CET banner Banner overlay

Keratoconus: the Athens protocol

Continuing the keratoconus theme from the last issue, this article explores an emerging treatment approach, which can yield significant improvements to visual outcome for patients with the condition.


The first article in this series outlined the signs, symptoms and management options for keratoconus. This article concentrates on when to refer patients with keratoconus and outlines the relevance of the Athens protocol, a treatment modality that reshapes the corneal surface and strengthens the corneal stroma. This procedure can enhance unaided vision and also improve tolerance to spectacles or contact lenses. Case studies will be presented which demonstrate the effectiveness of the Athens protocol.

When to refer to a specialist corneal service 

Many patients with keratoconus can be managed with spectacles and contact lenses in optometric practice, especially in the early to moderate stages of the disease. Referral for specialist opinion should take place if:
  • There is evidence of disease progression
  • The practitioner does not have the necessary experience of fitting complex contact lens designs for more advanced cases
  • When the best corrected visual acuity is reduced despite spectacle or contact lens correction
  • Contact lens intolerance occurs due to lens discomfort 
  • Complications develop requiring more urgent specialist intervention, such as scarring, neovascularisation or hydrops

Corneal cross-linking (CXL) is now a recognised intervention to help prevent progression of keratoconus.1-9 The Athens protocol combines cross-linking with topographic guided laser treatment. This has the advantage of creating a more regular corneal shape and may further enhance the quality of vision.1

Athens protocol 

This is a relatively new technique which combines CXL with photorefractive keratectomy (PRK), a topographic-guided laser surface ablation procedure, and was first used in 2005.1 It aims to both stabilise the cornea and reduce the irregularity of the surface to allow visual improvement either unaided or aided with spectacles and/or contact lenses.9 It can avoid the requirement for a corneal transplant and obtain a more rapid improvement in vision than other more conventional surgical techniques.3,4 During the technique,the excimer laser is programmed with the patient’s topography data to allow it to follow the exact shape of the cornea resulting in precise reshaping. Suitable patients are those with progressive keratoconus who have a corneal thickness of at least 400μm,10 and with no other coexisting ophthalmic condition. It must be noted that for the excimer laser to be safely used on an ectatic cornea, it must first be strengthened with CXL.9 Treatment results are dependent upon individual healing responses.

Athens procedure 

Figure 1

Following application of anaesthetic eye drops, a speculum is put in place to keep the eye open. A ring is placed over the treatment zone of the cornea and a 20% alcohol solution is applied for 30 seconds to soften the epithelium to enable manual debridement. Surface ablation using a topographic-guided excimer laser is performed to reshape the cornea. Riboflavin (vitamin B2) is then applied as a drop onto the surface of the eye every two minutes for 15 minutes.

Following this, UV light (wavelength 360–370nm and intensity 9mW/ cm2) is applied to the cornea for a further 10 minutes, with more regular applications of riboflavin drops (see Figure 1: Set up of the corneal crosslinking procedure. UV light is used to activate the riboflavin and increase the collagen bonds within the cornea. Image courtesy of Rakesh Jayaswal, Laservision). At the end of the procedure, a bandage contact lens is fitted to help reduce discomfort and to promote corneal epithelialisation. Antibiotic and anti-inflammatory eye drops are administered to prevent infection and a hyaluronic acid based lubricant issued to keep the eye comfortable during the healing period. Vision improves over the week following treatment and is usually back to normal after two to four weeks. The bandage contact lens is removed five to seven days after the initial treatment.

Simultaneous versus sequential treatment 

Research shows that performing PRK followed by CXL on the same day (simultaneous treatment) produces better results than CXL undertaken first and then PRK at a later date (sequential treatment).1-8

Simultaneous PRK followed by CXL shows an improvement in uncorrected visual acuity, corrected visual acuity, reduced spherical refractive error, keratometry readings and post-operative haze.1-5 In one study where sequential versus simultaneous CXL and topography-guided PRK were compared, there were statistically significant differences in several parameters favouring the same day procedure. The mean LogMAR uncorrected visual acuity improved from 0.96 to 0.30, corrected visual acuity improved from 0.39 to 0.10, mean spherical refractive error reduced by -3.20D and K value reduced by -3.50D.1 Other advantages of simultaneous CXL are less PRK scarring and better riboflavin and UVA penetration allowing a wider and deeper CXL effect.11 Data show that the corneal epithelium and Bowman’s membrane can act as barriers to the penetration of UVA light into the stroma so by performing the two procedures simultaneously with the ablation first, the efficacy of CXL increases.1-8 Furthermore, with a sequential treatment approach, removing cross-linked anterior cornea reduces the benefits of CXL.1,2,4

Contradictions to the Athens protocol 

Not all keratoconic cases are suitable for the Athens approach and the following are important contraindications:9,12,13
  • Corneal thickness <400μm at thinnest point
  • Clinically significant corneal scarring
  • Pregnant or breast-feeding mothers14
  • Diabetics (difficult to assess the healing response) 
  • Previous ocular herpes10,12 
  • Systemic autoimmune conditions
  • Ocular viral activity within the last six months

Advantages and disadvantages of Athens treatment 

The Athens protocol is at the very forefront of keratoconus treatment and is a safe and effective approach for improving the regularity of the cornea and enhancing the visual function of eyes with ectatic conditions.3,7,9 The risks and complications of Athens can be minimised with careful selection of suitable candidates for treatment, using an experienced surgeon, and ensuring patient compliance with instructions before, during and after the procedure. Successful treatment can prevent a patient progressing to the stage where a corneal transplant is required and allows patients to remain in spectacles and contact lenses with decent levels of corrected visual acuity.

Figure 2The main disadvantage of the Athens protocol is that the longer-term outcomes following treatment are yet to be established with a limited number of medium-term studies conducted to date.7,9,15-18 Therefore, there is no guarantee that the treatment will slow, reduce or prevent keratoconus progression in the long term. Nevertheless, the technique shows great promise to date.


The Athens protocol has a good safety profile with the majority of patients experiencing a positive outcome. However, as with all treatments there are risks. Minor complications, similar to CXL, in a small number of eyes have been reported and include:10,13
  • Postoperative haze which reduces after three to 12 months19
  • Glare especially in low light levels 
  • Haloes around bright lights 
  • Delayed epithelial healing 
  • Recurrent corneal erosion 
  • Microbial infection20,21
  • Endothelial damage
  • Very rarely, reactivation of herpes simplex keratitis22

Long-term stability? 

The key reservation from practitioners is the long-term stability following treatment. At present, there is a paucity of data detailing vision and topography changes following treatment over more than one year.6,7,15-18 It is important to know if the treatment stops ectasia progression and stabilises keratometry readings, visual acuity and refraction over the long term. One recent study investigated the safety and efficacy of the Athens protocol over three years.9 It considered the refractive, topographic, pachymetric and visual changes in a large number of cases. Uncorrected and corrected visual acuity improved by 0.38 and 0.20 LogMAR units, respectively. Anterior keratometry readings flattened over three years and pachymetry stabilised.

Post operative follow up 

Following treatment, patients should have uncorrected and corrected visual acuity monitored, along with refraction, corneal haze assessment and signs of infection checked. 

Contact lens fitting can be undertaken at a minimum of one month following treatment but it is advisable to wait about three months and only when there are two stable topography readings, six weeks apart.

IOP readings may be higher following treatment due to increased rigidity of the cornea. Follow up appointments are suggested at one week, one month, three months, six months and one year.


The Athens protocol presents an alternative treatment option and is a minimally invasive procedure, combining CXL to stabilise the cornea with topographic-guided laser ablation, which provides a more regular corneal surface thus optimising visual outcome. It is an exciting approach, which may delay or even prevent the need for corneal transplantation.

The three case studies presented show significant improvement in visual outcome for eyes treated using the Athens protocol although careful patient selection is important. The long- term efficacy of this treatment is unknown but results are encouraging thus far.

At present the Athens protocol is not available on the NHS; hence patients must be seen privately at an appropriate centre.

Figure 2: Abnormal growth of the cornea causes the central area to become conical.

About the authors

Prashant Shah BSc, MCOptom, PGDipOphth, DipClinOptom, is an optometrist with postgraduate diplomas in ophthalmology and in clinical optometry. He works in routine practice and within a laser clinic environment. Victoria Rowe BSc, MCoptom, is an experienced optometrist who has worked for LaserVision since 2012. She also works in a paediatric clinic as well as being a community optometrist.

The authors would like to thank consultant ophthalmologists Rakesh Jayaswal and Mike Tappin for their help and support with this article.


  1. Kanellopoulos AJ (2009) Comparison of sequential vs same-day simultaneous collagen cross-linking and topography-guided PRK for treatment of keratoconus. J Refract Surg. 25(9):S812-S818 
  2. Kymionis GD, Kontadakis GA, Kounis GA, et al (2009) Simultaneous topography-guided PRK followed by corneal collagen cross-linking for keratoconus. J Refract Surg.25(9):S807–S811 
  3. Krueger RR, Kanellopoulos AJ (2010) Stability of simultaneous topography-guided photorefractive keratectomy and riboflavin/UVA cross-linking for progressive keratoconus: case reports. J Refract Surg. 26(10):S827–S832 
  4. Kymionis GD, Portaliou DM, Kounis GA et al (2011) Simultaneous topography-guided photorefractive keratectomy followed by corneal collagen cross-linking for keratoconus. Am J Ophthalmol. 152(5):748–755 Ewald M, 
  5. Kanellopoulos J (2008) Limited topography-guided surface ablation (TGSA) followed by stabilization with collagen crosslinking with UV irradiation and riboflavin (UVACXL) for keratoconus (KC). Invest Ophthalmol Vis Sci. 49:E-Abstract 4338  
  6. Kanellopoulos AJ (2012) Long term results of a prospective randomized bilateral eye comparison trial of higher fluence, shorter duration ultraviolet A radiation, and riboflavin collagen cross linking for progressive keratoconus. ClinOphthalmol. 6:97-101 
  7. Raiskup-Wolf F, Hoyer A, Spoerl E et al (2008) Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: Long-term results. Journal of Cataract and Refractive Surgery 34:796-801 
  8. Caporossi A, Baiocchi S, Mazzotto C et al (2006) Parasurgical therapy for keratoconus by riboflavin ultraviolet type A rays induced cross-linking of corneal collagen: Preliminary refractive results in an Italian study. Journal of Cataract and Refractive Surgery 32:837-845 
  9. Kanellopoulos AJ, Asimellis G. (2014) Keratoconus Management: Long-Term Stability of Topography-Guided Normalization Combined With High-Fluence CXL Stabilization (The Athens Protocol). J Refract Surg. 30(2):88-92 
  10. Dhawan S, Rao K, Natrajan S (2011) Review Article: Complications of Corneal Collagen Cross-Linking. J Ophthalmology. 1-5 
  11. Wollensak G (2006) Crosslinking treatment of progressive keratoconus: new hope. Current Opinion in Ophthalmology Vol. 17 (4):356–360 
  12. Hafezi F, Mrochen M, Iseli HP et al. (2009) Collagen crosslinking with ultraviolet-A and hypo osmolar riboflavin solution in thin corneas. J Cataract Refract Surg 35, 621–4 
  13. Koller T, Mrochen M, Seiler T (2009) Complication and failure rates after corneal crosslinking. J Cataract Refract Surg 35, 1358–62 
  14. Hafezi F, Iseli HP (2008) Pregnancy-related exacerbation of iatrogenic keratectasia despite corneal collagen crosslinking. J Cataract Refract Surg 34, 1219–21 
  15. Greenstein SA, Fry KL, Hersh PS (2011). Corneal topography indices after corneal collagen crosslinking for keratoconus and corneal ectasia: one-year results. J Cataract Refract Surg. 37:1282-1290 
  16. Guedj M, Saad A, Audureau E et al(2013). Photorefractive keratectomy in patients with suspected keratoconus: five-year follow-up. J Cataract Refract Surg. 39:66-73 
  17. Alessio G, L’abbate M, Sborgia C et al (2013). Photorefractive keratectomy followed by cross-linking versus cross-linking alone for management of progressive keratoconus: two-year follow-up. Am J Ophthalmol. 155:54-65 
  18. Hersh PS, Greenstein SA, Fry KL (2011). Corneal collagen crosslinking for keratoconus and corneal ectasia: one-year results. J Cataract Refract Surg. 37:149-160 
  19. Greenstein SA, Fry KL, Bhatt J et al. (2010) Natural history of corneal haze after collagen crosslinking for keratoconus and corneal ectasia: Scheimpflug and biomicroscopic analysis. J Cataract Refract Surg36: 2105–14 
  20. Pérez-Santonja JJ, Artola A, Javaloy J et al. (2009) Microbial keratitis after corneal collagen crosslinking. J Cataract Refract Surg35: 1138–40 
  21. Pollhammer M, Cursiefen C (2009) Bacterial keratitis early after corneal crosslinking with riboflavin and ultraviolet-A. J Cataract Refract Surg 35, 588–9 
  22. G. D. Kymionis, D. M. Portaliou, D. I. Bouzoukis et al (2007) Herpetic keratitis with iritis after corneal crosslinking with riboflavin and ultraviolet A for keratoconus. Journal of Cataract and Refractive Surgery Vol. 33 (11) 1982–1984

Your comments

You must be logged in to join the discussion. Log in

Comments (0)