Used Equipment

Laser Surgery in Keratoconus

Is it reasonable to perform excimer laser treatment in patients with keratoconus?

The answer is a very qualified yes.

Let’s go back to some basics:

What is keratoconus?

Well it depends on whom you ask. For a clinician it’s an ectatic, non-inflammatory disorder in which corneal thinning and protrusion cause the cornea to assume a conical shape.

(1)A biochemist would say keratoconus is an imbalance in normal cell apoptosis due to insufficient processing of reactive oxygen and nitrogen species. Excessive mitochondrial DNA damage results in less cellular energy production and generation of reactive oxygen, and the result is sub-clinical corneal inflammation, stromal thinning and abnormal regulation of wound healing.A geneticist considers that there are nine different chromosomes associated with keratoconus. A topography expert would say that mild keratoconus has an increased area of corneal power surrounded by concentric areas of decreasing power, inferior and superior power asymmetry, or skewing of the steepest radial axes above and below the horizontal meridian with a flat meridian reading of less than 51 dioptres.

(2)So this is a tough area for clinicians who have to deal with an individual patient in the chair in front of them.Some things are easy. Advanced keratoconus with scarring, patients dependent on hard gas permeable contact lenses for reasonable best corrected acuity and extreme thinning; these patients require corneal transplant surgery, either DALK or penetrating keratoplasty. They are not candidates for laser treatment apart from the unusual circumstance of PTK to flatten a raised area of corneal scarring to get these patients back into contact lens wear.At the other extreme there is reasonable evidence to suggest that those with unusual topography, which does not fall into the pattern of keratoconus or ectatic disease, can be safely treated with PRK.Corneal fibres in the anterior portion of the cornea have inter-lamellar bridging fibres that help maintain the structural strength of the cornea. These fibres bifurcate at various depths in the anterior stroma, and the bifurcation helps tie all the anterior lamellar fibres together for structural support. In the deeper parts of the cornea there are fewer bridging fibres. Since the posterior lamellar fibres run parallel to each other and lack bridging fibres, the deeper part of the cornea is less stable and more susceptible to shearing motion and distension. Hence the more superficially we treat the better.

(3)There is reasonable evidence that those with form fruste and mild keratoconus can be treated with PRK with good short and long term results. Let’s look at this group first. If we apply the Randleman criteria

(4) form fruste keratoconus rates a point score of four. This puts the patient is in a “high risk category” and their recommendation is “do not perform LASIK; safety of surface ablation has not been established.”There are three studies which help us decide what to do. Koller et al

(5) looked at topography guided PRK in 11 eyes of 8 form fruste keratoconus patients. They produced a statistically significant reduction in manifest refractive error, corneal irregularity and subjective ghosting. There was no loss of BCVA and 7 of the 11 eyes gained BCVA. After laser treatment, all eyes had a central thickness of greater than 450µm, so these patients were carefully selected.Cennamo et al

(6) treated 18 eyes with keratoconus; 7 bilateral and 11 unilateral. They performed topographic customised PRK with a Zeiss MEL 70 laser and followed the patients for two years. Mean keratoconic index, keratoconic severity index and other keratoconic topography parameters all improved in a statistically significant way, as did mean uncorrected and best corrected visual acuity.The third paper worth considering is helpful in terms of long term analysis. Alpins

(7) treated 45 eyes with form fruste keratoconus (21) or mild keratoconus (24) with PRK. These patients were carefully selected. They had a mean age of 40. BCVA was 20/40 or better pre-operatively and mean K was less than 50 dioptres, and they had corneal and refractive stability for two years prior to treatment. No patient was under 25 years of age and they did not have slit lamp signs of keratoconus. At one year 7 eyes lost one line of BCVA and 16 gained one line. Most importantly, 32 eyes were followed for five years, and 9 eyes were followed for ten years. There was no progression of keratoconus over ten years.However, on the flip side, there are examples of surface ablation either inducing or exacerbating keratoconus. Malecaze

(8) published the case of a 22 year old French patient with mild pre-operative refractive error and topographic asymmetry, who underwent PRK and developed ectasia four years later.Reznik

(9) detailed a 25 year old man with uneventful bilateral PRK for moderately high myopia with ablation depths of 70µm in the right and 100µm in the left eye. Pre-operative topography revealed form fruste keratoconus in the right eye. Five years post-operatively the patient developed unilateral inferior keratectasia in the right eye with loss of best corrected visual acuity.So we have data to suggest that surface ablation in carefully selected mild and form fruste ketatoconus patients can be effective and safe, long term, but also a small number of individual cases who may possibly be made worse by the treatment.Can crosslinking these patients make PRK safer?Kanellopoulos

(10) has previously published on corneal cross-linking followed six months later by topography guided PRK. More recently, there are three reports on simultaneous cross-linking and topography guided PRK for mild keratoconus. (11, 12, 13).Kanellopoulos

(11) treated progressive keratoconus patients and all had to have 350µm total corneal thickness after PRK. 198 eyes were treated with the WaveLight customised platform for topography guided ablation using the Topolyzer. No treatment was greater than 50µm. Optical zones were kept to 5.5mm to minimise tissue removal with a transition of 1.5mm, and empirically they reduced the sphere and cylinder treatment by 30%. Topical Mitomycin 0.02% was applied for twenty seconds, and then corneal cross-linking with 0.1% riboflavin with UV light for thirty minutes. The 198 eyes treated with simultaneous PRK and cross-linking were compared with their previous study of 127 eyes treated with sequential cross-linking followed six months later by PRK. The simultaneous group performed better in terms of best spectacle corrected acuity (P < .001), spherical equivalent reduction (P < .005), mean K reduction (P < .005) and corneal haze score (P < .002) at final follow up.Stojanovic’s

(12) group was a smaller series of 12 eyes of 12 patients treated with topography guided ablation immediately followed by corneal cross-linking. Follow up was twelve months, and they had a mean improvement in BSCVA and UCVA with no progression of ectasia.Kymionis

(13) also had a small series of 14 eyes in 12 patients with progressive keratoconus, prospectively treated with topography guided PRK, and immediately followed by corneal cross-linking. Mean follow up was ten months with an improvement on measured parameters of uncorrected and best corrected acuity and a reduction in keratometry. They were careful about their inclusion criteria. The patients had progressive keratoconus, the mean age was 28 and the expected corneal thickness following treatment was greater than 400µm. Their topography treatment was with the Pulzar Z1 Custom Vis. This software allows the use of a percentage of customisation ranging from zero to 100%. For example zero would be equivalent to a conventional laser treatment, and 100% would be equivalent to a full customised treatment. They did not use topical Mitomycin.

As clinicians, we are now faced here with a real dilemma. Can the optimistic claims for this type of treatment be justified by the laboratory and clinical data? Certainly there seems to be valid reasons for performing simultaneous PRK and cross-linking.

1. The combination reduces the patient’s time away from work.
2. Cross-linking offers the advantage of de-populating keratocytes in the anterior stroma, which could reduce the possibility of haze formation. This was statistically significant in the Kanellopoulos study.
3. If the treatment is performed with cross-linking followed by topography six to twelve months later, some of the cross-linked anterior cornea is removed therefore minimising the potential benefits of cross-linking.Surgeons and patients will have to make up their own minds based on the following assumptions:

1. We still cannot diagnose keratoconus with a sufficient level of specificity.
2. Keratoconus is a diverse disease in its presentation and progression.
3. Corneal cross-linking is effective and promising, but is still evolving as a treatment modality.
4. Topography guided treatment algorithms are being refined, and are at the level of development whereby surgeons have no clear guidelines on what is the correct topographic treatment in terms of capturing the image, registering the image and delivering the treatment.With that in mind, what I currently do is as follows:

1. Treat moderate and advanced keratoconus with traditional corneal treatments such as DALK and penetrating keratoplasty.
2. In patients with slightly abnormal topography, which would not qualify as form fruste keratoconus, I avoid LASIK and instead treat with surface ablation and topical Mitomycin.
3. In patients over the age of 25, with form fruste keratoconus and mild keratoconus, I document progression and then proceed with simultaneous topographic based surface ablation, followed by topical Mitomycin .02% for fifteen seconds, then corneal cross-linking.

I limit the maximum depth of treatment to 50µm and make sure that the total corneal thickness following PRK is greater than 400µm.To those patients under the age of 25 and those who would not have enough corneal thickness remaining after treatment, I suggest they wait and reassess the technology and the data over the next few years.Bibliography:1. Fontes BM, Ambrosio R, Jardin D et alCorneal biomechanical metrics and anterior segment parameters in mild keratoconus.Ophthalmology 117.4.2010:673-679.2. McMahon TT, Szczotk A, Flynn L, Barr JT et alKLECK Study Group. A new method for grading the severity of keratoconus; the keratoconus severity score.Cornea 2006; 25:794-800.3. Smolek MKInterlamellar cohesive strength in the vertical meridian of human eye bank corneas.Investigative Ophthalmology and Visual Science 1993.4. Randleman JB, Stulting RD.Risk assessment for ectasia after corneal refractive surgery.Ophthalmology: 20085. Koller T, Iseli HP, Seiler TTopography guided surface ablation for form fruste keratoconus.Ophthalmology. December 2006.6. Cennamo G, Intravaja A, Boccuzzi DTreatment of keratoconus by topography guided customised PRK: Two year followup.Journal of Refractive Surgery. February 2008.7. AlpinsJournal of Cataract Refractive Surgery. April 2007.8. Malecaze F, Coullet J, Calvas P et aclCorneal ectasia after PRK for low myopia.Ophthalmology 2006: 113: 742-746.9. Reznik J, Salz JJ, Klimave A.Development of unilateral corneal ectasia after PRK with ipsilateral preoperative form frusta keratoconus.Journal Refractive Surgery. 2008; (8): 843-84710. Kanellopoulos AJ, Binder PSCollagen cross-linking with sequential topography guided PRK. A temporising alternative for keratoconus to penetrating keratoplasty.Cornea 2007; 26: 891-895.11. Kanellopoulos AJComparison of sequential versus same-day simultaneous collagen cross-linking and topography guided PRK for treatment of keratoconus.Journal of Refractive Surgery 2009: 25: S812-S818.12. Stojanovic A, Zhang J, Chen X.Topography guided trans-epithelial surface ablation followed by corneal collagen cross-linking performed in a single combined procedure for the treatment of keratoconus and pellucid marginal degeneration.Journal of Refractive Surgery 2010: (26) 2: 145-52.13. Kymionis GD, Kontadakis GA, Kounis GASimultaneous topography guided PRK followed by corneal collagen cross-linking for keratoconus.Journal of Refractive Surgery 2009: 25: S807-S811.

About the Author

Dr Michael Lawless is an ophthalmic surgeon with an in depth understanding of cataracts of the eye, corneal abrasion and Lens implant surgery. A refractive eye surgeon who is recognised in the field of Lasik and ASLA (Advanced Surface Laser Ablation, PRK) surgery. Dr lawless provides his specialist services at the laser eye surgery Chatswood clinic, Vision Eye Institute.

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