Corneal collagen cross-linking in patients with keratoconus from the Dresden protocol to customized solutions:theoretical basis

Keratoconus is an ectatic condition characterized by gradual corneal thinning,corneal protrusion,progressive irregular astigmatism,corneal fibrosis,and visual impairment.The therapeutic options regarding improvement of visual function include glasses or soft contact lenses correction for initial stages,gas-permeable rigid contact lenses,scleral lenses,implantation of intrastromal corneal ring or corneal transplants for most advanced stages.In keratoconus cases showing disease progression corneal collagen crosslinking(CXL)has been proven to be an effective,minimally invasive and safe procedure.CXL consists of a photochemical reaction of corneal collagen by riboflavin stimulation with ultraviolet A radiation,resulting in stromal crosslinks formation.The aim of this review is to carry out an examination of CXL methods based on theoretical basis and mathematical models,from the original Dresden protocol to the most recent developments in the technique,reporting the changes proposed in the last 15y and examining the advantages and disadvantages of the various treatment protocols.Finally,the limits of non-standardized methods and the perspectives offered by a customization of the treatment are highlighted.

Research Progress in Corneal Cross-linking Agents

Corneal collagen cross-linking with UVA-riboflavin is currently the only method for preventing the progression of keratoconus from the pathological perspective. Topical application of a direct cross-linking agent is now attracting widespread attention in clinical settings..This article reviews the research progress in the application of indirect or direct cross-linking agents(e.g., riboflavin, glucose, ribose, glutaraldehyde,formaldehyde,.glyceraldehyde,.short chain aliphatic β-nitro alcohol, and genipin) in the treatment of corneal diseases and analyzes the cross-linking efficacy,.toxicity,.and merits and disadvantages of each cross-linking agent,.providing clinical information for further studies.

PERVAPORATION PROPERTIES OF PDMS MEMBRANES CURED WITH DIFFERENT CROSS-LINKING REAGENTS FOR ETHANOL CONCENTRATION FROM AQUEOUS SOLUTIONS

Ethanol perm-selective PDMS/PVDF composite membranes were prepared by curing polydimethylsiloxane (PDMS) with various cross-linking reagents,such as tetraethoxylsilane(TEOS),γ-aminopropyltriethoxylsilane(APTEOS), phenyltrimethoxylsilane(PTMOS) and octyltrimethoxylsilane(OTMOS) as well.The cross-linking density and surface properties of the PDMS active layer were adjusted by varying cross-linking reagents.The pervaporation performance of PDMS membranes cured with different cross-linking reagents was investig...

Accelerated versus standard corneal cross linking in the treatment of ectasia post refractive surgery and penetrating keratoplasty: a medium term randomized trial

AIM: To compare the clinical outcomes of the standard corneal cross linking(CXL) and the accelerated CXL in patients with progressive corneal ectasia post refractive surgery and penetrating keratoplasty.METHODS: Totally 120 eyes of 83 patients scheduled to receive either standard CXL(3 m W/cm^2 for a period of 30 min) or accelerated CXL(18 m W/cm2 for a period of 5 min). The main outcomes for comparison were the change in: maximum-K reading(K-max), manifest refractive spherical equivalent(SE), central corneal thickness(CCT), and the best corrected distance visual acuity(CDVA).RESULTS: One hundred and eleven eyes completed the study. The main outcome measurement was the K-max reading. Both group showed significant improvement in the value postoperatively at 6 and 12 mo. The mean change in the standard group was 1.21±0.11 D and in the accelerated group was 0.90±0.05 D at the end of 12 mo postoperatively, with no statistically significant difference between the 2 groups. Similarly, CDVA improved significantly from their preoperative value in the standard group by 2.98±0.11 letters, and in the accelerated group by 2.20±0.06 letters, with no statistically significant difference between the two groups. Both of the SE, and CCT showed no statistically significant difference at the end of follow up period in each group.CONCLUSION: Both standard CXL and accelerated CXL are safe and effective treatment in halting ectasia after corneal refractive surgery. The accelerated CXL results are comparable to the standard CXL with short time exposure of the cornea to ultraviolet irradiation, leading to reduced operation time, reduced operative ocular discomfort, and corneal haze.

Long term efficacy and stability of corneal collagen cross linking for post-LASIK ectasia: an average of 80mo follow-up

This study was designed to evaluate efficacy and stability of corneal collagen crosslinking(CXL) in halting the progression of post-laser in situ keratomileusis(LASIK) ectasia and provide long-term follow-up results with an average of 80 mo. Patients with post-LASIK ectasia were treated with CXL between December 2007 and January 2012. Main outcome measures were uncorrected distance visual acuities(UDVA) and corrected distance visual acuities(CDVA), minimum and maximum keratometry(K) values, spherical and cylindrical refraction, and corneal thickness. The study evaluated 17 eyes for 13 patients(8 men, 5 women) with mean age of 31y(range 23 to 39) and mean follow-up of 80.7±15(range 57 to 102)mo. UDVA and CDVA improved from logMAR 0.53±0.36(20/63) to 0.49±0.4(20/50)(P=0.43) and from 0.18±0.17(20/28) to 0.16±0.16(20/27)(P=0.55) respectively. In 15 eyes UDVA and in 13 eyes CDVA either remained stable or improved ≥1 Snellen lines(88.2%) and(76.5%) respectively. Although statistically insignificant, spherical and cylindrical refraction decreased post-CXL from-1.26±2.87 to-0.38±2.32 diopters(D)(P=0.054) and from-3.80±2.47 to-3.04±2.18 D(P=0.13) respectively. Kmax significantly decreased from 44.23±3.76 to 42.85±3.08 D(P=0.013) and Kmin decreased from 41.07±3.61 to 40.00±2.65 D(P=0.057). Corneal thickness decreased from 470±42 to 460±41 μm, but was statistically non-significant(P=0.063). Therefore, CXL is effective in halting and partially reversing the progression of postLASIK ectasia on the long-term(mean follow-up of more than 80mo), thus highlighting the stability and maintained effect of CXL for such cases.

Correlation between corneal demarcation line depth in epithelium-off and trans-epithelium accelerated corneal cross linking and keratoconus progression

AIM:To compare corneal demarcation line(DL)depth in both accelerated epithelium-off and trans-epithelium cross linking(CXL)using anterior segment optical coherence tomography(AS-OCT)and its relation to maximum keratometry(Kmax)progression in both techniques.METHODS:A prospective comparative interventional study where patients with mild to moderate keratoconus(KC)were classified into two groups:accelerated epitheliumoff and trans-epithelium CXL based on corneal pachymetry.Assessment of corneal DL depth was carried out after 3mo by AS-OCT.Kmax readings were evaluated after one year follow up using the Scheimpflug imaging system.RESULTS:Study included 74 eyes of 44 patients.Group A underwent epithelium-off CXL(41 eyes),while Group B underwent trans-epithelium CXL(33 eyes).At 3mo follow up,mean corneal DL depth in Group A was 219.9±58.4μm while in Group B was 127.2±7.8μm(P<0.05).The mean Kmaxchangedfrom51.9±3.9to51.3±4.2dioptersin Group A and from 53.1±4.1 to 53.6±5 diopters in Group B with insignificant difference in Kmax changes in either group(P>0.05).In addition,no significant change in corneal pachymetry was found in both groups(meanchange at 1y:6.4±4.7 and-10.1±2.3μm in Groups A and B respectively).CONCLUSION:Despite a significantly deeper corneal DL depth created by accelerated epithelium-off CXL technique compared to accelerated trans-epithelium CXL,there is no significant impact on keratoconus progression.

Systematic review and Meta-analysis comparing modified cross-linking and standard cross-linking for progressive keratoconus

AIM：To compare the effectiveness and safety between modified cross-linking（MC）and standard cross-linking（SC）in mild or moderate progressive keratoconus.METHODS：Eligible studies were retrieved from four electronic databases,including CENTRAL,Clinical Trials gov,Pup Med and OVID MEDLINE.We set post-surgical maximum K value（Kmax）as the primary outcome.In addition,uncorrected and corrected distant visual acuity（UDVA and UDVA）,spherical equivalent（SE）,endothelial cell density（ECD）,central cornea thickness（CCT）and depth of demarcation line（DDL）were Meta-analyzed as secondary outcomes.Mean differences for these outcomes were pooled through either a random-effect model or fixed-effect model according to data heterogeneity.RESULTS：Twenty-four comparative studies either on accelerated cross-linking（AC）compared with SC or on transepithelial cross-linking（TC）compared with SC were included and pooled for analysis.The results indicated that MC was significantly inferior to SC at delaying Kmax deterioration[AC vs SC 0.49（95%CI：0.04-0.94,I2=75%,P=0.03）;TC vs SC 1.15（95%CI：0.54-1.75,I2=50%,P=0.0002）].SE decreased significantly for SC when compared to AC[0.62（95%CI：0.38-0.86,I2=22%,P〈0.00001）].DDL of SC was more significantly deeper than that of TC[-133.49（95%CI：-145.94 to-121.04,I2=33%,P〈0.00001）].Other outcomes demonstrated comparable results between MC and SC.CONCLUSION：SC is more favorable at halting the progression of keratoconus,but visual acuity improvement showed comparable results between MCs and SC.

Corneal collagen crosslinking in keratoconus and other eye disease

Keratoconus is a condition characterized by biomechanical instability of the cornea, presenting in a progressive, asymmetric and bilateral way. Corneal collagen crosslinking(CXL) with riboflavin and Ultraviolet-A(UVA) is a new technique of corneal tissue strengthening that combines the use of riboflavin as a photo sensitizer and UVA irradiation. Studies showed that CXL was effective in halting the progression of keratoconus over a period of up to four years. The published studies also revealed a reduction of max K readings by more than 2 D, while the postoperative spherical equivalent(SEQ) was reduced by an average of more than 1 D and refractive cylinder decreased by about1 D. The major indication for the use of CXL is to inhibit the progression of corneal ecstasies, such as keratoconus and pellucid marginal degeneration. CXL may also be effective in the treatment and prophylaxis of iatrogenic keratectasia, resulting from excessively aggressive photo ablation. This treatment has been used to treat infectious corneal ulcers with apparent favorable results. Most recent studies demonstrate the beneficial impact of CXL for iatrogenic ecstasies, pellucid marginal degeneration, infectious keratitis, bullous keratopathy and ulcerative keratitis. Several long-term and short-term complications of CXL have been studied and documented. The possibility of a secondary infection after the procedure exists because the patient is subject to epithelial debridement and the application of a soft contact lens. Formation of temporary corneal haze,permanent scars, endothelial damage, treatment failure,sterile infiltrates, bullous keratopathy and herpes reactivation are the other reported complications of this procedure.

Clinical Observation of Transepithelial Corneal Collagen Cross-linking by Iontophoresis of Riboflavin in Treatment of Keratoconus

Purpose: To evaluate the efficacy and safety of transepithelial collagen cross-linking by iontophoretic delivery of riboflavin in treatment of progressive keratoconus.Methods:.Eleven patients(15 eyes) with progressive keratoconus were enrolled. After 0.1% riboflavin-distilled water solution was deliveried via transepithelial iontophpresis for 5 min with 1 m A current, and ultraviolet radiation(370 nm,.3 m W /cm2) was performed at a 1.5 cm distance for 30 min. The follow up were 6 months in all eyes. The uncorrected visual acuity, corrected visual acuity,endothelial cell counting, corneal thickness,.intraocular pressure, corneal curvature, corneal topography,.OCT and corneal opacity before and 6-month after surgery were analyzed.Results: At 6 month postoperatively, mean uncorrected visual acuity and corrected visual acuity changed from 0.36 to 0.30 and from 0.42 to 0.57 without statistical significance..The mean value of each index of corneal curvature declined without statistical significance.Kmax value dereased from 60.91 to59.91, and the astigmatism declined from 3.86 to 3.19. Central corneal thickness decreased from 460.93 μm to 455.40μm,.and thinnest corneal thickness declined from 450.87 μm to 440.60 μm with no statistical significance..Intraocular pressure was significantly elevated from 10.85 mm Hg to 12.62 mm Hg. Endothelial cell count did not change significantly. No corneal haze occurred. Mean depth of corneal demarcation line was 288.46 μm at 1 month postoperatively..Conclusion:.Transepithelial corneal collagen cross-linking by iontophoresis is effective and safe in the treatment of progressive keratoconus, and yields stable clinical outcomes during 6-month follow up..However,.long-term follow up is urgently required.

Experimental study on the treatment of rabbit corneal melting after alkali burn with Collagen cross-linking

AIM: To evaluate the effect of Collagen cross-linking on the prevention of melting in rabbit corneas after alkali burn. METHODS: Twenty New Zealand white rabbits were randomly divided into model control group and collagen cross-linking treatment group. The second group of rabbits received collagen cross linked treatment. Both groups were applied with antibiotic eye drops to prevent infection. The corneas were evaluated for melting, opacity, pathological and immunohistochemistry, record the changes when 28 days after the animals were killed. RESULTS: In the control group, 6 out of 8 rabbits showed corneal melting after injury (14 +/- 4) days, while two corneal perforated. In collagen cross-linking treatment group, one rabbit showed corneal melting after injury 23 days, without corneal perforation; corneal dissolution rate between the two groups was significantly different (P <0.05). Pathological examination suggested that in the treatment group, mild corneal edema, mild damage to collagen fibers, inflammatory cell infiltration was significantly less than the control group. Immunohistochemistry showed that corneal collagen fibers arranged in neat rows in the control group. CONCLUSION: Collagen cross-linking treatment not only can prevent and delay the corneal melting after alkali burn, but also can reduce the destruction of corneal collagen fibers and infiltration of inflammatory cells in the corneal tissue.

A short-term study of corneal collagen cross-linking with hypo-osmolar riboflavin solution in keratoconic corneas

AIM: To report the 3mo outcomes of collagen crosslinking(CXL) with a hypo-osmolar riboflavin in thin corneas with the thinnest thickness less than 400 μm without epithelium.METHODS: Eight eyes in 6 patients with age 26.2±4.8y were included in the study. All patients underwent CXL using a hypo-osmolar riboflavin solution after its de-epithelization. Best corrected visual acuity, manifest refraction, the thinnest corneal thickness, and endothelial cell density were evaluated before and 3mo after the procedure.RESULTS: The mean thinnest thickness of the cornea was 408.5 ±29.0 μm before treatment and reduced to369.8 ±24.8 μm after the removal of epithelium. With the application of the hypo-osmolar riboflavin solution, the thickness increased to 445.0 ±26.5 μm before CXL and recover to 412.5 ±22.7 μm at 3mo after treatment, P =0.659). Before surgery, the mean K-value of the apex of the keratoconus corneas was 57.6 ±4.0 diopters, and slightly decreased(54.7±4.9 diopters) after surgery(P =0.085). Mean best-corrected visual acuity was 0.55 ±0.23 logarithm of the minimal angle of resolution, and increased to 0.53±0.26 logarithm after surgery(P =0.879).The endothelial cell density was 2706.4 ±201.6 cells/mm2 before treatment, and slightly decreased( 2641. 2 ±218.2 cells/mm2) at last fellow up(P =0.002).CONCLUSION: Corneal collagen cross-linking with a hypo-osmolar riboflavin in thin corneas seems to be a promising treatment. Further study should be done to evaluate the safety and efficiency of CXL in thin corneas for the long-term.

Corneal collagen cross-linking and liposomal amphotericin B combination therapy for fungal keratitis in rabbits

AIM： To observe the therapeutic effect of corneal collagen cross-linking（CXL） in combination with liposomal amphotericin B in fungal corneal ulcers.METHODS： New Zealand rabbits were induced fungal corneal ulcers by scratching and randomly divided into 3groups, i.e. control, treated with CXL, and combined therapy of CXL with 0.25% liposomal amphotericin B（n =5 each）. The corneal lesions were documented with slit-lamp and confocal microscopy on 3, 7, 14, 21 and 28 d after treatment. The corneas were examined with transmission electron microscopy（TEM） at 4wk.RESULTS： A rabbit corneal ulcer model of Fusarium was successfully established. The corneal epithelium defect areas in the two treatment groups were smaller than that in the control group on 3, 7, 14 and 21d（P 〈0.05）. The corneal epithelium defect areas of the combined group was smaller than that of the CXL group（P 〈0.05） on 7 and 14 d, but there were no statistical differences on 3, 21 and 28 d. The corneal epithelium defects of the two treatment groups have been healed by day 21. The corneal epithelium defects of the control group were healed on 28 d. The diameters of the corneal collagen fiber bundles（42.960 ±7.383 nm in the CXL group and 37.040±4.160 nm in the combined group） were thicker than that of the control group（24.900±1.868 nm）,but there was no difference between the two treatment groups. Some corneal collagen fiber bundles were distorted and with irregular arrangement, a large number of fibroblasts could be seen among them but no inflammatory cells in both treatment groups. CONCLUSION： CXL combined with liposomal amphotericin B have beneficial effects on fungal corneal ulcers. The combined therapy could alleviate corneal inflammattions, accelerate corneal repair, and shorten the course of disease.

Clinical Evaluation of Pranoprofen Combined with Fluorometholone Eye Drops on Postoperative Reaction of Corneal Cross-linking

Purpose:To evaluate the efficacy and safety of pranoprofen eye drops for reducing postoperative ocular pain and inflammation after corneal cross-linking (CXL). Methods:Twenty-seven patients (38 eyes) with keratoconus undergoing CXL were examined and randomly divided into control (12 cases; 18 eyes) and experimental groups (15 cases;20 eyes).The patients in the control group were given fluorometholone eye drops,and those in the experimental group were administered with fluorometholone combined with pranoprofen eye drops.Corneal irritation and haze were compared between the two groups at 1 month postoperatively. Results:At 1 to 3 days after surgery,the corneal irritation in the experimental group was significantly reduced compared with that in the control group (P<0.05), but there was no significant difference on 5 to 7 days postoperatively (P>0.05). The average degree of haze in the experimental group was significantly lower than that in the control group 1 month after surgery (P<0.05), but there was no significant difference in the best-corrected vision acuity and intraocular pressure between the two groups. There were 2 cases with >20 mmHg intraocular pressure in the control group. Conclusion:The combined use of fluorometholone and pranoprofen can significantly reduce inflammatory response,alleviate corneal irritation at early stage after CXL,effectively prevent and control the average of haze,and reduce the incidence of steroid-induced ocular hypertension after surgery.

A Facile Route for the Large Scale Fabrication of Graphene Oxide Papers and Their Mechanical Enhancement by Cross-linking with Glutaraldehyde

A facile route for the large scale production of graphene oxide(GO) papers and their mechanical enhancement has been presented in this work. The novel paper-like GO made from individual GO sheets in aqueous suspension can be achieved in large scale by a simple drop casting method on hydrophobic substrates.Significant enhancement in mechanical stiffness(341%) and fracture strength(234%) of GO paper have been achieved upon modification with a small amount(less than 10 wt%) of glutaraldehyde(GA). The cross-linking reaction takes place between hydroxyl groups on the surface of GO and aldehyde groups of GA, through forming hemiacetal structure, which can result in distinct mechanical enhancement of the GO papers.

Iontophoresis-assisted corneal crosslinking using 0.1% riboflavin for progressive keratoconus

AIM：To report the clinical results of iontophoresis-assisted epithelium-on corneal crosslinking（I-CXL） using 0.1% riboflavin in distilled water for progressive keratoconus. METHODS：In this prospective clinical study, we examined 94 eyes of 75 patients with progressive keratoconus who were treated with I-CXL using 0.1% riboflavin in distilled water. Best correct visual acuity（BCVA）, Scheimpflug tomography, corneal topography, anterior segment optical coherence tomography, intraocular pressure, and endothelial cell density were evaluated at baseline and 1, 3, 6, 12, and 24 mo after I-CXL.RESULTS：After 24 mo I-CXL, compared to the level at baseline, BCVA significantly improved 0.14±0.07（P=0.010）; mean keratometry signifi cantly decreased 0.72±1.97（P=0.021）; maximum keratometry significantly reduced 2.30±5.01（P=0.014）; central keratoconus index significantly reduced 0.04±0.08（P=0.007）. The demarcation line was visible in 83.1% of eyes at 1mo after treatment, with a depth of 298.95±51.97 μm, and gradually indistinguishable. One eye had repeat treatment. Intraocular pressure and endothelial cell density did not change significantly.CONCLUSION：I-CXL using 0.1% riboflavin halts keratoconus progression within 24 mo, resulting in a significant improvement in visual and topographic parameters. Moreover, the depth of the demarcation line is similar to that previously reported in standard epithelium-off CXL procedures.

Study on Various Compositions of Polyvinyl Alcohol and Starch Blends by Cross-Linking with Glyoxal

The aim of this study is to analyze the various compositions of polyvinyl alcohol (PVA) and starch blends. The blends have been cross-linked with glyoxal to enhance its properties. The hydroxyl groups of PVA and starch react with glyoxal via formation of acetal bonds;hence crosslinking could take place. The cross-linking of glyoxal is observed in various analytical methods such as DSC and FTIR. The cross-linked blends showed better thermal and mechanical properties. Viscosity, tensile shear strength, pencil hardness and ultimate stress were evaluated to estimate the changes due to cross-linking. It was observed that the cross-linking is directly proportional to starch, since the starch hydroxyl groups are easily accessible for reacting. The cross-linked blend showed better cohesion between its chains, thereby increasing glass transition temperature. It was reflected in the subsequent increase in tensile strength properties.

Synthesis and Applications of Tetra- functional Branched Poly(ethylene glycol) Derivative for the Decellularized Valve Leaflets Cross-linking

To investigate the effects of polyethylene glycol cross-linking on the mechanical properties, 80 porcine aortic valves were harvested, decellularized, and introduced with sulflaydryl. Then the valves were randomly assigned into 5 experimental groups and 1 control group （n=16）. For the valves in those experimental groups, branched polyethylene glycol diacrylate （PEG） of 5 different molecular weights （3.4, 8, 12, 20, 40 kDa） were synthesized and cross-linked with them respectively. The efficiency of the cross-linking was determined by measuring the amount of residual thiol group and the mechanical properties of the cross-linked valve leaflets were assessed by uni-axial planar tensile testing. The efficiency of the PEG 20 kDa group was 70.72±2.33%, obviously superior to that of the other groups （p〈0.05）. Tensile test proved that branched PEG cross-linking can significantly enhance the mechanical behaviors of the deeellularized valve leaflet and the Young＇s modulus of each group was positively correlated with the molecular weight of PEG. It was concluded that branched PEG with the molecular weight of 20 kDa can effectively cross-link the decellularized porcine aortic valves and improve their mechanical properties, which makes it a promising cross-linker that can be used in the modification of decellularized tissue engineering valves.

Preparation of Nano-porous Materials(Ⅱ) by Cross-linking of Amphiphilic Self-assemblies

Amphiphilic block copolymers can exhibit rich and complex morphologies in aqueous solutions, but these structures are usually delicate, easily disturbed by composition change or temperature change. In this work, the use of different methods to cross link block copolymer self assemblies in the presence of a selective solvent and to stabilize the structures is reviewed. In addition, the cross linking reaction kinetics of block copolymer amphiphilic self assemblies is briefly discussed.

5-year follow-up of combined non-topography guided photorefractive keratectomy and corneal collagen cross linking for keratoconus

AIM： To evaluate the visual outcomes of simultaneous non-topography guided photorefractive keratectomy（PRK） and corneal collagen cross-linking（CXL） in eyes with keratoconus 5 y after the procedure.METHODS： Prospective, interventional, non-randomized, and non-controlled case series design was used. Sixty eyes of 30 patients（16 males and 14 females; age： 21-41 y） with mild, non-progressive（stages 1-2） keratoconus were enrolled. Refraction, uncorrected distance visual acuity（UDVA） and corrected distance visual acuity（CDVA）, flat and steep keratometry readings, and adverse events were evaluated preoperatively and postoperatively. Data were collected preoperatively and postoperatively at 3 mo, 1, 2, 3, 4, and 5 y follow-up visits after combined non-topography-guided PRK with CXL was performed. All patients had at least 5 y of follow-up.RESULTS： All study parameters showed a statistically significant improvement at 5 y over baseline values. The mean follow-up time was 68.20±4.71 mo（range： 60-106 mo）. Patients showed a significant improvement in UDVA from 1.24±0.79 log MAR prior to combined non-TG-PRK＋CXL to 0.06±0.15 log MAR postoperatively at the time of their last follow-up visit. CDVA significantly increased from 0.06±0.19 log MAR preoperatively to 0.03±0.12 log MAR postoperatively. A significant decrease in the mean spherical equivalent（SE） refraction was observed from-2.28±1.8 to-0.79±0.93 diopters（D）（P〈0.05）, and the manifest sphere decreased from-1.62±1.23 to-0.27±0.21 D（P=0.001）. The manifest cylinder significantly decreased from-1.73±0.86 to-0.29±0.34 D postoperatively（P=0.001）. The mean steep keratometry was 45.13±1.32 vs 47.28±2.12 D preoperatively（P〈0.05）, and the preoperative mean steepest keratometry（Kmax） 48.6±3.1 was reduced significantly to 46.8±2.9 postoperatively（P〈0.05）. CONCLUSION： Combined non-TG-PRK with 15 min CXL is an effective and safe option for correcting mild refractive error and improving visual acuity in patients with mild stable keratoconus.

Clinical and microstructural changes with different iontophoresis-assisted corneal cross-linking methods for keratoconus

AIM: To compare the clinical and microstructural changes induced by different transepithelial iontophoresis-assisted corneal cross-linking(I-CXL) methods for keratoconus. METHODS: A total of 42 eyes of 42 patients with progressive keratoconus were divided into two groups. Group A received I-CXL for 5 min, while group B received I-CXL for 10 min. Visual acuity, optical coherence tomography(OCT), specular microscopy and confocal microscopy were evaluated preoperatively and at 1, 3, 6, and 12 mo postoperatively. RESULTS: Twelve months after the operation, uncorrected visual acuity(UCVA) and corrected distance visual acuity(CDVA) were improved in both groups, with a better outcome in the I-CXL 10 min group(P=0.025, 0.021, respectively). Kmax values decreased by 0.94±3.00 D in the I-CXL 10 min group(P=0.033) but increased by 1.87±3.29 D in the I-CXL 5 min group(P=0.012). OCT scans showed that the demarcation line was most visible and substantially deeper in the I-CXL 10 min group. Confocal microscopy showed greater anterior stromal keratocyte decreases in the I-CXL 10 min group than in the I-CXL 5 min group at 3 and 6 mo postoperatively(P<0.001); however, anterior stromal keratocytes and subbasal nerve density were not significantly different between the two groups at 12 mo postoperatively. CONCLUSION: I-CXL for 10 min more effectively halts the progression of keratoconus than I-CXL for 5 min after 12 mo of follow-up. However, long-term studies are needed to evaluate the efficacy and safety of I-CXL.