with RBT less than 300 mm. Increasing myopia after every operation is known as “dandelion keratectasia”.

The ablation diameter also plays a very important role in LASIK. Postoperative optical distortions are more common with diameters less than 5.5 mm. Use of larger ablation diameters implies a lesser RBT postoperatively. Considering the formula: Ablation depth [ mm] = 1/3 . (diameter [mm])2 x (intended correction diopters [D])), 4,5 it becomes clear that to preserve a sufficient bed thickness, the range of myopic correction is limited and the upper limit of possible myopic correction may be around 12 D.6

Detection of a mild keratectasia requires knowledge about the posterior curvature of the cornea. Posterior corneal surface topographic changes after LASIK are known. Increased negative keratometric diopters and oblate asphericity of the PCC, which correlate significantly with the intended correction are common after LASIK leading to mild keratectasia.6,7 This change in posterior power and the risk of keratectasia was more significant with a RBT of 250 µm or less.8 The difference in the refractive indices results in a 0.2 D difference at the back surface of the cornea becoming equivalent to a 2.0 D change in the front surface of the cornea.6 Increase in posterior power and asphericity also correlates with the difference between the intended and achieved correction 3 months after LASIK. This is because factors like drying of the stromal bed may result in an ablation depth more than that intended.6 Reinstein et al predict that the standard deviation of uncertainty in predicting the RBT preoperatively is around 30 µm. [Invest Ophthalmol Vis Sci 40 (Suppl):S403, 1999]. Age, attempted correction, the optical zone diameter and the flap thickness are other parameters that have to be considered to avoid post LASIK ectasia.9,10

The flap thickness may not be uniform throughout its length. In studies by Seitz et al, it has been shown that the Moris Model One microkeratome and the Supratome cut deeper towards the hinge, whereas the Automated Corneal Shaper and the Hansatome create flaps that are thinner towards the hinge. Thus, accordingly, the area of corneal ectasia may not be in the center but paracentral, especially if it is also associated with decentered ablation. Flap thickness has also been found to vary considerably, even upto 40 µm, under similar conditions and this may also result

154 in a lesser RBT than intended.11-17

It is known that corneal ectasias and keratoconus have posterior corneal elevation as the earliest manifestation.18 The precise course of progression of posterior corneal elevation to frank keratoconus is not known. Hence it is necessary to study the posterior corneal surface preoperatively in all LASIK candidates.

EFFECT OF POSTERIOR CORNEAL CHANGE ON IOL CALCULATION

IOL power calculation in post-LASIK eyes is different because of the inaccuracy of keratometry, change in anterior and posterior corneal curvatures, altered relation between the two and change in the standardized index of refraction of the cornea. Irregular astigmatism induced by the procedure, decentered ablations and central islands also add to the problem.

Routine keratometry is not accurate in these patients. Corneal refractive surgery changes the asphericity of the cornea and also produces a wide range of powers in the central 5 mm zone of the cornea. LASIK makes the cornea of a myope more oblate so that keratometry values may be taken from the more peripheral steeper area of the cornea, which results in calculation of a lower than required IOL power resulting in a hyperopic “surprise”. Hyperopic LASIK makes the cornea more prolate, thus resulting in a myopic “surprise” post-cataract surgery.

Post-PRK or LASIK, the relation between the anterior and posterior corneal surface changes. The relative thickness of the various corneal layers, each having a different refractive index also changes and there is a change in the curvature of the posterior corneal surface. All these result in the standardized refractive index of 1.3375 no longer being accurate in these eyes.

At present there is no keratometry, which can accurately measure the anterior and posterior curvatures of the cornea. The Orbscan also makes mathematical assumptions of the posterior surface rather than direct measurements. This is important in the LASIK patient because the procedure alters the relation between the anterior and posterior surfaces of the cornea as well as changes the curvature of the posterior cornea.

Thus direct measurements such as manual and automated keratometry and topography are inherently inaccurate in these patients. The corneal power is

therefore calculated by the calculation method, the contact lens overrefraction method and by the CVK method. The flattest K reading obtained by any method is taken for IOL power calculation (the steepest K is taken for hyperopes who had undergone LASIK). One can still aim for -1.00 D of myopia rather than emmetropia to allow for any error, which is almost always in the hyperopic direction in case of pre-LASIK myopes. Also, a third or fourth generation IOL calculating formula should be used for such patients.

REFERENCES

1.Fedor P, Kaufman S Corneal topography and imaging. eMedicine Journal 2001;2:6.

2.Seiler T, Koufala K, Richter G. Iatrogenic keratectasia after laser in situ keratomileusis. J Refract Surg 1998;14(3):31217.

3.Seiler T, Quurke A W. Iatrogenic keratectasia after laser in situ keratomileusis in a case of Forme Fruste keratoconus. J Refract Surg 1998;24(7):1007-09.

4.Probost LE, Machat JJ. Mathematics of laser in situ keratomileusis for high myopia. J Cataract refract Surg 1998;24.

5.Mc Donnell PJ. Excimer laser corneal surgery: new strategies and old enemies (review). Invest Ophthalmol Vis Sci 1995;36;4-8.

6.Seitz B, Torres F, Langenbucher A, et al. Posterior corneal curvature changes after myopic laser in situ keratomileusis. Ophthalmology 2001;108(4):666-72.

7.Geggel HS, Talley AR. Delayed onset keratectasia following laser in situ keratomileusis. J Cataract Refract Surg 1999;25(4):582-86.

8.Wang Z, Chen J, Yang B. Posterior corneal surface topographic changes after laser in situ keratomileusis are related to residual corneal bed thickness. Ophthalmology 1999;106(2):406-09.

9.Pallikaris IG, Kymionis GD, Astyrakakis NI. Corneal ectasia induced by laser in situ keratomileusis. J Cataract Refract Surg 2001;27(11):1796-802.

10.Argento C, Cosentino M J, Tytium A, et al. Corneal ectasia after laser in situ keratomileusis. J Cataract Refract Surg 2001;27(9):1440-48.

11.Binder PS, Moore M. Lambert RW et al. Comparison of two microkeratome systems. J refract Surg 1997;13;14253.

12.Hofmann RF, Bechara SJ. An independent evaluation of second generation suction microkeratomes. Refract Corneal Surg 1992;8:348-54.

13.Schuler A, Jessen K, Hoffmann F. accuracy of the microkeratome keratectomies in pig eyes. Invest Ophthalmol Vis Sci 1990;31:2022-30.

14.Behrens A, Seitz B, Langenbucher A, et al. Evaluation of corneal flap dimensions and cut quality using a manually guided microkeratome (published erratum appears in J Refract Surg 1999;15:400). J Refract Surg 1999;15:11823.

15.Behrens A, Seitz B, Langenbucher A, et al. Evaluation of corneal flap dimensions and cut quality using the Automated Corneal Shaper microkeratome. J Refract Surg 2000;16:83-89.

16.BehrensA, Langenbucher A, Kus MM, et al. Experimental evaluation of two current generation automated microkeratomes: The Hansatome® and the Supratome®. Am J Ophthalmol 2000;129:59-67.

17.Jacobs BJ, Deutsch TA, Rubenstein JB. Reproducibility of corneal flap thickness in LASIK. Ophthalmic Surg Lasers 1999;30:350-53.

18.McDermott G K Topography’s benefits for LASIK. Review of Ophthalmology. Editorial 9:03 issue.

We have employed collagen cross-linking with the last six years in the treatment of ectasia after refractive surgery such as LASIK and PRK as well as the treatment of primary keratoconus with relative success.

In our center, we have now treated over 800 cases of primary keratoconus and/or ectasia following refractive surgery and in over 500 cases we combined the cross-linking treatment with the use of partial topography-guided PRK procedure in order to facilitate visual rehabilitation.

Complications have been very seldom with our technique and they go as follows:

We have experimented in the laboratory with the use of different riboflavin solution concentrations and different levels of energy and we have found that by doubling the concentration of riboflavin one can enhance as it has been described literature CCL by tenfold and create opaque patches in the cornea that will present significantly cross linked tissue. We have not encountered this combination clinically even in our more recent studies in using high fluence UV light at the level of 7 mW and the level 15 mW.

In all cases performed that it remains a potential complication and one has to be careful to calibrate the distance that UV light sources place from the level of the cornea as well as the fluence of the light source are for each case to avoid over exposure and potential toxic levels of UV light that could create significant cornea opacities.

Second group of potential complication is infection. We have seen some such complications that are very rare and 750 cases that we have treated we have encountered only one infection that was cured within few days with the use of topical 45 vancomycin solution and it is attributed to either contamination of the surgical field during the removal of epithelium and/ or the contamination of riboflavin drops. Therefore, our technique is advised we have changed our technique of the epithelium removal and utilizing excimer laser episcrape looking into seriously advantage of the no touch technique of the cornea epithelium and the reduction of the possibility of transferring pathogens up to the cornea surface and to the stroma with the CCL process.

Obviously, single use packaging for the riboflavin solution is essential in order to avoid contamination, from patient to patient, through the riboflavin solution. The infection though since lot of these patients remain

with a bandage lens for the several days remains an important potential complication and it had been some reports in literature and some that I am unfamiliar with personal complications that mandate significant antibiotic prophylaxis and striae technique for the procedure whatsoever.

Third group of complications is potential endothelial toxicity from high levels of free oxygen radical information at the endothelial level and this can potentially happen with high fluence of riboflavin, with high concentration of riboflavin at the endothelial level, higher fluence of UV light and thinner cornea than expected. It has been reported by the zero group in the past, and it has been recommended by that group that cornea is thinner than 400 microns thinnest/total cornea thickness to use hypotonic riboflavin solution in order to induce some cornea edema, and for the cornea to reach thickness over 400 microns and avoid this potential complication.

In overall experience, we have used riboflavin solution created by Priavision that is likely hypotonic at 350 millios small and 0.1% riboflavin sodium phosphate concentration and we have not encountered even in corneas with total cornea thickness of 350 microns any endothelial toxicity.

We have encountered though in almost 1000 cases that we have treated so far, a couple cases that had transit cornea edema by interestingly enough did not drop the endothelium cell count when measured at 6 month interval.

The endothelium toxicity remains a significant fact to be considered and mandate caution as we had published in the past along with the original basic science work done on CCL.

Last combination treatments of using a partial PRK after CCL or a combination with CCL brings a new group of potential complication such as persistence epithelium defects by these two treatments are combined, especially when mitomycin is used to avoid cornea scarring. Permanent cornea scarring that we encountered more in cases that we treated with PRK after the cross-linking procedure, we reduce this complication significantly when the two treatments were combined, partial topography-guided PRK first and then collagen cross-linking , but potential scaring from cross-linking alone or from the combination treatment of cross-linking simultaneously with

refractive procedure or later time treated with refractive 157

procedure remains a potential complication since we have light poud of care sight at 300 microns depth with the CCL procedure which will generate has been shown in basic signs and treatments as well in within 3 months after the procedure.

This would mean that if one patient with crosslinking underwent a PRK procedure six months after the original CCL procedure, freshly we populate cure sight might be activated in higher scaring may be anticipated. This is definitely being our experience in we presented in several AAO meetings and press currently.

So basically, a collagen cross-linking although minimally invasive for the rest of the eye pauses the potential risk of cornea infection, thus mandating proper active treatment and sterile technique as well as good control of the surgical environment and the sterility of the riboflavin solution. The potential over or under cross-linking, the potential of endothelium toxicity, from free oxygen radicals reaching the level of the cornea endothelium and creating a permanent cornea endothelium damage as well as potentional

scaring when perform a lower combined with partial PRK.

Last potential complications that I have not mentioned is the potential of regeneration of ectasia following cross-linking, it had been some reports and this happening in otherwise stable patients that had become pregnant, so pregnancy may pause a high risk for ectasia in cornea even after collagen cross-linking and there had been some anecdotal reports of ectasia resulting after a cornea has been stabilized with collagen cross-linking and then treated with a PRK procedure. This would make sense if the PRK procedure removed significant amount of tissue and creating a significant biomechanical change in the cornea producing more vulnerable situation for ectasia.

The benefits though from this procedure are far away the potential risks and when used with caution I think we reward patients and clinicians are like as it has in our clinical practice by reducing significant in the number of penetrating keratoplasty utilized for visual rehabilitation with keratoconus and cornea ectasias.

A

Advances in corneoplastique™ 56 Applications of collagen corneal cross-

linking 64 applications 66

basic science behind C3-R treatment 65

C3-R and IOP values 68

C3-R and post-LASIK ectasia 66

C3-R and pseudophakic bullous keratopathy 68

C3-R enhanced PRK in keratoconic eyes 67

C3-R for progressive hyperopic following RK 67

C3-R treatment in pellucid marginal degeneration 67

C3-R with INTACS 66 corneal melts and C3-R 68

infectious corneal ulcers and C3-R 68

mechanism of C3-R treatment 65 pregnancy and estrogen 67

Avoiding keratoconus in patients undergoing refractive surgery 15

B

Biophysical aspects of collagen corneal cross-linking 25

relevant anatomy 26 risk and side effects 28 studies 26

surgical techniques 26 treatment 28

C

C3-R combined with intrastromal ring segment implantation and overnight contact lens molding in keratoconus 98

link to the video 101 purpose, methods and

materials 100 results 105

C3-R® (Collagen cross-linking) 125 Collagen corneal cross-linking in post-

LASIK corneal ectasia 21 collagen cross-linking 22 combined treatments 23 post-LASIK corneal ectasia 22 potential complications and

preventions 23 results 23

biomechanical results 23 clinical results 23

risk factors 22 surgical techniques 22 therapeutic options 22

Collagen corneal cross-linking techniques 140

Caporossi cross-linking technique Siena eye cross project 142

efficacy of collagen cross-linking 141

results 143

Seiler cross-linking techniques 141 Complications with the use of collagen

cross-linking 156 Considerations on endothelial safety in

UV-A–cross-linking treatment 44

materials and methods 46 Corneal biomechanical properties 5

terminology 6

corneal hysteresis 6 corneal resistance factor 6

Corneal biomechanical properties in normal, keratoconic eyes and post-LASIK eyes 7

Corneal collagen cross-liking in keratoconus 92

clinical results 95

effects of cross-linking on corneal stroma 93

biochemical effects 93 biomechanical effects 93 effect on collagenase resistance

93

effects on hydration behavior 93

morphological effects 93 thermomechanical effects 93

effects of cross-linking on keratocytes 93

contraindications in keratoconus 94

follow-up 94

indications in keratoconus 94 surgical procedure 94

risks and side effects 95

Corneal collagen cross-linking (C3-R) 1 exclusion criteria 3

future prospects 4

indications for C3-R treatment 3 parameters for C3-R treatment 3 physiology 2

postoperative follow-up 4 preoperative work up for C3-R

treatment 3

steps of C3-R technique 3 Corneal collagen cross-linking and

irregular astigmatism 83 clinical outcomes 84

Corneal collagen cross-linking with riboflavin and ultraviolet a light 51

preparation of 0.1% riboflavin solution 53

riboflavin and ultraviolet a light 52 safety 54

step by step technique 53 technique background 52

Corneal ectasia 9 assessment 10 orbscan 10 pentacam 11 risk factors 13

Corneoplastics using corneal collagen cross-linking and intracorneal rings 134

combining new and old techniques 135

combining treatments experiences 138

cross-linking and PRK 138 unfinished business 136

Corneoplastique™ in action 57 Cross-linking effect in eyes with

INTACS 111

Cross-linking in keratoconus 132 advantages 133 complications 133 disadvantages 133

Cross-linking plus topography-guided PRK for post-LASIK ectasia management 69

options for treatment 70

E

Effect of posterior corneal change on IOL calculation 154

Epithelium and cornea permeability 112

statistical analysis 115 surgical technique 114

G

Grid pattern epithelial debridement 31 Gulani classification system for laser

surgery in keratoconus 121 laser as primary treatment 121 laser as secondary treatment 121

I

Iatrogenic keratectasia 152 Importance of epithelial debridement

for riboflavin absorption 29 methodology 30

results 32

Improvement in visual acuity 71 INTACS combined with corneal

collagen cross-linking and irregular astigmatism 84

INTACS effect on keratoconic eyes 111

Intracorneal ring segments and irregular astigmatism 82

clinical outcomes 82

K

Kanellopoulos intralase cross-linking technique 143

methods 143 results 143

Keratoconus progression 28

M

Minimal corneal thickness 75

O

Ocular response analyzer ORA 6

P

Posterior corneal changes in refractive surgery 147

orbscan 148

primary posterior corneal elevation 148

Agarwal criteria to diagnose primary posterior corneal elevation 151

posterior corneal topography 148

preexisting posterior corneal abnormalities 149

topography 148 Prophylactic treatment 28

PTK cross-linking technique 144

R

Riboflavin and their mechanism of action on the cornea 25

Riboflavin plus UV-A 31

S

Sanchez-León modified technique for LASIK ectasia 144

Siena eye cross project 142 Simultaneous topo-guided PRK and

cross-linking 146 Spectrophotometry in porcine corneas

29

Spheric and cylindric values 117

T

Tetracaine plus riboflavin 31 Traditional technique vs transepithelial

technique 38 contraindications 39 indications 39 personal experience 39 results 40

Transepithelial cross-liking for the treatment of keratoconus 87

corneal collagen networks 88 corneal epithelium 89 photochemical cross-linking 89 riboflavin-UV-A treatment 89

Transepithelial cross-linking treatment in eyes with INTACS 110 Treatment of iatrogenic keratectasia 71

U

Unaided emmetropia 58