Genetic and biomechanical factors in keratoconus: a review of pathogenic mechanisms, diagnostic strategies, and risk stratification
DOI:
https://doi.org/10.12775/QS.2026.56.72548Keywords
Keratoconus, Corneal biomechanics, Genetics, Corneal imaging, Corneal ectasiaAbstract
Background. Keratoconus (KC) is a progressive, asymmetric corneal ectasia driven by inherited extracellular matrix variation that establishes a baseline biomechanical phenotype on which eye rubbing and atopy precipitate disease.
Aim. To synthesize current evidence on the genetic architecture, the biomechanical phenotype, and the diagnostic strategies that integrate them.
Materials and methods. A structured search of PubMed, Scopus, Web of Science, Google Scholar and bioRxiv covered primary research and meta-analyses on KC genetics, biomechanics, epidemiology, environmental risk, imaging and machine-learning diagnostics (1996–2026, plus selected earlier seminal papers).
Results. Tomography-era prevalence reaches 1:375 in Northern European registries and over 1% in Scheimpflug-screened cohorts. GWAS implicates matrix-organizing loci (ZNF469, LOX, COL5A1, WNT10A) and corneal-thickness genes shared with Mendelian connective-tissue disease; a corneal-hysteresis GWAS bridges the genetic and biomechanical strands. In vivo metrics (corneal hysteresis, stress-strain index, Brillouin shift) and combined tomographic-biomechanical indices achieve AUCs above 0.99 for manifest disease and for detecting subclinical KC below the tomographic floor.
Conclusions. Integrating genetic risk, biomechanical phenotyping and AI-based imaging enables earlier diagnosis, sharper risk stratification and better-timed cross-linking; multi-ancestry genetic studies and prospective biomechanical cohorts are research priorities.
References
References
1. JH Krachmer, RS Feder, MW Belin. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol. 1984;28(4):293–322. doi:10.1016/0039-6257(84)90094-8 PubMed PMID: 6230745.
2. YS Rabinowitz. Keratoconus. Surv Ophthalmol. 1998;42(4):297–319. doi:10.1016/s0039-6257(97)00119-7 PubMed PMID: 9493273.
3. RB Singh, S Koh, N Sharma, FA Woreta, F Hafezi, HS Dua, V Jhanji. Keratoconus. Nat Rev Dis Primers. 2024;10(1):81. doi:10.1038/s41572-024-00565-3 PubMed PMID: 39448666.
4. SEM Lucas, KP Burdon. Genetic and Environmental Risk Factors for Keratoconus. Annu Rev Vis Sci. 2020;6:25–46. doi:10.1146/annurev-vision-121219-081723 PubMed PMID: 32320633.
5. DA Godefrooij, GA de Wit, CS Uiterwaal, SM Imhof, RP Wisse. Age-specific Incidence and Prevalence of Keratoconus: A Nationwide Registration Study. Am J Ophthalmol. 2017;175:169–72. doi:10.1016/j.ajo.2016.12.015 PubMed PMID: 28039037.
6. S Bak-Nielsen, CH Ramlau-Hansen, A Ivarsen, O Plana-Ripoll, J Hjortdal. Incidence and prevalence of keratoconus in Denmark – an update. Acta Ophthalmol. 2019;97(8):752–5. doi:10.1111/aos.14082 PubMed PMID: 30964230.
7. S Hwang, DH Lim, TY Chung. Prevalence and Incidence of Keratoconus in South Korea: A Nationwide Population-based Study. Am J Ophthalmol. 2018;192:56–64. doi:10.1016/j.ajo.2018.04.027 PubMed PMID: 29750946.
8. H Hashemi, S Heydarian, E Hooshmand, M Saatchi, A Yekta, M Aghamirsalim, M Valadkhan, M Mortazavi, A Hashemi, M Khabazkhoob. The Prevalence and Risk Factors for Keratoconus: A Systematic Review and Meta-Analysis. Cornea. 2020;39(2):263–70. doi:10.1097/ICO.0000000000002150 PubMed PMID: 31498247.
9. E Chan, EW Chong, G Lingham, LJ Stevenson, PG Sanfilippo, AW Hewitt, DA Mackey, S Yazar. Prevalence of Keratoconus Based on Scheimpflug Imaging: The Raine Study. Ophthalmology. 2021;128(4):515–21. doi:10.1016/j.ophtha.2020.08.020 PubMed PMID: 32860813.
10. M Millodot, E Shneor, S Albou, E Atlani, A Gordon-Shaag. Prevalence and associated factors of keratoconus in Jerusalem: a cross-sectional study. Ophthalmic Epidemiol. 2011;18(2):91–7. doi:10.3109/09286586.2011.560747 PubMed PMID: 21401417.
11. H Hashemi, S Heydarian, A Yekta, H Ostadimoghaddam, M Aghamirsalim, A Derakhshan, M Khabazkhoob. High prevalence and familial aggregation of keratoconus in an Iranian rural population: a population-based study. Ophthalmic Physiol Opt. 2018;38(4):447–55. doi:10.1111/opo.12448 PubMed PMID: 29572900.
12. ST Awwad, M Yehia, CJ Mehanna, MA Fattah, A Saad, A Hatoum, C Al-Haddad. Tomographic and Refractive Characteristics of Pediatric First-Degree Relatives of Keratoconus Patients. Am J Ophthalmol. 2019;207:71–6. doi:10.1016/j.ajo.2019.05.032 PubMed PMID: 31194951.
13. KM Meek, SJ Tuft, Y Huang, PS Gill, S Hayes, RH Newton, AJ Bron. Changes in collagen orientation and distribution in keratoconus corneas. Invest Ophthalmol Vis Sci. 2005;46(6):1948–56. doi:10.1167/iovs.04-1253 PubMed PMID: 15914608.
14. N Morishige, AJ Wahlert, MC Kenney, DJ Brown, K Kawamoto, T Chikama, T Nishida, JV Jester. Second-harmonic imaging microscopy of normal human and keratoconus cornea. Invest Ophthalmol Vis Sci. 2007;48(3):1087–94. doi:10.1167/iovs.06-1177 PubMed PMID: 17325150.
15. SA Collier, MC Madigan, PL Penfold. Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) and MMP-2 in normal and keratoconus corneas. Curr Eye Res. 2000;21(2):662–8. PubMed PMID: 11148603.
16. M Kabza, JA Karolak, M Rydzanicz, MW Szcześniak, DM Nowak, B Ginter-Matuszewska, P Polakowski, R Ploski, JP Szaflik, M Gajecka. Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas. Eur J Hum Genet. 2017;25(5):582–90. doi:10.1038/ejhg.2017.4 PubMed PMID: 28145428.
17. Y Bykhovskaya, X Li, I Epifantseva, T Haritunians, D Siscovick, A Aldave, L Szczotka-Flynn, SK Iyengar, KD Taylor, JI Rotter, YS Rabinowitz. Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies. Invest Ophthalmol Vis Sci. 2012;53(7):4152–7. doi:10.1167/iovs.11-9268 PubMed PMID: 22661479.
18. MC Kenney, M Chwa, SR Atilano, A Tran, M Carballo, M Saghizadeh, V Vasiliou, W Adachi, DJ Brown. Increased levels of catalase and cathepsin V/L2 but decreased TIMP-1 in keratoconus corneas: evidence that oxidative stress plays a role in this disorder. Invest Ophthalmol Vis Sci. 2005;46(3):823–32. doi:10.1167/iovs.04-0549 PubMed PMID: 15728537.
19. M Chwa, SR Atilano, V Reddy, N Jordan, DW Kim, MC Kenney. Increased stress-induced generation of reactive oxygen species and apoptosis in human keratoconus fibroblasts. Invest Ophthalmol Vis Sci. 2006;47(5):1902–10. doi:10.1167/iovs.05-0828 PubMed PMID: 16638997.
20. V Navel, J Malecaze, B Pereira, JS Baker, F Malecaze, V Sapin, F Chiambaretta, F Dutheil. Oxidative and antioxidative stress markers in keratoconus: a systematic review and meta-analysis. Acta Ophthalmol. 2020;99(6):e777–94. doi:10.1111/aos.14714 PubMed PMID: 33354927.
21. C Engler, S Chakravarti, J Doyle, CG Eberhart, H Meng, WJ Stark, C Kelliher, AS Jun. Transforming growth factor-β signaling pathway activation in Keratoconus. Am J Ophthalmol. 2011;151(5):752–759.e2. doi:10.1016/j.ajo.2010.11.008 PubMed PMID: 21310385.
22. M Kabza, JA Karolak, M Rydzanicz, M Udziela, P Gasperowicz, R Ploski, JP Szaflik, M Gajecka. Multiple Differentially Methylated Regions Specific to Keratoconus Explain Known Keratoconus Linkage Loci. Invest Ophthalmol Vis Sci. 2019;60(5):1501–9. doi:10.1167/iovs.18-25916 PubMed PMID: 30994860.
23. I Lema, JA Durán. Inflammatory molecules in the tears of patients with keratoconus. Ophthalmology. 2005;112(4):654–9. doi:10.1016/j.ophtha.2004.11.050 PubMed PMID: 15808258.
24. V Galvis, T Sherwin, A Tello, J Merayo, R Barrera, A Acera. Keratoconus: an inflammatory disorder? Eye (Lond). 2015;29(7):843–59. doi:10.1038/eye.2015.63 PubMed PMID: 25931166.
25. Y Wang, YS Rabinowitz, JI Rotter, H Yang. Genetic epidemiological study of keratoconus: evidence for major gene determination. Am J Med Genet. 2000;93(5):403–9. PubMed PMID: 10951465.
26. SJ Tuft, H Hassan, S George, DG Frazer, CE Willoughby, P Liskova. Keratoconus in 18 pairs of twins. Acta Ophthalmol. 2012;90(6):e482–6. doi:10.1111/j.1755-3768.2012.02448.x PubMed PMID: 22682160.
27. SS Rong, STU Ma, XT Yu, L Ma, WK Chu, TCY Chan, YM Wang, AL Young, CP Pang, V Jhanji, LJ Chen. Genetic associations for keratoconus: a systematic review and meta-analysis. Sci Rep. 2017;7(1):4620. doi:10.1038/s41598-017-04393-2 PubMed PMID: 28676647.
28. J Lechner, LF Porter, A Rice, V Vitart, DJ Armstrong, DF Schorderet, FL Munier, AF Wright, CF Inglehearn, GC Black, DA Simpson, F Manson, CE Willoughby. Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus. Hum Mol Genet. 2014;23(20):5527–35. doi:10.1093/hmg/ddu253 PubMed PMID: 24895405.
29. Y Lu, V Vitart, KP Burdon, CC Khor, Y Bykhovskaya, A Mirshahi, AW Hewitt, D Koehn, PG Hysi, WD Ramdas, T Zeller, EN Vithana, BK Cornes, WT Tay, ES Tai, CY Cheng, J Liu, JN Foo, SM Saw, G Thorleifsson, K Stefansson, DP Dimasi, RA Mills, J Mountain, W Ang, R Hoehn, VJ Verhoeven, F Grus, R Wolfs, R Castagne, KJ Lackner, H Springelkamp, J Yang, F Jonasson, DY Leung, LJ Chen, CC Tham, I Rudan, Z Vatavuk, C Hayward, J Gibson, AJ Cree, A MacLeod, S Ennis, O Polasek, H Campbell, JF Wilson, AC Viswanathan, B Fleck, X Li, D Siscovick, KD Taylor, JI Rotter, S Yazar, M Ulmer, J Li, BL Yaspan, AB Ozel, JE Richards, SE Moroi, JL Haines, JH Kang, LR Pasquale, RR Allingham, A Ashley-Koch, P Mitchell, JJ Wang, AF Wright, C Pennell, TD Spector, TL Young, CC Klaver, NG Martin, GW Montgomery, MG Anderson, T Aung, CE Willoughby, JL Wiggs, CP Pang, U Thorsteinsdottir, AJ Lotery, CJ Hammond, CM van Duijn, MA Hauser, YS Rabinowitz, N Pfeiffer, DA Mackey, JE Craig, S Macgregor, TY Wong. Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nat Genet. 2013;45(2):155–63. doi:10.1038/ng.2506 PubMed PMID: 23291589.
30. E Héon, A Greenberg, KK Kopp, D Rootman, AL Vincent, G Billingsley, M Priston, KM Dorval, RL Chow, RR McInnes, G Heathcote, C Westall, JE Sutphin, E Semina, R Bremner, EM Stone. VSX1: a gene for posterior polymorphous dystrophy and keratoconus. Hum Mol Genet. 2002;11(9):1029–36. doi:10.1093/hmg/11.9.1029 PubMed PMID: 11978762.
31. Y Bykhovskaya, AL Caiado Canedo, KW Wright, YS Rabinowitz. C.57 C > T Mutation in MIR 184 is Responsible for Congenital Cataracts and Corneal Abnormalities in a Five-generation Family from Galicia, Spain. Ophthalmic Genet. 2015;36(3):244–7. doi:10.3109/13816810.2013.848908 PubMed PMID: 24138095.
32. N Udar, SR Atilano, DJ Brown, B Holguin, K Small, AB Nesburn, MC Kenney. SOD1: a candidate gene for keratoconus. Invest Ophthalmol Vis Sci. 2006;47(8):3345–51. doi:10.1167/iovs.05-1500 PubMed PMID: 16877401.
33. KP Burdon, S Macgregor, Y Bykhovskaya, S Javadiyan, X Li, KJ Laurie, D Muszynska, R Lindsay, J Lechner, T Haritunians, AK Henders, D Dash, D Siscovick, S Anand, A Aldave, DJ Coster, L Szczotka-Flynn, RA Mills, SK Iyengar, KD Taylor, T Phillips, GW Montgomery, JI Rotter, AW Hewitt, S Sharma, YS Rabinowitz, C Willoughby, JE Craig. Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus. Invest Ophthalmol Vis Sci. 2011;52(11):8514–9. doi:10.1167/iovs.11-8261 PubMed PMID: 22003120.
34. AI Iglesias, A Mishra, V Vitart, Y Bykhovskaya, R Höhn, H Springelkamp, G Cuellar-Partida, P Gharahkhani, JNC Bailey, CE Willoughby, X Li, S Yazar, A Nag, AP Khawaja, O Polašek, D Siscovick, P Mitchell, YC Tham, JL Haines, LS Kearns, C Hayward, Y Shi, EM van Leeuwen, KD Taylor, P Bonnemaijer, JI Rotter, NG Martin, T Zeller, RA Mills, E Souzeau, SE Staffieri, JB Jonas, I Schmidtmann, T Boutin, JH Kang, SEM Lucas, TY Wong, ME Beutel, JF Wilson, AG Uitterlinden, EN Vithana, PJ Foster, PG Hysi, AW Hewitt, CC Khor, LR Pasquale, GW Montgomery, CCW Klaver, T Aung, N Pfeiffer, DA Mackey, CJ Hammond, CY Cheng, JE Craig, YS Rabinowitz, JL Wiggs, KP Burdon, CM van Duijn, S MacGregor. Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. Nat Commun. 2018;9(1):1864. doi:10.1038/s41467-018-03646-6 PubMed PMID: 29760442.
35. G Cuellar-Partida, H Springelkamp, SE Lucas, S Yazar, AW Hewitt, AI Iglesias, GW Montgomery, NG Martin, CE Pennell, EM van Leeuwen, VJ Verhoeven, A Hofman, AG Uitterlinden, WD Ramdas, RC Wolfs, JR Vingerling, MA Brown, RA Mills, JE Craig, CC Klaver, CM van Duijn, KP Burdon, S MacGregor, DA Mackey. WNT10A exonic variant increases the risk of keratoconus by decreasing corneal thickness. Hum Mol Genet. 2015;24(17):5060–8. doi:10.1093/hmg/ddv211 PubMed PMID: 26049155.
36. AJ Hardcastle, P Liskova, Y Bykhovskaya, BJ McComish, AE Davidson, CF Inglehearn, X Li, H Choquet, M Habeeb, SEM Lucas, S Sahebjada, N Pontikos, KER Lopez, AP Khawaja, M Ali, L Dudakova, P Skalicka, BTH Van Dooren, AJM Geerards, CW Haudum, VL Faro, A Tenen, MJ Simcoe, K Patasova, D Yarrand, J Yin, S Siddiqui, A Rice, LA Farraj, YI Chen, JS Rahi, RM Krauss, E Theusch, JC Charlesworth, L Szczotka-Flynn, C Toomes, MA Meester-Smoor, AJ Richardson, PA Mitchell, KD Taylor, RB Melles, AJ Aldave, RA Mills, K Cao, E Chan, MD Daniell, JJ Wang, JI Rotter, AW Hewitt, S MacGregor, CCW Klaver, WD Ramdas, JE Craig, SK Iyengar, D O’Brart, E Jorgenson, PN Baird, YS Rabinowitz, KP Burdon, CJ Hammond, SJ Tuft, PG Hysi. A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus. Commun Biol. 2021;4(1):266. doi:10.1038/s42003-021-01784-0 PubMed PMID: 33649486.
37. AP Khawaja, KE Rojas Lopez, AJ Hardcastle, CJ Hammond, P Liskova, AE Davidson, DM Gore, NJ Hafford Tear, N Pontikos, S Hayat, N Wareham, KT Khaw, SJ Tuft, PJ Foster, PG Hysi. Genetic Variants Associated With Corneal Biomechanical Properties and Potentially Conferring Susceptibility to Keratoconus in a Genome-Wide Association Study. JAMA Ophthalmol. 2019;137(9):1005–12. doi:10.1001/jamaophthalmol.2019.2058 PubMed PMID: 31246245.
38. O Kristianslund, L Drolsum. Prevalence of keratoconus in persons with Down syndrome: a review. BMJ Open Ophthalmol. 2021;6(1):e000754. doi:10.1136/bmjophth-2021-000754 PubMed PMID: 33981858.
39. EMM Burkitt Wright, HL Spencer, SB Daly, FDC Manson, LAH Zeef, J Urquhart, N Zoppi, R Bonshek, I Tosounidis, M Mohan, C Madden, A Dodds, KE Chandler, S Banka, L Au, J Clayton-Smith, N Khan, LG Biesecker, M Wilson, M Rohrbach, M Colombi, C Giunta, GCM Black. Mutations in PRDM5 in brittle cornea syndrome identify a pathway regulating extracellular matrix development and maintenance. Am J Hum Genet. 2011;88(6):767–77. doi:10.1016/j.ajhg.2011.05.007 PubMed PMID: 21664999.
40. W He, U Võsa, T Palumaa, JS Ong, SD Torres, AW Hewitt, DA Mackey, P Gharahkhani, T Esko, S MacGregor. Developing and validating a comprehensive polygenic risk score to enhance keratoconus risk prediction. Hum Mol Genet. 2025;34(2):140–7. doi:10.1093/hmg/ddae157 PubMed PMID: 39535071.
41. J Sugar, MS Macsai. What causes keratoconus? Cornea. 2012;31(6):716–9. doi:10.1097/ICO.0b013e31823f8c72 PubMed PMID: 22406940.
42. CW McMonnies, GC Boneham. Keratoconus, allergy, itch, eye-rubbing and hand-dominance. Clin Exp Optom. 2003;86(6):376–84. doi:10.1111/j.1444-0938.2003.tb03082.x PubMed PMID: 14632614.
43. I Seth, G Bulloch, M Vine, J Outmezguine, N Seth, J Every, M Daniell. The association between keratoconus and allergic eye diseases: A systematic review and meta-analysis. Clin Exp Ophthalmol. 2023;51(4):O1–16. doi:10.1111/ceo.14215 PubMed PMID: 36882200.
44. A Mazharian, R Flamant, S Elahi, C Panthier, R Rampat, D Gatinel. Medium to long term follow up study of the efficacy of cessation of eye-rubbing to halt progression of keratoconus. Front Med (Lausanne). 2023;10:1152266. doi:10.3389/fmed.2023.1152266 PubMed PMID: 37293301.
45. K Jaskiewicz, M Maleszka-Kurpiel, A Michalski, R Ploski, M Rydzanicz, M Gajecka. Non-allergic eye rubbing is a major behavioral risk factor for keratoconus. PLoS One. 2023;18(4):e0284454. doi:10.1371/journal.pone.0284454 PubMed PMID: 37053215.
46. M Naderan, MT Rajabi, P Zarrinbakhsh, A Bakhshi. Effect of Allergic Diseases on Keratoconus Severity. Ocul Immunol Inflamm. 2016;25(3):418–23. doi:10.3109/09273948.2016.1145697 PubMed PMID: 27014800.
47. MC Kenney, DJ Brown. The cascade hypothesis of keratoconus. Cont Lens Anterior Eye. 2003;26(3):139–46. doi:10.1016/S1367-0484(03)00022-5 PubMed PMID: 16303509.
48. CJ Roberts, WJ Dupps. Biomechanics of corneal ectasia and biomechanical treatments. J Cataract Refract Surg. 2014;40(6):991–8. doi:10.1016/j.jcrs.2014.04.013 PubMed PMID: 24774009.
49. N Falgayrettes, E Patoor, F Cleymand, Y Zevering, JM Perone. Biomechanics of keratoconus: Two numerical studies. PLoS One. 2023;18(2):e0278455. doi:10.1371/journal.pone.0278455 PubMed PMID: 36730305.
50. DA Luce. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg. 2005;31(1):156–62. doi:10.1016/j.jcrs.2004.10.044 PubMed PMID: 15721708.
51. A Eliasy, KJ Chen, R Vinciguerra, BT Lopes, A Abass, P Vinciguerra, R Ambrósio, CJ Roberts, A Elsheikh. Determination of Corneal Biomechanical Behavior for Healthy Eyes Using CorVis ST Tonometry: Stress-Strain Index. Front Bioeng Biotechnol. 2019;7:105. doi:10.3389/fbioe.2019.00105 PubMed PMID: 31157217.
52. G Scarcelli, S Besner, R Pineda, SH Yun. Biomechanical characterization of keratoconus corneas ex vivo with Brillouin microscopy. Invest Ophthalmol Vis Sci. 2014;55(7):4490–5. doi:10.1167/iovs.14-14450 PubMed PMID: 24938517.
53. C Kirwan, D O’Malley, M O’Keefe. Corneal hysteresis and corneal resistance factor in keratoectasia: findings using the Reichert ocular response analyzer. Ophthalmologica. 2008;222(5):334–7. doi:10.1159/000145333 PubMed PMID: 18628636.
54. P Padmanabhan, BT Lopes, A Eliasy, A Abass, R Vinciguerra, P Vinciguerra, R Ambrósio, A Elsheikh. Evaluation of corneal biomechanical behavior in vivo for healthy and keratoconic eyes using the stress-strain index. J Cataract Refract Surg. 2022;48(10):1162–7. doi:10.1097/j.jcrs.0000000000000945 PubMed PMID: 35333824.
55. R Vinciguerra, R Ambrósio, A Elsheikh, CJ Roberts, B Lopes, E Morenghi, C Azzolini, P Vinciguerra. Detection of Keratoconus With a New Biomechanical Index. J Refract Surg. 2016;32(12):803–10. doi:10.3928/1081597X-20160629-01 PubMed PMID: 27930790.
56. R Ambrósio, BT Lopes, F Faria-Correia, MQ Salomão, J Bühren, CJ Roberts, A Elsheikh, R Vinciguerra, P Vinciguerra. Integration of Scheimpflug-Based Corneal Tomography and Biomechanical Assessments for Enhancing Ectasia Detection. J Refract Surg. 2017;33(7):434–43. doi:10.3928/1081597X-20170426-02 PubMed PMID: 28681902.
57. R Ambrósio, AP Machado, E Leão, JMG Lyra, MQ Salomão, LGP Esporcatte, JBR da Fonseca Filho, E Ferreira-Meneses, NB Sena, JS Haddad, A Costa Neto, GC de Almeida, CJ Roberts, A Elsheikh, R Vinciguerra, P Vinciguerra, J Bühren, T Kohnen, GM Kezirian, F Hafezi, NL Hafezi, EA Torres-Netto, N Lu, DSY Kang, O Kermani, S Koh, P Padmanabhan, S Taneri, W Trattler, L Gualdi, J Salgado-Borges, F Faria-Correia, E Flockerzi, B Seitz, V Jhanji, TCY Chan, PM Baptista, DZ Reinstein, TJ Archer, KM Rocha, GO Waring, RR Krueger, WJ Dupps, R Khoramnia, H Hashemi, S Asgari, H Momeni-Moghaddam, S Zarei-Ghanavati, R Shetty, P Khamar, MW Belin, BT Lopes. Optimized Artificial Intelligence for Enhanced Ectasia Detection Using Scheimpflug-Based Corneal Tomography and Biomechanical Data. Am J Ophthalmol. 2023;251:126–42. doi:10.1016/j.ajo.2022.12.016 PubMed PMID: 36549584.
58. G Wollensak, E Spoerl, T Seiler. Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-A-induced cross-linking. J Cataract Refract Surg. 2003;29(9):1780–5. doi:10.1016/s0886-3350(03)00407-3 PubMed PMID: 14522301.
59. R Vinciguerra, R Ambrósio, CJ Roberts, C Azzolini, P Vinciguerra. Biomechanical Characterization of Subclinical Keratoconus Without Topographic or Tomographic Abnormalities. J Refract Surg. 2017;33(6):399–407. doi:10.3928/1081597X-20170213-01 PubMed PMID: 28586501.
60. JB Randleman, H Zhang, L Asroui, I Tarib, WJ Dupps, G Scarcelli. Subclinical Keratoconus Detection and Characterization Using Motion-Tracking Brillouin Microscopy. Ophthalmology. 2024;131(3):310–21. doi:10.1016/j.ophtha.2023.10.011 PubMed PMID: 37839561.
61. YS Rabinowitz, K Rasheed. KISA% index: a quantitative videokeratography algorithm embodying minimal topographic criteria for diagnosing keratoconus. J Cataract Refract Surg. 1999;25(10):1327–35. doi:10.1016/s0886-3350(99)00195-9 PubMed PMID: 10511930.
62. MW Belin, JK Duncan. Keratoconus: The ABCD Grading System. Klin Monbl Augenheilkd. 2016;233(6):701–7. doi:10.1055/s-0042-100626 PubMed PMID: 26789119.
63. E Flockerzi, K Xanthopoulou, SC Goebels, E Zemova, S Razafimino, L Hamon, T Jullien, U Klühspies, T Eppig, A Langenbucher, B Seitz. Keratoconus staging by decades: a baseline ABCD classification of 1000 patients in the Homburg Keratoconus Center. Br J Ophthalmol. 2020;105(8):1069–75. doi:10.1136/bjophthalmol-2020-316789 PubMed PMID: 32830125.
64. DZ Reinstein, TJ Archer, R Urs, M Gobbe, A RoyChoudhury, RH Silverman. Detection of Keratoconus in Clinically and Algorithmically Topographically Normal Fellow Eyes Using Epithelial Thickness Analysis. J Refract Surg. 2015;31(11):736–44. doi:10.3928/1081597X-20151021-02 PubMed PMID: 26544561.
65. RH Silverman, R Urs, A RoyChoudhury, TJ Archer, M Gobbe, DZ Reinstein. Combined tomography and epithelial thickness mapping for diagnosis of keratoconus. Eur J Ophthalmol. 2017;27(2):129–34. doi:10.5301/ejo.5000850 PubMed PMID: 27515569.
66. D Smadja, D Touboul, A Cohen, E Doveh, MR Santhiago, GR Mello, RR Krueger, J Colin. Detection of subclinical keratoconus using an automated decision tree classification. Am J Ophthalmol. 2013;156(2):237–246.e1. doi:10.1016/j.ajo.2013.03.034 PubMed PMID: 23746611.
67. A Lavric, P Valentin. KeratoDetect: Keratoconus Detection Algorithm Using Convolutional Neural Networks. Comput Intell Neurosci. 2019;2019:8162567. doi:10.1155/2019/8162567 PubMed PMID: 30809255.
68. BI Kuo, WY Chang, TS Liao, FY Liu, HY Liu, HS Chu, WL Chen, FR Hu, JY Yen, IJ Wang. Keratoconus Screening Based on Deep Learning Approach of Corneal Topography. Transl Vis Sci Technol. 2020;9(2):53. doi:10.1167/tvst.9.2.53 PubMed PMID: 33062398.
69. H Abdelmotaal, RM Hazarbassanov, R Salouti, MH Nowroozzadeh, S Taneri, AH Al-Timemy, A Lavric, S Yousefi. Keratoconus Detection-based on Dynamic Corneal Deformation Videos Using Deep Learning. Ophthalmol Sci. 2023;4(2):100380. doi:10.1016/j.xops.2023.100380 PubMed PMID: 37868800.
70. H Hashemi, F Doroodgar, S Niazi, M Khabazkhoob, Z Heidari. Comparison of different corneal imaging modalities using artificial intelligence for diagnosis of keratoconus: a systematic review and meta-analysis. Graefes Arch Clin Exp Ophthalmol. 2023;262(4):1017–39. doi:10.1007/s00417-023-06154-6 PubMed PMID: 37418053.
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Copyright (c) 2026 Wiktoria Pielak, Jakub Koszewski , Anna Janiszewska, Wiktor Kołkowski, Jan Jakubczyk , Monika Wądołowska, Magdalena Antoszewska, Maria Grabowska, Katarzyna Gozdera, Katarzyna Oszast
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