Keratoconus Treatment & Management
- Author: Barry A Weissman, OD, PhD, FAAO; Chief Editor: Hampton Roy, Sr, MD more...
The current paradigm of care for keratoconus is shifting from correcting the vision to slowing the disease process.
Rigid contact lenses and scleral lenses are the mainstay of vision treatment for keratoconus.
Patients with early keratoconus may successfully use spectacles or spherical/toric soft contact lenses. They may even rarely find that spectacle vision is superior to rigid contact lenses. More sophisticated soft contact lenses with aberration-controlled designs are now available and yield variable success.
Patients with modest-to-advanced keratoconus almost always require rigid contact lenses. When rigid contact lenses are no longer tolerated, some patients can maintain contact lens wear and usable visions with hydrogel contact lenses, piggyback contact lenses, or scleral contact lenses.
Scleral lenses are becoming more popular because of their excellent vision with improved comfort over cornea rigid gas-permeable contact lenses. Gas-permeable scleral lenses should be made of the highest oxygen-transmissible (Dk) material, and the tear layer should not be excessive to prevent hypoxia.
Contact lens wear is often complicated by episodes of intolerance, allergic reactions (eg, giant papillary conjunctivitis), corneal abrasions, neovascularization, and other problems, sometimes leading to total intolerance.
Ultraviolet corneal collagen cross-linking (UV-CXL) is the only procedure that is believed to slow the progression of keratoconus. It is used to increase the rigidity of the cornea by inducing additional cross-links within or between collagen fibers using UVA light and a photomediator, riboflavin, with the goal of slowing, possibly stabilizing, and even perhaps reversing, the progression of corneal ectasia in patients with keratoconus.[39, 40]
Riboflavin 5´-phosphate topical ophthalmic (Photrexa, Photrexa Viscous) was approved by the US Food and Drug Administration (FDA) in April 2016 for use in corneal collagen cross-linking (CXL) in combination with the KXL System for the treatment of progressive keratoconus. Both Photrexa and Photrexa Viscous (in 20% dextran) topical ophthalmic solutions are used during various stages of the procedure with the electronic device (KXL System), which irradiates the solutions with ultraviolet A light after they have been applied to the debrided cornea.
Approval of riboflavin 5´-phosphate topical ophthalmic was based on 3 prospective, randomized, parallel-group, open-label, placebo-controlled, 12-month trials conducted in the United States. Patients (n = 205) enrolled in the studies had 1 eye designated as the study eye and were randomized to receive CXL or sham in their study eye. From month 3 through month 12, the cross-linked eyes showed increasing improvement in Kmax (defined as the maximum corneal curvature and measured in diopters [D]).
An average Kmax reduction of 1.4-1.7 D at month 12 was observed in the cross-linked eyes, while the untreated eyes had an average increase of 0.5-0.6 D. The difference (95% CI) between the cross-linked and untreated groups in the mean change from baseline Kmax was -1.9 (-3.4, -0.3) D in Study 1 and -2.3 (-3.5, -1.0) D in Study 2.
Variations of UV-CXL include including accelerated cross-linking and UV-CXL corneal epithelium intact (epi-on) or removed (epi-off) techniques.[43, 44] UV-CXL has also been combined with same-day photorefractive keratectomy (PRK) or ICRS to improve the corneal integrity prior to surgery on keratoconic eyes. UV-CXL generally does not improve visual acuity (or at most improves 1-2 lines), although UV-CXL improves corneal clarity over untreated keratoconic corneas.
Long-term studies are still needed to determine the success and adverse effects of UV-CXL, as well as the long-term biomechanical effect. UV-CXL is not recommended in thinner corneas because of the risk of endothelial damage. Currently, there is no effective way to measure collagen turnover, so the stability of the collagen cross-links remains a concern. To date, endothelial damage has not been reported as a result of the standard procedure. Complications of UV-CXL have included corneal haze, continual progression of keratoconus, and, more rarely, diffuse lamellar keratitis, corneal melting, and persistent corneal edema.[51, 52, 53]
More studies are also needed to identify high-risk patients perhaps related to their age, diagnosis, corneal shape, and/or stages of ectasia.
Surgically removing central nodular scars by shaving the corneal surface (superficial keratectomy with a blade or excimer laser phototherapeutic keratectomy) may improve contact lens tolerance, decrease the rate of associated corneal abrasions, and preclude the need for corneal transplant.
Intrastromal corneal rings
Intrastromal corneal rings (ICRS) have been implanted in patients who have become intolerant to contact lenses, but these have been found to be more successful in mild than in advanced disease.[19, 20] ICRS does not halt the progression of keratoconus but may somewhat improve the unaided visual function of the patient after the disease is stable.
Bowman layer transplantation
Midstromal transplantation of Bowman layer (also known as anterior limiting lamina [ALL]) is a newer procedure used to flatten and strengthen advanced keratoconic corneas that may be too thin for UV-CXL. A midstromal pocket is created with air. The Bowman layer is removed and replaced by a donor Bowman layer graft. The overall flattening of the cornea could make contact lens wear more comfortable and hence postpone PKP or DALK indefinitely. Bowman layer transplantation usually improves 1-2 lines of visual acuity.
Deep anterior lamellar keratoplasty
Deep anterior lamellar keratoplasty (DALK) is becoming the preferred surgical option for keratoconic eyes without hydrops because of the avoidance of endothelial rejection, quicker heal time, and increased wound strength.[55, 56] Improved graft survival compared to PKP is still controversial. Currently, DALK represents 10%-20% of all keratoconic transplants and 30% when hydrops are excluded. Visual acuity results of DALK are similar if not slightly inferior to those of PKP.
Penetrating keratoplasty (PKP) is still the more commonly performed surgery used to treat keratoconus in patients whose vision is not correctable to better than 20/40. PKP yields good success rates, especially in eyes with endothelial dysfunction and central opacities, resulting in clear visual axes in greater than 90% of all cases. PKP for keratoconus exhibits excellent visual and survival results, but young patients may require one or more grafts during their lifetime.
The introduction of the femtosecond laser to trephine the recipient and donor tissues has improved tissue apposition and hastened healing. Best corrected visual acuities range from 20/50 to 20/100 after PKP, although visual acuities fall to less than 20/200 in 18.9% of advanced keratoconic eyes 15 years after surgery. PKP requires continuing professional care to monitor for rejection, suture-related problems, wound dehiscence, and other difficulties. Although extremely rare, keratoconus can recur in a graft.
Consult with a cornea specialist (a graduate of a cornea fellowship program) and/or contact lens specialist who provides appropriate (primarily rigid gas-permeable) contact lens care.
An ophthalmologist who is a cornea specialist assists in identifying appropriate clinical conditions and timing for surgical intervention, such as superficial keratectomy, PKP, DALK, Bowman layer transplantation, ICRS, or UV-CXL. Alternatively, topography-guided conductive keratoplasty has been shown to be modestly effective in reshaping the cornea in keratoconic eyes, at least temporarily.
A specialty contact lens practitioner (usually an optometrist but can be an optician or ophthalmologist) monitors contact lens care to optimize vision while minimizing complications of contact lens wear. This practitioner also helps to establish the appropriate clinical conditions and timing of surgical intervention, should this become necessary.
Patients should avoid (vigorous) eye rubbing.
Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998 Jan-Feb. 42(4):297-319. [Medline].
Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epidemiologic study of keratoconus. Am J Ophthalmol. 1986 Mar 15. 101(3):267-73. [Medline].
Critchfield JW, Calandra AJ, Nesburn AB, Kenney MC. Keratoconus: I. Biochemical studies. Exp Eye Res. 1988 Jun. 46(6):953-63. [Medline].
Sawaguchi S, Yue BY, Sugar J, Gilboy JE. Lysosomal enzyme abnormalities in keratoconus. Arch Ophthalmol. 1989 Oct. 107(10):1507-10. [Medline].
Gondhowiardjo TD, van Haeringen NJ. Corneal aldehyde dehydrogenase, glutathione reductase, and glutathione S-transferase in pathologic corneas. Cornea. 1993 Jul. 12(4):310-4. [Medline].
Sawaguchi S, Twining SS, Yue BY, et al. Alpha 2-macroglobulin levels in normal human and keratoconus corneas. Invest Ophthalmol Vis Sci. 1994 Nov. 35(12):4008-14. [Medline].
Fukuchi T, Yue BY, Sugar J, Lam S. Lysosomal enzyme activities in conjunctival tissues of patients with keratoconus. Arch Ophthalmol. 1994 Oct. 112(10):1368-74. [Medline].
Kenney MC, Nesburn AB, Burgeson RE, Butkowski RJ, Ljubimov AV. Abnormalities of the extracellular matrix in keratoconus corneas. Cornea. 1997 May. 16(3):345-51. [Medline].
Behndig A, Karlsson K, Johansson BO, Brännström T, Marklund SL. Superoxide dismutase isoenzymes in the normal and diseased human cornea. Invest Ophthalmol Vis Sci. 2001 Sep. 42(10):2293-6. [Medline].
Zadnik K, Barr JT, Edrington TB, et al. Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Invest Ophthalmol Vis Sci. 1998 Dec. 39(13):2537-46. [Medline].
Buddi R, Lin B, Atilano SR, Zorapapel NC, Kenney MC, Brown DJ. Evidence of oxidative stress in human corneal diseases. J Histochem Cytochem. 2002 Mar. 50(3):341-51. [Medline].
Cristina Kenney M, Brown DJ. The cascade hypothesis of keratoconus. Cont Lens Anterior Eye. 2003 Sep. 26(3):139-46. [Medline].
Sherwin T, Brookes NH. Morphological changes in keratoconus: pathology or pathogenesis. Clin Experiment Ophthalmol. 2004 Apr. 32(2):211-7. [Medline].
Woodward MA, Blachley TS, Stein JD. The Association Between Sociodemographic Factors, Common Systemic Diseases, and Keratoconus: An Analysis of a Nationwide Heath Care Claims Database. Ophthalmology. 2015 Dec 16. [Medline].
Atilano SR, Coskun P, Chwa M, Jordan N, Reddy V, Le K. Accumulation of mitochondrial DNA damage in keratoconus corneas. Invest Ophthalmol Vis Sci. 2005 Apr. 46(4):1256-63. [Medline].
Kenney MC, Chwa M, Atilano SR, Tran A, Carballo M, Saghizadeh M. 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 Mar. 46(3):823-32. [Medline].
Meek KM, Tuft SJ, Huang Y, Gill PS, Hayes S, Newton RH, et al. Changes in collagen orientation and distribution in keratoconus corneas. Invest Ophthalmol Vis Sci. 2005 Jun. 46(6):1948-56. [Medline].
Määttä M, Heljasvaara R, Sormunen R, Pihlajaniemi T, Autio-Harmainen H, Tervo T. Differential expression of collagen types XVIII/endostatin and XV in normal, keratoconus, and scarred human corneas. Cornea. 2006 Apr. 25(3):341-9. [Medline].
Määttä M, Väisänen T, Väisänen MR, Pihlajaniemi T, Tervo T. Altered expression of type XIII collagen in keratoconus and scarred human cornea: Increased expression in scarred cornea is associated with myofibroblast transformation. Cornea. 2006 May. 25(4):448-53. [Medline].
Ku JY, Niederer RL, Patel DV, Sherwin T, McGhee CN. Laser scanning in vivo confocal analysis of keratocyte density in keratoconus. Ophthalmology. 2008 May. 115(5):845-50. [Medline].
Lema I, Durán JA. Inflammatory molecules in the tears of patients with keratoconus. Ophthalmology. 2005 Apr. 112(4):654-9. [Medline].
Lema I, Durán JA, Ruiz C, Díez-Feijoo E, Acera A, Merayo J. Inflammatory response to contact lenses in patients with keratoconus compared with myopic subjects. Cornea. 2008 Aug. 27(7):758-63. [Medline].
Millodot M, Ortenberg I, Lahav-Yacouel K, Behrman S. Effect of ageing on keratoconic corneas. J Optom. 2015 Jun 30. [Medline].
Dienes L, Kiss HJ, Perényi K, Nagy ZZ, Acosta MC, Gallar J, et al. Corneal Sensitivity and Dry Eye Symptoms in Patients with Keratoconus. PLoS One. 2015. 10 (10):e0141621. [Medline].
Aldave AJ, Ann LB, Frausto RF, Nguyen CK, Yu F, Raber IM. Classification of posterior polymorphous corneal dystrophy as a corneal ectatic disorder following confirmation of associated significant corneal steepening. JAMA Ophthalmol. 2013 Dec. 131 (12):1583-90. [Medline].
Gupta PK, Stinnett SS, Carlson AN. Prevalence of sleep apnea in patients with keratoconus. Cornea. 2012 Jun. 31(6):595-9. [Medline].
Macsai MS, Varley GA, Krachmer JH. Development of keratoconus after contact lens wear. Patient characteristics. Arch Ophthalmol. 1990 Apr. 108(4):534-8. [Medline].
Li X, Yang H, Rabinowitz YS. Keratoconus: classification scheme based on videokeratography and clinical signs. J Cataract Refract Surg. 2009 Sep. 35 (9):1597-603. [Medline].
Rabinowitz YS, Li X, Canedo AL, Ambrósio R Jr, Bykhovskaya Y. Optical coherence tomography combined with videokeratography to differentiate mild keratoconus subtypes. J Refract Surg. 2014 Feb. 30 (2):80-7. [Medline].
Steinberg J, Aubke-Schultz S, Frings A, Hülle J, Druchkiv V, Richard G, et al. Correlation of the KISA% index and Scheimpflug tomography in 'normal', 'subclinical', 'keratoconus-suspect' and 'clinically manifest' keratoconus eyes. Acta Ophthalmol. 2015 May. 93 (3):e199-207. [Medline].
Zadnik K, Barr JT, Gordon MO, Edrington TB. Biomicroscopic signs and disease severity in keratoconus. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study Group. Cornea. 1996 Mar. 15(2):139-46. [Medline].
Wagner H, Barr JT, Zadnik K. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study: methods and findings to date. Cont Lens Anterior Eye. 2007 Sep. 30(4):223-32. [Medline].
Zadnik K, Barr JT, Gordon MO, Edrington TB. Biomicroscopic signs and disease severity in keratoconus. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study Group. Cornea. 1996 Mar. 15(2):139-46. [Medline].
Ridley F. EYE-RUBBING AND CONTACT LENSES. Br J Ophthalmol. 1961 Sep. 45(9):631. [Medline].
Karseras AG, Ruben M. Aetiology of keratoconus. Br J Ophthalmol. 1976 Jul. 60(7):522-5. [Medline].
Mathew JH, Goosey JD, Söderberg PG, Bergmanson JP. Lamellar changes in the keratoconic cornea. Acta Ophthalmol. 2015 Dec. 93 (8):767-73. [Medline].
Jaynes J, Weissman BA, Edrington T. Predicting scleral GP lens entrapped tear layer oxygen tensions. Cont Lens Anterior Eye. 2015 Oct. 38 (5):392. [Medline].
Rabinowitz YS. The genetics of keratoconus. Ophthalmol Clin North Am. 2003 Dec. 16(4):607-20, vii. [Medline].
Bykhovskaya Y, Li X, Epifantseva I, Haritunians T, Siscovick D, Aldave A. 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. [Medline].
Nielsen K, Hjortdal J, Pihlmann M, Corydon TJ. Update on the keratoconus genetics. Acta Ophthalmol. 2012 Apr 4. [Medline].
Chang CY, Hersh PS. Corneal collagen cross-linking: a review of 1-year outcomes. Eye Contact Lens. 2014 Nov. 40 (6):345-52. [Medline].
Tomita M, Mita M, Huseynova T. Accelerated versus conventional corneal collagen crosslinking. J Cataract Refract Surg. 2014 Jun. 40 (6):1013-20. [Medline].
Acar BT, Utine CA, Ozturk V, Acar S, Ciftci F. Can the effect of transepithelial corneal collagen cross-linking be improved by increasing the duration of topical riboflavin application? An in vivo confocal microscopy study. Eye Contact Lens. 2014 Jul. 40 (4):207-12. [Medline].
Wittig-Silva C, Chan E, Islam FM, Wu T, Whiting M, Snibson GR. A randomized, controlled trial of corneal collagen cross-linking in progressive keratoconus: three-year results. Ophthalmology. 2014 Apr. 121 (4):812-21. [Medline].
Sherif AM, Ammar MA, Mostafa YS, Gamal Eldin SA, Osman AA. One-Year Results of Simultaneous Topography-Guided Photorefractive Keratectomy and Corneal Collagen Cross-Linking in Keratoconus Utilizing a Modern Ablation Software. J Ophthalmol. 2015. 2015:321953. [Medline].
Ferenczy PA, Dalcegio M, Koehler M, Pereira TS, Moreira H, Luciane Bugmann M. Femtosecond-assisted intrastromal corneal ring implantation for keratoconus treatment: a comparison with crosslinking combination. Arq Bras Oftalmol. 2015 Mar-Apr. 78 (2):76-81. [Medline].
Alnawaiseh M, Rosentreter A, Eveslage M, Eter N, Zumhagen L. Changes in Corneal Transparency After Cross-linking for Progressive Keratoconus: Long-term Follow-up. J Refract Surg. 2015 Sep. 31 (9):614-8. [Medline].
Tuft SJ, Hassan H, George S, Frazer DG, Willoughby CE, Liskova P. Keratoconus in 18 pairs of twins. Acta Ophthalmol. 2012 Sep. 90(6):e482-6. [Medline].
Farjadnia M, Naderan M. Corneal cross-linking treatment of keratoconus. Oman J Ophthalmol. 2015 May-Aug. 8 (2):86-91. [Medline].
Shalchi Z, Wang X, Nanavaty MA. Safety and efficacy of epithelium removal and transepithelial corneal collagen crosslinking for keratoconus. Eye (Lond). 2015 Jan. 29 (1):15-29. [Medline].
Kymionis GD, Bouzoukis DI, Diakonis VF, Portaliou DM, Pallikaris AI, Yoo SH. Diffuse lamellar keratitis after corneal crosslinking in a patient with post-laser in situ keratomileusis corneal ectasia. J Cataract Refract Surg. 2007 Dec. 33 (12):2135-7. [Medline].
Ferrari G, Iuliano L, Viganò M, Rama P. Impending corneal perforation after collagen cross-linking for herpetic keratitis. J Cataract Refract Surg. 2013 Apr. 39 (4):638-41. [Medline].
Sharma A, Nottage JM, Mirchia K, Sharma R, Mohan K, Nirankari VS. Persistent corneal edema after collagen cross-linking for keratoconus. Am J Ophthalmol. 2012 Dec. 154 (6):922-926.e1. [Medline].
van Dijk K, Liarakos VS, Parker J, Ham L, Lie JT, Groeneveld-van Beek EA, et al. Bowman layer transplantation to reduce and stabilize progressive, advanced keratoconus. Ophthalmology. 2015 May. 122 (5):909-17. [Medline].
Reddy JC, Hammersmith KM, Nagra PK, Rapuano CJ. The role of penetrating keratoplasty in the era of selective lamellar keratoplasty. Int Ophthalmol Clin. 2013 Spring. 53 (2):91-101. [Medline].
Wisse RP, van den Hoven CM, Van der Lelij A. Does lamellar surgery for keratoconus experience the popularity it deserves?. Acta Ophthalmol. 2014 Aug. 92 (5):473-7. [Medline].
Coster DJ, Lowe MT, Keane MC, Williams KA, Australian Corneal Graft Registry Contributors. A comparison of lamellar and penetrating keratoplasty outcomes: a registry study. Ophthalmology. 2014 May. 121 (5):979-87. [Medline].
Arnalich-Montiel F, Alió Del Barrio JL, Alió JL. Corneal surgery in keratoconus: which type, which technique, which outcomes?. Eye Vis (Lond). 2016. 3:2. [Medline].
Lowe MT, Keane MC, Coster DJ, Williams KA. The outcome of corneal transplantation in infants, children, and adolescents. Ophthalmology. 2011 Mar. 118 (3):492-7. [Medline].
Pramanik S, Musch DC, Sutphin JE, Farjo AA. Extended long-term outcomes of penetrating keratoplasty for keratoconus. Ophthalmology. 2006 Sep. 113 (9):1633-8. [Medline].
Yeung KK et al. Where have all the keratoconics gone?. Int Cont Lens Clin. 1998. 25(4):109-13.
Georgiou T, Funnell CL, Cassels-Brown A, O'Conor R. Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asians and white patients. Eye (Lond). 2004 Apr. 18(4):379-83. [Medline].
Alió JL, Shabayek MH. Corneal higher order aberrations: a method to grade keratoconus. J Refract Surg. 2006 Jun. 22(6):539-45. [Medline].
American Academy of Ophthalmology 2013 Annual Meeting. Presented November 16, 2013.
Colin J, Malet FJ. Intacs for the correction of keratoconus: two-year follow-up. J Cataract Refract Surg. 2007 Jan. 33(1):69-74. [Medline].
Fontana L, Parente G, Tassinari G. Clinical outcomes after deep anterior lamellar keratoplasty using the big-bubble technique in patients with keratoconus. Am J Ophthalmol. 2007 Jan. 143(1):117-124. [Medline].
Goodman A. Crosslinking safe in children, adolescents with keratoconus. Medscape Medical News. November 28, 2013. Available at http://www.medscape.com/viewarticle/815184. Accessed: December 7, 2013.
Jafri B, Li X, Yang H, Rabinowitz YS. Higher order wavefront aberrations and topography in early and suspected keratoconus. J Refract Surg. 2007 Oct. 23(8):774-81. [Medline].
Kelly TL, Williams KA, Coster DJ. Corneal transplantation for keratoconus: a registry study. Arch Ophthalmol. 2011 Jun. 129(6):691-7. [Medline].
Kosaki R, Maeda N, Bessho K, Hori Y, Nishida K, Suzaki A. Magnitude and orientation of Zernike terms in patients with keratoconus. Invest Ophthalmol Vis Sci. 2007 Jul. 48(7):3062-8. [Medline].
Kymionis GD, Portaliou DM, Kounis GA, Limnopoulou AN, Kontadakis GA, Grentzelos MA. Simultaneous topography-guided photorefractive keratectomy followed by corneal collagen cross-linking for keratoconus. Am J Ophthalmol. 2011 Nov. 152(5):748-55. [Medline].
Rabinowitz YS. Intacs for keratoconus. Curr Opin Ophthalmol. 2007 Jul. 18(4):279-83. [Medline].
Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg. 2008 May. 34(5):796-801. [Medline].
Schlegel Z, Hoang-Xuan T, Gatinel D. Comparison of and correlation between anterior and posterior corneal elevation maps in normal eyes and keratoconus-suspect eyes. J Cataract Refract Surg. 2008 May. 34(5):789-95. [Medline].
Shimmura S, Tsubota K. Deep anterior lamellar keratoplasty. Curr Opin Ophthalmol. 2006 Aug. 17(4):349-55. [Medline].
Sorbara L, Dalton K. The use of video-keratoscopy in predicting contact lens parameters for keratoconic fitting. Cont Lens Anterior Eye. 2010 Jun. 33(3):112-8. [Medline].
Weissman B, Chun MW, Barnhart LA. Corneal abrasion associated with contact lens correction of keratoconus--a retrospective study. Optom Vis Sci. 1994 Nov. 71(11):677-81. [Medline].