collagen cross - linking ( cxl ) has been employed for many years as a means of stabilizing cornea ectasia [ 1 , 2 ] . among the multitude of treatments and technique variations applied , cxl has been well documented to almost invariably result in some central anterior corneal flattening [ 3 , 4 , 5 , 6 , 7 ] . disease regression. we present herein a custom application with a novel device , enabling the topographically customizable administration of very high - fluence cxl , applied in a specific toric pattern , in order to achieve , besides ectasia stabilization , predictable corneal astigmatic changes . this study received approval by the ethics committee of our institution , and adhered to the tenets of the declaration of helsinki . written informed consent we report herein a case of a 6-month postoperative evaluation of an innovative customized toric application of transepithelial cross - linking . the patient was a 37-year - old female with a preoperative clinical diagnosis of progressive moderate keratoconus of the left eye , minimum corneal pachymetry of 450 m , and uncorrected distance visual acuity ( udva ) between 20/32 and 20/25 . the patient was enrolled due to keratoconus progression noted over the previous year . in the past , the patient 's other eye ( right ) had a more evident keratoconic manifestation and had been treated a few years ago with the athens protocol procedure [ 8 , 9 ] . the left eye was not treated at that time due to the patient 's age and because it was less affected ; however , the progression , in combination with the patient 's desire for quick visual rehabilitation played a role in the decision to treat this keratoconic eye with this novel approach . the riboflavin penetration through the intact epithelium ( transepithelial ) into the stroma involved a two - step process . the manufacturer cautions against administering paracel for over 4 min to minimize the risk of epithelial sloughing . the second step was the application of vibex xtra ( avedro inc . ) , 0.25% riboflavin isotonic saline solution . application time was 6 min , with a drop every 30 s. with this two - step soaking process , the riboflavin passage to the anterior chamber was approximately complete in 10 min . the kxl ii cross - linking system ( avedro inc . ) was employed for the uva exposure . following alignment and focusing by the surgeon , the toric treatment pattern and orientation relative to the astigmatic axes were investigated in preclinical computational modeling studies [ 10 , 11 ] . as shown in fig . 1 , the specific toric irradiation pattern had a  butterfly - wing shape , extending to 5-mm , axis oriented at 129 ( orthogonal to the steep axis of astigmatism ) , with a total energy of 14.0 j / cm applied for 10 min and 22 s. overlapped to this was a circular irradiation area extending to a 6-mm diameter , with a total energy of 4.0 j / cm applied for 2 min and 56 s. the uva power was 45 mw / cm , delivered with a pulsed mode of 1-second on and a 1-second off . during the uva irradiation , the cornea was moistened every couple of minutes with a drop of balanced salt solution . the patient was postoperatively treated with a combination of antibiotic / corticosteroid drops for 10 days . the patient was examined the first day , the first week , and every month for a total duration of 6 months . at each visit , the cornea was assessed with placido topography ( topolyzer vario ; wavelight , erlangen , germany ) by means of curvature maps and simulated keratometry , scheimpflug imaging ( oculyzer ii ; wavelight ) by means of curvature maps and simulated keratometry , anterior surface irregularity indices and keratoconus classification , autorefraction and keratometry ( nidek ar 1 ; nidek co. ltd . , tokyo , japan ) , anterior segment optical coherence tomography ( oct )   ( rtvue-100 ; optovue inc . , usa ) providing corneal pachymetry and epithelial pachymetry maps , and endothelial cell counts measurement with a confocal specular microscopy device ( cellchek xl ; konan , irvine , calif . the riboflavin penetration through the intact epithelium ( transepithelial ) into the stroma involved a two - step process . the first step was the application of a paracel solution ( avedro inc . , waltham , mass . , usa ) , a slightly hypotonic specially formulated 0.25%-riboflavin solution with 0.02% benzalconium chloride . the manufacturer cautions against administering paracel for over 4 min to minimize the risk of epithelial sloughing . the second step was the application of vibex xtra ( avedro inc . ) , 0.25% riboflavin isotonic saline solution . application time was 6 min , with a drop every 30 s. with this two - step soaking process , the riboflavin passage to the anterior chamber was approximately complete in 10 min . the kxl ii cross - linking system ( avedro inc . ) was employed for the uva exposure . following alignment and focusing by the surgeon , the toric treatment pattern and orientation relative to the astigmatic axes were investigated in preclinical computational modeling studies [ 10 , 11 ] . as shown in fig . 1 , the specific toric irradiation pattern had a  butterfly - wing shape , extending to 5-mm , axis oriented at 129 ( orthogonal to the steep axis of astigmatism ) , with a total energy of 14.0 j / cm applied for 10 min and 22 s. overlapped to this was a circular irradiation area extending to a 6-mm diameter , with a total energy of 4.0 j / cm applied for 2 min and 56 s. the uva power was 45 mw / cm , delivered with a pulsed mode of 1-second on and a 1-second off . during the uva irradiation , the cornea was moistened every couple of minutes with a drop of balanced salt solution . the patient was postoperatively treated with a combination of antibiotic / corticosteroid drops for 10 days . the patient was examined the first day , the first week , and every month for a total duration of 6 months . at each visit , the cornea was assessed with placido topography ( topolyzer vario ; wavelight , erlangen , germany ) by means of curvature maps and simulated keratometry , scheimpflug imaging ( oculyzer ii ; wavelight ) by means of curvature maps and simulated keratometry , anterior surface irregularity indices and keratoconus classification , autorefraction and keratometry ( nidek ar 1 ; nidek co. ltd . , tokyo , japan ) , anterior segment optical coherence tomography ( oct )   ( rtvue-100 ; optovue inc . , usa ) providing corneal pachymetry and epithelial pachymetry maps , and endothelial cell counts measurement with a confocal specular microscopy device ( cellchek xl ; konan , irvine , calif . the patient achieved udva of 20/32 at the first postoperative week and 20/25 at 6 months . the patient reported no pain ( 0 on a scale of 010 ) and minimal discomfort during the procedure . during the immediate postoperative follow - up visits , endothelial cell counts were stable , preoperatively at 2,430 cells / mm and postoperatively at 2,400 cells / mm . preoperative and postoperative visual acuity , pachymetry and keratometry average data are reported in table 1 . 3 illustrate examples of placido disc and scheimpflug imaging sagittal curvature preoperative , 6-month postoperative and difference maps . a significant astigmatic reduction was noted ( on average 0.8 d ) as measured by all keratometric modalities employed in the study . topography ( fig . 3 ) , reaching a maximum of 2.5 d at the steepest preoperative location . based on the scheimpflug imaging ( amsler - krumeich criteria ) analysis , preoperatively , the cornea was classified for the topographic keratoconus classification of kc1 and the values for the anterior irregularity indices of height decentration ( ihd ) and surface variance ( isv ) were 0.039 and 43 , respectively ( fig . poss ( possible kc ) , while the anterior surface irregularity indices of surface variance and height decentration were lower , with values of 32 and 0.024 , respectively , indicating a trend towards a more normalized cornea . 4 illustrates oct - derived corneal and epithelial thickness pachymetry maps preoperatively , at 1-week and 6-month postoperatively . the significant refractive changes as a result of classic cxl [ 3 , 4 , 5 , 6 , 7 , 14 , 15 , 16 ] , when applying the dresden protocol ( 3 mw / cm for 30 min ) , as well as higher uva fluence , either superficially , via riboflavin placed within a femtosecond laser - created pocket or icrs channels can be established by a number of reports [ 18 , 19 ] . such flattening , which constitutes a refractive effect resulting from differential cross - linking - induced stiffening effects , has been described by a number of clinicians as  disease regression. we have reported on the use of higher fluence cxl as an agent for refractive stabilization in high - myopic and hyperopic lasik [ 20 , 21 , 22 ] , and have also recently reported significant refractive changes in astigmatic keratotomy , when facilitated by the development of a customizable differential uv delivery system by avedro and the ability to perform feasibility studies with the kxl ii device , the current study provides additional evidence for the potential of patterned cxl in the deliberate treatment of refractive error . we have recently reported in vivo , topographically regular and predictable central cornea flattening effects consistent with a correction of myopia of about 2.5 d . the available interim data appear promising with regard to the potential for correcting low myopic refractive errors without tissue removal in an excimer - like fashion or other previously described thermal techniques combined with cxl . myopic , hyperopic and astigmatic corrections are other novel applications that are currently under study with this technology . the novel toric topographically customized application of cross - linking presented herein ( photorefractive intrastromal cross - linking ) employed preferential corneal flattening along the flat refractive axis . six months postoperatively , a very specific reduction of astigmatism of 0.8 d ( reaching up to 2.5 d at certain loci ) was observed . the epithelial remodeling maps in the first 6 months , when compared to normal eyes , suggest that there was some modest change in the epithelial distribution , with the treated area having initially a slight reduction in the average epithelial thickness , and recovering at the 6-month follow - up to a more regular distribution than the preoperative distribution . the epithelial data suggest that the achieved refractive effect is not a result of epithelial remodeling , and thus may be attributed to direct stromal remodeling . as shown in the oct pachymetry data illustrated in fig . 4 , preoperatively , the difference between the minimum corneal thickness of 503 m to the pupil center corneal thickness of 535 m was 32 m , while 6 months postoperatively , the minimum corneal thickness was 542 m and the center corneal thickness 557 m , with a difference of 15 m . additionally , the procedure has neither an obvious corneal thinning effect nor an apparent haze following treatment . since it is essentially performed through the intact epithelium , the procedure required minimal postoperative adjustment of the daily activities by the patient and produced essentially no pain or discomfort even within the first few hours after the procedure . the rapid recovery and relative safety of transepithelial cxl may additionally offer the possibility to titrate the effect through two or more treatments over time as needed . as the patient is under continuous follow - up , and as more patients are being enrolled for the procedure , we anticipate reporting on the stability of the procedure , as well as on further refinement of treatment patterns , diameter , and centration for specific topographic patterns . we have herein introduced a novel technique based on refractive cxl application on previously untreated keratoconic cornea as a conservative management option . at 6-month follow - up , a stable reduction in astigmatism this is a nonablative and nonincisional approach to treat irregular astigmatism in ectatic cornea with rapid visual rehabilitation . alcon / wavelight , allegran , avedro , i - optics ; optovue ( a.j.k . ) .