Primum Non Nocere: Resources & Litrature

Question: Where Can a Practice Find Everything They Need to Manage Keratoconus?

Answer: You Can Get Off to a Flying Start Right Here!



Keratoconus (KC) broadly requires a thorough comprehension of the disorder and of its management. In simple sum-up, KC is a corneal disorder that progresses and necessitates prompt early diagnosis and  treatment of progression when required and on-going monitoring as required too. 

Detection of early Keratoconus remains challenging as there is no globally accepted definition for defining the diagnosis and progression of Keratoconus. There is currently no standard diagnostic or grading system for keratoconus which everyone agrees on. Additionally, there is no accepted definition of progression, and no ability to predict the prognosis and outcomes of treatment for individual patients.

The economic burden and vision-related quality of life are factors which can be run away to be disproportionately high in it's toll, which is a real concern including the incidence of the disease being historically reported significantly lower than we at length have known it to really be. Furthermore than that, there are much more increased incidences in certain populations which are very concerning in scope.

The aetiology of Keratoconus remains unknown, although it appears to be a complex, heterogeneous disorder with multiple causative factors that can be broadly classified as environmental, biomechanical, biochemical and genetic. The most likely mode of inheritance has been suggested as autosomal dominant although recessive genes may also exist. An association with environmental and biomechanical factors is often described, with mechanical trauma from eye-rubbing, stimulation through contact lens wear or kerato-refractive laser surgery reported as contributing factors in the progression of Keratoconus. The possible role of biochemical factors has also been implicated in the aetiology of this disease with elevated levels of matrix metalloproteinases and inflammatory cytokines found in Keratoconus. However, it is unclear if this is reflective of a cause or effect.

Contact lenses and surgical procedures can both be used to improve vision. The most crucial aspect of management is provider cooperation to achieve the best outcome. If you want to learn more, you should use other educational resources in addition to what information you have. Sadly, numerous resources will cover approaches which are contradictory or conflicting to each other. This may be due to 'bad science' or incomplete science or because there is one or more financial interests at play, and which is what is at the center of the matters becoming skewed and the reason for the information being corrupt. However Peer-Reviewed studies from respected Journals are the standard bearers to rely on for well developed critical observation, examination and scrutiny, which may take long term results to achieve. 

‘The patient is the final judge’

 Literature 

For further insight on the key topics please take a moment to lookup (the resources listed above and) the following widely accepted literature publications.

Further Reading Index

Keratoconus Prevalence

Etiology, Pathophysiology, Genetics, and Associated Disease

Corneal Biomechanics and Its Relationship to Keratoconus

Optics of Keratoconus and Correcting Aberrations with Wavefront-Guided Lenses

Diagnostics and Monitoring

Pediatrics and Keratoconus

Corneal Crosslinking for Keratoconus and Corneal Ectasia

Surgical Management of Keratoconus

Specialty Contact Lenses for Keratoconus

Collaborative Care in Keratoconus

Clinical Pearls for Communicating with Keratoconic Patients

Keratoconus Prevalence

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4 Gorskova EN, Sevost’ianov EN. Epidemiology of keratoconus in the Urals. Vestn Oftalmol. 1998;114(4):38-40.

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7 Nielsen K, Hjortdal J, Pihlmann M, Corydon TJ. Update on the keratoconus genetics. Acta Ophthalmol. 2013;91(2):106-113.

8 Pizzarello LD. Refractive changes in pregnancy. Graefes Arch Clin Exp Ophthalmol. 2003;241(6):484-488.

9 Tanabe U, Fujiki K, Ogawa A, Ueda S, Kanai A. Prevalence of keratoconus patients in Japan. Nippon Ganka Gakkai Zasshi. 1985;89(3):407-411.

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11 Jonas JB, Nangia V, Matin A, Kulkarni M, Bhojwani K. Prevalence and associations of 

keratoconus in rural maharashtra in central India: the central India eye and medical study. Am J Ophthalmol. 2009;148(5):760-765.

12 Xu L, Wang YX, Guo Y, You QS, Jonas JB, Beijing Eye Study G. Prevalence and asso ciations of steep cornea/keratoconus in Greater Beijing. The Beijing Eye Study. PLoS One. 2012;7(7):e39313.

13 Assiri AA, Yousuf BI, Quantock AJ, Murphy PJ. Incidence and severity of keratoconus in Asir province, Saudi Arabia. Br J Ophthalmol. 2005;89(11):1403-1406.

14 Hashemi H, Khabazkhoob M, Fotouhi A. Topographic Keratoconus is not Rare in an Iranian population: the Tehran Eye Study. Ophthalmic Epidemiol. 2013;20(6):385-391.

15 Hashemi H, Khabazkhoob M, Yazdani N, et al. The prevalence of keratoconus in a young population in Mashhad, Iran. Ophthalmic Physiol Opt. 2014;34(5):519-527.

16 Millodot M, Shneor E, Albou S, Atlani E, Gordon-Shaag A. Prevalence and associated factors of keratoconus in Jerusalem: a cross-sectional study. Ophthalmic Epidemiol. 2011;18(2):91-97.

17 Ziaei H, Jafarinasab MR, Javadi MA, et al. Epidemiology of keratoconus in an Iranian population. Cornea. 2012;31(9):1044-1047.

18 Torres Netto EA, Al-Otaibi WM, Hafezi NL, et al. Prevalence of keratoconus in paedi atric patients in Riyadh, Saudi Arabia. Br J Ophthalmol. 2018;102(10):1436-1441.

19 Lucas SEM, Burdon KP. Genetic and Environmental Risk Factors for Keratoconus. Annu Rev Vis Sci. 2020;6:25-46.

20 Weed KH, MacEwen CJ, Giles T, Low J, McGhee CN. The Dundee University Scottish Keratoconus study: demographics, corneal signs, associated diseases, and eye rubbing. Eye (Lond). 2008;22(4):534-541

21 Gordon-Shaag A, Millodot M, Shneor E, Liu Y. The genetic and environmental factors for keratoconus. Biomed Res Int. 2015;2015:795738.

22 Hafezi F, Hafezi NL, Pajic B, et al. Assessment of the mechanical forces applied during eye rubbing. BMC Ophthalmol. 2020;20(1):301.

23 Mazharian A, Panthier C, Courtin R, et al. Incorrect sleeping position and eye rubbing in patients with unilateral or highly asymmetric keratoconus: a case-control study. Graefes Arch Clin Exp Ophthalmol. 2020;258(11):2431-2439.

24 Zadnik K, Barr JT, Edrington TB, et al. Baseline «ndings in the Collaborative 

Longitudinal Evaluation of Keratoconus (CLEK) Study. Invest Ophthalmol Vis Sci. 1998;39(13):2537-2546.

25 Nowak DM, Gajecka M. The genetics of keratoconus. Middle East Afr J Ophthalmol. 2011;18(1):2-6.

26 Gupta PD, Johar K, Sr., Nagpal K, Vasavada AR. Sex hormone receptors in the human 

eye. Surv Ophthalmol. 2005;50(3):274-284.

27 Spoerl E, Zubaty V, Raiskup-Wolf F, Pillunat LE. Oestrogen-induced changes in 

biomechanics in the cornea as a possible reason for keratectasia. Br J Ophthalmol. 2007;91(11):1547-1550.

28 Pobelle-Frasson C, Velou S, Huslin V, Massicault B, Colin J. Keratoconus: what 

happens with older patients?. J Fr Ophtalmol. 2004;27(7):779-782.

29 Torres-Netto EA, Randleman JB, Hafezi NL, Hafezi F. Late-onset progression of kera toconus after therapy with selective tissue estrogenic activity regulator. J Cataract Refract Surg. 2019;45(1):101-104.

30 Lee R, Hafezi F, Randleman JB. Bilateral Keratoconus Induced by Secondary Hypo thyroidism After Radioactive Iodine Therapy. J Refract Surg. 2018;34(5):351-353.

31 Tuft SJ, Hassan H, George S, Frazer DG, Willoughby CE, Liskova P. Keratoconus in 18 pairs of twins. Acta Ophthalmol. 2012;90(6):e482-486.

32 Wang Y, Rabinowitz YS, Rotter JI, Yang H. Genetic epidemiological study of kerato conus: Evidence for major gene determination. American Journal of Medical Genetics. 2000;93(5):403-409.

33 McComish BJ, Sahebjada S, Bykhovskaya Y, et al. Association of Genetic Variation With Keratoconus. JAMA Ophthalmol. 2020;138(2):174-181.

34 Lapeyre G, Fournie P, Vernet R, et al. Keratoconus Prevalence in Families: A French 

Study. Cornea. 2020;39(12):1473-1479.

35 Abu-Amero KK, Al-Muammar AM, Kondkar AA. Genetics of keratoconus: where do we stand? J Ophthalmol. 2014;2014:641708.

36 Burdon KP, Vincent AL. Insights into keratoconus from a genetic perspective. Clin Exp Optom. 2013;96(2):146-154.

37 Sza¥ik JP, Sza¥ik J, Blasiak J, Wojcik KA. Role of biochemical factors in the pathogen esis of keratoconus. Acta Biochimica Polonica. 2014;61(1


Etiology, Pathophysiology, Genetics, and Associated Disease

1 Mathan JJ, Gokul A, Simkin SK, Meyer JJ, Patel DV, McGhee CNJ. Topographic screening reveals keratoconus to be extremely common in Down syndrome. Clin Experiment Ophthalmol. 2020;48(9):1160-1167. doi:10.1111/ceo.13852

2 Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42(4):297-319. doi:10.1016/s0039-6257(97)00119-7

3 Loukovitis E, Sfakianakis K, Syrmakesi P, et al. Genetic Aspects of Keratoco[1]nus: A Literature Review Exploring Potential Genetic Contributions and Possi[1]ble Genetic Relationships with Comorbidities. Ophthalmol Ther. 2018;7(2):263-292. doi:10.1007/s40123-018-0144-8

4. Rabinowitz YS. The genetics of keratoconus. Ophthalmol Clin N Am. 2003;16(4):607-620, vii. doi:10.1016/s0896-1549(03)00099-3

5 Zadnik K, Barr JT, Edrington TB, et al. Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Invest Ophthalmol Vis Sci. 1998;39(13):2537-2546.

6 Wang Y, Rabinowitz YS, Rotter JI, Yang H. Genetic epidemiological study

of keratoconus: evidence for major gene determination. Am J Med Genet. 2000;93(5):403-409.

7 Romero-Jiménez M, Santodomingo-Rubido J, Wolffsohn JS. Keratoconus: a

review. Contact Lens Anterior Eye J Br Contact Lens Assoc. 2010;33(4):157-166;

quiz 205. doi:10.1016/j.clae.2010.04.006

8 Burdon KP, Vincent AL. Insights into keratoconus from a genetic perspective.

Clin Exp Optom. 2013;96(2):146-154. doi:10.1111/cxo.12024

9 Tyynismaa H, Sistonen P, Tuupanen S, et al. A locus for autosomal dominant

keratoconus: linkage to 16q22.3-q23.1 in Finnish families. Invest Ophthalmol Vis Sci. 2002;43(10):3160-3164.

10 Pathak D, Nayak B, Singh M, et al. Mitochondrial complex 1 gene analysis in

keratoconus. Mol Vis. 2011;17:1514-1525.

11 Cankaya C, Gunduz A, Cumurcu T, Demirel S, Savaci SS, Cavdar M. Familial

association of keratoconus and granular corneal dystrophy: The familial case

series. North Clin Istanb. 2019;6(2):176-183. doi:10.14744/nci.2018.08860

12 Bechara SJ, Waring GO, Insler MS. Keratoconus in two pairs of identical twins. Cornea. 1996;15(1):90-93.

13 Hao X dan, Chen X nian, Zhang Y yang, et al. Multi-level consistent changes

of the ECM pathway identified in a typical keratoconus twin’s family by

multi-omics analysis. Orphanet J Rare Dis. 2020;15(1):227. doi:10.1186/s13023-020-01512-7

14 Gordon-Shaag A, Millodot M, Essa M, Garth J, Ghara M, Shneor E. Is consan[1]guinity a risk factor for keratoconus? Optom Vis Sci O‹ Publ Am Acad Optom.

2013;90(5):448-454. doi:10.1097/OPX.0b013e31828da95c

15 Shapiro MB, France TD. The ocular features of Down’s syndrome. Am J Oph[1]thalmol. 1985;99(6):659-663. doi:10.1016/s0002-9394(14)76031-3

16 Hardcastle AJ, Liskova P, Bykhovskaya Y, et al. 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

17 Jafri, B., Lichter, H., & Stulting, R. D. (2004). Asymmetric keratoconus

attributed to eye rubbing. Cornea, 23(6), 560–564. https://doi.org/10.1097/01.

ico.0000121711.58571.8d

18 Goldich Y, Barkana Y, Gerber Y, et al. Effect of diabetes mellitus on biomechan[1]ical parameters of the cornea. J Cataract Refract Surg. 2009;35(4):715-719. doi:10.1016/j.jcrs.2008.12.013

19 Kuo IC, Broman A, Pirouzmanesh A, Melia M. Is there an association between diabetes and keratoconus? Ophthalmology. 2006;113(2):184-190. doi:10.1016/j.ophtha.2005.10.009

20 Seiler T, Huhle S, Spoerl E, Kunath H. Manifest diabetes and keratoconus: a retrospective case-control study. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol. 2000;238(10):822-825. doi:10.1007/s004179900111

21 Woodward MA, Blachley TS, Stein JD. The Association Between Sociodemo[1]graphic Factors, Common Systemic Diseases, and Keratoconus: An Analysis of a Nationwide Heath Care Claims Database. Ophthalmology. 2016;123(3):457 465.e2. doi:10.1016/j.ophtha.2015.10.035

22 Merdler I, Hassidim A, Sorkin N, et al. Keratoconus and allergic diseases among Israeli adolescents between 2005 and 2013. Cornea. 2015;34:525–9.

23 Thyssen, J. P., Toft, P. B., Halling-Overgaard, A. S., Gislason, G. H., Skov, L., & Egeberg, A. (2017). Incidence, prevalence, and risk of selected ocular disease in adults with atopic dermatitis. Journal of the American Academy of Derma[1]tology, 77(2), 280–286.e1. https://doi.org/10.1016/j.jaad.2017.03.003

24 Harrison RJ, Klouda PT, Easty DL, Manku M, Charles J, Stewart CM. Associa[1]tion between keratoconus and atopy. Br J Ophthalmol. 1989;73(10):816-822. doi:10.1136/bjo.73.10.816

25 Bawazeer AM, Hodge WG, Lorimer B. Atopy and keratoconus: a multivariate analysis. Br J Ophthalmol. 2000;84(8):834-836. doi:10.1136/bjo.84.8.834

26 Bak-Nielsen S, Ramlau-Hansen CH, Ivarsen A, Plana-Ripoll O, Hjortdal J. A nationwide population-based study of social demographic factors, associated diseases and mortality of keratoconus patients in Denmark from 1977 to 2015. Acta ophthalmologica. 2019B;97(5):497-504. doi: 10.1111/aos.13961. PubMed PMID: 30426693.

27 Farjadnia M, Naderan M, Mohammadpour M. Gene therapy in keratoconus. Oman J Ophthalmol. 2015;8(1):3-8. doi:10.4103/0974-620X.149854

28 Karolak JA, Gajecka M. Genomic strategies to understand causes of kerato[1]conus. Mol Genet Genomics. 2017;292(2):251-269. doi:10.1007/s00438-016-1283-z

29 Moussa S, Grabner G, Ruckhofer J, Dietrich M, Reitsamer H. Genetics in Keratoconus – What is New? Open Ophthalmol J. 2017;11(1):201-210. doi:10.2174/1874364101711010201

30 Bykhovskaya Y, Margines B, Rabinowitz YS. Genetics in Keratoconus: where are we? Eye Vis. 2016;3(1):16. doi:10.1186/s40662-016-0047-5

31 Abu-Amero KK, Al-Muammar AM, Kondkar AA. Genetics of Keratoconus: Where Do We Stand? J Ophthalmol. 2014;2014:1-11. doi:10.1155/2014/641708

32 Burdon KP, Macgregor S, Bykhovskaya Y, et al. Association of Polymorphisms in the Hepatocyte Growth Factor Gene Promoter with Keratoconus. Investig Opthalmology Vis Sci. 2011;52(11):8514. doi:10.1167/iovs.11-8261

33 Fram, Nicole R., Say Anything: What Is the Role of Genetic Testing for Kerato[1]conus and Corneal Dystrophies in Your Practice? CRST 20


Corneal Biomechanics and Its Relationship to Keratoconus

1 Abahussin, M., Hayes, S., Cartwright, N. E. K., Kamma-Lorger, C. S., Khan, Y.,

Marshall, J., & Meek, K. M. (2009). 3D collagen orientation study of the human

cornea using X-ray diffraction and femtosecond laser technology. Investigative

Ophthalmology & Visual Science, 50(11), 5159–5164.

2 Meek, K. M., Tuft, S. J., Huang, Y., Gill, P. S., Hayes, S., Newton, R. H., & Bron,

A. J. (2005). Changes in collagen orientation and distribution in keratoconus

corneas. Investigative Ophthalmology & Visual Science, 46(6), 1948–1956.

3 Sherwin, T., & Brookes, N. H. (2004). Morphological changes in keratoconus:

Pathology or pathogenesis. Clinical & Experimental Ophthalmology, 32(2),

211–217.

4 Seiler, T. G., Shao, P., Eltony, A., Seiler, T., & Yun, S.-H. (2019). Brillouin

spectroscopy of normal and keratoconus corneas. American Journal of

Ophthalmology, 202, 118–125.

5 Torres-Netto, E. A., Hafezi, F., Spiru, B., Gilardoni, F., Hafezi, N., Gomes, J. A.

P., Randleman, J. B., Sekundo, W., & Kling, S. (2020). Contribution of Bowman

layer to corneal biomechanics. Journal of Cataract & Refractive Surgery.

6 Kling, S., Torres-Netto, E. A., Spiru, B., Sekundo, W., & Hafezi, F. (2020).

Quasi-Static Optical Coherence Elastography to Characterize Human Corneal

Biomechanical Properties. Investigative Ophthalmology & Visual Science, 61(6), 29–29.

7 Gatinel, D. (2016). Eye rubbing, a sine qua non for keratoconus. Int J Kerat Ect Cor Dis, 5(1), 6–12.

8 Kenney, M. C., & Brown, D. J. (2003). The cascade hypothesis of keratoconus. Contact Lens and Anterior Eye, 26(3), 139–146.

9 Torres-Netto, E. A., Abdshahzadeh, H., Abrishamchi, R., Hafezi, N. L., Hillen,

M., Ambrósio Jr, R., Randleman, J. B., Spoerl, E., Gatinel, D., & Hafezi, F. (2022).

The Impact of Repetitive and Prolonged Eye Rubbing on Corneal Biomechanics.

Journal of Refractive Surgery, 38(9), 610–616.

10 Li, D.-Q., & Pflugfelder, S. C. (2005). Matrix metalloproteinases in corneal

inflammation. The Ocular Surface, 3(4), S-198.

11 Nishtala, K., Pahuja, N., Shetty, R., Nuijts, R. M., & Ghosh, A. (2016).

Tear biomarkers for keratoconus. Eye and Vision, 3(1), 1–7.

12 Shao, P., Eltony, A. M., Seiler, T. G., Tavakol, B., Pineda, R., Koller, T., Seiler, T.,

& Yun, S.-H. (2019). Spatially-resolved Brillouin spectroscopy reveals

biomechanical abnormalities in mild to advanced keratoconus in vivo. Scientific Reports, 9(1), 1–12.

13 Lopes, B. T., Padmanabhan, P., Eliasy, A., Zhang, H., Abass, A., & Elsheikh, A. (2022). In vivo Assessment of Localised Corneal Biomechanical Deterioration With Keratoconus Progression. Frontiers in Bioengineering and Biotechnology, 10.

14 Scarcelli, G., Besner, S., Pineda, R., & Yun, S. H. (2014). Biomechanical characterization of keratoconus corneas ex vivo with Brillouin microscopy. Investigative Ophthalmology & Visual Science, 55(7), 4490–4495.

15 De Stefano, V. S., Ford, M. R., Seven, I., & Dupps, W. J. (2020). Depth-depen[1]dent corneal biomechanical properties in normal and keratoconic subjects by

optical coherence elastography. Translational Vision Science & Technology, 9(7), 4–4.

16 Andreassen, T. T., Simonsen, A. H., & Oxlund, H. (1980). Biomechanical prop[1]erties of keratoconus and normal corneas. Experimental Eye Research, 31(4), 435–441.

17 Nash, I. S., Greene, P. R., & Foster, C. S. (1982). Comparison of mechanical

properties of keratoconus and normal corneas. Experimental Eye Research,

35(5), 413–424.

18 Fontes, B. M., Ambrósio Jr, R., Velarde, G. C., & Nosé, W. (2011). Ocular

response analyzer measurements in keratoconus with normal central corneal

thickness compared with matched normal control eyes. Journal of Refractive

Surgery, 27(3), 209–215.

19 Hafezi, F., Frigelli, Matteo, Torres-Netto, Emilio A., & Kling, Sabine. (2022).

OCT Elastography In Normal And Keratoconus Subjects. Annual Meeting of the

European Society of Cataract and Refractive Surgery, Milano.

20 Blackburn, B. J., Gu, S., Ford, M. R., de Stefano, V., Jenkins, M. W., Dupps, W. J.,

& Rollins, A. M. (2019). Noninvasive assessment of corneal crosslinking with

phase-decorrelation optical coherence tomography. Investigative Ophthalmology

& Visual Science, 60(1), 41–51.

21 Blackburn, B., Murray, J., Ford, M. R., Jenkins, M. W., Dupps, W. J., & Rollins, A.

M. (2020). Detection of weakening in an enzymatic ex vivo model of corneal

ectasia with phase-decorrelation OCT. Optical Coherence Tomography, OW1E-4

 

Optics of Keratoconus and Correcting Aberrations with Wavefront-Guided Lenses

1 Mannis M, Ling J, Kyrillos R, et al. Keratoconus and personality—a review:

Cornea 2018; 37: 400–4.

2 Applegate R, Donnelly III W, Marsack J, et al. Three-dimensional relationship

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errors. J Cataract Refract Surg. 2006; 32: 2064-74.

4 Pantanelli S, MacRae S, Jeong TM, et al. Characterizing the wave aberration

in eyes with keratoconus or penetrating keratoplasty using a high-dynamic

range wavefront sensor. Ophthalmol. 2007; 114:2013-21.

5 Hastings GD, Applegate RA, Nguyen LC, et al. Comparison of wavefront-guided

and best conventional scleral lenses after habituation in eyes with corneal

ectasia. Optom Vis Sci. 2019; 96: 238–47.

6 Chen M, Yoon G. Posterior corneal aberrations and their compensation effects

on anterior corneal aberrations in keratoconic eyes. Invest Ophthalmol Vis Sci.

2008; 49: 5645-52.

7 Sabesan R, Johns L, Tomashevskaya O, et al. Wavefront-guided scleral lens

prosthetic device for keratoconus. Optom Vis Sci 2013; 90: 314–23.

8 Marsack JD, Ravikumar A, Nguyen C, Ticak A, Koenig DE, Elswick JD, Applegate

RA. Wavefront-guided scleral lens correction in keratoconus. Optom Vis Sci.

2014 Oct;91(10):1221-30. doi: 10.1097/OPX.0000000000000275. PMID:

24830371; PMCID: PMC4232493.

9 Gelles JD, Cheung B, Akilov S, et al.. Ocular Impression-Based Scleral Lens

With Wavefront-Guided Optics for Visual Improvement in Keratoconus. Eye

Contact Lens. 2022 Jul 29.

10 https://patents.google.com/patent/US6086204A/en?inventor=Peter+C.+Mag[1]nante


Diagnostics and Monitoring

1 Shah H, Pagano L, Vakharia A, Coco G, Gadhvi KA, Kaye SB, Romano V. Impact

of COVID-19 on keratoconus patients waiting for corneal cross linking. Eur J

Ophthalmol. 2021 Nov;31(6):3490-3493. doi: 10.1177/11206721211001315. Epub

2021 Mar 15. PMID: 33719638.

2 Wilson SE, Lin DT, Klyce SD. Corneal topography of keratoconus. Cornea 1991;10:2-8.

3 Wilson SE, Ambrosio R. Computerized corneal topography and its importance to wavefront technology. Cornea 2001;20:441-54.

4 Rabinowitz YS, McDonnell PJ. Computer-assisted corneal topography in

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5 Maeda N, Klyce SD, Smolek MK, Thompson HW. Automated keratoconus

screening with corneal topography analysis. Investigative ophthalmology & visual science 1994;35:2749-57.

6 Maguire LJ, Bourne WM. Corneal topography of early keratoconus. American journal of ophthalmology 1989;108:107-12.

7 Maeda N, Klyce SD, Smolek MK. Comparison of methods for detecting keratoconus using videokeratography. Archives of ophthalmology 1995;113:870-4.

8 Wilson SE, Klyce SD. Advances in the analysis of corneal topography. Surv

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9 Klyce SD. Chasing the suspect: keratoconus. Br J Ophthalmol 2009;93:845-7.

10 Ambrosio R, Jr., Alonso RS, Luz A, Coca Velarde LG. Corneal-thickness spatial

pro«le and corneal-volume distribution: tomographic indices to detect keratoconus.

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11 Reinstein DZ, Silverman RH, Rondeau MJ, Coleman DJ. Epithelial and corneal

thickness measurements by high-frequency ultrasound digital signal processing.

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12 Salomao MQ, Ho¥ing-Lima AL, Lopes BT, et al. Role of the corneal epithe[1]lium measurements in keratorefractive surgery. Curr Opin Ophthalmol

2017;28:326-36.

13 Reinstein DZ, Gobbe M, Archer TJ, Silverman RH, Coleman DJ. Epithelial,

stromal, and total corneal thickness in keratoconus: three-dimensional display

with artemis very-high frequency digital ultrasound. Journal of refractive

surgery (Thorofare, NJ : 1995) 2010;26:259-71.

14 Reinstein DZ, Archer TJ, Urs R, Gobbe M, RoyChoudhury A, Silverman RH.

Detection of Keratoconus in Clinically and Algorithmically Topographically

Normal Fellow Eyes Using Epithelial Thickness Analysis. Journal of refractive

surgery (Thorofare, NJ : 1995) 2015;31:736-44.

15 Li Y, Chamberlain W, Tan O, Brass R, Weiss JL, Huang D. Subclinical kerato[1]conus detection by pattern analysis of corneal and epithelial thickness maps

with optical coherence tomography. Journal of cataract and refractive surgery

2016;42:284-95.

16 Li Y, Tan O, Brass R, Weiss JL, Huang D. Corneal epithelial thickness mapping

by Fourier-domain optical coherence tomography in normal and keratoconic

eyes. Ophthalmology 2012;119:2425-33.

17 Chandapura R, Salomao MQ, Ambrosio R, Jr., Swarup R, Shetty R, Sinha Roy A.

Bowman’s topography for improved detection of early ectasia. J Biophotonics

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43 Bykhovskaya Y, Li X, Taylor KD, Haritunians T, Rotter JI, Rabinowitz YS.

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44 Aknin C, Allart J, Rouland J. Unilateral keratoconus and mirror image in a pair

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45 Stabuc-Silih M, Strazisar M, Ravnik-Glavac M, Hawlina M, Glavac D. Genetics

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46 Nowak DM, Gajecka M. The genetics of keratoconus. Middle East Afr J

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47 Khaled ML, Helwa I, Drewry M, Seremwe M, Estes A, Liu Y. Molecular and

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48 Shetty R, Ghosh A, Lim RR, et al. Elevated expression of matrix metallopro[1]teinase-9 and inflammatory cytokines in keratoconus patients is inhibited by

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49 Hashemi H, Asgari S, Panahi P, Mehravaran S, Fotouhi A, Ambrósio R. Corneal

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50 Akoto T, Li JJ, Estes AJ, Karamichos D, Liu Y. The Underlying Relationship

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51 Regueiro U, López-López M, Varela-Fernández R, Sobrino T, Diez-Feijoo E, Lema I. Immunomodulatory Effect of Human Lactoferrin on Toll-like Receptors 2 Expression as Therapeutic Approach for Keratoconus. International Journal of Molecular Sciences 2022;23:12350.

52 Rabinowitz YS, Rasheed K. KISA% index: a quantitative videokeratography

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53 Randleman JB, Woodward M, Lynn MJ, Stulting RD. Risk assessment for ectasia

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54 Randleman JB, Trattler WB, Stulting RD. Validation of the Ectasia Risk Score

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55 Reinstein DZ, Archer TJ, Gobbe M. Stability of LASIK in topographically

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59 Ambrosio R, Jr., Nogueira LP, Caldas DL, et al. Evaluation of corneal shape and

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60 Lopes BT, Ramos IC, Dawson DG, Belin MW, Ambrosio R, Jr. Detection of ec[1]tatic corneal diseases based on pentacam. Zeitschrift fur medizinische Physik

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61 Ambrosio R, Jr., Valbon BF, Faria-Correia F, Ramos I, Luz A. Scheimp©ug imaging

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62 Ambrosio Jr R, Belin M. Enhanced screening for ectasia risk prior to laser laser

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63 Lopes BT, Ramos IC, Salomao MQ, et al. Enhanced Tomographic Assessment

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64 Ambrósio Jr R, Ramos I, Lopes B, et al. Assessing ectasia susceptibility prior

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66 Flockerzi E, Vinciguerra R, Belin MW, Vinciguerra P, Ambrosio R, Jr., Seitz B.

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72 Ambrosio R, Jr., Lopes BT, Faria-Correia F, et al. Integration of Scheimp©ug-Based

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74 Kataria P, Padmanabhan P, Gopalakrishnan A, Padmanaban V, Mahadik S,

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Pediatrics and Keratoconus

1 Mukhtar S, Ambati BK. Pediatric keratoconus: a review of the literature.

Int Ophthalmol. 2018 Oct;38(5):2257-2266. doi: 10.1007/s10792-017-0699-8.

Epub 2017 Aug 29. PMID: 28852910; PMCID: PMC5856649.

2 Leoni-Mesplie, S., et al. Scalability and Severity of Keratoconus in Children.

American Journal of Ophthalmology, July 2012: 154(1)56-62.

3 Gordon MO, Steger-May K, Szczotka-Flynn L, Riley C, Joslin CE, Weissman BA,

Fink BA, Edrington TB, Olafsson HE, Zadnik K; Clek Study Group. Baseline

factors predictive of incident penetrating keratoplasty in keratoconus. Am J

Ophthalmol. 2006 Dec;142(6):923-30. doi: 10.1016/j.ajo.2006.07.026. Epub

2006 Sep 1. PMID: 17157577.

4 Al-Mahrouqi H, et al. Retinoscopy as a Screening Tool for Keratoconus. Cornea

April 2019; 38(4):442-445.

5 Zadnik K, et al. CLEK Study Group. Collaborative longitudinal evaluation of

keratoconus. Between-eye asymmetry in keratoconus. Cornea. 2002; 21:671-679.

6 Bykhovskaya Y, Rabinowitz YS. Update on the genetics of keratoconus.

Exp Eye Res. 2021 Jan;202:108398. doi: 10.1016/j.exer.2020.108398. Epub

2020 Dec 13. PMID: 33316263.

7 Caporossi A, et al. Age-related long-term functional results after ribo[1]flavin UV A corneal cross-linking. J Ophthalmol. 2011;2011:608041. doi.org/10.1155/2011/60804

8 Glaukos Announces Positive Phase 3 Trial Results for iLink Epi-on Investiga[1]tional Therapy That Met the Primary Efficacy Endpoint

9 Gaster RN, Margines JB, Li X, Canedo AC, Rabinowitz YS. Results of corneal

crosslinking in adolescents with progressive keratoconus: prospective study. J Cataract Refract Surg. 2021 Oct 1;47(10):1333-1337. doi: 10.1097/j. jcrs.0000000000000617. PMID: 33769766.

10 Perez-Straziota C, Gaster RN, Rabinowitz YS. Corneal Cross-Linking for Pediatric Keratcoconus Review. Cornea. 2018 Jun;37(6):802-809. doi: 10.1097/ ICO.0000000000001579. PMID: 29601364; PMCID: PMC5938128.

11 Akkaya Turhan S, Aydın FO, Toker E. Clinical Results of Repeated Corneal

Collagen Cross-linking in Progressive Keratoconus. Cornea. 2020 Jan;39(1):84- 87. doi: 10.1097/ICO.0000000000002128. PMID: 31490276.

12 Michaud L, Breton L. Contact Lens Fitting Post-Corneal Cross-linking. Contact Lens Spectrum. 2018 Mar;33:30-34,51.

13 Perez-Straziota C, Gaster RN, Rabinowitz YS. Corneal Cross-Linking for Pediatric Keratcoconus Review. Cornea. 2018 Jun;37:802-809.

14 Olivo-Payne A, et al. Optimal management of pediatric keratoconus: challenges and solutions. Clinical Ophthalmology. 2019;13:1183-1191.

15 Anitha, V. et al. Pediatric Keratoconus – Current perspectives and clinical challenges. Indian J Ophthalmology. 2021 Feb; 69(2): 214-225.

16 Huang C, O’Hara M, Mannis MJ. Primary pediatric keratoplasty: indications and outcomes. Cornea 2009;28(9):1003–8.

17 Asuri MK, Garg P, Gokhle N, Gupta S. Penetrating keratoplasty in children. Cornea 2000;19(2):140–4.

18 Koppen C, Kreps EO, Anthonissen L, Van Hoey M, Dhubhghaill SN, Vermeulen L. Scleral lenses reduce the need for corneal transplants in severe keratoconus. Am J Ophthalmol 2018;185:43–7.

 

Corneal Crosslinking for Keratoconus and Corneal Ectasia

Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen cross[1]linking for the treatment of keratoconus. Am J Ophthalmol 2003;135:620-7.

2 Brooks NO, Greenstein S, Fry K, Hersh PS. Patient subjective visual function after corneal collagen crosslinking for keratoconus and corneal ectasia. J Cataract Refract Surg 2012;38:615-9.

3 Greenstein SA, Fry KL, Bhatt J, Hersh PS. Natural history of corneal haze after

collagen crosslinking for keratoconus and corneal ectasia: Scheimpflug and

biomicroscopic analysis. J Cataract Refract Surg 2010;36:2105-14.

4 Greenstein SA, Fry KL, Hersh MJ, Hersh PS. Higher-order aberrations after

corneal collagen crosslinking for keratoconus and corneal ectasia. J Cataract

Refract Surg 2012;38:292-302.

5 Greenstein SA, Fry KL, Hersh PS. Corneal topography indices after corneal

collagen crosslinking for keratoconus and corneal ectasia: one-year results.

J Cataract Refract Surg 2011;37:1282-90.

6 Greenstein SA, Fry KL, Hersh PS. In vivo biomechanical changes after corneal

collagen cross-linking for keratoconus and corneal ectasia: 1-year analysis of a

randomized, controlled, clinical trial. Cornea 2012;31:21-5.

7 Hersh PS, Greenstein SA, Fry KL. Corneal collagen crosslinking for keratoconus

and corneal ectasia: One-year results. J Cataract Refract Surg 2011;37:149-60.

8 Wollensak G, Spoerl E, Seiler T. Stress-strain measurements of human and

porcine corneas after riboflavin-ultraviolet-A-induced cross-linking. J Cataract

Refract Surg 2003;29:1780-5.

9 Sawaguchi S, Yue BY, Chang I, Sugar J, Robin J. Proteoglycan molecules in

keratoconus corneas. Invest Ophthalmol Vis Sci 1991;32:1846-53.

10 Hersh PS, Stulting RD, Muller D, Durrie DS, Rajpal RK. U.S. Multicenter Clinical

Trial of Corneal Collagen Crosslinking for Treatment of Corneal Ectasia after

Refractive Surgery. Ophthalmology 2017;124:1475-84.

11 Hersh PS, Stulting RD, Muller D, Durrie DS, Rajpal RK. United States Multi[1]center Clinical Trial of Corneal Collagen Crosslinking for Keratoconus Treatment.

Ophthalmology 2017;124:1259-70.

12 Henriquez MA, Villegas S, Rincon M, Maldonado C, Izquierdo L, Jr. Long-term

efficacy and safety after corneal collagen crosslinking in pediatric patients:

Three-year follow-up. Eur J Ophthalmol 2018;28:415-8.

13 Mazzotta C, Traversi C, Baiocchi S, et al. Corneal Collagen Cross-Linking With

Riboflavin and Ultraviolet A Light for Pediatric Keratoconus: Ten-Year Results.

Cornea 2018;37:560-6.

14 Raiskup F, Theuring A, Pillunat LE, Spoerl E. Corneal collagen crosslinking with

riboflavin and ultraviolet-A light in progressive keratoconus: ten-year results.

J Cataract Refract Surg 2015;41:41-6.

15 Vinciguerra R, Romano V, Arbabi EM, et al. In Vivo Early Corneal Biomechanical

Changes After Corneal Cross-linking in Patients With Progressive Keratoconus. J

Refract Surg 2017;33:840-6.

16 Kucumen RB, Sahan B, Yildirim CA, Ciftci F. Evaluation of Corneal Biomechanical

Changes After Collagen Crosslinking in Patients with Progressive Keratoconus

by Ocular Response Analyzer. Turk J Ophthalmol 2018;48:160-5.

17 Scarcelli G, Pineda R, Yun SH. Brillouin optical microscopy for corneal biomechanics.

Invest Ophthalmol Vis Sci 2012;53:185-90.

18 Seiler T, Hafezi F. Corneal cross-linking-induced stromal demarcation line.

Cornea 2006;25:1057-9.

19 Greenstein SA, Hersh PS. Characteristics influencing outcomes of corneal

collagen crosslinking for keratoconus and ectasia: implications for patient

selection. J Cataract Refract Surg 2013;39:1133-40.

20 Stulting RD, Trattler WB, Woolfson JM, Rubinfeld RS. Corneal crosslinking

without epithelial removal. J Cataract Refract Surg 2018;44:1363-70.

21 Hersh PS, Lai MJ, Gelles JD, Lesniak SP. Transepithelial corneal crosslinking for

keratoconus. J Cataract Refract Surg 2018;44:313-22.

22 Rosenblat E, Hersh PS. Intraoperative corneal thickness change and clinical

outcomes after corneal collagen crosslinking. J Cat Refract Surg 2016; 42:

596-605.

23 Alio JL, Shabayek MH, Artola A. Intracorneal ring segments for keratoconus

correction: long-term follow-up. J Cataract Refract Surg 2006;32:978-85.

24 Hersh PS, R; Greenstein, S.A. Corneal Collagen Crosslinking and Intracorneal

Ring Segments for Keratoconus: A Randomized Study of Concurrent versus

Sequential Treatment. Journal of Cataract and Refractive Surgery 2019.

25 Sakla H, Altroudi W, Munoz G, Albarran-Diego C. Simultaneous topography-guided

partial photorefractive keratectomy and corneal collagen crosslinking for keratoconus. J Cataract Refract Surg 2014;40:1430-8.

 

Practice Considerations in Managing Keratoconus and Cross-Linking

REFERENCES:

1.Eisenberg JS. First Treatment for Keratoconus Itself. Optometry Times, June 1, 2012.

2.Lindstrom RL et al. J Med Econ 2021;24:410. 3. Godefrooij DA, Gans R, Imhof SM, et al. Acta Ophthalmol 2016; 94:675 678

INDICATIONS

Photrexa Viscous (riboflavin 5’-phosphate in 20% dextran ophthalmic solution) and Photrexa (riboflavin 5’-phos phate ophthalmic solution) are indicated for use with the KXL System in corneal collagen cross-linking for the treatment of progressive keratoconus and corneal ectasia following refractive surgery.

IMPORTANT SAFETY INFORMATION

Corneal collagen cross-linking should not be performed on pregnant women.

Ulcerative keratitis can occur. Patients should be monitored for resolution of epithelial defects. The most common ocular adverse reaction was corneal opacity (haze). Other ocular side e‡ects include punctate keratitis, corneal striae, dry eye, corneal epithelium defect, eye pain, light sensitivity, reduced visual acuity, and blurred vision.

 These are not all of the side effects of the corneal collagen cross-linking treatment. For more information, go to www.livingwithkeratoconus.com to obtain the FDA-approved product labeling.

You are encouraged to report all side effects to the FDA.

Optometry’s Role in the Patient Journey

1. Koller T et al. J Cataract Refract Surg 2009;35:1358. 2. Davidson AE et al. Eye (Lond) 2014;28:189. 3. Tan JCK, et al. Cornea 2019;38:600. 4. Kandel H, et al. Clin Exp Ophthalmol 2022;Epub ahead of print. 5. Lindstrom RL et al. J Med Econ 2021;24:410. 6. American Academy of Ophthalmology Preferred Practice Pattern, Corneal Ectasia, 2018

INDICATIONS

Photrexa Viscous (riboflavin 5’-phosphate in 20% dextran ophthalmic solution) and Photrexa (riboflavin 5’-phos[1]phate ophthalmic solution) are indicated for use with the KXL System in corneal collagen cross-linking for the treatment of progressive keratoconus and corneal ectasia following refractive surgery.

IMPORTANT SAFETY INFORMATION

Corneal collagen cross-linking should not be performed on pregnant women.

Ulcerative keratitis can occur. Patients should be monitored for resolution of epithelial defects. The most common ocular adverse reaction was corneal opacity (haze). Other ocular side e‡ects include punctate keratitis, corneal striae, dry eye, corneal epithelium defect, eye pain, light sensitivity, reduced visual acuity, and blurred vision.

 These are not all of the side effects of the corneal collagen cross-linking treatment. For more information, go to www.livingwithkeratoconus.com to obtain the FDA-approved product labeling.

You are encouraged to report all side effects to the FDA.

Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.


Surgical Management of Keratoconus

1 Hersh PS, Stulting RD, Muller D, Durrie DS, Rajpal RK, United States Cross[1]linking Study G. United States Multicenter Clinical Trial of Corneal Collagen

Crosslinking for Keratoconus Treatment. Ophthalmology 2017;124:1259-70.

2 Greenstein SA, Hersh PS. Corneal Crosslinking for Progressive Keratoconus

and Corneal Ectasia: Summary of US Multicenter and Subgroup Clinical Trials.

Transl Vis Sci Technol 2021;10:13.

3 Holmes-Higgin DK, Burris TE. Corneal surface topography and associated

visual performance with INTACS for myopia: phase III clinical trial results. The

INTACS Study Group. Ophthalmology 2000;107:2061-71.

4 Rabinowitz YS. INTACS for keratoconus. Int Ophthalmol Clin 2006;46:91-103.

5 Hersh PS, Issa R, Greenstein SA. Corneal crosslinking and intracorneal ring

segments for keratoconus: A randomized study of concurrent versus sequen[1]tial surgery. J Cataract Refract Surg 2019;45:830-9.

6 Greenstein SA, Chung D, Rosato L, Gelles JD, Hersh PS. Corneal higher-order

aberrations after crosslinking and intrastromal corneal ring segments for

keratoconus. J Cataract Refract Surg 2020;46:979-85.

7 Nguyen N, Gelles JD, Greenstein SA, Hersh PS. Incidence and associations of

intracorneal ring segment explantation. J Cataract Refract Surg 2019;45:153-8.

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11 Pearson RM. Kalt, keratoconus, and the contact lens. Optom Vis Sci. 1989;66(9):643-6.

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22 Cressey A, Jacobs DS, Carrasquillo KG. Management of vascularized limbal

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23 Koh S, Inoue R, Maeda N, et al. Corneal tomographic changes during corneal rigid

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24 Walker MK, Bergmanson JP, Miller WL, et al. Complications and «tting challenges

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27 Bawazeer AM, Hodge WG, Lorimer B. Atopy and keratoconus: a multivariate analysis. Br J Ophthalmol. 2000;84(8):834-836. doi:10.1136/bjo.84.8.834

28 Douglas JP, Lowder CY, Lazorik R, et al. Giant papillary conjunctivitis associated with rigid gas permeable contact lenses. CLAO J. 1988 Jul-Sep;14(3):143-7. PMID: 3208429

29 Jupiter D, Karesh J. Ptosis associated with PMMA/rigid gas permeable contact lens wear. CLAO J. 1999 Jul;25(3):159-62. PMID: 10444052

30 Kobashi H, Rong SS. Corneal Collagen Cross-Linking for Keratoconus: Systematic Review. Biomed Res Int. 2017;2017:8145651. doi: 10.1155/2017/8145651. Epub 2017 Jun 11.

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32 Greenstein SA, Fry KL, Bhatt J, Hersh PS. Natural history of corneal haze after collagen crosslinking for keratoconus and corneal ectasia: Scheimpflug and biomicroscopic analysis. J Cataract Refract Surg. 2010 Dec;36(12):2105-14. doi: 10.1016/j.jcrs.2010.06.067. PMID: 21111314.

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37 Nepomuceno RL, Boxer Wachler BS, Weissman BA. Feasibility of contact lens fitting on keratoconus patients with INTACS inserts. Cont Lens Anterior

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38 Bautista-Llamas MJ, Sánchez-González MC, López-Izquierdo I, López-Muñoz

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Clinical Pearls for Communicating with Keratoconic Patients

1 McMahon J. Patient centred care in keratoconus. Optician. Vol.2016 Issue 4, April 2016.

2 Amiri F, Ghiyasvandian S, Navab E, Zakerimoghadam M. Corneal transplantation: A new view of life. Electron Physician. 2017 Apr 25;9(4):4055-4063.

3 Subasinghe SK, Ogbuehi KC, Dias GJ. Current perspectives on corneal collagen crosslinking (CXL). Graefes Arch Clin Exp Ophthalmol. 2018 Aug;256(8):1363-1384.

4 Najmi H, Mobarki Y, Mania K, Altowairqi B, Basehi M, Mahfouz MS, Elmahdy M. The correlation between keratoconus and eye rubbing: a review. Int J Ophthal[1]mol. 2019 Nov 18;12(11):1775-1781.

5 Lim L, Lim EWL. Current perspectives in the management of keratoconus with contact lenses. Eye (Lond). 2020 Dec;34(12):2175-2196.

6 Castro-Luna, G., & Pérez-Rueda, A. (2020). A predictive model for early diagno[1]sis of keratoconus. BMC ophthalmology, 20(1), 263.

7 Gordon-Shaag, A., Millodot, M., Shneor, E., & Liu, Y. (2015). The genetic and environmental factors for keratoconus. BioMed research international, 2015, 795738.

8 Mannis MJ, Ling JJ, Kyrillos R, Barnett M. Keratoconus and Personality-A Review. Cornea. 2018 Mar;37(3):400-404. doi: 10.1097/ICO.0000000000001479. PMID: 29215397.

9 Mannis MJ, Morrison TL, Zadnik K, et al. Personality trends in keratoconus. An analysis. Arch Ophthalmol. 1987 Jun;105(6):798-800.

10 Yildiz M, Turhan SA, Yargı B, et al. Psychiatric morbidity of patients with keratoconus: A cross-sectional study. J Psychosom Res. 2021 Apr;143:110384.doi: 10.1016/j.jpsychores.2021.110384. Epub 2021 Feb 3. PMID: 33611072.

11 Lim, L., & Lim, E. (2020). Current perspectives in the management of keratoconus with contact lenses. Eye (London, England), 34(12), 2175–2196.

12 Vastardis I, Sagri D, Fili S, et al. Current Trends in Modern Visual Intraocular Lens Enhancement Surgery in Stable Keratoconus: A Synopsis of Do’s, Don’tsand Pitfalls. Ophthalmol Ther. 2019 Oct;8(Suppl 1):33-47. doi: 10.1007/s40123-019-00212-1. Epub 2019 Oct 11. PMID: 31605318; PMCID: PMC6789053.

13 Yahalomi, T., Achiron, A., Hecht, I., et al. Refractive Outcomes of Non-Toric and Toric Intraocular Lenses in Mild, Moderate and Advanced Keratoconus: A Systematic Review and Meta-Analysis. J Clin Med. 2022 Apr 27;11(9):2456. doi: 10.3390/jcm11092456. PMID: 35566583; PMCID: PMC9101494.