Differential Diagnosis of Keratoconus Based on New Technologies

Abstract

Keratoconus (KC) must be distinguished from other corneal ectatic diseases and thinning disorders for stage-appropriate and suitable management of each condition. The most relevant corneal pathologies that may imitate the tomographic KC pattern are pellucid marginal degeneration (PMD), keratoglobus, posterior keratoconus, and Fuchs-Terrien marginal degeneration (FTMD). In moderate cases of KC, differentiation is typically possible using slit lamp examination and corneal tomography with evaluation of the location of the corneal thinning region. In early cases, however, differential diagnosis may be more challenging since the cornea may look relatively normal. In severe cases, the extended area of corneal thinning also complicates differentiation. Biomicroscopic findings cannot always give all the information needed to distinguish KC from related ectatic corneal conditions. The aim of this work is to discuss contemporary techniques and findings to assist physicians to identify the correct diagnosis. Corneal topography has been used in recent decades as the main tool for imaging in ectatic corneal diseases. Moreover, Scheimpflug cameras (corneal tomographers), which analyze both anterior and posterior corneal surfaces, curvatures, pachymetry, elevation data, higher order aberrations, Fourier analysis of keratometric data, and corneal density have become the most promising tools for diagnosis and follow-up of ectatic diseases. A noninvasive air pulse tonometer in conjunction with an ultrahigh-speed Scheimpflug camera complements tomographic findings by analyzing biomechanical corneal properties. Α confocal microscopy system, which is a novel clinical technique for the study of corneal cellular structure, could contribute effectively in the same direction. Moreover, anterior segment optical coherence tomography (AS-OCT) creates cross-sections, which can be generated into a three-dimensional structure to produce corneal epithelial thickness (ET) measurements. ET mapping is increasingly recognized as a sensitive tool for the diagnosis of ocular surface disorders. Combining information of all these systems could lead to a more effective identification and differential diagnosis of ectatic corneal disorders.

Zusammenfassung

Die Unterscheidung zwischen Keratokonus (KK) und anderen ektatischen Hornhauterkrankungen ist für eine angemessene Behandlung der jeweiligen Erkrankung unerlässlich. Die wichtigsten Hornhautpathologien, die bei der Differenzialdiagnose des KK in Betracht gezogen werden müssen, sind die pelluzide marginale Degeneration (PMD), der Keratoglobus, der posteriore Keratokonus und die Fuchs-Terrienʼsche marginale Degeneration (FTMD). In mittelschweren KK-Fällen ist die Differenzierung aufgrund der klassischen Lage der Hornhautverdünnungsregion möglich. In frühen Fällen ist die Differenzialdiagnose jedoch schwierig, da die Hornhaut relativ normal aussehen kann. In fortgeschrittenen Stadien hingegen ist die Differenzierung aufgrund des ausgedehnten Bereichs der Hornhautverdünnung mitunter ebenfalls schwierig. Biomikroskopische Befunde können nicht alle Informationen liefern, die zur Unterscheidung des KK von anderen ektatischen Hornhauterkrankungen erforderlich sind. Daher werden moderne Techniken und Befunde diskutiert, um die richtige Differenzialdiagnose sicherstellen zu können. Hornhauttopografiekarten wurden in den letzten Jahrzehnten als Hauptinstrument für die bildgebende Differenzialdiagnose verwendet. Darüber hinaus wurden Scheimpflug-Kameras (Hornhauttomografen), die sowohl die vordere als auch die hintere Hornhautfläche anhand von Krümmungsdaten, Pachymetrie, Elevationsmessungen, Aberrationen höherer Ordnung, Fourier-Analysen keratometrischer Daten und die Hornhautdichte analysieren, zum wichtigsten Instrument für die Diagnose und Verlaufskontrolle ektatischer Hornhauterkrankungen. Seit neuestem zeichnet ein nicht invasives Luftstoßtonometer in Verbindung mit einer Ultrahochgeschwindigkeits-Scheimpflug-Kamera die Reaktion der Hornhaut auf diesen mechanischen Stimulus auf und analysiert so ihre biomechanischen Eigenschaften. Des Weiteren könnte die konfokale Mikroskopie effektiv zur Differenzialdiagnose beitragen. Darüber hinaus erzeugt die optische Kohärenztomografie des vorderen Segments (AS-OCT) Querschnitte, die in eine 3-dimensionale Struktur umgewandelt werden können, um die Hornhautepitheldicke zu messen. Das Endothel-Mapping wird zunehmend als wirksames Instrument für die Diagnose von Erkrankungen der Augenoberfläche anerkannt. Die Kombination der Informationen all dieser Systeme könnte eine umfassendere Identifizierung und Differenzialdiagnose ektatischer Hornhauterkrankungen ermöglichen.

Key words

keratoconus - pellucid marginal degeneration - keratoglobus - posterior keratoconus - Fuchs Terrien marginal degeneration - differential diagnosis

Schlüsselwörter

Keratokonus - pelluzide marginale Degeneration - Keratoglobus - posteriorer Keratokonus - Fuchs-Terrienʼsche marginale Hornhautdegeneration - Differenzialdiagnose

Publication History

Received: 22 December 2021

Accepted: 30 July 2022

Accepted Manuscript online:
08 August 2022

Article published online:
27 November 2022

• References

• 1 Rabinowitz YS. Keratoconus. Surv Ophthalmol 1998; 42: 297-319
• 2 Shakir O. Stromal Degenerations. In: Schmidt-Erfurth U, Kohnen T. eds. Encyclopedia of Ophthalmology. Berlin, Heidelberg: Springer; 2018: 931-939
• 3 Ertan A, Muftuoglu O. Keratoconus clinical findings according to different age and gender groups. Cornea 2008; 27: 1109-1113
• 4 Gokhale NS. Epidemiology of keratoconus. Indian J Ophthalmol 2013; 61: 382-383
• 5 Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epidemiologic study of keratoconus. Am J Ophthalmol 1986; 101: 267-273
• 6 Flockerzi E, Xanthopoulou K, Goebels SC. et al. Keratoconus staging by decades: a baseline ABCD classification of 1000 patients in the Homburg Keratoconus Center. Br J Ophthalmol 2021; 105: 1069-1075
• 7 Krachmer JH. Pellucid marginal corneal degeneration. Arch Ophthalmol 1978; 96: 1217-1221
• 8 Stankovic I, Stankovic M. Ein Beitrag zur Kenntnis des Keratotorus. Klin Monbl Augenheilkd 1966; 148: 873-879
• 9 Zucchini G. Su di un case di degenerazione marginale della cornea – varieta inferiore pellucida – studio clinic ed istologico. Ann Ottalmol Clin Oculitl 1962; 88: 47-56
• 10 Nelson ME, Talbot JF. Keratoglobus in Rubinstein-Taybi syndrome. Br J Ophthalmol 1989; 73: 385-387
• 11 Biglan AW, Brown SI, Johnson BL. Keratoglobus and blue sclera. Am J Ophthalmol 1977; 83: 225-233
• 12 Meghpara B, Nakamura H, Vemuganti G. et al. Histopathologic and immunohistochemical studies of keratoglobus. Arch Ophthalmol 2009; 127: 1029-1035
• 13 Perkins ES. Myopia and scleral stress. Doc Ophthalmol Proc Series 1981; 28: 121-127
• 14 Butler TH. Two Rare Corneal Conditions: I. Acute Conical Corneal II. Posticus Circumscriptus. Br J Ophthalmol 1932; 16: 30-35
• 15 Silas M, Hilkert S, Reidy J. et al. Posterior keratoconus. Br J Ophthalmol 2018; 102: 863-867
• 16 Krachmer JH, Rodrigues MM. Posterior keratoconus. Arch Ophthalmol 1978; 96: 1867-1873
• 17 Süveges I, Levai G, Alberth B. Pathology of Terrienʼs Disease. Histochemical and electron microscopic study. Am J Ophthalmol 1972; 74: 1191-1200
• 18 Chan AT, Ulate R, Goldich Y. et al. Terrien Marginal Degeneration. Clinical Characteristics and Outcomes. Am J Ophthalmol 2015; 160: 867-872
• 19 Zarei-Ghanavati S, Javadi MA, Yazdani S. Bilateral Terrienʼs Marginal Degeneration and Posterior Polymorphous Dystrophy in a Patient with Rheumatoid Arthritis. J Ophthalmic Vis Res 2012; 7: 60-63
• 20 Imbornoni LM, McGhee CNJ, Belin MW. Evolution of keratoconus: from the diagnosis to therapeutics. Klin Monbl Augenheilkd 2018; 235: 680-688
• 21 Ross JV. Keratoconus posticus generalis. Am J Ophthalmol 1950; 33: 801-803
• 22 Belin MW, Asota IM, Ambrosio jr. R. et al. Whatʼs in a name: keratoconus, pellucid marginal degeneration, and related thinning disorders. Am J Ophthalmol 2011; 152: 157-162
• 23 Fuchihata M, Maeda N, Toda R. et al. Characteristics of corneal topographic and pachymetric patterns in patients with pellucid marginal corneal degeneration. Jpn J Ophthalmol 2013; 58: 131-138
• 24 Koçluk Y, Yalnoz-Akkaya Z, Burcu A. et al. Comparison of Scheimpflug imaging analysis of pellucid marginal corneal degeneration and keratoconus. Ophthalmic Res 2015; 53: 21-27
• 25 Wallang BS, Das S. Keratoglobus. Eye (Lond) 2013; 27: 1004-1012
• 26 Rao S, Padmanabhan P. Posterior keratoconus. An expanded classification scheme based on corneal topography. Ophthalmology 1998; 105: 1206-1212
• 27 Tummanapalli SS, Maseedupally V, Mandathara P. et al. Evaluation of corneal elevation and thickness indices in pellucid marginal degeneration and keratoconus. J Cataract Refract Surg 2013; 39: 56-65
• 28 Martinez-Abad A, Pinero D. Pellucid marginal degeneration: Detection, discrimination from other corneal ectatic disorders and progression. Cont Lens Anterior Eye 2019; 42: 341-349
• 29 Pircher N, Lammer J, Holzer S. et al. Corneal crosslinking for pellucid marginal degeneration. J Cataract Refract Surg 2019; 45: 1163-1167
• 30 Piñero DP, Nieto JC, Lopez-Miguel A. Characterization of corneal structure in keratoconus. J Cataract Refract Surg 2012; 38: 2167-2183
• 31 Sideroudi H, Labiris G, Giarmoukakis A. et al. Contribution of reference bodies in diagnosis of keratoconus. Optom Vis Sci 2014; 91: 676-681
• 32 Koc M, Tekin K, Inanc M. et al. Crab claw pattern on corneal topography: pellucid marginal degeneration or inferior keratoconus?. Eye (Lond) 2018; 32: 11-18
• 33 Piñero DP, Alió JL, Alesón A. et al. Pentacam posterior and anterior corneal aberrations in normal and keratoconic eyes. Clin Exp Optom 2009; 92: 297-303
• 34 Oie Y, Maeda N, Kosaki R. et al. Characteristics of ocular higher order aberrations in patients with pellucid marginal corneal degeneration. J Cataract Refract Surg 2008; 34: 1928-1934
• 35 Sideroudi H, Labiris G, Georgatzoglou K. et al. Fourier analysis of videokeratography data. Clinical usefulness in grade I and subclinical keratoconus. J Cataract Refract Surg 2016; 42: 731-737
• 36 Sideroudi H, Labiris G, Georgantzoglou K. et al. Fourier analysis algorithm for the posterior corneal keratometric data. Clinical usefulness in keratoconus. Ophthalmic Physiol Opt 2017; 37: 460-466
• 37 Grünauer-Kloevekorn C, Fischer U, Kloevekorn-Norgall K. et al. Pellucid marginal corneal degeneration. Evaluation of the corneal surface and contact lens fitting. Br J Ophthalmol 2006; 90: 318-323
• 38 Grünauer-Kloevekorn C, Kloevekorn-Fischer U, Kloevekorn-Norgall K. et al. [Quantitative assessment of topographical parameters to differentiate keratoconus from pellucid marginal corneal degeneration. Klin Monbl Augenheilkd 2005; 222: 874-882
• 39 Lopes B, Ramos I, Ambrósio Jr. R. Corneal densitometry in keratoconus. Cornea 2014; 33: 1282-1286
• 40 Gatzioufas Z, Seitz B. [New aspects on biomechanics of the cornea in keratoconus]. Ophthalmologe 2013; 110: 812-817
• 41 Ren S, Xu L, Fan Q. et al. Accuracy of new Corvis ST parameters for detecting subclinical and clinical keratoconus eyes in a Chinese population. Sci Rep 2021; 11: 4962-4972
• 42 Flockerzi E, Häfner L, Xanthopoulou K. et al. Reliability analysis of successive Corneal Visualization Scheimpflug Technology measurements in different keratoconus stages. Acta Ophthalmol 2022; 100: e83-e90
• 43 Flockerzi E, Vinciguerra R, Belin MW. et al. Combined biomechanical and tomographic keratoconus staging: Adding a biomechanical parameter to the ABCD keratoconus staging system. Acta Ophthalmol 2022; 100: e1135-e1142
• 44 Labiris G, Giarmoukakis A, Gatzioufas Z. et al. Diagnostic capacity of the keratoconus match index and keratoconus match probability in subclinical keratoconus. J Cataract Refract Surg 2014; 40: 999-1005
• 45 Elham R, Jafarzadehpur E, Hashemi H. et al. Keratoconus diagnosis using Corvis ST measured biomechanical parameters. J Curr Ophthalmol 2017; 29: 175-181
• 46 Labiris G, Giarmoukakis A, Sideroudi H. et al. Diagnostic capacity of biomechanical indices from a dynamic bidirectional applanation device in pellucid marginal degeneration. J Cataract Refract Surg 2014; 40: 1006-1012
• 47 Sedaghat MR, Ostadi-Maghadam H, Jabbarvand M. et al. Corneal hysteresis and corneal resistance factor in pellucid marginal degeneration. J Curr Ophthalmol 2017; 30: 42-47
• 48 Uçakhan OO, Kanpolat A, Ylmaz N. et al. In vivo confocal microscopy findings in keratoconus. Eye Contact Lens 2006; 32: 183-191
• 49 Flockerzi E, Daas L, Seitz B. Structural changes in the corneal nerve plexus in keratoconus. Acta Ophthalmol 2020; 98: 928-932
• 50 Di Silvestre L, Mularoni A, Casamenti V. et al. Cornea in Pellucid Marginal Degeneration: In vivo Confocal Microscopy Analysis Before and After the Treatment with Intra Corneal Ring (ICR). IOVS 2005; (46) 2719
• 51 Chen T, Li Q, Tang X. et al. In Vivo Confocal Microscopy of Cornea in Patients with Terrienʼs Marginal Corneal Degeneration. J Ophthalmol 2019; 2019: 1-8
• 52 Levy A, Georgeon C, Knoeri J. et al. Corneal Epithelial Thickness Mapping in the Diagnosis of Ocular Surface Disorders Involving the Corneal Epithelium: A Comparative Study. Cornea 2022;
• 53 Lahme L, Storp JJ, Diener R. et al. [Corneal epithelial thickness in keratoconus patients compared to healthy controls]. Ophthalmologe 2022;
• 54 Serrao S, Lombardo G, Calì C, Lombardo M. Role of corneal epithelial thickness mapping in the evaluation of keratoconus. Cont Lens Anterior Eye 2019; 42: 662-665
• 55 Mohr N, Shajari M, Krause D. et al. Pellucid marginal degeneration versus keratoconus: distinction with wide-field SD-OCT corneal sublayer pachymetry. Br J Ophthalmol 2021; 105: 1638-1644