Purpose: Long term results of 163 keratoconic eyes treated in Italy by combined Riboflavin UV A collagen cross-linking in the open non randomized phase II clinical trial: “Siena Eye-Cross Study 2004”.

Setting: ¹Department Ophthalmology, Siena University, Italy.

Methods: After local IRB approval, since September 2004 to September 2008, 163 eyes of 194 patients with progressive keratoconus were treated by Riboflavin UVA collagen Cross-Linking at Department of Ophthalmology of Siena University. In all cases, corneal epithelium was removed (blunt metal spatula) under topical anaesthesia (lidocaine 4% drops). The Riboflavin 0,1%-Dextrane 20 % sterile, disposable solution (Ricrolin, Sooft, Italy ^®) was instilled every two minutes for 10 minutes of corneal soaking, then after the aiming beam assisted focus positioning, UV A irradiation of 3 mW/cm² was by using the Caporossi, Baiocchi, Mazzotta Vega X-linker C.S.O. for 6 steps of 5 minutes, in a 30 minutes total exposure. Treated eyes were medicated by antibiotics (ofloxacin drops) and dressed with a therapeutic soft contact lens for 4 days. All eyes were evaluated preoperatively and 1,3,6,12,18,24,36 and 48 months after surgery analyzing: UCVA, BSCVA, SSCVA, Endothelial cell count (I Conan, Non Con Robo V), Optical Pachometry (Visante OCT, Zeiss, Germany), US Pachometry (DGH Pachette), corneal topography (C.S.O., Italy) and tomography (Orbscan IIz, B&L), Surface aberrometry (C.S.O, Italy), posterior segment OCT (Stratus, Zeiss, Germany), in vivo confocal microscopy (HRT II, Rostock Cornea Module, Heidelberg, Germany).

Results: No progression of keratoconus was detected in all treated eyes in the long term follow up of 48 months. The fellow control eyes showed a progression meanly of 1,5 D in over 45% in the first 12 months after the treatment and in over 65% in the longer time. The reduction of mean K value was meanly of 2 D and the early reduction of comatic aberration with corneal symmetry (SI) index improvement was observed in over 85% after 12 months continuing thereafter. After 48 months BSCVA improved meanly of 2.5 Snellen lines and UCVA of 2.3 Snellen lines, starting from third postoperative month to 48 months of follow up.

Conclusion: Long term results of the Siena Eye Cross Study showed a clinical, topographical and wave-front improvements after CXL after 4 years of follow up without relevant side effects. According to our results, Riboflavin UV A corneal Cross-Linking maintain its stability after 4 years of evaluation. The recorded long term stability seems to be related to biochemical and micro-structural changes induced by photo-polymerization reaction and corneal collagen replacement. The better results were recorded in young Keratoconic patients under 26 years with progressive disease. The thinnest-point 400 microns and preoperative epithelial debridment are mandatory parameters in order to obtain an effective Cross-linking in a minimum depth of 250 microns.