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.

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.

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.

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.

Scheimpflug imaged corneal changes on anterior and posterior surfaces after collagen cross-linking

AIM:To compare the anterior and posterior corneal parameters before and after collagen cross-linking therapy for keratoconus.METHODS:Collagen cross-linking was performed in31 eyes of 31 keratoconus patients(mean age 30.6±8.9y).Prior to treatment and an average 7mo after therapy,Scheimpflug analysis was performed using Pentacam HR.In addition to corneal thickness assessments,corneal radius,elevation,and aberrometric measurements were performed both on anterior and posterior corneal surfaces.Data obtained before and after surgery were statistically analyzed.RESULTS:In terms of horizontal and vertical corneal radius,and central corneal thickness no deviations were observed an average 7mo after operation.Corneal higher order aberration showed no difference neither on anterior nor on posterior corneal surfaces.During follow-up period,no significant deviation was detected regarding elevation values obtained by measurement in mm units between the 3.0-8.0 mm-zones.CONCLUSION:Corneal stabilization could be observed in terms of anterior and posterior corneal surfaces,elevation and higher order aberration values 7mo after collagen cross-linking therapy for keratoconus.

Comparison of Central Corneal Thickness using Ultrasound Pachymetry during Corneal Collagen Cross-linking

Purpose:To study variation in central corneal thickness (CCT) during corneal collagen cross-linking(CXL) using ultrasound pachymetry. Methods:Twenty patients (26 eyes) with progressing keratoconus undergoing riboflavin-UVA-induced CXL were involved in this study. Intraoperative CCT measurement using ultrasonic pachymetry was performed during the procedure.Measurements were obtained before operation, after epithelial removal, after riboflavin drop instillation, and after UVA irradiation. Results:Mean CCT was 495±56 and 450±52 μm before and after epithelial removal, respectively. Mean CCT was 443±42 and 411±39 μm after riboflavin drop instillation and after UVA irradiation, respectively. Statistically significant decreases in CCT occurred between the preoperative period and after epithelial removal, after riboflavin drop instillation and after UVA irradiation. Twenty-six eyes from 20 patients undergoing CXL were divided into 2 groups (I with CCT≥400 μm after UVA irradiation and II with CCT<400 μm after UVA irradiation). No statistically significant difference was noted between I and II in preoperative endothelial cell count, but a statistically greater postoperative endothelial cell count was noted in I compared to II. A statistically significant difference was evident between preoperative and postoperative endothelial cell counts in Group II (P<0.05). Conclusion:Performing CXL with the use of riboflavin and UVA irradiation resulted in a statistically significant decrease in CCT, to a level where the corneal endothelium may be damaged.(Eye Science 2013; 28:15-19)

Variation in Central Corneal Thickness during Open- or Closed-Eye Riboflavin Instillation for Corneal Collagen Cross-linking

Purpose:To assess the effect of having an open or closed eye on the variation in central corneal thickness during riboflavin instillation for corneal collagen cross-linking (CXL).Methods:.Thirty eyes of 15 New Zealand White rabbits underwent an in vivo anterior segment optical coherence tomography (OCT) examination at 0,10,20,and 30 min after riboflavin instillation on the de-epithelialized corneal surface.Each eye of every rabbit was randomly placed into one of two different treatment groups(open-eye or closed-eye)during the instillation;.the examinations were performed one after the other.After instillation for 30 min,the changes in the corneal stroma and anterior chamber were observed by slit lamp.Results:.A significant decrease in the central corneal thickness(CCT).was demonstrated during riboflavin instillation;.the variations were smaller in the measurements performed with the eye closed than with the eye open.(81.36±15.13μm and129.20±12.05μm respectively)..Both methods turned the corneal stroma and anterior chamber yellow.Conclusion:Keeping the eye closed during riboflavin instillation reduced the decrease in the CCT..The same yellow change in the corneal stroma and anterior chamber occurred,but the exposure time of the ocular surface was shorter.Therefore,.keeping the eye closed was a more effective and safer method than keeping the eye open.

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.

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.

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.

Analysis of the effective dose of ultraviolet light in corneal cross-linking

AIM: To analyze the efficacy of ultraviolet (UV) light initiating corneal cross-linking (CXL). METHODS: The time-dependent absorption of UV light due to the depletion of the initiator (riboflavin) was calculated. The effective dose of CXL with corneal surface covered by a thin layer of riboflavin was derived analytically. The cross linking time was calculated by the depletion level of the riboflavin concentration. A comprehensive method was used to derive analytic formulas. RESULTS: The effective dose of CXL was reduced by a factor (R) which was proportional to the thickness (d) and concentrations (C-0) of the riboflavin surface layer. Our calculations showed that the conventional dose of 5.4 J/cm(2) had a reduced effective dose of 4.3 and 3.45 J/cm(2), for d was 100 and 200 pm, respectively, and C-0=0.1%. The surface cross linking time was calculated to be T*=10.75s, for a depletion level of 0.135 and UV initial intensity of 30 mW/cm(2). The volume T* was exponentially increasing and proportional to exp (bdC(0)), with b being the steady state absorption coefficient. CONCLUSION: The effective dose of CXL is reduced by a factor proportional to the thickness and concentrations of the riboflavin surface layer. The wasted dose should be avoided by washing out the extra riboflavin surface layer prior to the UV light exposure.

Clinical outcomes at one year following keratoconus treatment with accelerated transepithelial cross-linking

This study evaluated the clinical outcomes in keratoconus corneas following accelerated transepithelial corneal collagen cross-linking（CXL）（Avedro KXL system,Waltham,MA,USA） over one year of follow-up.The mean depth of the demarcation line measured by optical coherence tomography（OCT） was 205.19 μm.One month after surgery,a non-statistically significant change was noted in sphere（P= 0.18） and in spherical equivalent（P= 0.17）,whereas a significant improvement was observed in corrected distance visual acuity（P=0.04）.A significant change was observed in topographic astigmatism（P= 0.03） and posterior corneal a sphericity（P= 0.04）.Accelerated transepithelial CXL may be a useful technique for the management of progressive keratoconus.

角膜基质透镜联合跨上皮快速角膜胶原交联术治疗重度圆锥角膜

目的:评估角膜基质透镜联合跨上皮快速角膜胶原交联术(SC-A-TE-CXL)治疗重度圆锥角膜的临床疗效。方法:前瞻性自身前后对照研究。收集2019-03/2022-07于南京医科大学附属眼科医院确诊为重度圆锥角膜且最薄点角膜厚度(含上皮)<400μm的患者10例14眼,其中男8例12眼,女2例2眼,予以SC-A-TE-CXL进行治疗。观察并记录术前和术后1、3、6、12 mo的角膜曲率、裸眼视力(UCVA)、最佳矫正视力(BCVA)、角膜最薄点厚度(TCT)、角膜中心厚度(CCT)、非接触式眼压、内皮细胞密度(ECD)和前后表面最薄点高度以及术后1 mo角膜交联深度。结果:患者行SC-A-TE-CXL术后1、3、6、12 mo UCVA和BCVA较术前提高,但总体无差异(F=0.793,P=0.535;F=0.783,P=0.542)。术后各时间点K1、K2、Km和Kmax较术前下降,但总体无差异(F=0.627,P=0.574;F=1.264,P=0.296;F=0.727,P=0.520;F=1.115,P=0.359)。术后各时间点前后表面最薄点高度较术前均下降,但总体无差异(F=1.046,P=0.359;F=1.164,P=0.337)。术后各时间点非接触式眼压较术前提高,但总体无差异(F=0.814,P=0.522)。术后各时间点CCT、TCT和术前相比总体无差异(F=0.931,P=0.453;F=0.782,P=0.542)。术后12 mo ECD与术前相比无差异(t=1.266,P=0.228)。术后1 mo,前节光学相干层析成像术(AS-OCT)显示角膜浅层基质密度增高,前后基质间存在“分界线”,平均深度为124.07±25.13μm。结论:SC-A-TE-CXL能延缓重度圆锥角膜患者的病情进展,安全性高,其远期疗效有待进一步观察,可以作为一种治疗重度圆锥角膜的手术方式。

FSLASIK联合快速角膜交联术后角膜透明度的临床观察

目的研究飞秒激光辅助准分子激光原位角膜磨镶术(FSLASIK)联合快速角膜交联手术(CXL)矫正近视手术术后患者早期的角膜光密度(CD)、视力、屈光度的变化特点。方法回顾性临床研究。本研究筛选了2019年至2021年在本院行FSLASIK联合快速角膜交联手术矫正近视和散光的30例(60只眼)患者,进行回顾性的分析,分别于术前、术后1个月、术后3个月进行常规检查,检查项目包括屈光度、裸眼视力(UCVA)、裂隙灯检查和Pentacam眼前节分析仪。观察记录手术前后角膜光密度的变化;观察记录等效球镜度数(SE)的变化,数据统计完成后,采用IBM SPSS 24.0统计软件进行分析,通过KolmogorovSmirnov测试对各组数据进行正态性检验。对符合正态分布的数据进行重复方差检验,进一步两两比较采用LSDt检验,对于不符合正态分布的采用Friedman检验分析。结果(1)术后1个月UCVA与术前最佳矫正视力(BCVA)相比,略微降低(P<0.05)。术后3个月UCVA与术后1个月UCVA相比差异无统计学意义(P>0.05)。术后3个月UCVA与术前BCVA相比,差异无统计学意义(P>0.05)。(2)术后等效球镜度明显降低,较术前差异有统计学意义(P<0.05),术后1个月与术后3个月的SE之间差异无统计学意义(P>0.05)。(3)从整体光密度上看,术后1个月的角膜光密度与术前相比差异无统计学意义。术后3个月的角膜光密度与术前相比略微降低(P<0.05),术后3个月与术后1月相比略微降低(P<0.05)。(4)从不同直径范围的角膜光密度上看,术后1个月,角膜直径0~2 mm、2~6 mm区域内的角膜光密度与术前相比略微提高(均P<0.05),角膜直径6~10 mm内的角膜光密度与术前相比略降低(P<0.05);术后3个月,在角膜直径0~2 mm、2~6 mm区域内的角膜光密度与术前比差异均无统计学意义;角膜直径6~10 mm区域内的角膜光密度与术前相比略微降低(P<0.05)。(5)从不同分层的角膜光密度上看,术后1个月,角膜前层(前120μm)和角膜后层(后60μm)的角膜光密度与术前相比差异无统计学意义(P>0.05);角膜中央层的角膜光密度与术前相比略微降低(P<0.05)。术后3个月,角膜前层、中央层、后层角膜光密度与术前相比均略微降低(均P<0.05)。结论FSLASIK Xtra术后早期可以维持较好的角膜透明度,具有较好的安全性、有效性与准确性。

应用带蒂角膜上皮瓣下等渗核黄素及恢复上皮瓣的快速角膜胶原交联术治疗薄圆锥角膜

目的:评估带蒂角膜上皮瓣下等渗核黄素及恢复上皮瓣的快速角膜胶原交联术(A-CXL)治疗过薄圆锥角膜(去上皮后角膜厚度小于400μm)患者的疗效和安全性。方法:回顾性研究。纳入2017-09/2020-12于成都中医大银海眼科医院屈光手术科治疗圆锥角膜患者46例74眼。根据术前最薄点角膜厚度(TCT)分为两组:TCT为400-<450μm的患者行带蒂角膜上皮瓣下等渗核黄素及恢复上皮瓣A-CXL 16例20眼,手术方法为做带蒂角膜上皮瓣并掀开,等渗核黄素滴眼,将角膜上皮瓣重新恢复后,进行紫外线照射,照射结束后,刮除角膜上皮瓣。TCT≥450μm的患者行去上皮A-CXL手术30例54眼。随访12 mo,收集所有患者手术前后最佳矫正视力(BCVA)、Sirius三维角膜地形图、角膜内皮细胞密度检查结果。结果:术后12 mo,带蒂角膜上皮瓣A-CXL组患者Kmax较术前无差异(P>0.005),去上皮A-CXL组患者Kmax较术前显著降低(P<0.005)。两组术后12 mo BCVA(LogMAR)、角膜前后表面曲率(K1、K2)及角膜内皮细胞密度较术前均无差异(均P>0.005)。两组各指标术后12 mo与术前变化量比较均无差异(均P>0.05)。结论:带蒂角膜上皮瓣下等渗核黄素及恢复上皮瓣A-CXL对于TCT为400-<450μm圆锥角膜患者安全可行,与去上皮A-CXL手术控制圆锥角膜进展的趋势相似。

Combined corneal CXL and photorefractive keratectomy for treatment of keratoconus: a review

Keratoconus and iatrogenic keratectasia are the corneal ectatic disorders occurring due to biomechanical weakening of the cornea resulting in distorted images,myopia, and irregular astigmatism. Corneal collagen cross-linking(CXL) is performed to arrest keratoconus successfully. The main aim of this review is to discuss the safety and efficacy of the adjuvant therapies, such as the combination of CXL and photorefractive keratectomy(PRK) for the treatment of corneal ectatic disorders. A comprehensive literature search was performed using PubM ed, MEDLINE, and Scopus using keywords ‘collagen’‘keratoconus’,‘keratectasia’,‘collagen cross-linking’,and ‘photorefractive keratectomy’. Search results were restricted to clinical studies published in English. Corneal CXL effectively arrests the progression of keratoconus by enhancing corneal rigidity. However, functional vision is not improved by cross-linking. Combining CXL to refractive surgeries such as topography-guided PRK or transepithelial PRK is found to be a safe and effective method in providing corneal stability as well as significantly improving functional visual acuity with few minor complications. This combined technique also prevents regression of keratoconus and reduce the risk of keratectasia. CXL combined with PRK is a promising therapeutic approach in ophthalmology that can be successfully used to treat progressive keratoconus and other corneal ectatic disorders and to enhance visual acuity.

角膜基质透镜植入联合角膜胶原交联术治疗圆锥角膜术后角膜上皮重塑

目的:观察飞秒激光辅助下的角膜基质透镜植入联合角膜胶原交联术(SLAK-CXL)治疗进展期圆锥角膜术后角膜上皮重塑情况,探讨角膜上皮重塑规律和影响因素,为进一步屈光矫正提供良好的时机选择。方法:回顾性、观察性研究。纳入2020-09/2021-10于我院接受SLAK-CXL的圆锥角膜患者28例29眼,记录手术前后视力、眼压(IOP)、屈光度、角膜曲率及角膜上皮厚度(CET),观察CET变化趋势,并根据透镜厚度和植入深度分析影响CET变化的因素。结果:与术前比较,纳入患者术后1mo角膜前表面曲率平坦值(K_(f))和陡峭值(K_(s))均升高(P<0.05),术后1、2、6mo,1a角膜最薄点厚度(TCT)均升高(P<0.05)。纳入患者术后CET随时间变化而变化,中央区CET变化趋势较明显。与术前相比,术后1、2、6mo,1a旁中央区上方、鼻上方、鼻侧和颞上方CET均降低,中周区上方、颞侧、颞上方CET均降低,外周区鼻上方CET均增加。术后1a,不同植入透镜深度和厚度患者各分区角膜上皮厚度变化量均无差异(P>0.05)。结论:首次发现SLAK-CXL治疗圆锥角膜术后角膜形态发生变化,CET呈先减少再增加再减少趋势,术后1a中央区、旁中央区CET降低,中周区、外周区CET增加,且角膜上皮重塑程度与术中植入透镜深度和厚度均无关。

角膜胶原交联术后无菌性角膜炎的临床特征及治疗转归

目的探讨圆锥角膜患者进行角膜胶原交联(CXL)术后无菌性角膜炎的临床特点、治疗及愈后。方法回顾性系列病例研究。选择2018年1月至2020年9月河南省立眼科医院屈光手术中心281例(387眼)圆锥角膜患者,其中行CXL术后发生无菌性角膜炎的患者为炎症组(9例11眼),选取同期CXL术后无并发症的圆锥角膜患者为对照组(23例30眼),比较炎症组与对照组患者的年龄、性别、平坦角膜曲率(K_(1))、陡峭角膜曲率(K_(2))、散光(Astig)及最薄点角膜厚度(TCT)的差异。采用多因素Logistic回归分析无菌性角膜炎发生的影响因素。结果CXL术后发生无菌性角膜炎患者9例11眼,发生率为2.84%,均发生在去上皮CXL术后。9例11眼均于术后1周内出现无菌性角膜炎,1眼同时累及角膜中央区、旁中央区及周边部,1眼累及旁中央区,其余9眼均位于角膜周边部。炎症组与对照组患者的年龄、性别、K_(1)、K_(2)、Astig及TCT差异均无统计学意义(均为P>0.05)。经皮质类固醇激素治疗,预防性使用抗生素滴眼可以取得良好效果。Logistic回归分析结果显示,年龄、性别、K_(1)、K_(2)、Astig及TCT均不是无菌性角膜炎发生的危险因素(均为P>0.05)。结论圆锥角膜患者行CXL后无菌性角膜炎常见于去上皮CXL患者中,一般发生在术后早期,病灶多在角膜周边部,以皮质类固醇激素为主的治疗可以取得良好效果。

圆锥角膜不同交联方法术后基质分界线发生特点及其对交联效果的影响

目的比较早期圆锥角膜接受核黄素/紫外线A角膜胶原交联术(CXL)不同手术方式术后基质分界线的特点,并分析基质分界线对交联效果的影响。方法采用非随机对照临床研究方法,选取2019年5月至2021年2月于山东第一医科大学附属眼科医院就诊的圆锥角膜患者69例69眼,所有患者均行CXL治疗,其中经上皮交联组21眼,去上皮交联组48眼;5.4 J能量组25眼,7.2 J能量组44眼。分别于术后2周、1个月、3个月、4个月进行随访,观察角膜基质交联反应(基质分界线)的形态及变化特点;记录角膜最薄处厚度(TCT)、裸眼视力(UCVA,LogMAR)、最佳矫正视力(BCVA,LogMAR)和角膜最大曲率(Kmax)等的变化。结果术后出现基质分界线占63.77%(44/69),未出现基质分界线占36.23%(25/69)。去上皮交联组出现基质分界线占79.17%(38/48),明显高于经上皮交联组的28.57%(6/21),差异有统计学意义(χ^(2)=16.186,P<0.01);5.4 J能量组出现基质分界线占72.00%(18/25),7.2 J能量组占56.80%(25/44),差异无统计学意义(χ^(2)=1.565,P=0.302)。裂隙灯显微镜及眼前节光学相干断层扫描显示基质分界线于术后1~2周时出现,1个月时逐渐汇聚、增强;2~3个月后基质分界线开始变得弥散、边界模糊,并逐渐变淡;4个月时基质分界线基本消失。基质分界线深度可达141~423μm,平均(263.44±84.22)μm。激光扫描共聚焦显微镜观察结果显示,交联术后角膜基质细胞激活,反光增强,胶原纤维纵横伸展并相互交错,纤维排列呈网状。术后4个月,TCT由术前的(458.69±38.28)μm降至(443.86±36.54)μm,差异有统计学意义(t=6.705,P<0.001);有基质分界线组与无基质分界线组术后TCT下降幅度比较,差异无统计学意义(t=1.684,P=0.100)。术后4个月所有术眼UCVA由术前的0.74±0.37提高至0.69±0.38,差异有统计学意义(t=2.109,P=0.039);手术前后BCVA比较,差异无统计学意义(t=1.006,P=0.319)。有基质分界线组与无基质分界线组术后UCVA和BCVA变化量比较,差异均无统计学意义(t=0.065,P=0.949;t=0.346,P=0.730)。手术前后所有患者Kmax比较,差异无统计学意义(t=0.050,P=0.950);有基质分界线组和无基质分界线组术后Kmax变化量比较,差异无统计学意义(t=-0.739,P=0.464)。去上皮交联组术后TCT变化量明显大于经上皮交联组,差异有统计学意义(t=2.815,P=0.008),2个组间术眼术后UCVA、BCVA和Kmax变化量比较,差异均无统计学意义(均P>0.05)。所有患者术后无明显角膜瘢痕、感染性角膜炎、角膜内皮失代偿等并发症。结论圆锥角膜CXL术后出现基质分界线可能是交联反应深度的标志;去上皮手术方式术后更容易出现基质分界线;2种角膜胶原交联模式有相似的治疗效果;圆锥角膜不同交联方法术后基质分界线的发生与否对交联效果无明显影响。