Iridoschisis in patients with atopic dermatitis Leads to Intractable Bullous Keratopathy

Iridoschisis in patients with atopic dermatitis Leads to Intractable Bullous Keratopathy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Iridoschisis in patients with atopic dermatitis Leads to Intractable Bullous Keratopathy Yuki Kusano, Takefumi Yamaguchi, Jun Shimazaki, Murat Dogru This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5284476/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background To report iridoschisis in patients with atopic dermatitis and the outcome of repeat corneal transplantations for intractable bullous keratopathy. Case presentation: Three patients with atopic dermatitis, iridoschisis and bullous keratopathy, underwent numerous corneal transplantation procedures including penetrating keratoplasty (PKP), and endothelial keratoplasty (EK), which failed within a short period due to rapid corneal endothelial cell (CEnC) loss without graft rejection. Aqueous humor total protein levels were overwhelmingly higher in all patients. Case1 : A 26-year-old man with atopic dermatitis had iridoschisis and bullous keratopathy in the left eye. During the 10-year follow-up, he underwent six corneal transplantations (three EK, followed by three PKP). However, all grafts failed because of rapid CEnC loss without graft rejection. Case 2 : A 53-year-old man with severe atopic dermatitis had iridoschisis and bullous keratopathy in the right eye. He underwent three corneal transplantations (one EK, followed by two PK) over five years. All grafts failed within short periods due to rapid CEnC loss and endothelial decompensation without graft rejection. Case 3 : A 54-year-old man with severe atopic dermatitis had iridoschisis and bullous keratopathy in the right eye. He underwent two EK within short periods due to rapid CEnC loss. Conclusions We hereby report the association of iridoschisis with bullous keratopathy in atopic dermatitis for the first time in the literature. Clinicians should be aware that the prognosis of corneal transplants in such patients appears to be poor necessitating repeat procedures. atopic dermatitis corneal transplantation bullous keratopathy iridoschisis corneal endothelial cell Figures Figure 1 Figure 2 Background Iridoschisis is a rare condition in which the iris stroma separates into two layers. It is mostly seen in the inferior iris in elderly people and is usually associated with angle-closure glaucoma, nanophthalmos, ocular trauma, atopic dermatitis, syphilitic interstitial keratitis, lens subluxation, keratoconus, and bullous keratopathy. 1 , 2 The cause and prognosis of iridoschisis remain largely unknown. A recent study showed that pathological alterations of the aqueous humor (AqH) in eyes with iris abnormalities increases early graft failure risk due to rapid corneal endothelial cell (CEnC) loss. 3 Management of the eyes with iridocorneal endothelial (ICE) syndrome and iridoschisis is particularly challenging because of the progression of peripheral anterior synechiae (PAS), intraocular pressure (IOP) elevation and endothelial decompensation, necessitating repeat keratoplasties. 4 , 5 Herein, we report three cases with atopic dermatitis, iridoschisis and intractable bullous keratopathy, in which corneal grafts failed due to rapid CEnC loss without graft rejection. Case presentations We documented three patients with atopic dermatitis who had iridoschisis and intractable bullous keratopathy, ending up with iris atrophy, repeated corneal graft failures and poor prognosis after corneal transplantation. Case 1 A 26-year-old man with atopic dermatitis suffered retinal detachment and vision loss in the right eye and bullous keratopathy in the left eye. His best-corrected visual acuity (BCVA) was 20/2000 OS. Anterior segment optical coherence tomography (AS-OCT) showed iridoschisis and stromal strands floating in the anterior chamber (Fig. 1 A). After the first Descemet stripping automated endothelial keratoplasty (DSAEK), his BCVA improved to 20/20. However, all grafts failed because of rapid CEnC loss without graft rejection. During 10-year follow-up, he underwent six corneal transplantations (three endothelial keratoplasties [EKs], followed by three penetrating keratoplasties [PKs], Fig. 2 A). The protein level in the AqH was 0.80 mg/mL (normal: 0.25–0.40 mg/mL). He gradually developed severe iris atrophy (Fig. 1 B) and secondary end-stage glaucoma after the third PKP. Case 2 A 53-year-old man with severe atopic dermatitis had bullous keratopathy in the right eye. At the initial visit, slit-lamp examination showed corneal edema, mild corectopia, and ectropion uveae (Fig. 1 C). AS-OCT showed extensive PAS formation, iridoschisis, and stromal splitting. To treat the bullous keratopathy, he underwent three corneal transplantations (one EK followed by two PKs, Fig. 2 B) over five years. Although his vision improved to 20/60 after corneal transplantation, all grafts performed afterward failed within short periods due to rapid CEnC loss and endothelial decompensation without apparent graft rejection. The protein level in the AqH was 0.95 mg/mL. Iridoschisis eventually led to severe iris atrophy (Fig. 1 D). Case 3 A 54-year-old male patient with atopic dermatitis and bullous keratopathy was admitted to the visual decline in the right eye (Fig. 1 E). The initial BCVA was 20/100 OD. The left eye had a history of 3 retinal detachment procedures over a course of 8 years. The BCVA in the left eye was HM. AS-OCT revealed iridoschisis in the right eye. An initial DSAEK procedure improved the right BCVA to 20/20. The AqH total protein obtained during the procedure was 1.40 mg/mL, which was four folds increase compared to the normal range. However, a graft endothelial decompensation without any graft rejection developed 2 years later, when a second DSAEK was performed. Although the BCVA improved to 20/20, graft ECD decreased from 2538 cells/mm 2 to 738 cell/mm 2 withing a year after second DSAEK. The patient developed angle closure glaucoma, ending in end-stage visual field loss (Fig. 1 F). Discussion and conclusions This is the first report on iridoschisis in patients with atopic dermatitis, leading to intractable bullous keratopathy. Thorough PubMed and Medline database search employing terms “atopic dermatitis”, “iridoschisis” and “bullous keratopathy”, reviewed solitary associations between “atopic dermatitis” and “iridoschisis”, 6 – 7 as well as “iridoschisis” and “bullous keratopathy”, 8 – 10 revealing no reports on the presence of bullous keratopathy in patients with both atopic dermatitis and iridoschisis. Iridoschisis is a rare condition that was first described in 1922 by Schmitt. It most commonly develops in the sixth or seventh decade of life and is often accompanied by lens subluxation, bullous keratopathy, angle-closure glaucoma due to PAS formation. 1 In this report, we described three young cases with both atopic dermatitis and iridoschisis who had intractable bullous keratopathy. The patients’ BCVA improved after each corneal transplantation, however, the prognosis was extremely poor, where all three patients required repeat grafts due to rapid CEnC loss without graft rejection. The pathophysiology of iridoschisis in atopic dermatitis remains unclear. Patients with atopic dermatitis have increased frequency and duration of eye rubbing. 6 Chronic eye rubbing induces repeated insults to the iris through mechanical trauma and intraocular pressure spikes, which over the years, may contribute to iridoschisis development. 7 Our observations by proteomic analysis of the aqueous humor obtaining during keratoplasties reviewed surprisingly high levels of total protein in the anterior chamber, suggesting increased vascular permeability and seepage of proteins presumably from the schitic sites, resulting in pathological milieu shift, which might have paved the way to repeat graft failure. 3 , 11 , 12 Corneal grafts were obtained from an eye bank in the USA and were cleared for highest medical standards according to Eye Bank Association of America (EBAA). Therefore, we could not attribute the graft failure in our cases to the grafts or preservation status. Careful attention must be paid in such patients with both atopic dermatitis, iridoschisis and bullous keratopathy, who are prone to iris atrophy, glaucoma, and graft decompensation. AS-OCT will help the clinicians in detecting the early sign of iridoschisis and assess progression of iris atrophy even in eye with corneal edema or corneal opacity. Declarations Acknowledgement: We would like to thank Editage company for English language editing. Funding: This study is supported by the Grant-in-Aid for Scientific Research 15K10906 and 23H03063 from the Ministry of Education, Culture, Sports, Science and Technology (T.Y.). The funding organization had no role in the design or conduct of this research. Author Contributions: Concept and design: T.Y., and M.D. Acquisition of patient photograph: Y.K., T.Y., and J.S. Critical revision of the manuscript for important intellectual content: J.S., and M.D. Management of this project: T.Y. Obtained funding and supervision: T.Y. and J.S. Conflict of Interest Disclosures: None. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Data availability: The data that support the findings of this study are available on request from the corresponding author (T.Y.). The data are not publicly available due to them containing information that could compromise research participant privacy/consent. Ethical approval: This study was approved by the Institutional Ethics Review Board of Tokyo Dental College Ichikawa General Hospital (Institution Review Board No.: I-15-42R). All the procedures conformed to the tenets of the Declaration of Helsinki and the Japanese Guidelines for Life Science and Medical Research. References Salmon JF, Murray AD. The association of iridoschisis and primary angle-closure glaucoma. Eye (Lond). 1992;6:267-272. Eiferman RA, Law M, Lane L. Iridoschisis and keratoconus. Cornea. 1994;13:78-79. Yamaguchi T, Higa K, Yagi-Yaguchi Y, et al. Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice. Sci Adv. 2020;6:eaaz5195. Kusano Y, Yamaguchi T, Nishisako S, et al. Aqueous cytokine levels are associated with progression of peripheral anterior synechiae after Descemet stripping automated endothelial keratoplasty. Trans Vis Sci Technol. 2021;10;12. Kusano Y, Yamaguchi T, Nishisako S, et al. Elevated cytokine levels in aqueous humor are associated with peripheral anterior synechiae after penetrating keratoplasty. Int J Mol Sci. 2021;22:12268. Ben-Eli H, Erdinest N, Solomon A. Pathogenesis and complications of chronic eye rubbing in ocular allergy. Curr Opin Allergy Clin Immunol. 2019;19(5):526-534. Yusuf IH, Salmon JF. Iridoschisis and keratoconus in a patient with severe allergic eye disease and compulsive eye rubbing: a case report. J Med Case Rep. 2016;10:134. Rodrigues MC, Spaeth GL, Krachmer JH, Laibson PR. Iridoschisis associated with glaucoma and bullous keratopathy. Am J Ophthalmol. 1983;95:73-81. Srinivasan S, Batterbury M, Hiscott P. Bullous keratopathy and corneal decompensation secondary to iridoschisis: a clinicopathological report. Cornea . 2005;24:867-9. Greenwald MF, Niles PI, Johnson AT, Vislisel JM, Greiner MA. Descemet membrane endothelial keratoplasty for corneal decompensation due to iridoschisis. Am J Ophthalmol Case Rep. 2018;9:34-37. Mori-Ogiwara Y, Yagi-Yaguchi Y, Ibrahim OMA, Higa K, Kasamatsu H, Kanda T, et al. Intracellular dark spots are associated with endothelial cell loss after Descemet's stripping automated endothelial keratoplasty. Br J Ophthalmol in press. Yazu H, Yamaguchi T, Aketa N, Higa K, Suzuki T, Yagi-Yaguchi Y, et al. Preoperative Aqueous Cytokine Levels are Associated With Endothelial Cell Loss After Descemet's Stripping Automated Endothelial Keratoplasty. Invest Ophthalmol Vis Sci. 2018;59:612-620. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5284476","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":367595662,"identity":"8a4fcdec-e83d-4b4e-ac25-aa4e747555bf","order_by":0,"name":"Yuki Kusano","email":"","orcid":"","institution":"Tokyo Dental College Ichikawa General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuki","middleName":"","lastName":"Kusano","suffix":""},{"id":367595663,"identity":"671709b2-6516-43b9-896d-03355ef7471d","order_by":1,"name":"Takefumi Yamaguchi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIiWNgGAWjYBCDBDYG5gMMPFAOkVrY2BIbSNPCwMZjCNOCHxgcP5348WubXR6ffM/3B29qGOT5GxiePcCr5UzuZmnZtuRiNjbejY1zjjEYzjjAkG6AV8uB3A3Skm0HEtuAWpp5GxgYNzAwpEng1XL+7ebfEC08D0Fa7AlruZG7TfIjRAsjSEsiQS2SN95us2Y4lwzUkmY4c84xieQZhwn4he987uabP8rsEuc3H37w4U2NjW1/e0/aA3xaFA4wMDAjRYcEiJuGTweDfAMDA+MPVDH2Y3i1jIJRMApGwYgDAEauTKvnfVygAAAAAElFTkSuQmCC","orcid":"","institution":"Tokyo Dental College Ichikawa General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Takefumi","middleName":"","lastName":"Yamaguchi","suffix":""},{"id":367595664,"identity":"83c386dd-9832-4e98-ae55-e6f4648edd66","order_by":2,"name":"Jun Shimazaki","email":"","orcid":"","institution":"Tokyo Dental College Ichikawa General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Shimazaki","suffix":""},{"id":367595665,"identity":"df8ef1f4-a7bb-4d8f-8a0e-1382f4a00a89","order_by":3,"name":"Murat Dogru","email":"","orcid":"","institution":"Tokyo Dental College Ichikawa General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Murat","middleName":"","lastName":"Dogru","suffix":""}],"badges":[],"createdAt":"2024-10-17 17:08:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5284476/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5284476/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":67731492,"identity":"ed7492a3-0ac5-48fd-8afb-c40388b9088c","added_by":"auto","created_at":"2024-10-29 07:18:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":693752,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA-B\u003c/strong\u003e: Case1. Anterior segment OCT (AS-OCT) showing iridoschisis and stromal strands floating in the anterior chamber (yellow arrow heads) since the initial visit. \u003cstrong\u003eB\u003c/strong\u003e: After six corneal transplantations due to rapid CEnC loss in 10 years, he developed severe iris atrophy. \u003cstrong\u003eC-D:\u003c/strong\u003e Case 2. Slit-lamp examination showing corneal edema, mild corectopia, ectropion uveae, peripheral anterior synechiae formation, and iridoschisis in AS-OCT (yellow arrow heads) at the initial visit. \u003cstrong\u003eD: \u003c/strong\u003eAfter 3 corneal transplantations in 4 years, iridoschisis led to iris atrophy and graft failure. \u003cstrong\u003eE-F\u003c/strong\u003e: Case 3. AS-OCT showing iridoschisis and PAS at the initial visit (\u003cstrong\u003eE\u003c/strong\u003e) and last visit (\u003cstrong\u003eF\u003c/strong\u003e).\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5284476/v1/ce721f261c0b3593bf48617b.png"},{"id":67731490,"identity":"1888c09c-8acf-4881-8875-e19c17fe5186","added_by":"auto","created_at":"2024-10-29 07:18:04","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":55089,"visible":true,"origin":"","legend":"\u003cp\u003eTimeline of clinical course, corneal transplantations, visual acuity and events (A: case 1, B: case 2)\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5284476/v1/942e2f5f59602b2a73a97b68.png"},{"id":72481195,"identity":"b26f5d93-4943-4f37-8acf-79f4627533d4","added_by":"auto","created_at":"2024-12-27 17:01:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1204359,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5284476/v1/19e4dd01-a3c8-43f0-80ea-8b066119e2cb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Iridoschisis in patients with atopic dermatitis Leads to Intractable Bullous Keratopathy","fulltext":[{"header":"Background","content":"\u003cp\u003eIridoschisis is a rare condition in which the iris stroma separates into two layers. It is mostly seen in the inferior iris in elderly people and is usually associated with angle-closure glaucoma, nanophthalmos, ocular trauma, atopic dermatitis, syphilitic interstitial keratitis, lens subluxation, keratoconus, and bullous keratopathy.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e The cause and prognosis of iridoschisis remain largely unknown. A recent study showed that pathological alterations of the aqueous humor (AqH) in eyes with iris abnormalities increases early graft failure risk due to rapid corneal endothelial cell (CEnC) loss.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Management of the eyes with iridocorneal endothelial (ICE) syndrome and iridoschisis is particularly challenging because of the progression of peripheral anterior synechiae (PAS), intraocular pressure (IOP) elevation and endothelial decompensation, necessitating repeat keratoplasties.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Herein, we report three cases with atopic dermatitis, iridoschisis and intractable bullous keratopathy, in which corneal grafts failed due to rapid CEnC loss without graft rejection.\u003c/p\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003e\u003c/p\u003e"},{"header":"Case presentations","content":"\u003cp\u003eWe documented three patients with atopic dermatitis who had iridoschisis and intractable bullous keratopathy, ending up with iris atrophy, repeated corneal graft failures and poor prognosis after corneal transplantation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase 1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 26-year-old man with atopic dermatitis suffered retinal detachment and vision loss in the right eye and bullous keratopathy in the left eye. His best-corrected visual acuity (BCVA) was 20/2000 OS. Anterior segment optical coherence tomography (AS-OCT) showed iridoschisis and stromal strands floating in the anterior chamber (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA). After the first Descemet stripping automated endothelial keratoplasty (DSAEK), his BCVA improved to 20/20. However, all grafts failed because of rapid CEnC loss without graft rejection. During 10-year follow-up, he underwent six corneal transplantations (three endothelial keratoplasties [EKs], followed by three penetrating keratoplasties [PKs], Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA). The protein level in the AqH was 0.80 mg/mL (normal: 0.25\u0026ndash;0.40 mg/mL). He gradually developed severe iris atrophy (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB) and secondary end-stage glaucoma after the third PKP.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase 2\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 53-year-old man with severe atopic dermatitis had bullous keratopathy in the right eye. At the initial visit, slit-lamp examination showed corneal edema, mild corectopia, and ectropion uveae (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eC). AS-OCT showed extensive PAS formation, iridoschisis, and stromal splitting. To treat the bullous keratopathy, he underwent three corneal transplantations (one EK followed by two PKs, Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB) over five years. Although his vision improved to 20/60 after corneal transplantation, all grafts performed afterward failed within short periods due to rapid CEnC loss and endothelial decompensation without apparent graft rejection. The protein level in the AqH was 0.95 mg/mL. Iridoschisis eventually led to severe iris atrophy (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eD).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase 3\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 54-year-old male patient with atopic dermatitis and bullous keratopathy was admitted to the visual decline in the right eye (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eE). The initial BCVA was 20/100 OD. The left eye had a history of 3 retinal detachment procedures over a course of 8 years. The BCVA in the left eye was HM. AS-OCT revealed iridoschisis in the right eye. An initial DSAEK procedure improved the right BCVA to 20/20. The AqH total protein obtained during the procedure was 1.40 mg/mL, which was four folds increase compared to the normal range. However, a graft endothelial decompensation without any graft rejection developed 2 years later, when a second DSAEK was performed. Although the BCVA improved to 20/20, graft ECD decreased from 2538 cells/mm\u003csup\u003e2\u003c/sup\u003e to 738 cell/mm\u003csup\u003e2\u003c/sup\u003e withing a year after second DSAEK. The patient developed angle closure glaucoma, ending in end-stage visual field loss (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eF).\u003c/p\u003e"},{"header":"Discussion and conclusions","content":"\u003cp\u003eThis is the first report on iridoschisis in patients with atopic dermatitis, leading to intractable bullous keratopathy. Thorough PubMed and Medline database search employing terms “atopic dermatitis”, “iridoschisis” and “bullous keratopathy”, reviewed solitary associations between “atopic dermatitis” and “iridoschisis”,\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e–\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e as well as “iridoschisis” and “bullous keratopathy”,\u003csup\u003e\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e–\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e revealing no reports on the presence of bullous keratopathy in patients with both atopic dermatitis and iridoschisis.\u003c/p\u003e \u003cp\u003eIridoschisis is a rare condition that was first described in 1922 by Schmitt. It most commonly develops in the sixth or seventh decade of life and is often accompanied by lens subluxation, bullous keratopathy, angle-closure glaucoma due to PAS formation.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e In this report, we described three young cases with both atopic dermatitis and iridoschisis who had intractable bullous keratopathy. The patients’ BCVA improved after each corneal transplantation, however, the prognosis was extremely poor, where all three patients required repeat grafts due to rapid CEnC loss without graft rejection. The pathophysiology of iridoschisis in atopic dermatitis remains unclear. Patients with atopic dermatitis have increased frequency and duration of eye rubbing.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Chronic eye rubbing induces repeated insults to the iris through mechanical trauma and intraocular pressure spikes, which over the years, may contribute to iridoschisis development.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOur observations by proteomic analysis of the aqueous humor obtaining during keratoplasties reviewed surprisingly high levels of total protein in the anterior chamber, suggesting increased vascular permeability and seepage of proteins presumably from the schitic sites, resulting in pathological milieu shift, which might have paved the way to repeat graft failure.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Corneal grafts were obtained from an eye bank in the USA and were cleared for highest medical standards according to Eye Bank Association of America (EBAA). Therefore, we could not attribute the graft failure in our cases to the grafts or preservation status. Careful attention must be paid in such patients with both atopic dermatitis, iridoschisis and bullous keratopathy, who are prone to iris atrophy, glaucoma, and graft decompensation. AS-OCT will help the clinicians in detecting the early sign of iridoschisis and assess progression of iris atrophy even in eye with corneal edema or corneal opacity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement:\u0026nbsp;\u003c/strong\u003eWe would like to thank Editage company for English language editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This study is supported by the Grant-in-Aid for Scientific Research 15K10906 and 23H03063 from the Ministry of Education, Culture, Sports, Science and Technology (T.Y.). The funding organization had no role in the design or conduct of this research.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e Concept and design: T.Y., and M.D. Acquisition of patient photograph: Y.K., T.Y., and J.S. Critical revision of the manuscript for important intellectual content: J.S., and M.D. Management of this project: T.Y. Obtained funding and supervision: T.Y. and J.S.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosures:\u003c/strong\u003e None. Role of the\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunder/Sponsor:\u003c/strong\u003e The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u0026nbsp;\u003c/strong\u003eThe data that support the findings of this study are available on request from the corresponding author (T.Y.). The data are not publicly available due to them containing information that could compromise research participant privacy/consent.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e This study was approved by the Institutional Ethics Review Board of Tokyo Dental College Ichikawa General Hospital (Institution Review Board No.: I-15-42R). All the procedures conformed to the tenets of the Declaration of Helsinki and the Japanese Guidelines for Life Science and Medical Research.\u0026emsp;\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSalmon JF, Murray AD. The association of iridoschisis and primary angle-closure glaucoma. \u003cem\u003eEye (Lond). \u003c/em\u003e1992;6:267-272.\u003c/li\u003e\n\u003cli\u003eEiferman RA, Law M, Lane L. Iridoschisis and keratoconus. \u003cem\u003eCornea. \u003c/em\u003e1994;13:78-79.\u003c/li\u003e\n\u003cli\u003eYamaguchi T, Higa K, Yagi-Yaguchi Y, et al. Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice. \u003cem\u003eSci Adv. \u003c/em\u003e2020;6:eaaz5195.\u003c/li\u003e\n\u003cli\u003eKusano Y, Yamaguchi T, Nishisako S, et al. Aqueous cytokine levels are associated with progression of peripheral anterior synechiae after Descemet stripping automated endothelial keratoplasty. \u003cem\u003eTrans Vis Sci Technol. \u003c/em\u003e2021;10;12. \u003c/li\u003e\n\u003cli\u003eKusano Y, Yamaguchi T, Nishisako S, et al. Elevated cytokine levels in aqueous humor are associated with peripheral anterior synechiae after penetrating keratoplasty. \u003cem\u003eInt J Mol Sci.\u003c/em\u003e 2021;22:12268.\u003c/li\u003e\n\u003cli\u003eBen-Eli H, Erdinest N, Solomon A. Pathogenesis and complications of chronic eye rubbing in ocular allergy. \u003cem\u003eCurr Opin Allergy Clin Immunol. \u003c/em\u003e2019;19(5):526-534.\u003c/li\u003e\n\u003cli\u003eYusuf IH, Salmon JF. Iridoschisis and keratoconus in a patient with severe allergic eye disease and compulsive eye rubbing: a case report. \u003cem\u003eJ Med Case Rep. \u003c/em\u003e2016;10:134.\u003c/li\u003e\n\u003cli\u003eRodrigues MC, Spaeth GL, Krachmer JH, Laibson PR. Iridoschisis associated with glaucoma and bullous keratopathy. \u003cem\u003eAm J Ophthalmol.\u003c/em\u003e 1983;95:73-81.\u003c/li\u003e\n\u003cli\u003eSrinivasan S, Batterbury M, Hiscott P. Bullous keratopathy and corneal decompensation secondary to iridoschisis: a clinicopathological report.\u003cem\u003e Cornea\u003c/em\u003e. 2005;24:867-9.\u003c/li\u003e\n\u003cli\u003eGreenwald MF, Niles PI, Johnson AT, Vislisel JM, Greiner MA. Descemet membrane endothelial keratoplasty for corneal decompensation due to iridoschisis. \u003cem\u003eAm J Ophthalmol Case Rep.\u003c/em\u003e 2018;9:34-37.\u003c/li\u003e\n\u003cli\u003eMori-Ogiwara Y, Yagi-Yaguchi Y, Ibrahim OMA, Higa K, Kasamatsu H, Kanda T, et al. Intracellular dark spots are associated with endothelial cell loss after Descemet\u0026apos;s stripping automated endothelial keratoplasty. \u003cem\u003eBr J Ophthalmol \u003c/em\u003ein press.\u003c/li\u003e\n\u003cli\u003eYazu H, Yamaguchi T, Aketa N, Higa K, Suzuki T, Yagi-Yaguchi Y, et al. Preoperative Aqueous Cytokine Levels are Associated With Endothelial Cell Loss After Descemet\u0026apos;s Stripping Automated Endothelial Keratoplasty. \u003cem\u003eInvest Ophthalmol Vis Sci.\u003c/em\u003e 2018;59:612-620.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"atopic dermatitis, corneal transplantation, bullous keratopathy, iridoschisis, corneal endothelial cell","lastPublishedDoi":"10.21203/rs.3.rs-5284476/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5284476/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTo report iridoschisis in patients with atopic dermatitis and the outcome of repeat corneal transplantations for intractable bullous keratopathy.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eThree patients with atopic dermatitis, iridoschisis and bullous keratopathy, underwent numerous corneal transplantation procedures including penetrating keratoplasty (PKP), and endothelial keratoplasty (EK), which failed within a short period due to rapid corneal endothelial cell (CEnC) loss without graft rejection. Aqueous humor total protein levels were overwhelmingly higher in all patients. \u003cb\u003eCase1\u003c/b\u003e: A 26-year-old man with atopic dermatitis had iridoschisis and bullous keratopathy in the left eye. During the 10-year follow-up, he underwent six corneal transplantations (three EK, followed by three PKP). However, all grafts failed because of rapid CEnC loss without graft rejection. \u003cb\u003eCase 2\u003c/b\u003e: A 53-year-old man with severe atopic dermatitis had iridoschisis and bullous keratopathy in the right eye. He underwent three corneal transplantations (one EK, followed by two PK) over five years. All grafts failed within short periods due to rapid CEnC loss and endothelial decompensation without graft rejection. \u003cb\u003eCase 3\u003c/b\u003e: A 54-year-old man with severe atopic dermatitis had iridoschisis and bullous keratopathy in the right eye. He underwent two EK within short periods due to rapid CEnC loss.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eWe hereby report the association of iridoschisis with bullous keratopathy in atopic dermatitis for the first time in the literature. Clinicians should be aware that the prognosis of corneal transplants in such patients appears to be poor necessitating repeat procedures.\u003c/p\u003e","manuscriptTitle":"Iridoschisis in patients with atopic dermatitis Leads to Intractable Bullous Keratopathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-29 07:17:59","doi":"10.21203/rs.3.rs-5284476/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4b423d94-6cde-4fdb-a401-05724517c7fa","owner":[],"postedDate":"October 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-27T16:53:31+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-29 07:17:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5284476","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5284476","identity":"rs-5284476","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}