A Clinical Study Of Riboflavin-UVA Accelerated Corneal Collagen Cross-linking In Progressive Keratoconus

ObjectiveTo observe the efficacy and safety of riboflavin-ultraviolet A accelerated corneal collagen cross-linking(UVA parameters:30mW/cm2×4min,7.2J/cm2) in progressive keratoconus. MethodsTwenty cases(thirty eyes)were treated with A-CXL in Huaxia Lumi Vision Opthalmic Hospital of Zhengzhou from December 2013 to March 2015.The UVA light dose was 7.2J/cm2,at 30 mW/cm2 for 4 minutes.Preoperative and postoperative examinations were conducted at 1 week; 1, 3, 6, and 12 months, including RGP corrected vision acuity(RGPVA),RGP tolerance, cornea-compensated intraocular pressure(IOPcc),endothelial cells density(ECD), spherical equivalent refractive error(SEQ), Kmax,and Kmin. Slit-lamp biomicroscopy,anterior segment photography,optical coherence tomography(OCT),and in vivo corneal confocal microscopy were also used to examine corneal transparency,stromal demarcation line,and cellular morphologic changes. Complications were recorded.The entire follow-up period lasted at least 12 months.Statistical analysis was performed using Statistical Package for Social Science, version 21.0.Paired t-tests were used to compare pre- and postoperative outcomes.Repeated measures analysis of variance was used to compare postoperative outcomes at different time.Results of P < 0.05 were considered statistically significant. Results(1)RGP tolerance and RGPVA:RGP tolerance ratio improved from 36.7% before the operation to 80%,12 months after the operation,while mean RGPVA improved from 0.49 to 0.71, with statistically significant difference(t=-6.661,P=0.000).(2)IOPcc:Paired t-tests comparing pre- and postoperative IOPcc at different time showed no statistically significant difference(Pall>0.05).Repeated measures analysis of variance comparing postoperative outcomes at different time showed no statistically significant difference(F=0.680,P=0.607).(3)ECD:Paired t-tests comparing pre- and postoperative endothelial cells density at different time showed no statistically significant difference(Pall>0.05).Repeated measures analysis of variance comparing postoperative outcomes at different time showed no statistically significant difference(F=0.654,P=0.625).(4)SEQ:The mean spherical equivalent refractive error was reduced by 1.63 D at 12 months follow-up,the reduction was statistically significant(t=-4.012,P=0.000).(5)Kmax and Kmin:There were initial increases of cornea mean Kmax and Kmin readings at 1 week and 1 month,then the mean Kmax and Kmin readings decreased after 3 months and stayed at a level lower than preoperative readings,but kept a slight downtrend even at 12 months follow-up. The mean Kmax reading had a greater variational amplitude.It was increased by 1.8D,1.9D at 1 week and 1 month respectively,and reduced by 1.1D,1.3D,1.4D at 3,6,12 months respectively, the changes were all statistically significant(Pall=0.000).Repeated measures analysis of variance comparing postoperative mean Kmax readings at 3,6,12 months follow-up showed no statistically significant difference(F=3.094,P=0.061).The mean Kmin reading was both increased by 0.9D at 1 week and 1 month,and reduced by 1.0D,1.1D,1.1D at 3,6,12 months respectively, the changes were all statistically significant( Pall=0.000).Repeated measures analysis of variance comparing postoperative mean Kmin readings at 3,6,12 months follow-up showed no statistically significant difference(F=1.286,P=0.284).(6)Slit-lamp biomicroscopy: The mean epithelium healing time was 4.3±0.9 days. Haze of different degrees appeared at the first postoperative week in all treated eyes,gradually decreased with topical steroids and over time,and disappeared in most eyes at 12 months follow-up.6 eyes still had faint anterior stromal opacity at 12 months follow-up, but without any loss of UDVA or CDVA.(7)OCT:The density of anterior-mid stroma changed and hyper-reflective stromal demarcation line appeared after the operation. The mean central corneal demarcation line depth was 268.3±79.2?m,about three fifths of the mean corneal thickness.The demarcation line was earliest found at 1 week and usually became clear at 1 month follow-up,gradually decreased after 3 months,and became difficult to identify or disappeared at 12 months follow-up.(8)In vivo corneal confocal microscopy:Subepithelial plexus nerves showed considerable decrease at 1 month, then gradually regenerated and almost returned to baseline 12 months postoperatively.The anterior-mid stroma showed a variable increase in density of the extracellular matrix,and the disappearance of keratocytes and lacunar edema at 1 month,followed by regeneration of keratocytes, reduction of edema and return to baseline 12 months postoperatively.Hyper-reflective needle-shaped microbands were aiso detectable in the mid-stroma.The endothelial cells showed no morphological changes at different time.(9)Complications:26 eyes of 16 cases(86.7% of all eyes) had postoperative reactions including pain, photophobia, tearing,foreign body sensation and burning. These symptoms disappeared when the epithelium healing was achieved.1eye of delayed epithelial healing(completed in day seven) and 2 eyes of filamentary keratitis recovered after corresponding medication therapy. No other adverse effects were noted in any of the cases studied. ConclusionsA-CXL(UVA parameters:30mW/cm2×4min,7.2J/cm2)is efficient and safe in treating progressive keratoconus. Patients can improve their vision acuity by using RGP postoperatively.