. S2CID 1948763.
  10. ^ Gottsch, John D.; Liu, Sammy H.; Stark, Walter J. (April 1992). "Mooren's Ulcer and Evidence of Stromal Graft Rejection After Penetrating Keratoplasty". American Journal of Ophthalmology. 113 (4): 412–417. doi:10.1016/s0002-9394(14)76164-1. ISSN 0002-9394. PMID 1558115.
  11. ^ Gottsch, J. D.; Li, Q.; Ashraf, F.; O'Brien, T. P.; Stark, W. J.; Liu, S. H. (1999-04-01). "Cytokine-Induced Calgranulin C Expression in Keratocytes". Clinical Immunology. 91 (1): 34–40. doi:10.1006/clim.1998.4681. ISSN 1521-6616. PMID 10219252.
  12. ^ Brown, S. I. (1975-11-01). "Mooren's ulcer. Histopathology and proteolytic enzymes of adjacent conjunctiva". British Journal of Ophthalmology. 59 (11): 670–674. doi:10.1136/bjo.59.11.670. ISSN 0007-1161. PMC 1017431. PMID 173387.
  13. ^ Xia, Annie; Dietrich-Ntoukas, Tina; Pleyer, Uwe (2022-01-20). "Effect of Anti-TNF Treatment on Mooren's Ulcer: A Case Series and Review of the Literature". Ocular Immunology and Inflammation: 1–7. doi:10.1080/09273948.2021.2023581. ISSN 0927-3948. PMID 35050832. S2CID 246164471.
  14. ^ Guindolet, Damien; Reynaud, Clotilde; Clavel, Gaelle; Belangé, Georges; Benmahmed, Maycene; Doan, Serge; Hayem, Gilles; Cochereau, Isabelle; Gabison, Eric E (2016-07-22). "Management of severe and refractory Mooren's ulcers with rituximab". British Journal of Ophthalmology. 101 (4): 418–422. doi:10.1136/bjophthalmol-2016-308838. ISSN 0007-1161. PMID 27450147. S2CID 206875244.
  15. ^ Kalogeropoulos, Christos D.; Malamou–Mitsi, Vassiliki D.; Aspiotis, Miltiadis B.; Psilas, Konstantinos G. (2004-01-01). "Bilateral Mooren's Ulcer in Six Patients: Diagnosis, Surgery and Histopathology". International Ophthalmology. 25 (1): 1–8. doi:10.1023/B:INTE.0000018510.06715.c9. ISSN 1573-2630. PMID 15085968. S2CID 24410012.
  16. ^ Ngan, Nguyen D; Chau, Hoang TM (July 2011). "Amniotic membrane transplantation for Mooren's ulcer: Amniotic membrane for Mooren's ulcer". Clinical & Experimental Ophthalmology. 39 (5): 386–392. doi:10.1111/j.1442-9071.2010.02479.x. PMID 21176038. S2CID 43523619.
  17. ^ Kubo, Masato; Sonoda, Yasushi; Muramatsu, Ryuji; Usui, Masahiko (2001-06-01). "Immunogenicity of Human Amniotic Membrane in Experimental Xenotransplantation". Investigative Ophthalmology & Visual Science. 42 (7): 1539–1546. ISSN 1552-5783. PMID 11381058.

January 01, 1970
mooren, ulcer, rare, idiopathic, ocular, disorder, that, lead, blindness, progressive, destruction, peripheral, cornea, although, etiology, poorly, understood, recent, evidence, suggests, that, pathogenesis, this, disease, appears, result, autoimmune, process,. Mooren s ulcer is a rare idiopathic ocular disorder that may lead to blindness due to progressive destruction of the peripheral cornea Although the etiology of Mooren s ulcer is poorly understood recent evidence suggests that the pathogenesis of this disease appears to be the result of an autoimmune process directed against molecules expressed in the corneal stroma 1 Mooren s ulcer is also defined as a special and the most common type of peripheral ulcerative keratitis PUK Contents 1 Signs and symptoms 2 Classification 3 Risk factors 3 1 Corneal trauma 3 2 HLA association 4 Pathology 5 Diagnosis 6 Treatment 6 1 Medical treatment 6 2 Surgical treatment 7 ReferencesSigns and symptoms editSymptoms of Mooren s ulcer can include 1 Pain in the affected eye s Redness of the affected eye s Progressive ulceration of the cornea Blurred vision Photophobia Tearing Some epidemiological studies have noted that men tend to be affected more than women 2 3 Classification editThe most commonly used classification was proposed by Watson in 1997 He divided the disease into three types based on the clinical picture 4 Unilateral Mooren s ulceration is characterized by extremely painful progressive ulceration of the cornea in one eye This form is more common in elderly patients Bilateral aggressive Mooren s ulceration which is observed more often in young patients and progresses along the entire circumference then captures the central area of the cornea Bilateral indolent Mooren s ulceration BIM usually occurs in middle aged patients and manifested by a progressive peripheral corneal guttering in both eyes Risk factors editSeveral risk factors affecting the development of Mooren s ulcer have been suggested citation needed Corneal trauma edit Previous ocular trauma or infection can cause disruption of the corneal integrity resulting in the expression of tissue specific antigens that are normally hidden from the immune system It may lead to an increased risk of a sensitization to corneal antigens and an autoimmune reaction against antigens expressed in corneal tissues HLA association edit Like most autoimmune diseases Mooren s ulcer is thought to be associated with specific HLA haplotypes In some studies HLA DR17 and HLA DQ2 have been found in increased frequencies in affected patients compared to healthy controls These results propose a possible association between HLA and Mooren s ulcer 5 Pathology editThe precise pathophysiological mechanism of Mooren s ulcer remains unclear but most data suggest that both cell mediated immunity and humoral immunity are involved in the pathogenesis of the disease 6 Reduces numbers of suppressor T cells have been found in peripheral blood from patients with Mooren s ulcer This deficit in systematic immunoregulatory mechanism may lead to loss of a control over autoreactive T and B cells and contributes to disease pathogenesis 7 Immunohistochemical studies in patients suffered from Mooren s ulcer showed massive infiltration of multiple types of inflammatory cells in the conjunctival tissue The cell types in the inflammatory lesion includes CD4 and CD8 T lymphocytes B lymphocytes macrophages a small amount of neutrophils was also observed in the conjunctiva from patients with Mooren s ulcer 6 8 9 In addition circulating IgG antibodies with specificity for corneal and conjunctival antigens have been isolated from patients with Mooren s ulcer 10 Gottsch and colleagues have suggested that calgranulin C a protein expressed in the corneal stroma may be a possible main target for autoimmune response causing Mooren s ulcer 11 Also significantly increased expression levels of adhesion and co stimulatory molecules have been found in ocular tissues affected by Mooren s ulcer compared to healthy eyes Upregulation of adhesion molecules allows leukocyte migration into inflamed tissues Co stimulatory molecules may contribute to sustained local immune activation Therefore blockage of these molecules suppose to be a protentional therapeutic strategy for suppressing the inflammatory progression 9 Elevated levels of proteases and collagenases which damage the corneal stroma have also been found in affected conjunctival tissues 12 Diagnosis editIn view of rarity and limited knowledge of the etiology of Mooren s ulcer the diagnosis of the disease is complicated The absence of any systematic disorders which can lead to peripheral corneal ulceration supports the diagnosis of Mooren s ulcer To diagnose Mooren s ulcer it is necessary to rule out other forms of non infectious peripheral ulcerative keratitis 3 Treatment editMedical treatment edit Topical corticosteroids are usually used as first line of therapy Severe cases require administration of systemic immunosuppressive agents The more commonly used drugs are cyclosporine A methotrexate and cyclophosphamide Several case reports showed that biological agents such as anti tumor necrosis factor alpha anti TNF or monoclonal antibodies against CD20 also can be used as an effective treatment of progressive Mooren s ulceration 13 14 Surgical treatment edit If patients do not respond to medication surgical intervention must be performed Conjunctival excision has been shown to be an effective method The principle of this surgery is based on the removal of unhealthy limbal conjunctiva adjacent to the ulcer slow down the disease progression due to eliminating the local source of inflammatory cells mediators and enzymes which cause the tissue damage 15 Another surgical treatment option which has been successfully used as a treatment for Mooren s ulcer is Amniotic Membrane Transplantation AMT This method consists of applying a piece of amniotic membrane to the ocular surface Amniotic membrane patches are prepared from placental tissues from women who had a planned cesarean sections AMT appears to be a useful therapy which results with stabilization of the ulcer progression and corneal epithelial defect healing 16 It is most likely that amniotic membrane used as an ocular graft stop the inflammation process because of the expression of immunoregulatory molecules including Fas ligand and HLA G antigens In addition the amniotic membrane contains a large number of collagens growth factors and protease inhibitors which can promote healing and reconstruction of the conjunctival epithelium 17 Other surgical interventions such as lamellar keratectomy keratoepithelioplasty and corneal transplantation have also been reported as effective treatment options for Mooren s ulcer References edit a b Zelefsky Joseph R Srinivasan Muthiah Cunningham Emmett T August 2011 Mooren s ulcer Expert Review of Ophthalmology 6 4 461 467 doi 10 1586 eop 11 46 ISSN 1746 9899 S2CID 29415711 Dong Yanling Zhang Yangyang Xie Lixin Ren Jianmei February 2017 Risk Factors Clinical Features and Treatment Outcomes of Recurrent Mooren Ulcers in China Cornea 36 2 202 209 doi 10 1097 ico 0000000000001084 ISSN 0277 3740 PMID 28060068 S2CID 13508732 a b Srinivasan M Zegans M E Zelefsky J R Kundu A Lietman T Whitcher J P Cunningham E T 2006 10 11 Clinical characteristics of Mooren s ulcer in South India British Journal of Ophthalmology 91 5 570 575 doi 10 1136 bjo 2006 105452 ISSN 0007 1161 PMC 1954782 PMID 17035269 Watson P G May 1997 Management of Mooren s ulceration Eye 11 3 349 356 doi 10 1038 eye 1997 74 ISSN 0950 222X PMID 9373475 S2CID 12163492 Taylor Craig J Smith Sheila I Morgan Catherine H Stephenson Susan F Key Tim Srinivasan M Cunningham Emmett Watson Peter G 2000 01 01 HLA and Mooren s ulceration British Journal of Ophthalmology 84 1 72 75 doi 10 1136 bjo 84 1 72 ISSN 0007 1161 PMC 1723219 PMID 10611103 a b Lee Hyun Ju Kim Mee Kum Wee Won Ryang Oh Joo Youn September 2015 Interplay of Immune Cells in Mooren Ulcer Cornea 34 9 1164 1167 doi 10 1097 ICO 0000000000000471 ISSN 0277 3740 PMID 25970436 S2CID 30578961 Murray P I Rahi A H March 1984 Pathogenesis of Mooren s ulcer some new concepts The British Journal of Ophthalmology 68 3 182 187 doi 10 1136 bjo 68 3 182 ISSN 0007 1161 PMC 1040283 PMID 6230102 Shinomiya Katsuhiko Ueta Mayumi Sotozono Chie Inatomi Tsutomu Yokoi Norihiko Koizumi Noriko Kinoshita Shigeru 2013 03 01 Immunohistochemical analysis of inflammatory limbal conjunctiva adjacent to Mooren s ulcer British Journal of Ophthalmology 97 3 362 366 doi 10 1136 bjophthalmol 2012 302631 ISSN 0007 1161 PMID 23292924 S2CID 7491218 a b Kafkala Chrysanthi Choi John Zafirakis Panayotis Baltatzis Stefanos Livir Rallatos Charalampos Rojas Blanca Foster C Stephen July 2006 Mooren Ulcer An Immunopathologic Study Cornea 25 6 667 673 doi 10 1097 01 ico 0000214216 75496 7e ISSN 0277 3740 PMID 17077658 S2CID 1948763 Gottsch John D Liu Sammy H Stark Walter J April 1992 Mooren s Ulcer and Evidence of Stromal Graft Rejection After Penetrating Keratoplasty American Journal of Ophthalmology 113 4 412 417 doi 10 1016 s0002 9394 14 76164 1 ISSN 0002 9394 PMID 1558115 Gottsch J D Li Q Ashraf F O Brien T P Stark W J Liu S H 1999 04 01 Cytokine Induced Calgranulin C Expression in Keratocytes Clinical Immunology 91 1 34 40 doi 10 1006 clim 1998 4681 ISSN 1521 6616 PMID 10219252 Brown S I 1975 11 01 Mooren s ulcer Histopathology and proteolytic enzymes of adjacent conjunctiva British Journal of Ophthalmology 59 11 670 674 doi 10 1136 bjo 59 11 670 ISSN 0007 1161 PMC 1017431 PMID 173387 Xia Annie Dietrich Ntoukas Tina Pleyer Uwe 2022 01 20 Effect of Anti TNF Treatment on Mooren s Ulcer A Case Series and Review of the Literature Ocular Immunology and Inflammation 1 7 doi 10 1080 09273948 2021 2023581 ISSN 0927 3948 PMID 35050832 S2CID 246164471 Guindolet Damien Reynaud Clotilde Clavel Gaelle Belange Georges Benmahmed Maycene Doan Serge Hayem Gilles Cochereau Isabelle Gabison Eric E 2016 07 22 Management of severe and refractory Mooren s ulcers with rituximab British Journal of Ophthalmology 101 4 418 422 doi 10 1136 bjophthalmol 2016 308838 ISSN 0007 1161 PMID 27450147 S2CID 206875244 Kalogeropoulos Christos D Malamou Mitsi Vassiliki D Aspiotis Miltiadis B Psilas Konstantinos G 2004 01 01 Bilateral Mooren s Ulcer in Six Patients Diagnosis Surgery and Histopathology International Ophthalmology 25 1 1 8 doi 10 1023 B INTE 0000018510 06715 c9 ISSN 1573 2630 PMID 15085968 S2CID 24410012 Ngan Nguyen D Chau Hoang TM July 2011 Amniotic membrane transplantation for Mooren s ulcer Amniotic membrane for Mooren s ulcer Clinical amp Experimental Ophthalmology 39 5 386 392 doi 10 1111 j 1442 9071 2010 02479 x PMID 21176038 S2CID 43523619 Kubo Masato Sonoda Yasushi Muramatsu Ryuji Usui Masahiko 2001 06 01 Immunogenicity of Human Amniotic Membrane in Experimental Xenotransplantation Investigative Ophthalmology amp Visual Science 42 7 1539 1546 ISSN 1552 5783 PMID 11381058 Retrieved from https en wikipedia org w index php title Mooren 27s ulcer amp oldid 1221090503, wikipedia, wiki, book, books, library,

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