Corneal Oedema: Aetiology, Diagnostic Testing, and Treatment

Abstract

Corneal oedema results from an underlying pathology, which can be diverse in origin, and may be mechanical, dystrophic, or inflammatory, and affect any layer of the cornea. Diagnostic tools such as Scheimpflug imaging and anterior segment optical coherence tomography have standardised quantification of corneal oedema and have become important aids in clinical practice. Timely diagnosis and treatment are key to preventing irreversible damage to the corneal ultrastructure, such as anterior corneal fibrosis or endothelial cell damage. The oedema usually resolves quickly when the underlying cause has been addressed. Symptomatic treatment using hyperosmolar agents has failed to show any benefits in oedema resolution or improvement in visual acuity compared to placebo. In contrast, rho-associated protein kinase (ROCK) inhibitors offer a promising option for medical treatment in cases of endothelial dysfunction, but their safety and efficacy must be further validated in large scale clinical trials. Until then, endothelial or penetrating keratoplasties remain the mainstay treatment where structural changes to the cornea have occurred.

Zusammenfassung

Hornhautödeme entwickeln sich als Folge einer mechanischen, dystrophischen oder inflammatorischen Erkrankung der Hornhaut, die alle Schichten der Hornhaut betreffen kann. Diagnostische Instrumente, wie die Scheimpflug-Tomografie und die optische Kohärenztomografie des Vorderabschnitts, erlauben eine standardisierte Quantifizierung des Hornhautödems und sind so zu wichtigen Hilfsmitteln in der klinischen Praxis geworden. Die frühzeitige Diagnose und Behandlung kornealer Ödeme ist wichtig, um dauerhafte Schäden wie Endothelzellverlust oder Fibrosierung im Bereich der anterioren Hornhaut zu vermeiden. Meist bildet sich das Hornhautödem schnell zurück, wenn die ursächliche Erkrankung behandelt wird. Die symptomatische Behandlung des Hornhautödems mit hyperosmolaren Augentropfen zeigte im Vergleich zu Placebo keinen Mehrwert in Bezug auf die Abnahme des Ödems oder eine Verbesserung der Sehfunktion. Im Gegensatz dazu scheinen Rho-kinase-(ROCK-)Inhibitoren eine vielversprechende nicht chirurgische Therapieoption bei endothelialer Dysfunktion zu sein, deren Sicherheit und Wirksamkeit in klinischen Studien überprüft werden muss. Bis dahin bleiben die endotheliale oder penetrierende Keratoplastik die Therapie der Wahl bei strukturellen Veränderungen der Hornhaut.

Key words

corneal oedema resolution - Descemet membrane endothelial keratoplasty - corneal dystrophy - pathophysiology - endothelial cell function

Schlüsselwörter

Reduktion des Hornhautödems - Pathophysiologie - Endotheltransplantation - Hornhautdystrophie - Endothelzellfunktion

Publication History

Received: 29 November 2021

Accepted: 01 February 2022

Article published online:
14 April 2022

• References

• 1 Dunn SP, Mah FS, Akpek EK. et al. Corneal Edema and Opacification Preferred Practice Pattern^® . Ophthalmology 2019; 126: P216-P285 DOI: 10.1016/j.ophtha.2018.10.022.
• 2 Wacker K, Baratz KH, Fautsch MP. et al. Medical and Semi-surgical Treatments for Fuchs Endothelial Corneal Dystrophy. Klin Monbl Augenheilkd 2018; 235: 709-713 DOI: 10.1055/a-0577-7953.
• 3 Leung BK, Bonanno JA, Radke CJ. Oxygen-deficient metabolism and corneal edema. Prog Retin Eye Res 2011; 30: 471-492 DOI: 10.1016/j.preteyeres.2011.07.001.
• 4 Ciralsky JB, Lai E, Bouchard CS. A Matrix of Pathologic Responses in the Cornea. In: Krachmer JH, Mannis MF, Holland EJ. eds. Cornea. 5th ed. St. Louis: Mosby-Year Book, Inc.; 2020: 46-71
• 5 Hatton MP, Perez VL, Dohlman CH. Corneal oedema in ocular hypotony. Exp Eye Res 2004; 78: 549-552 DOI: 10.1016/j.exer.2003.06.003.
• 6 Klyce SD, Crosson CE. Transport processes across the rabbit corneal epithelium: a review. Curr Eye Res 1985; 4: 323-331
• 7 Ousler 3rd GW, Hagberg KW, Schindelar M. et al. The ocular protection index. Cornea 2008; 27: 509-513
• 8 Bonanno JA. Molecular mechanisms underlying the corneal endothelial pump. Exp Eye Res 2012; 95: 2-7 DOI: 10.1016/j.exer.2011.06.004.
• 9 Bonanno JA. Identity and regulation of ion transport mechanisms in the corneal endothelium. Prog Retin Eye Res 2003; 22: 69-94
• 10 Bourne WM. Biology of the corneal endothelium in health and disease. Eye (Lond) 2003; 17: 912-918
• 11 Senoo T, Joyce NC. Cell cycle kinetics in corneal endothelium from old and young donors. Invest Ophthalmol Vis Sci 2000; 41: 660-667
• 12 McGowan SL, Edelhauser HF, Pfister RR. et al. Stem cell markers in the human posterior limbus and corneal endothelium of unwounded and wounded corneas. Mol Vis 2007; 13: 1984-2000
• 13 Armitage WJ, Dick AD, Bourne WM. Predicting endothelial cell loss and long-term corneal graft survival. Invest Ophthalmol Vis Sci 2003; 44: 3326-3331
• 14 Meek KM, Leonard DW, Connon CJ. et al. Transparency, swelling and scarring in the corneal stroma. Eye (Lond) 2003; 17: 927-936 DOI: 10.1038/sj.eye.6700574.
• 15 Lee D, Wilson G. Non-uniform swelling properties of the corneal stroma. Curr Eye Res 1981; 1: 457-461
• 16 Costagliola C, Romano V, Forbice E. et al. Corneal oedema and its medical treatment. Clin Exp Optom 2013; 96: 529-535 DOI: 10.1111/cxo.12060.
• 17 Levenson JE. Corneal edema: cause and treatment. Surv Ophthalmol 1975; 20: 190-204
• 18 Reinhard T, Böhringer D, Hüschen D. et al. [Chronic endothelial cell loss of the graft after penetrating keratoplasty: influence of endothelial cell migration from graft to host]. Klin Monbl Augenheilkd 2002; 219: 410-416 DOI: 10.1055/s-2002-32876.
• 19 Patel SR, Chu DS, Ayres BD. et al. Corneal edema and penetrating keratoplasty after anterior chamber phakic intraocular lens implantation. J Cataract Refract Surg 2005; 31: 2212-2215
• 20 Tao A, Chen Z, Shao Y. et al. Phacoemulsification induced transient swelling of corneal Descemetʼs Endothelium Complex imaged with ultra-high resolution optical coherence tomography. PLoS One 2013; 8: e80986 DOI: 10.1371/journal.pone.0080986.
• 21 Price MO, Mehta JS, Jurkunas UV. et al. Corneal endothelial dysfunction: Evolving understanding and treatment options. Prog Retin Eye Res 2021; 82: 100904 DOI: 10.1016/j.preteyeres.2020.100904.
• 22 Bourne WM, Hodge DO, McLaren JW. Estimation of corneal endothelial pump function in long-term contact lens wearers. Invest Ophthalmol Vis Sci 1999; 40: 603-611
• 23 Weiss JS, Møller HU, Aldave AJ. et al. IC3D classification of corneal dystrophies–edition 2. Cornea 2015; 34: 117-159
• 24 Baratz KH, Tosakulwong N, Ryu E. et al. E2-2 protein and Fuchsʼs corneal dystrophy. N Engl J Med 2010; 363: 1016-1024 DOI: 10.1056/NEJMoa1007064.
• 25 Fuchs E. Dystrophia epithelialis corneae. Graefes Arch Klin Exp Ophthalmol 1910; 76: 478-508
• 26 Wacker K, McLaren JW, Patel SV. Optical and anatomic Changes in Fuchs Endothelial Dystrophy Corneas. In: Cursiefen C, Jun AS. eds. Current Treatment Options for Fuchs Endothelial Dystrophy. 1st ed.. Basel: Springer International Publishing Switzerland; 2017: 51-72
• 27 Wacker K, Reinhard T, Maier P. [Pathogenesis and diagnostic evaluation of Fuchsʼ endothelial corneal dystrophy]. Ophthalmologe 2019; 116: 221-227 DOI: 10.1007/s00347-018-0799-5.
• 28 Seitz B, Heiligenhaus A. Herpeskeratitis. Ophthalmologe 2011; 108: 385-398
• 29 Alfawaz AM, Holland GN, Yu F. et al. Corneal Endothelium in Patients with Anterior Uveitis. Ophthalmology 2016; 123: 1637-1645 DOI: 10.1016/j.ophtha.2016.04.036.
• 30 Friedenwald JS, Buschke W. Some factors concerned in the mitotic and wound-healing activities of the corneal epithelium. Trans Am Ophthalmol Soc 1944; 42: 371
• 31 Fraunfelder FW. Corneal toxicity from topical ocular and systemic medications. Cornea 2006; 25: 1133-1138 DOI: 10.1097/01.ico.0000240084.27663.fd.
• 32 Mamalis N, Edelhauser HF, Dawson DG. et al. Toxic anterior segment syndrome. J Cataract Refract Surg 2006; 32: 324-333
• 33 van den Berg TJ, Franssen L, Kruijt B. et al. History of ocular straylight measurement: a review. Z Med Phys 2013; 23: 6-20
• 34 Fritz M, Grewing V, Maier P. et al. Diurnal Variation in Corneal Edema in Fuchs Endothelial Corneal Dystrophy. Am J Ophthalmol 2019; 207: 351-355 DOI: 10.1016/j.ajo.2019.08.002.
• 35 Wacker K, Baratz KH, Bourne WM. et al. Patient-Reported Visual Disability in Fuchsʼ Endothelial Corneal Dystrophy Measured by the Visual Function and Corneal Health Status (V-FUCHS) Instrument. Ophthalmology 2018; 125: 1854-1861
• 36 McLaren JW, Wacker K, Kane KM. et al. Measuring Corneal Haze by Using Scheimpflug Photography and Confocal Microscopy. Invest Ophthalmol Vis Sci 2016; 57: 227-235 DOI: 10.1167/iovs.15-17657.
• 37 Sun SY, Wacker K, Baratz KH. et al. Determining Subclinical Edema in Fuchs Endothelial Corneal Dystrophy. Revised Classification using Scheimpflug Tomography for Preoperative Assessment. Ophthalmology 2019; 126: 195-205
• 38 Zander D, Grewing V, Glatz A. et al. Predicting Edema Resolution After Descemet Membrane Endothelial Keratoplasty for Fuchs Dystrophy Using Scheimpflug Tomography. JAMA Ophthalmol 2021; 139: 423-430 DOI: 10.1001/jamaophthalmol.2020.6994.
• 39 Wacker K, McLaren JW, Kane KM. et al. Corneal Hydration Control in Fuchsʼ Endothelial Corneal Dystrophy. Invest Ophthalmol Vis Sci 2016; 57: 5060-5065 DOI: 10.1167/iovs.16-20205.
• 40 Zeboulon P, Ghazal W, Gatinel D. Corneal Edema Visualization With Optical Coherence Tomography Using Deep Learning: Proof of Concept. Cornea 2021; 40: 1267-1275 DOI: 10.1097/ICO.0000000000002640.
• 41 Seitz B, Hager T. Clinical phenotypes of Fuchs Endothelial Corneal Dystrophy (FECD), disease progression, differential diagnosis, and medical therapy. In: Cursiefen C, Jun AS. eds. Current Treatment Options for Fuchs Endothelial Dystrophy. 1st ed.. Basel: Springer International Publishing Switzerland; 2017: 25-50
• 42 Zander DB, Böhringer D, Fritz M. et al. Hyperosmolar Eye Drops for Diurnal Corneal Edema in Fuchsʼ Endothelial Dystrophy: A Double-Masked, Randomized Controlled Trial. Ophthalmology 2021; 128: 1527-1533 DOI: 10.1016/j.ophtha.2021.04.015.
• 43 Wilson SE, Bourne WM, Brubaker RF. Effect of dexamethasone on corneal endothelial function in Fuchsʼ dystrophy. Invest Ophthalmol Vis Sci 1988; 29: 357-361
• 44 Böhringer D, Schindler A, Reinhard T. [Satisfaction with penetrating keratoplasty. Results of a questionnaire census]. Ophthalmologe 2006; 103: 677-681 DOI: 10.1007/s00347-006-1373-0.
• 45 Okumura N, Koizumi N, Kay EP. et al. The ROCK inhibitor eye drop accelerates corneal endothelium wound healing. Invest Ophthalmol Vis Sci 2013; 54: 2493-2502 DOI: 10.1167/iovs.12-11320.
• 46 Okumura N, Ueno M, Koizumi N. et al. Enhancement on primate corneal endothelial cell survival in vitro by a ROCK inhibitor. Invest Ophthalmol Vis Sci 2009; 50: 3680-3687 DOI: 10.1167/iovs.08-2634.
• 47 Moloney G, Petsoglou C, Ball M. et al. Descemetorhexis Without Grafting for Fuchs Endothelial Dystrophy-Supplementation With Topical Ripasudil. Cornea 2017; 36: 642-648 DOI: 10.1097/ICO.0000000000001209.
• 48 Price MO, Price Jr. FW. Randomized, Double-Masked, Pilot Study of Netarsudil 0.02 % Ophthalmic Solution for Treatment of Corneal Edema in Fuchs Dystrophy. Am J Ophthalmol 2021; 227: 100-105 DOI: 10.1016/j.ajo.2021.03.006.
• 49 Macsai MS, Shiloach M. Use of Topical Rho Kinase Inhibitors in the Treatment of Fuchs Dystrophy After Descemet Stripping Only. Cornea 2019; 38: 529-534 DOI: 10.1097/ICO.0000000000001883.
• 50 Schlötzer-Schrehardt U, Zenkel M, Strunz M. et al. Potential Functional Restoration of Corneal Endothelial Cells in Fuchs Endothelial Corneal Dystrophy by ROCK Inhibitor (Ripasudil). Am J Ophthalmol 2021; 224: 185-199 DOI: 10.1016/j.ajo.2020.12.006.
• 51 Kinoshita S, Koizumi N, Ueno M. et al. Injection of Cultured Cells with a ROCK Inhibitor for Bullous Keratopathy. N Engl J Med 2018; 378: 995-1003 DOI: 10.1056/NEJMoa1712770.
• 52 Wahlig S, Kocaba V, Mehta JS. Cultured Cells and ROCK Inhibitor for Bullous Keratopathy. N Engl J Med 2018; 379: 1184 DOI: 10.1056/NEJMc1805808.
• 53 Davies E, Jurkunas U, Pineda 2nd R. Pilot Study of Corneal Clearance With the Use of a Rho-Kinase Inhibitor After Descemetorhexis Without Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy. Cornea 2021; 40: 899-902 DOI: 10.1097/ICO.0000000000002691.
• 54 Flockerzi E, Maier P, Bohringer D. et al. Trends in Corneal Transplantation from 2001 to 2016 in Germany: A Report of the DOG-Section Cornea and its Keratoplasty Registry. Am J Ophthalmol 2018; 188: 91-98 DOI: 10.1016/j.ajo.2018.01.018.
• 55 Birnbaum F, Maier P, Reinhard T. [Femtosecond laser-assisted penetrating keratoplasty]. Ophthalmologe 2010; 107: 186-188 DOI: 10.1007/s00347-009-2092-0.
• 56 Birnbaum F, Schwartzkopff J, Böhringer D. et al. The intrastromal corneal ring in penetrating keratoplasty-long-term results of a prospective randomized study. Cornea 2011; 30: 780-783 DOI: 10.1097/ICO.0b013e318206caa9.
• 57 Böhringer D, Böhringer S, Poxleitner K. et al. Long-term graft survival in penetrating keratoplasty: the biexponential model of chronic endothelial cell loss revisited. Cornea 2010; 29: 1113-1117 DOI: 10.1097/ICO.0b013e3181d21d07.
• 58 Dunker SL, Dickman MM, Wisse RPL. et al. Descemet Membrane Endothelial Keratoplasty versus Ultrathin Descemet Stripping Automated Endothelial Keratoplasty: A Multicenter Randomized Controlled Clinical Trial. Ophthalmology 2020; 127: 1152-1159 DOI: 10.1016/j.ophtha.2020.02.029.
• 59 Seitz B, Daas L, Flockerzi E. et al. [Descemet membrane endothelial keratoplasty DMEK – donor and recipient step by step]. Ophthalmologe 2020; 117: 811-828
• 60 Glatz A, Böhringer D, Zander DB. et al. Three-Dimensional Map of Descemet Membrane Endothelial Keratoplasty Detachment: Development and Application of a Deep Learning Model. Ophthalmol Sci 2021; 1: 100067 DOI: 10.1016/j.xops.2021.100067.
• 61 Borkar DS, Veldman P, Colby KA. Treatment of Fuchs Endothelial Dystrophy by Descemet Stripping Without Endothelial Keratoplasty. Cornea 2016; 35: 1267-1273 DOI: 10.1097/ICO.0000000000000915.
• 62 Auffarth GU, Son HS, Koch M. et al. Implantation of an Artificial Endothelial Layer for Treatment of Chronic Corneal Edema. Cornea 2021; 40: 1633-1638 DOI: 10.1097/ico.0000000000002806.