Refractive Lenticule-Assisted Accelerated Corneal Cross-linking: A Three-Year Clinical Observation in Patients with Thin Keratoconus

Refractive Lenticule-Assisted Accelerated Corneal Cross-linking: A Three-Year Clinical Observation in Patients with Thin Keratoconus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Refractive Lenticule-Assisted Accelerated Corneal Cross-linking: A Three-Year Clinical Observation in Patients with Thin Keratoconus Ying Li, Mingyan Wang, Dian Zhao, Chunyang Zhou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7440942/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Dec, 2025 Read the published version in International Ophthalmology → Version 1 posted 13 You are reading this latest preprint version Abstract Objective Accelerated corneal cross-linking (A-CXL) is unsuitable for thin keratoconus treatment. We developed refractive lenticule-assisted A-CXL by overlaying lenticules during A-CXL to optimize therapy for thin keratoconus. This retrospective study evaluates its 3-year efficacy and safety. Methods This study retrospectively included 63 eyes (42 cases) with progressive keratoconus who underwent A-CXL in our hospital from September 2017 to December 2020. The surgical method is determined based on the patients' corneal thickness. Patients received refractive lens-assisted A-CXL (10 cases with 18 eyes) were designated as Group A, while those undergowent A-CXL alone (32 cases with 45 eyes) were classified as Group B. The follow-up duration for both groups was 3 years. Preoperative and postoperative evaluation (6 months, 12 months, 24 months, and 36 months) included best corrected visual acuity (BCVA), endothelial cell density (ECD), thinnest corneal thickness (TCT), keratoconus vertex back (Kvb) and corneal curvature. Any adverse events like delayed corneal healing, corneal infections, haze, etc that occurred during this period should be record. Results During follow-up, no significant changes were observed in TCT, Kmax, K1, K2, or Kvb in Group A, while BCVA significantly improved at 36 months postoperatively, and ECD significantly increased at 12 months postoperatively ( P <0.016). Over the same period, Group B showed decreases in TCT and ECD compared to baseline ( P < 0.05), increases in anterior surface K1 and K2 values, and improvements in BCVA and Kmax ( P < 0.05), with no significant change in Kvb. During the 36-month postoperative period, Group A exhibited more substantial improvements in BCVA and more pronounced elevation in Kvb than Group B. Both groups exhibited uneventful healing with no adverse events. Conclusions Over the 3-year follow-up period, the refractive lenticule-assisted A-CXL and A-CXL showed similar efficacy and safety in controlling the progression of keratoconus. keratoconus ultrathin cornea accelerated corneal cross-linking A-CXL refractive lenticule Small Incision Lenticule Extraction SMILE Refractive Lenticule-assisted A-CXL Background Keratoconus (KC) is an ocular disorder characterized by central or para-central expansion and thinning of the cornea, resulting in a conical protrusion of the corneal tissue anteriorly [ 1 ] . It usually onset during adolescence, often affecting both eyes simultaneously, with a subtle and insidious presentation. and be considered one of the significant causes of blindness in our country. Corneal cross-linking (CXL) is a common and effective method for treating KC [ 2 ] . It induces a chemical cross-linking reaction between the amino groups of collagen fibers, triggered by riboflavin and Ultraviolet A (UVA) rays, to enhance the biomechanical stability of collagen fibers, reinforcing the cornea’s structural integrity against ectatic deformation, and thereby halting the progression of KC [ 3 – 5 ] . Conventional CXL, adhering to the Dresden protocol [ 6 ] , involves the removal of corneal epithelium followed by exposure of the treated eye to UVA radiation at an intensity of 0.36 mW/cm² for a duration of 30 minutes. The process resulted in cytotoxic effects on endothelial cells within a depth of 400 µm. Consequently, this approach is not suitable for KC with a thickness of less than 400 µm following epithelial debridement [ 7 , 8 ] . Furthermore, long time of radiation elevates the risk of epithelial complications, infection, and other potential injury to the corneal endothelium and other intraocular structures. Over the past two decades, a variety of modified CXL protocols have been developed and implemented in clinical. A-CXL is generated based on the Bunsen-Roscoe law, which employs high-intensity UVA irradiation to reduce the duration of ultraviolet exposure [ 9 ] . This approach minimizes patient discomfort associated with prolonged irradiation and decreases the risks of corneal infection, dehydration, and thinning. Extensive research has demonstrated its efficacy and safety [ 10 , 11 ] . However, it is still not suitable for patients with thin Keratoconus. For Asian and African populations, who inherently have thinner corneas [ 12 , 13 ] , It is particularly urgent to develop modified surgical techniques for the treatment of thin keratoconus. There are several modified CXL procedures have been developed in clinical for the treatment of KC with thin corneal, such as the use of hypotonic riboflavin to swell the corneal stroma [ 14 ] , transepithelial CXL (TE-CXL) [ 15 ] , contact lens-assisted CXL (CACXL) [ 16 , 17 ] , etc. In 2015, Sachdev et al . first reported a technique utilizing SMILE-derived donor lenticules to augment traditional CXL by expanding stromal thickness in thin corneas [ 18 ] , Subsequently, in 2024, they published 5-year follow-up results of this procedure [ 19 ] , demonstrating an average reduction in Kmax of 4.30D in the treated eyes, with significant improvements in UDVA and CDVA without any complications or significant endothelial cell loss observed during the follow-up period. Cagini et al . similarly reported favorable outcomes [ 20 ] . Refractive lens-assisted CXL augments stromal depth via SMILE-derived allogenic lenticule overlay to minimize radiation-induced damage to corneal endothelium and intraocular tissues in thin KC. While preliminary studies show encouraging results, long-term clinical data are required to fully validate its safety and efficacy. In an effort to minimize damage to the corneal endothelium and other intraocular tissues from radiation while shortening surgical time, we attempted to cover the refractive lenticule on the eyes undergoing A-CXL surgery (Refractive Lenticule-assisted A-CXL) to provide a novel surgical option for patients with thin keratoconus. Herein, we report a retrospective clinical study to evaluate the efficacy and safety of Refractive Lenticule-assisted A-CXL over a 3-year follow-up period. Materials and Methods This retrospective study enrolled 63 eyes from 42 patients who underwent A-CXL for keratoconus at the Refractive Surgery Department of Ineye Hospital of Chengdu University of TCM in China between September 2017 and December 2020. Patients with a predicted corneal stromal thickness of less than 400 μm following epithelial debridement were treated with Refractive Lenticule-assisted A-CXL and assigned to Group A (10 cases with 18 eyes). The rest of the patients, who had a thicker stroma, received conventional A-CXL only and were assigned to Group B (32 cases with 45 eyes). The study adhered to the tenets of declaration of Helsinki. Ethics committee approval was taken (protocol number 2021yh-016), and written informed consent was obtained from all participants. Inclusion Criteria: ①A definitive diagnosis of progressive keratoconus. ②No history of contact lens wear within the past month. ③Age between 9 and 37 years. ④No other corneal diseases expect keratoconus. ⑤No family history of hereditary diseases. Exclusion Criteria: ①Acute keratoconus. ②History of poor epithelial healing after corneal trauma. ③Severe ocular comorbidities. ④Systemic conditions affecting corneal health or surgical recovery. ⑤Previous corneal surgery. ⑥Allergic reactions during treatment ⑦Female patients who are lactating or pregnant. ⑧Severe psychological or psychiatric disorders. ⑨Inability to complete the required follow-up. Preoperative and postoperative evaluation (6 months, 12 months, 24 months, and 36 months) included the assessments of BCVA, slit lamp examination of the anterior segment, fundus examination, ECD measurement, and corneal topography. Visual acuity was assessed using the International Standard Visual Acuity Chart and recorded in logMAR. Fundus examination was performed by Dayton. ECD were obtained by TOMEYEM-400. Topography and curvature of the anterior and posterior corneal surfaces were captured using the Sirius System (Schwind, CSO SpA, Italy). All measurements were taken by a trained ophthalmologist with over 10 years of experience. Surgical technique 1. Refractive Lenticule-assisted A-CXL 1.1 Lenticule Acquisition: Refractive lenticules were obtained from patients underwent SMILE correction for myopia. The donor cases for lenticules were checked preoperatively for no infectious diseases. The thickness of the lenticules was determined by the actual need for stromal expansion in patients receiving A-CXL. After extraction, the micro-lenticules were placed in a balanced salt solution. 1.2 Surgical Technique: The procedure was performed under topical anesthesia and aseptic conditions. After removing the central 9 mm area of corneal epithelium using 20% ethanol and an epithelial scraper, VibeX Rapid riboflavin solution (0.1% riboflavin salt solution with hydroxypropyl methylcellulose) was applied every 30 seconds for a total of 10 minutes. The eye was then flushed with balanced salt solution, and the allogeneic corneal stromal lenticule was placed on the stromal bed of the operative eye, centered and spread evenly. Subsequently, the UV Crosslinking Accelerator (Avedro Inc, USA) was used to irradiate the surgical eye with UV-A pulsed mode for 8 minutes (UV wavelength 365nm, irradiance 30mW/cm², total irradiation energy 7.2J/cm²). Balanced salt solution drops were administered during the procedure to keep the cornea moist. After UV exposure, the corneal stromal lenticule was removed, the cornea was rinsed with balanced salt solution, and a bandage contact lens was placed on the operative eye to conclude the surgery. 2. Conventional A-CXL Surgical Technique: The procedure was performed under topical anesthesia and aseptic conditions. Initially, the central 9 mm area of the corneal epithelium was debrided using 20% ethanol solution and an epithelial scraper. Subsequently, VibeX Rapid riboflavin solution was applied every 30 seconds for a total of 10 minutes. After rinsing with balanced salt solution, the UV Crosslinking Accelerator (Avedro Inc, USA) was used to irradiate the surgical eye with continuous mode for 4 minutes (UV wavelength 365nm, irradiance 30mW/cm², total irradiation energy 7.2J/cm²). Balanced salt solution drops were used to maintain corneal hydration during the UV exposure. Following the irradiation, the conjunctival sac was washed with balanced salt solution again, and a bandage contact lens was placed on the operative eye to complete the surgery. Statistical analysis Data analysis was performed using SPSS 26.0. Normality and variance homogeneity were assessed for all variables. Normally distributed and variance-homogeneous continuous data are expressed as mean ± standard deviation (x̄ ± s). Repeated measures ANOVA was used to assess within-group changes over time, with LSD-t tests for post-hoc analysis if significant differences were found. Independent samples t-tests were utilized for between-group comparisons. Non-normally distributed or variance-heterogeneous data are presented as median [interquartile range, M(P25, P75)], with Friedman tests for within-group comparisons and Bonferroni-adjusted post-hoc tests following significant findings. Wilcoxon rank-sum tests were employed for between-group contrasts. A P -value < 0.05 denoted statistical significance. Results 1. Study subjects In this study, patients were allocated to different surgical methods based on corneal thickness, resulting in baseline differences between two groups that precluded intergroup comparisons. The baseline characteristics in the two groups are as follows in Table1 and Tanble2: Table 1: Baseline Characteristics of Study Participants Group Gender Age （n=patients number） Male Female Group A（n=10) 6 4 17（15,29） Group B（n=32) 19 13 20（17,25） Table 2: Baseline Characteristics of Study eyes Group BCVA UCVA ECD （n=eyes number） Group A（n=18) 1.10(0.72,1.26) 0.40(0.16,1.16) 2614.11±341.193 Group B（n=45) 1.00(0.70,1.30) 0.30(0.10,0.61) 2873.36±261.648 t/Z -0.163 1.392 2.156 P 0.870 0.164 0.057 2. Outcomes of Efficacy Metrics 2.1 In Group A, no statistically significant differences were observed in TCT, Kvb, Kmax, K1 and K2 at all time points before and after surgery ( P > 0.05).BCVA showed a significant improvement during the follow-up period ( P = 0.030), with a particularly notable improvement at 36 months postoperatively ( P = 0.006). Detailed data are presented in Table 3. 2.2 In Group B, significant changes were detected in BCVA, TCT, Kmax, K1, and K2 at all time points before and after surgery ( P 0.05). Postoperative TCT values were significantly lower than preoperative measurements at all time points ( P < 0.001, P = 0.011, P = 0.001, P = 0.003), with the most substantial reduction observed at 6 months postoperatively; however, a thickening trend was noted from 12 to 36 months postoperatively. Kmax showed a significant decrease at 36 months postoperatively compared to baseline ( P = 0.007). K1 and K2 values significantly increased at 6 months postoperatively ( P = 0.001, P = 0.009) and then trended downward. BCVA demonstrated significant improvement during follow-up ( P = 0.026). Detailed data are presented in Table 4. Table 3: Variations in TCT, Corneal Curvature, Kvb, and BCVA across time in Group A Group GROUP A （n=18） Parameter Preoperative 6mo postoperative 12mo postoperative 24mo postoperative 36mo postoperative F/ χ 2 , P BCVA[M(P25,P75), logMAR] 0.4(0.16,1.16) 0.10(0.05,0.66) 0.10(0.00,0.07) 0.10(0.10,0.61) 0.10(-0.04,0.61) a 15.807,=0.030 TCT[M(P25,P75), μm] 414(385,419) 388(374,393) 395(370,403) 395(383,412) 399(380,407) 7.514,=0.111 K max (x±s, D) 58.43±4.95 58.31±4.13 56.99±5.64 57.75±5.99 57.69±6.14 1.381,=0.280 K1(x±s, D) 49.49±4.83 49.26±4.26 49.13±4.83 49.52±5.22 49.13±4.88 0.403,0.674 K2(x±s, D) 52.20±4.67 52.31±4.56 51.97±5.48 52.70±5.35 51.79±5.41 0.699,=0.599 Kvb(x±s, μm) 91.78±51.36 94±48.70 104.56±40.78 104.56±42.95 105.44±43.92 5.112,=0.054 Table 4: Variations in TCT, Corneal Curvature, Kvb, and BCVA across time in Group B Group Parameter Preoperative 6mo postoperative 12mo postoperative 24mo postoperative 36mo postoperative F/ χ 2 , P BCVA[M(P25,P75)，logMAR] 0.30(0.10,0.61) 0.30(0.10,0.76) 0.10(0.00,0.30) 0.10(0.00,0.30) 0.10(0.00,0.35) 11.063,0.026 TCT(x±s, μm) 483.29±22.28 469.91±24.95 478.77±23.97 474.93±27.88 475.54±25.80 13.519,＜0.001 GROUP B （n=45） K max [M(P25,P75)，D] 51.39(48.89,57.83) 51.23(49.31,56.68) 50.89(48.81,55.57) 51.10(48.17,56.30) 51.41(49.15,55.87) a 22.693,＜0.001 K1 [M(P25,P75)，D] 44.79(43.16,46.50) 45.02(43.39,47.32) 44.84(43.19,47.69) 44.58(43.22,47.82) 44.62(43.18,47.46) 16.73,=0.02 K2 [M(P25,P75)，D] 47.16(45.75,52.84) 47.77(46.52,53.41) 47.79(45.87,51.72) 46.89(45.73,52.09) 47.31(45.76,51.70) 35.88,＜0.001 Kvb(x±s, μm) 47.00(27.50,64.50) 46.00(29.00,66.00) 45.00(27.50,64.00) 43.00(31.00,68.00) 44.00(25.00,65.34) 5.808,＝0.214 3. Safety Outcomes 3.1 During the 3-year follow-up period of this retrospective study, patients in both groups successfully had their corneal contact lenses removed 4 to 7 days postoperatively, and the corneal epithelium of the surgical eyes healed completely. As of the final follow-up, no lens or retinal photodamage was observed in either group. Additionally, there were no complications such as delayed healing of the corneal epithelium, aseptic or infectious stromal infiltration, subepithelial haze, corneal endothelial decompensation, or corneal scarring. The incidence of complications between the two groups showed no statistically significant difference ( P > 0.05). 3.2 The ECD in Group A increased significantly from preoperative to 12 months postoperative ( P = 0.016), with a mean increase from 2614.11 to 2731.89 cells/mm². In contrast, the ECD of Group B significantly decreased ( P = 0.014), with a median decrease from 2856 to 2792 cells/mm². Detailed data are presented in Table 5. Table 5: Changes in ECD at 12 Months Postoperatively in Group A and B Group Parameter Preoperative 12mo postoperative t/Z, P GROUP A ECD （x±s cells/mm 2 ） 2614.11±341.19 2731.89±309.00 -3.038，0.016 GROUP B ECD [M(P25,P75) cells/mm2] 2856(2708.5,3031) 2792(2593,2983.5) -2.245, 0.014 4. Comparison of the Changes in Indicators Between the Two Groups During the Follow-up Period 4.1 Define the changes in observation indicators during the 12-month postoperative period as Δ 12 . We found there were no statistically significant differences between the two groups in terms of Δ 12 BCVA, Δ 12 Kmax, and Δ 12 K2 ( P >0.05). Concurrently, We observed Kvb decreased in Group B but increased in Group A ( P =0.012). Group B also showed a less pronounced reduction in TCT ( P =0.013), while Group A exhibited a greater decline in K1 ( P =0.036). Notably, at 12 months postoperatively, ECD declined in Group B but increased significantly in Group A ( P =0.002). Detailed data are provided in Table 6. Table 6: Comparison of Δ12BCVA,Δ12TCT, Δ12Kmax, Δ12K1, Δ12K2 Δ12Kvb, and Δ12ECD Between the Group A and Group B Group Δ 12 BCVA [M(P25,P75), logMAR] Δ 12 TCT （x±s, μm） Δ 12 Kmax [M(P25,P75)，D] Δ 12 K1 [M(P25,P75), D] Δ 12 K2 [M(P25,P75), D] Δ 12 Kvb [M(P25,P75), μm] Δ 12 ECD [M(P25,P75) cells/mm2] Group A -0.12(-0.40,0) -16.44±18.53 -2.00(-2.53,0.36) -0.55(-0.86,0.48) -0.77(-1.16,0.82) 9.00(-0.50,28.50) 144(41,200) Group B 0(-0.30,0.10) -4.52±11.37 -0.41(-1.56,0.31) 0.20(-0.24,0.63) -0.07(-0.74,0.36) -1.00(-4.50,2.00) -45(-164,32.5) Z/t , P -1.370,0.171 2.564,0.013 -1.079,0.280 -2.101,0.036 -1.056,0.291 2.510,0.012 -3.087,0.002 4.2 . Define the changes in observation indicators during the 24-month postoperative period as Δ 24 . There were no statistically significant differences in the changes of various indicators between the two groups. Detailed data are provided in Table 7. Table 7: Comparison of Δ24BCVA,Δ24TCT, Δ24Kmax, Δ24K1, Δ24K2, and Δ24Kvb Between the Group A and Group B Group Δ 24 BCVA [M(P25,P75), logMAR] Δ 24 TCT （x±s, μm） Δ 24 Kmax [M(P25,P75)，D] Δ 24 K1 [M(P25,P75), D] Δ 24 K2 [M(P25,P75), D] Δ 24 Kvb (x±s, μm) Group A -0.18(-0.40,0) -9.56±12.40 -1.46(-2.04,1.10) -0.27(-0.84,0.92) -0.97(-1.44,3.05) 12.78±16.12 Group B -0.08(-0.30,0.09) -8.36±16.20 -0.77(-1.78,0.26) 0.11(-0.27,0.38) -0.33(-1.13,0.26) 0.42±7.09 Z/t , P -1.060,0.289 0.209,0.835 -0.499,0.618 -0.963,0.335 -0.232,0.816 -2.257,0.052 4.3 Define the changes in observation indicators during the 36-month postoperative period as Δ 36 . There were no statistically significant differences in Δ 36 TCT, Δ 36 Kmax, Δ 36 K1 and Δ 36 K2 between the two groups ( P >0.05). Moreover, we observed Kvb decreased in Group B but increased in Group A ( P =0.012). Additionally, Group A exhibited significantly greater changes in BCVA. Detailed data are provided in Table 8. Table 8: Comparison of Δ36BCVA,Δ36TCT, Δ36Kmax, Δ36K1, Δ36K2, and Δ36Kvb Between the Group A and Group B Group Δ 36 BCVA [M(P25,P75), logMAR] Δ 36 TCT （x±s, μm） Δ 36 Kmax [M(P25,P75)，D] Δ 36 K1 [M(P25,P75), D] Δ 36 K2 [M(P25,P75), D] Δ 36 Kvb (x±s, μm) Group A -0.30(-0.48,-0.11) -11.00±8.94 -1.15(-2.48,1.605) -0.47(-0.80,0.38) -0.77(-1.44,0.60) 13.67±13.33 Group B -0.08(-0.30,0.09) -7.75±16.66 -0.83(-2.39,0.08) 0.40(-0.345,0.69) -0.51(-1.04,0.22) -0.72±6.22 Z/t , P -2.050,0.04 0.838,0.412 -0.244,0.807 -1.486,0.137 -0.522,0.601 -3.170，0.012 Discussion In this study, surgical approaches were stratified by corneal thickness, yielding significant baseline disparities in select clinical parameters between groups, which precluded direct intergroup comparisons of the metrics. However, considering that baseline demographic characteristics (age, sex) and preoperative visual parameters (UCVA, BCVA) were statistically balanced between the two groups ( P > 0.05), we can evaluate the efficacy and safety of Refractive Lenticule-assisted A-CXL by analyzing longitudinal trends in postoperative observational metrics and comparing within-group changes (Δvalues) in each parameter after surgery. Over the course of the 3-year follow-up, we observed that the mean BCVA (LogMAR) in the Group A improved from 0.4 preoperatively to 0.1 postoperatively, with no significant changes in TCT, Kmax, anterior corneal K1 and K2 values, or Kvb. These findings suggest that Refractive Lenticule-assisted A-CXL effectively and stably controlled the progression of thin keratoconus, demonstrating similar efficacy to that of conventional A-CXL. The results of this study reveal that Refractive Lenticule-assisted A-CXL demonstrates better improvement in BCVA at 3 years postoperatively. This effect may be associated with alterations in the arrangement of collagen fibers in the corneal stroma, enhanced biomechanical strength, and improved corneal curvature [ 21 ] . Previous studies have indicated that patients with poorer baseline visual acuity and steeper corneal curvature may experience greater improvements following CXL [ 22 ] . In this study, the steeper preoperative corneal curvature in Group A may explain the more significant improvement in BCVA compared to Group B. furthermore, The covering pressure of refractive lenticule can transiently increase epithelial permeability, assisting riboflavin in penetrating into the stromal layer. meanwhile, it reduces tear flushing, prolongs the retention time of riboflavin within the stroma, promotes deep collagen cross-linking, and enhances the cornea's resistance to ectasia [ 23 ] . This mechanism may also explain the more significant improvement in BCVA observed in Group A. In comparison to the patients accepted Refractive Lenticule-assisted A-CXL, who showed stable TCT levels during the follow-up period, the patients that underwent A-CXL only experienced a decrease in TCT of approximately 13 µm at 6 months postoperatively, followed by a gradual and fluctuating increase. This pattern of initial decrease and subsequent increase in TCT has also been observed in studies by Konrad and Arbelaez [ 24 , 25 ] 。The early decrease in TCT may be associated with the compression of collagen fiber spacing due to the cross-linking reaction [ 26 ] , apoptosis of corneal stromal cells, and changes in the composition of glycosaminoglycans and proteoglycans [ 27 ] . Over time, as the diameter of the corneal collagen fibers thickens and stromal cell regeneration occurs, the corneal thickness may increase once again. We speculate that refractive lenticule makes the ultraviolet light scatter more uniformly on the corneal surface, avoiding local energy accumulation that may cause thermal damage or excessive collagen contraction, thereby reducing postoperative TCT regression. Corneal curvature plays a crucial role in the diagnosis, grading and evaluation of the progression of KC [ 28 ] , It serves as a critical tool for assessing the efficacy of CXL. Kmax is a pivotal metric for assessing the success of CXL. A progression of Kmax by ≥ 1.0 D within one year can be regarded as indicative of the progression of KC [ 29 ] . In our study, both groups effectively controlled the progression of Kmax. However, compared to Group A, which exhibited stable anterior corneal curvature, Group B showed a transient increase in K1 and K2 in the early postoperative period. This temporary elevation was not significant. It may be attributed to corneal edema and epithelial remodeling occurring in the early postoperative phase (1–3 months) after A-CXL, which consequently gives rise to an elevation in irregular astigmatism. There were no significant differences in the changes of K1 and K2 values between the two groups during the 2-year and 3-year postoperative periods. Given the characteristics of KC and its progression, any reduction, stabilization, or deceleration of the increase in corneal curvature after surgery may serve as an indicator of a positive treatment outcome for KC management [ 30 ] . Therefore, it can be concluded that during the 3-year follow-up period, the two surgical techniques demonstrated comparable efficacy in inhibiting the progression of corneal curvature on the anterior surface in KC. The expansive changes in KC typically initiate at the posterior corneal surface [ 31 ] . Additionally, the data of posterior surface remain unaffected by the ablation of the epithelial flap during surgery or by corneal epithelial healing, providing a more accurate and sensitive reflection of the progression of KC. During the follow-up period of this study, no significant changes in Kvb were observed in both groups, indicating that both approaches effectively mitigated the expansion of the corneal posterior surface. However, the intergroup comparison of changes in Kvb during the follow-up period revealed an increasing trend in Group A, whereas Group B exhibited a slight decrease. This could be attributed to postoperative corneal haze or interference from cross-linking lines, which may have affected the corneal topography measurements, leading to artifacts. In terms of safety, no complications were observed throughout the follow-up period for both surgical modalities. Furthermore, No significant endothelial cell loss was observed in both groups, demonstrating similar safety profiles for corneal endothelium. Due to the refractive lenticule's coverage, which establishes an optical barrier for endothelial cytoprotection, Refractive Lenticule-assisted A-CXL may exhibit greater endothelial friendliness [ 32 ] . Hypoosmotic riboflavin can cause transient corneal swelling. However, the actual cross-linking depth after dehydration may be less than the cross-linking depth measured during the operation [ 33 ] ;TE-CXL preserves the corneal epithelium, which can enhance patient comfort and reduce the risk of keratitis. Nevertheless, some researchers have suggested that the riboflavin film and the soaked corneal epithelium may absorb incident ultraviolet light [ 34 ] , thus leading to attenuation of the cross-linking effect. CACXL employs a contact lens to temporarily augment corneal thickness, which affects oxygen diffusion. Moreover, the ultraviolet transmittance of the contact lens diverges from that of the corneal stroma; this disparity impedes ultraviolet absorption, thereby compromising the cross-linking efficacy [ 35 ] . Refractive Lenticule-assisted A-CXL augments corneal thickness by using allogeneic refractive lenticules that better match the patient's own corneal characteristics. This approach maintains the cross-linking effect of CXL while improving patient comfort, striking a balance between safety and therapeutic effectiveness. In summary, Refractive Lenticule-assisted A-CXL for thin Keratoconus demonstrates comparable efficacy and safety to conventional A-CXL in the management of keratoconus over the medium to long term (3 years). Limitations The study utilized a non-randomized design, and the sample size in Group A was relatively small, which may have introduced selection bias. Additionally, the surgical technique has not undergone statistical comparison with alternative therapeutic modalities for thin keratoconus (e.g., CACXL, TE-CXL). Further investigations are necessary to fully assess its relative benefits and limitations. Abbreviations CXL: Corneal cross-linking UVA: Ultraviolet A A-CXL: Accelerated corneal cross-linking RLA-ACXL/Refractive Lenticule-assisted A-CXL: Refractive Lenticule-assisted Accelerated corneal cross-linking KC: keratoconus BCVA: best corrected visual acuity ECD: endothelial cell density TCT: thinnest corneal thickness Kvb: keratoconus vertex back Kmax: Anterior corneal surface vertex K value K1: anterior corneal K1 value K2: anterior corneal K2 value Declarations Acknowledgements N/A. Author contributions YL: Data curation, Statistical analysis, Writing – original draft, Writing - review& editing. MW: Conceptualization, investigation, data collection. LG: Conceptualization, investigation, data collection. DZ: Statistical analysis, Writing - review & editing. CZ: Conceptualization, supervision, project administration, Writing - review & editing. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors . Data availability In our institutional policy, it is not stated that the data should be made public and a data and material transfer agreement should not allow further transfer of data without the provider’s prior written consent. However, the data can be made available upon request from the corresponding author, who is a member of this team. Ethical approval and consent to participate The research protocol was approved by the Ethics Committee of Ineye Hospital of Chengdu University of TCM (Ethical Approval Number: 2021yh-026). This study was conducted in strict accordance with the ethical standards of the institutional and/or national research committee, as well as the 1964 Helsinki Declaration and its subsequent amendments or comparable ethical frameworks. Prior to enrollment, all patients or their guardians provided written informed consent. Additionally, written consent for both study participation and publication was secured from either the participants themselves or their legal guardians at the time of admission. Consent for publication Not Applicable. Competing interests The authors declare no competing interests. Author details 1.Eye School of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China 2.Ineye Hospital of Chengdu University of TCM, Chengdu, Sichuan, China References KRACHMER J H, FEDER R S, BELIN M W. Keratoconus and related noninflammatory corneal thinning disorders[J]. Survey of Ophthalmology , 1984, 28(4): 293–322. Chinese Society of Ophthalmology, Ophthalmic Optics and Visual Science Group, Chinese Medical Doctor Association, Ophthalmologist Branch, Ophthalmic Optics Professional Committee, Chinese Medical Doctor Association, Ophthalmologist Branch, Refractive Surgery Professional Committee. Chinese Expert Consensus on Corneal Cross-Linking for the Treatment of Progressive Keratoconus (2023). Chin J Ophthalmol Optom Vis Sci 2023; 25(12): 881–888. KOHLHAAS M, SPOERL E, SCHILDE T, et, al. Biomechanical evidence of the distribution of cross-links in corneastreated with riboflavin and ultraviolet A light[J]. Journal of Cataract & Refractive Surgery , 2006, 32(2): 279. HAYES S, KAMMA-LORGER C S, BOOTE C, et, al. The Effect of Riboflavin/UVA Collagen Cross-linking Therapy on the Structure and Hydrodynamic Behaviour of the Ungulate and Rabbit Corneal Stroma[J]. PLOS ONE , 2013, 8(1): e52860. SPOERL E, HUHLE M, SEILER T. Induction of Cross-links in Corneal Tissue[J]. Experimental Eye Research , 1998, 66(1): 97–103. Wollensak G, Spörl E, Seiler T. Riboflavin/ultraviolet-a–induced collagen crosslinking for the treatment of keratoconus[J]. American Journal of Ophthalmology , 2003, 135(5): 620–627. Wollensak G, Spörl E, Reber F, Pillunat L, Funk R. Corneal endothelial cytotoxicity of riboflavin/UVA treatment in vitro[J]. Ophthalmic research . 2003;35(6):324–8.. KYMIONIS G D, PORTALIOU D M, DIAKONIS V F, et, al. Corneal Collagen Cross-linking With Riboflavin and Ultraviolet-A Irradiation in Patients With Thin Corneas[J]. American Journal of Ophthalmology , 2012, 153(1): 24–28. MROCHEN M. Current status of accelerated corneal cross-linking[J]. Indian Journal of Ophthalmology , 2013, 61(8): 428. KATO N, NEGISHI K, SAKAI C, et, al. Five Year Outcomes of Corneal Collagen Crosslinking: Accelerated Crosslinking Induces Less Corneal Haze and Less Continuous Corneal Flattening Compared to Conventional Crosslinking.[J]. Investigative Ophthalmology & Visual Science , 2019, 60(9): 313. JIANG Y, YANG S, LI Y, et, al. Accelerated Versus Conventional Corneal Collagen Cross-Linking in the Treatment of Keratoconus: A Meta-analysis and Review of the Literature[J]. Interdisciplinary Sciences: Computational Life Sciences , 2019, 11(2): 282–286. DAI E, GUNDERSON C A. Pediatric central corneal thickness variation among major ethnic populations[J]. Journal of AAPOS: the official publication of the American Association for Pediatric Ophthalmology and Strabismus , 2006, 10(1): 22–25. Haider KM, Mickler C, Oliver D, Moya FJ, Cruz OA, Davitt BV. Age and racial variation in central corneal thickness of preschool and school-aged children[J]. Journal of Pediatric Ophthalmology & Strabismus . 2008;45(4):227–33. CELIK BUYUKTEPE T, UCAKHAN O O. Long-term visual, refractive, tomographic and aberrometric outcomes of corneal collagen crosslinking (CXL) with or without hypoosmolar riboflavin solution in the treatment of progressive keratoconus patients with thin corneas[J]. Graefe’s Archive for Clinical and Experimental Ophthalmology , 2022, 260(4): 1225–1235. FILIPPELLO M, STAGNI E, O’BRART D. Transepithelial corneal collagen crosslinking: Bilateral study[J]. Journal of Cataract & Refractive Surgery , 2012, 38(2): 283. Jacob S, Kumar DA, Agarwal A, Basu S, Sinha P, Agarwal A. Contact lens-assisted collagen cross-linking (CACXL): a new technique for cross-linking thin corneas[J]. Journal of Refractive Surgery . 2014;30(6):366–72. Nour MM, El-Agha MS, Sherif AM, Shousha SM. Efficacy and safety of contact lens–assisted corneal crosslinking in the treatment of keratoconus with thin corneas[J]. Eye & contact lens . 2021;47(9):500–4.. Sachdev, M. S, Gupta, D, Sachdev, G, & Sachdev, R. (2015). Tailored stromal expansion with a refractive lenticule for crosslinking the ultrathin cornea[J]. Journal of Cataract & Refractive Surgery, 41(5), 918–923. SACHDEV G S, THULASIDAS M, SACHDEV M S. Long-term outcomes of tailored stromal expansion with refractive lenticule for crosslinking thin corneas[J]. Indian Journal of Ophthalmology , 2024, 72(1): 94. Cagini C, Riccitelli F, Messina M, Piccinelli F, Torroni G, Said D, Al Maazmi A, Dua HS. Epi-off-lenticule-on corneal collagen cross-linking in thin keratoconic corneas[J]. International Ophthalmology. 2020;40:3403–12. Akhtar S, Almubrad T, Paladini I, Mencucci R. Keratoconus corneal architecture after riboflavin/ultraviolet A cross-linking: ultrastructural studies. Molecular vision. 2013;19:1526. KANDEL H, ABBONDANZA M, GUPTA A. Comparison of standard versus accelerated corneal collagen cross-linking for keratoconus: 5-year outcomes from the Save Sight Keratoconus Registry[J]. Eye , 2024, 38(1): 95–102. Caixia W, Xiaojiao G, Jialiang W. Comparison of De-epithelialized and Tran-epithelial Accelerated Corneal Collagen Crosslinking for Keratoconus [J]. Practical Clinical Medicine , 2023,24(3):78–82. KONRAD E M, BLUMENSTOCK G, BARTZ-SCHMIDT K U. Langzeiterfahrungen des kornealen Crosslinkings bei Patienten mit progredientem Keratokonus an der Universitäts-Augenklinik Tübingen[J]. Ophthalmologe , 2019, 117(6)[2024-05-30]. ARBELAEZ M C, SEKITO M B, VIDAL C et, al. Collagen cross-linking with riboflavin and ultraviolet-A light in keratoconus: One-year results[J]. Oman Journal of Ophthalmology , 2009, 2(1): 33. BRADFORD S, LUO S, BROWN D, et, al. A review of the epithelial and stromal effects of corneal collagen crosslinking[J]. The Ocular Surface , 2023, 30: 150–159. SANTHIAGO M R, RANDLEMAN J B. The biology of corneal cross-linking derived from ultraviolet light and riboflavin[J]. Experimental Eye Research , 2021, 202: 108355. FeRACO ML, Douglas J, Phil AJ, FRACO ML. Keratoconus: diagnosis and management[J]. Australian and New Zealand journal of ophthalmology . 1989;17(1):33–60. GOMES J A P, TAN D, RAPUANO C J, et, al. Global Consensus on Keratoconus and Ectatic Diseases[J]. Cornea , 2015, 34(4): 359. WAJNSZTAJN D, SHMUELI O, ZUR K, et, al. Predicting factors for the efficacy of cross-linking for keratoconus[J]. PloS One , 2022, 17(2): e0263528. PIÑERO D P, NIETO J C, LOPEZ-MIGUEL A. Characterization of corneal structure in keratoconus[J]. Journal of Cataract & Refractive Surgery , 2012, 38(12): 2167. YANG Q, WANG S, HE Y, et, al. The research progress on the molecular mechanism of corneal cross-linking in keratoconus treatment[J]. Contact Lens and Anterior Eye , 2023, 46(2): 101795. Kaya V, Utine CA, Ylmaz ÖF. Intraoperative corneal thickness measurements during corneal collagen cross-linking with hypoosmolar riboflavin solution in thin corneas. Cornea. 2012;31(5):486–90. Wollensak G, Aurich H, Wirbelauer C, Sel S. Significance of the riboflavin film in corneal collagen crosslinking. Journal of Cataract & Refractive Surgery. 2010;36(1):114–20. Wollensak G, Spörl E, Herbst H. Biomechanical efficacy of contact lens-assisted collagen cross‐linking in porcine eyes. Acta ophthalmologica . 2019;97(1):e84-90. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7440942","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":508667081,"identity":"04828cc8-a05d-4391-95a7-2db1f76517d4","order_by":0,"name":"Ying Li","email":"","orcid":"","institution":"University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Li","suffix":""},{"id":508667082,"identity":"f917643a-16bb-4011-bc0e-fd268ac003d6","order_by":1,"name":"Mingyan Wang","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Mingyan","middleName":"","lastName":"Wang","suffix":""},{"id":508667083,"identity":"766a96b5-eedb-494d-b444-342c24b68ba9","order_by":2,"name":"Dian Zhao","email":"","orcid":"","institution":"University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Dian","middleName":"","lastName":"Zhao","suffix":""},{"id":508667084,"identity":"c49da3fd-9fb9-4fe5-96a3-4ac41f9b5eeb","order_by":3,"name":"Chunyang Zhou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCUlEQVRIiWNgGAWjYDACCSBmbIByPjAwQ1lsRGphnAHUwkOSFmYeYrTIz24+JvFzx+E8g+NnD7+2qbFO3M9+OoHhQ9lhBv7ZDVi1MM45libZe+ZwscGZvDTrnGPpiT08uRsYZ5w7zCBx5wBWLcwSOWbSjG2HEzccyDEzzm04nNgjwbuBmbftMIOBRAJWLWxwLeffmBlbwrT8xaOFB67lRo7xY0aYFkY8WiQk0pIte9vSE2feeGPG2HMs3bjnTO6Ggz3n0nkkbmDXIj8j+eCNn23WiX3nc4w//Kixlm1vP7vxwY8yazn+Gdi1wIHCAaC/YJwDICfjVw+yroGB+QNBVaNgFIyCUTAiAQBFj2H4DI+YVgAAAABJRU5ErkJggg==","orcid":"","institution":"University of Traditional Chinese Medicine","correspondingAuthor":true,"prefix":"","firstName":"Chunyang","middleName":"","lastName":"Zhou","suffix":""}],"badges":[],"createdAt":"2025-08-23 11:23:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7440942/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7440942/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10792-025-03891-x","type":"published","date":"2025-12-12T15:57:32+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":98243523,"identity":"f57bc9cf-cf8c-4435-8472-c598e8613cbb","added_by":"auto","created_at":"2025-12-15 16:08:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":919502,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7440942/v1/f06f17bf-39a3-43a6-aca3-8a461856414f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Refractive Lenticule-Assisted Accelerated Corneal Cross-linking: A Three-Year Clinical Observation in Patients with Thin Keratoconus","fulltext":[{"header":"Background","content":"\u003cp\u003eKeratoconus (KC) is an ocular disorder characterized by central or para-central expansion and thinning of the cornea, resulting in a conical protrusion of the corneal tissue anteriorly\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. It usually onset during adolescence, often affecting both eyes simultaneously, with a subtle and insidious presentation. and be considered one of the significant causes of blindness in our country. Corneal cross-linking (CXL) is a common and effective method for treating KC\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. It induces a chemical cross-linking reaction between the amino groups of collagen fibers, triggered by riboflavin and Ultraviolet A (UVA) rays, to enhance the biomechanical stability of collagen fibers, reinforcing the cornea\u0026rsquo;s structural integrity against ectatic deformation, and thereby halting the progression of KC\u003csup\u003e[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Conventional CXL, adhering to the Dresden protocol\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e, involves the removal of corneal epithelium followed by exposure of the treated eye to UVA radiation at an intensity of 0.36 mW/cm\u0026sup2; for a duration of 30 minutes. The process resulted in cytotoxic effects on endothelial cells within a depth of 400 \u0026micro;m. Consequently, this approach is not suitable for KC with a thickness of less than 400 \u0026micro;m following epithelial debridement\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Furthermore, long time of radiation elevates the risk of epithelial complications, infection, and other potential injury to the corneal endothelium and other intraocular structures.\u003c/p\u003e\u003cp\u003eOver the past two decades, a variety of modified CXL protocols have been developed and implemented in clinical. A-CXL is generated based on the Bunsen-Roscoe law, which employs high-intensity UVA irradiation to reduce the duration of ultraviolet exposure\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. This approach minimizes patient discomfort associated with prolonged irradiation and decreases the risks of corneal infection, dehydration, and thinning. Extensive research has demonstrated its efficacy and safety\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. However, it is still not suitable for patients with thin Keratoconus. For Asian and African populations, who inherently have thinner corneas\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e, It is particularly urgent to develop modified surgical techniques for the treatment of thin keratoconus. There are several modified CXL procedures have been developed in clinical for the treatment of KC with thin corneal, such as the use of hypotonic riboflavin to swell the corneal stroma\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e, transepithelial CXL (TE-CXL)\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, contact lens-assisted CXL (CACXL)\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e, etc.\u003c/p\u003e\u003cp\u003eIn 2015, Sachdev \u003cem\u003eet al\u003c/em\u003e. first reported a technique utilizing SMILE-derived donor lenticules to augment traditional CXL by expanding stromal thickness in thin corneas\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e, Subsequently, in 2024, they published 5-year follow-up results of this procedure\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e, demonstrating an average reduction in Kmax of 4.30D in the treated eyes, with significant improvements in UDVA and CDVA without any complications or significant endothelial cell loss observed during the follow-up period. Cagini \u003cem\u003eet al\u003c/em\u003e. similarly reported favorable outcomes\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Refractive lens-assisted CXL augments stromal depth via SMILE-derived allogenic lenticule overlay to minimize radiation-induced damage to corneal endothelium and intraocular tissues in thin KC. While preliminary studies show encouraging results, long-term clinical data are required to fully validate its safety and efficacy.\u003c/p\u003e\u003cp\u003eIn an effort to minimize damage to the corneal endothelium and other intraocular tissues from radiation while shortening surgical time, we attempted to cover the refractive lenticule on the eyes undergoing A-CXL surgery (Refractive Lenticule-assisted A-CXL) to provide a novel surgical option for patients with thin keratoconus. Herein, we report a retrospective clinical study to evaluate the efficacy and safety of Refractive Lenticule-assisted A-CXL over a 3-year follow-up period.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis retrospective study enrolled 63 eyes from 42 patients who underwent A-CXL for keratoconus at the Refractive Surgery Department of Ineye Hospital of Chengdu University of TCM in China between September 2017 and December 2020. Patients with a predicted corneal stromal thickness of less than 400 μm following epithelial debridement were treated with Refractive Lenticule-assisted A-CXL and assigned to Group A (10 cases with 18 eyes). The rest of the patients, who had a thicker stroma, received conventional A-CXL only and were assigned to Group B (32 cases with 45 eyes). The study adhered to the tenets of declaration of Helsinki. Ethics committee approval was taken (protocol number 2021yh-016), and written informed consent was obtained from all participants. \u003cstrong\u003eInclusion Criteria:\u0026nbsp;\u003c/strong\u003e①A definitive diagnosis of progressive keratoconus. ②No history of contact lens wear within the past month. ③Age between 9 and 37 years. ④No other corneal diseases expect keratoconus. ⑤No family history of hereditary diseases. \u003cstrong\u003eExclusion Criteria:\u003c/strong\u003e ①Acute keratoconus. ②History of poor epithelial healing after corneal trauma. ③Severe ocular comorbidities. ④Systemic conditions affecting corneal health or surgical recovery. ⑤Previous corneal surgery. ⑥Allergic reactions during treatment ⑦Female patients who are lactating or pregnant. ⑧Severe psychological or psychiatric disorders. ⑨Inability to complete the required follow-up.\u003c/p\u003e\n\u003cp\u003ePreoperative and postoperative evaluation (6 months, 12 months, 24 months, and 36 months) included the assessments of BCVA, slit lamp\u0026nbsp;examination of the anterior segment, fundus examination, ECD measurement, and corneal topography. Visual acuity was assessed using the International Standard Visual Acuity Chart and recorded in logMAR. Fundus examination was performed by Dayton. ECD were obtained by TOMEYEM-400. Topography and curvature of the anterior and posterior corneal surfaces were captured using the Sirius System (Schwind, CSO SpA, Italy). All measurements were taken by a trained ophthalmologist with over 10 years of experience.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurgical technique\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1. Refractive Lenticule-assisted A-CXL\u003c/p\u003e\n\u003cp\u003e1.1 Lenticule Acquisition: Refractive lenticules were obtained from patients underwent SMILE correction for myopia. The donor cases for lenticules were checked preoperatively for no infectious diseases. The thickness of the lenticules was determined by the actual need for stromal expansion in patients receiving A-CXL. After extraction, the micro-lenticules were placed in a balanced salt solution.\u003c/p\u003e\n\u003cp\u003e1.2 Surgical Technique: The procedure was performed under topical anesthesia and aseptic conditions. After removing the central 9 mm area of corneal epithelium using 20% ethanol and an epithelial scraper, VibeX Rapid riboflavin solution (0.1% riboflavin salt solution with hydroxypropyl methylcellulose) was applied every 30 seconds for a total of 10 minutes. The eye was then flushed with balanced salt solution, and the allogeneic corneal stromal lenticule was placed on the stromal bed of the operative eye, centered and spread evenly. Subsequently, the UV Crosslinking Accelerator (Avedro Inc, USA) was used to irradiate the surgical eye with UV-A pulsed mode for 8 minutes (UV wavelength 365nm, irradiance 30mW/cm², total irradiation energy 7.2J/cm²). Balanced salt solution drops were administered during the procedure to keep the cornea moist. After UV exposure, the corneal stromal lenticule was removed, the cornea was rinsed with balanced salt solution, and a bandage contact lens was placed on the operative eye to conclude the surgery.\u003c/p\u003e\n\u003cp\u003e2. Conventional A-CXL\u003c/p\u003e\n\u003cp\u003eSurgical Technique: The procedure was performed under topical anesthesia and aseptic conditions. Initially, the central 9 mm area of the corneal epithelium was debrided using 20% ethanol solution and an epithelial scraper.\u0026nbsp;Subsequently, VibeX Rapid riboflavin solution was applied every 30 seconds for a total of 10 minutes. After rinsing with balanced salt solution, the UV Crosslinking Accelerator (Avedro Inc, USA) was used to irradiate the surgical eye with continuous mode for 4 minutes (UV wavelength 365nm, irradiance 30mW/cm², total irradiation energy 7.2J/cm²). Balanced salt solution drops were used to maintain corneal hydration during the UV exposure. Following the irradiation, the conjunctival sac was washed with balanced salt solution again, and a bandage contact lens was placed on the operative eye to complete the surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData analysis was performed using SPSS 26.0. Normality and variance homogeneity were assessed for all variables. Normally distributed and variance-homogeneous continuous data are expressed as mean ± standard deviation (x̄ ± s). Repeated measures ANOVA was used to assess within-group changes over time, with LSD-t tests for post-hoc analysis if significant differences were found. Independent samples t-tests were utilized for between-group comparisons. Non-normally distributed or variance-heterogeneous data are presented as median [interquartile range, M(P25, P75)], with Friedman tests for within-group comparisons and Bonferroni-adjusted post-hoc tests following significant findings. Wilcoxon rank-sum tests were employed for between-group contrasts. A \u003cem\u003eP\u003c/em\u003e-value \u0026lt; 0.05 denoted statistical significance.\u003c/p\u003e"},{"header":"Results","content":"\u003ch3\u003e1. Study subjects\u003c/h3\u003e\n\u003cp\u003eIn this study, patients were allocated to different surgical methods based on corneal thickness, resulting in baseline differences between two groups that precluded intergroup comparisons. The baseline characteristics in the two groups are as follows in Table1 and Tanble2:\u003c/p\u003e\n\u003cp\u003eTable 1: Baseline Characteristics of Study Participants\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e（n=patients number）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003eGroup A（n=10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e17（15,29）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003eGroup B（n=32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e20（17,25）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2: Baseline Characteristics of Study eyes\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBCVA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUCVA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eECD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e（n=eyes number）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eGroup A（n=18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e1.10(0.72,1.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.40(0.16,1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e2614.11\u0026plusmn;341.193\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003eGroup B（n=45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e1.00(0.70,1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.30(0.10,0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e2873.36\u0026plusmn;261.648\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cem\u003et/Z\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e-0.163\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e1.392\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e2.156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e0.870\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch3\u003e2. Outcomes of Efficacy Metrics\u003c/h3\u003e\n\u003cp\u003e\u003cstrong\u003e2.1\u003c/strong\u003e In Group A, no statistically significant differences were observed in TCT, Kvb, Kmax, K1 and K2 at all time points before and after surgery (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).BCVA showed a significant improvement during the follow-up period (\u003cem\u003eP\u003c/em\u003e = 0.030), with a particularly notable improvement at 36 months postoperatively (\u003cem\u003eP\u003c/em\u003e = 0.006). Detailed data are presented in Table 3.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2\u003c/strong\u003e In Group B, significant changes were detected in BCVA, TCT, Kmax, K1, and K2 at all time points before and after surgery (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05), while Kvb exhibited no statistically significant changes (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05). Postoperative TCT values were significantly lower than preoperative measurements at all time points (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001, \u003cem\u003eP\u003c/em\u003e = 0.011, \u003cem\u003eP\u003c/em\u003e = 0.001, \u003cem\u003eP\u003c/em\u003e = 0.003), with the most substantial reduction observed at 6 months postoperatively; however, a thickening trend was noted from 12 to 36 months postoperatively. Kmax showed a significant decrease at 36 months postoperatively compared to baseline (\u003cem\u003eP\u003c/em\u003e = 0.007). K1 and K2 values significantly increased at 6 months postoperatively (\u003cem\u003eP\u003c/em\u003e = 0.001, \u003cem\u003eP\u003c/em\u003e = 0.009) and then trended downward. BCVA demonstrated significant improvement during follow-up (\u003cem\u003eP\u003c/em\u003e = 0.026). Detailed data are presented in Table 4.\u003c/p\u003e\n\u003cp\u003eTable 3: Variations in TCT, Corneal Curvature, Kvb, and BCVA across time in Group A\u0026nbsp;\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"699\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eGROUP A\u003c/p\u003e\n \u003cp\u003e（n=18）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreoperative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6mo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003epostoperative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 97px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e12mo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003epostoperative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e24mo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003epostoperative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e36mo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003epostoperative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eF/\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u0026chi;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e, \u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eBCVA[M(P25,P75), logMAR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.4(0.16,1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.10(0.05,0.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.10(0.00,0.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.10(0.10,0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.10(-0.04,0.61)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e15.807,=0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eTCT[M(P25,P75), \u0026mu;m]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e414(385,419)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e388(374,393)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e395(370,403)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e395(383,412)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e399(380,407)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e7.514,=0.111\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eK\u003csub\u003emax\u003c/sub\u003e(x\u0026plusmn;s, D)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e58.43\u0026plusmn;4.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e58.31\u0026plusmn;4.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e56.99\u0026plusmn;5.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e57.75\u0026plusmn;5.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e57.69\u0026plusmn;6.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1.381,=0.280\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eK1(x\u0026plusmn;s, D)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e49.49\u0026plusmn;4.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e49.26\u0026plusmn;4.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e49.13\u0026plusmn;4.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e49.52\u0026plusmn;5.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e49.13\u0026plusmn;4.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.403,0.674\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eK2(x\u0026plusmn;s, D)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e52.20\u0026plusmn;4.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e52.31\u0026plusmn;4.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e51.97\u0026plusmn;5.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e52.70\u0026plusmn;5.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e51.79\u0026plusmn;5.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.699,=0.599\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eKvb(x\u0026plusmn;s, \u0026mu;m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e91.78\u0026plusmn;51.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e94\u0026plusmn;48.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e104.56\u0026plusmn;40.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e104.56\u0026plusmn;42.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e105.44\u0026plusmn;43.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e5.112,=0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable 4: Variations in TCT, Corneal Curvature, Kvb, and BCVA across time in Group B\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"699\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\u0026nbsp;\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\u0026nbsp;\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreoperative\u003c/strong\u003e\u003c/p\u003e\u0026nbsp;\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6mo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003epostoperative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e12mo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003epostoperative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e24mo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003epostoperative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e36mo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003epostoperative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eF/\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u0026chi;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e, \u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\u0026nbsp;\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 57px;\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eBCVA[M(P25,P75)，logMAR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.30(0.10,0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.30(0.10,0.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.10(0.00,0.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.10(0.00,0.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.10(0.00,0.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e11.063,0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eTCT(x\u0026plusmn;s, \u0026mu;m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e483.29\u0026plusmn;22.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e469.91\u0026plusmn;24.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e478.77\u0026plusmn;23.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e474.93\u0026plusmn;27.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e475.54\u0026plusmn;25.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e13.519,＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eGROUP B\u003c/p\u003e\n \u003cp\u003e（n=45）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eK\u003csub\u003emax\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75)，D]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e51.39(48.89,57.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e51.23(49.31,56.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e50.89(48.81,55.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e51.10(48.17,56.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e51.41(49.15,55.87)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e22.693,＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003cp\u003e[M(P25,P75)，D]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e44.79(43.16,46.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e45.02(43.39,47.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e44.84(43.19,47.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e44.58(43.22,47.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e44.62(43.18,47.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e16.73,=0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eK2\u003c/p\u003e\n \u003cp\u003e[M(P25,P75)，D]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e47.16(45.75,52.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e47.77(46.52,53.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e47.79(45.87,51.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e46.89(45.73,52.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e47.31(45.76,51.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e35.88,＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003eKvb(x\u0026plusmn;s, \u0026mu;m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e47.00(27.50,64.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e46.00(29.00,66.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e45.00(27.50,64.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e43.00(31.00,68.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e44.00(25.00,65.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e5.808,＝0.214\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003ch3\u003e3. Safety Outcomes\u003c/h3\u003e\n\u003cp\u003e\u003cstrong\u003e3.1\u003c/strong\u003e During the 3-year follow-up period of this retrospective study, patients in both groups successfully had their corneal contact lenses removed 4 to 7 days postoperatively, and the corneal epithelium of the surgical eyes healed completely. As of the final follow-up, no lens or retinal photodamage was observed in either group. Additionally, there were no complications such as delayed healing of the corneal epithelium, aseptic or infectious stromal infiltration, subepithelial haze, corneal endothelial decompensation, or corneal scarring. The incidence of complications between the two groups showed no statistically significant difference (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2\u003c/strong\u003e The ECD in Group A increased significantly from preoperative to 12 months postoperative (\u003cem\u003eP\u003c/em\u003e = 0.016), with a mean increase from 2614.11 to 2731.89 cells/mm\u0026sup2;. In contrast, the ECD of Group B significantly decreased (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.014), with a median decrease from 2856 to 2792 cells/mm\u0026sup2;. Detailed data are presented in Table 5.\u003c/p\u003e\n\u003cp\u003eTable 5: Changes in ECD at 12 Months Postoperatively in Group A and B\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"587\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreoperative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e12mo postoperative\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003et/Z, P\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003eGROUP A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eECD\u003c/p\u003e\n \u003cp\u003e（x\u0026plusmn;s cells/mm\u003csup\u003e2\u003c/sup\u003e）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e2614.11\u0026plusmn;341.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e2731.89\u0026plusmn;309.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e-3.038，0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003eGROUP B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003eECD\u003c/p\u003e\n \u003cp\u003e[M(P25,P75) cells/mm2]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e2856(2708.5,3031)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e2792(2593,2983.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e-2.245, 0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ch3\u003e4. Comparison of the Changes in Indicators Between the Two Groups During the Follow-up Period\u003c/h3\u003e\n\u003cp\u003e\u003cstrong\u003e4.1\u003c/strong\u003e Define the changes in observation indicators during the 12-month postoperative period as \u0026Delta;\u003csub\u003e12\u003c/sub\u003e. We found there were no statistically significant differences between the two groups in terms of \u0026Delta;\u003csub\u003e12\u003c/sub\u003eBCVA, \u0026Delta;\u003csub\u003e12\u003c/sub\u003eKmax, and \u0026Delta;\u003csub\u003e12\u003c/sub\u003eK2 (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05). Concurrently, We observed Kvb decreased in Group B but increased in Group A (\u003cem\u003eP\u003c/em\u003e=0.012). Group B also showed a less pronounced reduction in TCT (\u003cem\u003eP\u003c/em\u003e=0.013), while Group A exhibited a greater decline in K1 (\u003cem\u003eP\u003c/em\u003e=0.036). Notably, at 12 months postoperatively, ECD declined in Group B but increased significantly in Group A (\u003cem\u003eP\u003c/em\u003e=0.002). Detailed data are provided in Table 6.\u003c/p\u003e\n\u003cp\u003eTable 6: Comparison of \u0026Delta;12BCVA,\u0026Delta;12TCT, \u0026Delta;12Kmax, \u0026Delta;12K1, \u0026Delta;12K2 \u0026Delta;12Kvb, and \u0026Delta;12ECD Between the Group A and Group B\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"122%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e12\u003c/sub\u003e\u003cstrong\u003eBCVA\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75), logMAR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e12\u003c/sub\u003e\u003cstrong\u003eTCT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e（x\u0026plusmn;s, \u0026mu;m）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e12\u003c/sub\u003e\u003cstrong\u003eKmax\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75)，D]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e12\u003c/sub\u003e\u003cstrong\u003eK1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75), D]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e12\u003c/sub\u003e\u003cstrong\u003eK2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75), D]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e12\u003c/sub\u003e\u003cstrong\u003eKvb\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75), \u0026mu;m]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e12\u003c/sub\u003e\u003cstrong\u003eECD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75) cells/mm2]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eGroup A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e-0.12(-0.40,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e-16.44\u0026plusmn;18.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-2.00(-2.53,0.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e-0.55(-0.86,0.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e-0.77(-1.16,0.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e9.00(-0.50,28.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e144(41,200)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eGroup B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0(-0.30,0.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e-4.52\u0026plusmn;11.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.41(-1.56,0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.20(-0.24,0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e-0.07(-0.74,0.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e-1.00(-4.50,2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e-45(-164,32.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cem\u003eZ/t\u003c/em\u003e, \u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e-1.370,0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e2.564,0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-1.079,0.280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e-2.101,0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e-1.056,0.291\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e2.510,0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e-3.087,0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e4.2\u003c/strong\u003e. Define the changes in observation indicators during the 24-month postoperative period as \u0026Delta;\u003csub\u003e24\u003c/sub\u003e. There were no statistically significant differences in the changes of various indicators between the two groups. Detailed data are provided in Table 7.\u003c/p\u003e\n\u003cp\u003eTable 7: Comparison of \u0026Delta;24BCVA,\u0026Delta;24TCT, \u0026Delta;24Kmax, \u0026Delta;24K1, \u0026Delta;24K2, and \u0026Delta;24Kvb Between the Group A and Group B\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"107%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e24\u003c/sub\u003e\u003cstrong\u003eBCVA\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75), logMAR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e24\u003c/sub\u003e\u003cstrong\u003eTCT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e（x\u0026plusmn;s, \u0026mu;m）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e24\u003c/sub\u003e\u003cstrong\u003eKmax\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75)，D]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e24\u003c/sub\u003e\u003cstrong\u003eK1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75), D]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e24\u003c/sub\u003e\u003cstrong\u003eK2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75), D]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e24\u003c/sub\u003e\u003cstrong\u003eKvb\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(x\u0026plusmn;s, \u0026mu;m)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003eGroup A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e-0.18(-0.40,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-9.56\u0026plusmn;12.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e-1.46(-2.04,1.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.27(-0.84,0.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.97(-1.44,3.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e12.78\u0026plusmn;16.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003eGroup B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e-0.08(-0.30,0.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-8.36\u0026plusmn;16.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e-0.77(-1.78,0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.11(-0.27,0.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.33(-1.13,0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.42\u0026plusmn;7.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cem\u003eZ/t\u003c/em\u003e, \u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e-1.060,0.289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.209,0.835\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e-0.499,0.618\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.963,0.335\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.232,0.816\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-2.257,0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e4.3\u003c/strong\u003e Define the changes in observation indicators during the 36-month postoperative period as \u0026Delta;\u003csub\u003e36\u003c/sub\u003e. There were no statistically significant differences in \u0026Delta;\u003csub\u003e36\u003c/sub\u003eTCT, \u0026Delta;\u003csub\u003e36\u003c/sub\u003eKmax, \u0026Delta;\u003csub\u003e36\u003c/sub\u003eK1 and \u0026Delta;\u003csub\u003e36\u003c/sub\u003eK2 between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05). Moreover, we observed Kvb decreased in Group B but increased in Group A (\u003cem\u003eP\u003c/em\u003e=0.012). Additionally, Group A exhibited significantly greater changes in BCVA. Detailed data are provided in Table 8.\u003c/p\u003e\n\u003cp\u003eTable 8: Comparison of \u0026Delta;36BCVA,\u0026Delta;36TCT, \u0026Delta;36Kmax, \u0026Delta;36K1, \u0026Delta;36K2, and \u0026Delta;36Kvb Between the Group A and Group B\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"107%\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e36\u003c/sub\u003e\u003cstrong\u003eBCVA\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75), logMAR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e36\u003c/sub\u003e\u003cstrong\u003eTCT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e（x\u0026plusmn;s, \u0026mu;m）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e36\u003c/sub\u003e\u003cstrong\u003eKmax\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75)，D]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e36\u003c/sub\u003e\u003cstrong\u003eK1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75), D]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e36\u003c/sub\u003e\u003cstrong\u003eK2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[M(P25,P75), D]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026Delta;\u003csub\u003e36\u003c/sub\u003e\u003cstrong\u003eKvb\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(x\u0026plusmn;s, \u0026mu;m)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003eGroup A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e-0.30(-0.48,-0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-11.00\u0026plusmn;8.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e-1.15(-2.48,1.605)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.47(-0.80,0.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.77(-1.44,0.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e13.67\u0026plusmn;13.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003eGroup B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e-0.08(-0.30,0.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-7.75\u0026plusmn;16.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e-0.83(-2.39,0.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.40(-0.345,0.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.51(-1.04,0.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.72\u0026plusmn;6.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cem\u003eZ/t\u003c/em\u003e, \u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17px;\"\u003e\n \u003cp\u003e-2.050,0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.838,0.412\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e-0.244,0.807\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-1.486,0.137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-0.522,0.601\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e-3.170，0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, surgical approaches were stratified by corneal thickness, yielding significant baseline disparities in select clinical parameters between groups, which precluded direct intergroup comparisons of the metrics. However, considering that baseline demographic characteristics (age, sex) and preoperative visual parameters (UCVA, BCVA) were statistically balanced between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), we can evaluate the efficacy and safety of Refractive Lenticule-assisted A-CXL by analyzing longitudinal trends in postoperative observational metrics and comparing within-group changes (Δvalues) in each parameter after surgery.\u003c/p\u003e\u003cp\u003eOver the course of the 3-year follow-up, we observed that the mean BCVA (LogMAR) in the Group A improved from 0.4 preoperatively to 0.1 postoperatively, with no significant changes in TCT, Kmax, anterior corneal K1 and K2 values, or Kvb. These findings suggest that Refractive Lenticule-assisted A-CXL effectively and stably controlled the progression of thin keratoconus, demonstrating similar efficacy to that of conventional A-CXL.\u003c/p\u003e\u003cp\u003eThe results of this study reveal that Refractive Lenticule-assisted A-CXL demonstrates better improvement in BCVA at 3 years postoperatively. This effect may be associated with alterations in the arrangement of collagen fibers in the corneal stroma, enhanced biomechanical strength, and improved corneal curvature\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. Previous studies have indicated that patients with poorer baseline visual acuity and steeper corneal curvature may experience greater improvements following CXL\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. In this study, the steeper preoperative corneal curvature in Group A may explain the more significant improvement in BCVA compared to Group B. furthermore, The covering pressure of refractive lenticule can transiently increase epithelial permeability, assisting riboflavin in penetrating into the stromal layer. meanwhile, it reduces tear flushing, prolongs the retention time of riboflavin within the stroma, promotes deep collagen cross-linking, and enhances the cornea's resistance to ectasia\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. This mechanism may also explain the more significant improvement in BCVA observed in Group A.\u003c/p\u003e\u003cp\u003eIn comparison to the patients accepted Refractive Lenticule-assisted A-CXL, who showed stable TCT levels during the follow-up period, the patients that underwent A-CXL only experienced a decrease in TCT of approximately 13 \u0026micro;m at 6 months postoperatively, followed by a gradual and fluctuating increase. This pattern of initial decrease and subsequent increase in TCT has also been observed in studies by Konrad and Arbelaez\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e。The early decrease in TCT may be associated with the compression of collagen fiber spacing due to the cross-linking reaction\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e, apoptosis of corneal stromal cells, and changes in the composition of glycosaminoglycans and proteoglycans\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. Over time, as the diameter of the corneal collagen fibers thickens and stromal cell regeneration occurs, the corneal thickness may increase once again. We speculate that refractive lenticule makes the ultraviolet light scatter more uniformly on the corneal surface, avoiding local energy accumulation that may cause thermal damage or excessive collagen contraction, thereby reducing postoperative TCT regression.\u003c/p\u003e\u003cp\u003eCorneal curvature plays a crucial role in the diagnosis, grading and evaluation of the progression of KC\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e, It serves as a critical tool for assessing the efficacy of CXL. Kmax is a pivotal metric for assessing the success of CXL. A progression of Kmax by \u0026ge;\u0026thinsp;1.0 D within one year can be regarded as indicative of the progression of KC\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. In our study, both groups effectively controlled the progression of Kmax. However, compared to Group A, which exhibited stable anterior corneal curvature, Group B showed a transient increase in K1 and K2 in the early postoperative period. This temporary elevation was not significant. It may be attributed to corneal edema and epithelial remodeling occurring in the early postoperative phase (1\u0026ndash;3 months) after A-CXL, which consequently gives rise to an elevation in irregular astigmatism. There were no significant differences in the changes of K1 and K2 values between the two groups during the 2-year and 3-year postoperative periods. Given the characteristics of KC and its progression, any reduction, stabilization, or deceleration of the increase in corneal curvature after surgery may serve as an indicator of a positive treatment outcome for KC management\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. Therefore, it can be concluded that during the 3-year follow-up period, the two surgical techniques demonstrated comparable efficacy in inhibiting the progression of corneal curvature on the anterior surface in KC.\u003c/p\u003e\u003cp\u003eThe expansive changes in KC typically initiate at the posterior corneal surface\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. Additionally, the data of posterior surface remain unaffected by the ablation of the epithelial flap during surgery or by corneal epithelial healing, providing a more accurate and sensitive reflection of the progression of KC. During the follow-up period of this study, no significant changes in Kvb were observed in both groups, indicating that both approaches effectively mitigated the expansion of the corneal posterior surface. However, the intergroup comparison of changes in Kvb during the follow-up period revealed an increasing trend in Group A, whereas Group B exhibited a slight decrease. This could be attributed to postoperative corneal haze or interference from cross-linking lines, which may have affected the corneal topography measurements, leading to artifacts.\u003c/p\u003e\u003cp\u003eIn terms of safety, no complications were observed throughout the follow-up period for both surgical modalities. Furthermore, No significant endothelial cell loss was observed in both groups, demonstrating similar safety profiles for corneal endothelium. Due to the refractive lenticule's coverage, which establishes an optical barrier for endothelial cytoprotection, Refractive Lenticule-assisted A-CXL may exhibit greater endothelial friendliness\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eHypoosmotic riboflavin can cause transient corneal swelling. However, the actual cross-linking depth after dehydration may be less than the cross-linking depth measured during the operation\u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e;TE-CXL preserves the corneal epithelium, which can enhance patient comfort and reduce the risk of keratitis. Nevertheless, some researchers have suggested that the riboflavin film and the soaked corneal epithelium may absorb incident ultraviolet light\u003csup\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e, thus leading to attenuation of the cross-linking effect. CACXL employs a contact lens to temporarily augment corneal thickness, which affects oxygen diffusion. Moreover, the ultraviolet transmittance of the contact lens diverges from that of the corneal stroma; this disparity impedes ultraviolet absorption, thereby compromising the cross-linking efficacy\u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e. Refractive Lenticule-assisted A-CXL augments corneal thickness by using allogeneic refractive lenticules that better match the patient's own corneal characteristics. This approach maintains the cross-linking effect of CXL while improving patient comfort, striking a balance between safety and therapeutic effectiveness.\u003c/p\u003e\u003cp\u003eIn summary, Refractive Lenticule-assisted A-CXL for thin Keratoconus demonstrates comparable efficacy and safety to conventional A-CXL in the management of keratoconus over the medium to long term (3 years).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003cp\u003eThe study utilized a non-randomized design, and the sample size in Group A was relatively small, which may have introduced selection bias. Additionally, the surgical technique has not undergone statistical comparison with alternative therapeutic modalities for thin keratoconus (e.g., CACXL, TE-CXL). Further investigations are necessary to fully assess its relative benefits and limitations.\u003c/p\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCXL: Corneal cross-linking\u003c/p\u003e\n\u003cp\u003eUVA: Ultraviolet A\u003c/p\u003e\n\u003cp\u003eA-CXL: Accelerated corneal cross-linking\u003c/p\u003e\n\u003cp\u003eRLA-ACXL/Refractive Lenticule-assisted A-CXL: Refractive Lenticule-assisted Accelerated corneal cross-linking\u003c/p\u003e\n\u003cp\u003eKC: keratoconus\u003c/p\u003e\n\u003cp\u003eBCVA: best corrected visual acuity\u003c/p\u003e\n\u003cp\u003eECD: endothelial cell density\u003c/p\u003e\n\u003cp\u003eTCT: thinnest corneal thickness\u003c/p\u003e\n\u003cp\u003eKvb: keratoconus vertex back\u003c/p\u003e\n\u003cp\u003eKmax: Anterior corneal surface vertex K value\u003c/p\u003e\n\u003cp\u003eK1: anterior corneal K1 value\u003c/p\u003e\n\u003cp\u003eK2: anterior corneal K2 value\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN/A.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYL: Data curation, Statistical analysis, Writing – original draft, Writing - review\u0026amp; editing. MW: Conceptualization, investigation, data collection. LG: Conceptualization, investigation, data collection. DZ: Statistical analysis, Writing - review \u0026amp; editing. CZ: Conceptualization, supervision, project administration, Writing - review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn our institutional policy, it is not stated that the data should be made public and a data and material transfer agreement should not allow further transfer of data without the provider’s prior written consent. However, the data can be made available upon request from the corresponding author, who is a member of this team.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research protocol was approved by the Ethics Committee of Ineye Hospital of Chengdu University of TCM (Ethical Approval Number: 2021yh-026). This study was conducted in strict accordance with the ethical standards of the institutional and/or national research committee, as well as the 1964 Helsinki Declaration and its subsequent amendments or comparable ethical frameworks. Prior to enrollment, all patients or their guardians provided written informed consent. Additionally, written consent for both study participation and publication was secured from either the participants themselves or their legal guardians at the time of admission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.Eye School of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China\u003c/p\u003e\n\u003cp\u003e2.Ineye Hospital of Chengdu University of TCM, Chengdu, Sichuan, China\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKRACHMER J H, FEDER R S, BELIN M W. 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Comparison of standard versus accelerated corneal collagen cross-linking for keratoconus: 5-year outcomes from the Save Sight Keratoconus Registry[J]. \u003cem\u003eEye\u003c/em\u003e, 2024, 38(1): 95\u0026ndash;102.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCaixia W, Xiaojiao G, Jialiang W. Comparison of De-epithelialized and Tran-epithelial Accelerated Corneal Collagen Crosslinking for Keratoconus [J]. \u003cem\u003ePractical Clinical Medicine\u003c/em\u003e, 2023,24(3):78\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKONRAD E M, BLUMENSTOCK G, BARTZ-SCHMIDT K U. Langzeiterfahrungen des kornealen Crosslinkings bei Patienten mit progredientem Keratokonus an der Universit\u0026auml;ts-Augenklinik T\u0026uuml;bingen[J]. \u003cem\u003eOphthalmologe\u003c/em\u003e, 2019, 117(6)[2024-05-30].\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eARBELAEZ M C, SEKITO M B, VIDAL C et, al. 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The research progress on the molecular mechanism of corneal cross-linking in keratoconus treatment[J]. \u003cem\u003eContact Lens and Anterior Eye\u003c/em\u003e, 2023, 46(2): 101795.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKaya V, Utine CA, Ylmaz \u0026Ouml;F. Intraoperative corneal thickness measurements during corneal collagen cross-linking with hypoosmolar riboflavin solution in thin corneas. Cornea. 2012;31(5):486\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWollensak G, Aurich H, Wirbelauer C, Sel S. Significance of the riboflavin film in corneal collagen crosslinking. Journal of Cataract \u0026amp; Refractive Surgery. 2010;36(1):114\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWollensak G, Sp\u0026ouml;rl E, Herbst H. Biomechanical efficacy of contact lens-assisted collagen cross‐linking in porcine eyes. \u003cem\u003eActa ophthalmologica\u003c/em\u003e. 2019;97(1):e84-90.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"keratoconus, ultrathin cornea, accelerated corneal cross-linking, A-CXL, refractive lenticule, Small Incision Lenticule Extraction, SMILE, Refractive Lenticule-assisted A-CXL","lastPublishedDoi":"10.21203/rs.3.rs-7440942/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7440942/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eAccelerated corneal cross-linking (A-CXL) is unsuitable for thin keratoconus treatment. We developed refractive lenticule-assisted A-CXL by overlaying lenticules during A-CXL to optimize therapy for thin keratoconus. This retrospective study evaluates its 3-year efficacy and safety.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis study retrospectively included 63 eyes (42 cases) with progressive keratoconus who underwent A-CXL in our hospital from September 2017 to December 2020. The surgical method is determined based on the patients' corneal thickness. Patients received refractive lens-assisted A-CXL (10 cases with 18 eyes) were designated as Group A, while those undergowent A-CXL alone (32 cases with 45 eyes) were classified as Group B. The follow-up duration for both groups was 3 years. Preoperative and postoperative evaluation (6 months, 12 months, 24 months, and 36 months) included best corrected visual acuity (BCVA), endothelial cell density (ECD), thinnest corneal thickness (TCT), keratoconus vertex back (Kvb) and corneal curvature. Any adverse events like delayed corneal healing, corneal infections, haze, etc that occurred during this period should be record.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eDuring follow-up, no significant changes were observed in TCT, Kmax, K1, K2, or Kvb in Group A, while BCVA significantly improved at 36 months postoperatively, and ECD significantly increased at 12 months postoperatively (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.016). Over the same period, Group B showed decreases in TCT and ECD compared to baseline (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), increases in anterior surface K1 and K2 values, and improvements in BCVA and Kmax (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with no significant change in Kvb. During the 36-month postoperative period, Group A exhibited more substantial improvements in BCVA and more pronounced elevation in Kvb than Group B. Both groups exhibited uneventful healing with no adverse events.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eOver the 3-year follow-up period, the refractive lenticule-assisted A-CXL and A-CXL showed similar efficacy and safety in controlling the progression of keratoconus.\u003c/p\u003e","manuscriptTitle":"Refractive Lenticule-Assisted Accelerated Corneal Cross-linking: A Three-Year Clinical Observation in Patients with Thin Keratoconus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-02 17:53:34","doi":"10.21203/rs.3.rs-7440942/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-17T14:02:26+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"182142771877699158632344563458517815752","date":"2025-10-15T00:04:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-14T23:42:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"57427728254011501402082876105528818926","date":"2025-10-05T21:51:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-26T08:28:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"276470603607381149592953388115137296061","date":"2025-09-24T08:18:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"305566387014085630188672263873972808326","date":"2025-09-22T10:23:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"321694204101355348344283371334883390543","date":"2025-09-10T18:39:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"193909818514729866144165271327616294033","date":"2025-09-07T12:20:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-26T17:19:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-25T08:17:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-25T08:16:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Ophthalmology","date":"2025-08-23T11:19:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"1c68051f-00e5-4ffc-abcf-e42262e0b462","owner":[],"postedDate":"September 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-15T16:01:18+00:00","versionOfRecord":{"articleIdentity":"rs-7440942","link":"https://doi.org/10.1007/s10792-025-03891-x","journal":{"identity":"international-ophthalmology","isVorOnly":false,"title":"International Ophthalmology"},"publishedOn":"2025-12-12 15:57:32","publishedOnDateReadable":"December 12th, 2025"},"versionCreatedAt":"2025-09-02 17:53:34","video":"","vorDoi":"10.1007/s10792-025-03891-x","vorDoiUrl":"https://doi.org/10.1007/s10792-025-03891-x","workflowStages":[]},"version":"v1","identity":"rs-7440942","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7440942","identity":"rs-7440942","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}