Journal of Refractive Surgery

Original Article Supplemental Data

Efficacy and Safety of Accelerated Corneal Cross-linking for Progressive Keratoconus: A 5-Year Follow-up Study

Antonio Moramarco, MD; Valentina Mastrofilippo, MS; Maria Grazia Romano, COA; Danilo Iannetta, MD; Luca Braglia, MS; Luigi Fontana, MD, PhD

Abstract

PURPOSE:

To investigate the long-term efficacy and safety of continuous light-accelerated corneal cross-linking (CXL) in patients with progressive keratoconus.

METHODS:

This retrospective study analyzed 29 eyes of 29 consecutive patients with progressive keratoconus treated with epithelium-off riboflavin-ultraviolet induced accelerated CXL (30 mW/cm2–7.2 joules/cm2). Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, keratometry measurements at 3 and 6 mm (Kmax, Kmin, and Kmean), topographic astigmatism, central corneal thickness, anterior corneal aberrometric analysis (at 3 and 6 mm), endothelial cell density, and central foveal thickness were evaluated before and 24 and 60 months after surgery.

RESULTS:

UDVA significantly improved at 60 months postoperatively (P = .028). Kmax and Kmean at 3 mm significantly decreased at 24 (P = .009 and .006, respectively) and 60 (P = .017 and .034, respectively) months postoperatively, whereas Kmin significantly decreased only at 24 months postoperatively (P = .032). Kmax at 6 mm significantly decreased at 24 and 60 months postoperatively (P = .035 and .027, respectively). Cylinder error significantly decreased at 24 and 60 months postoperatively (P = .001 and .023, respectively). Wavefront aberration variables remained unchanged after surgery, except for spherical aberration at 6 mm that decreased at 24 and 60 months postoperatively (P = .038 and .031, respectively) and trefoil at 0° that significantly decreased at 24 months postoperatively (P < .005). Endothelial cell density and central foveal thickness showed no changes from baseline.

CONCLUSIONS:

Accelerated CXL was found to be effective in halting keratoconus progression and improving some of the visual, topographic, and wavefront aberration variables evaluated. High energy irradiance did not induce significant changes in corneal transparency, endothelial cell density, and central foveal thickness.

[J Refract Surg. 2020;36(11):724–730.]

Abstract

PURPOSE:

To investigate the long-term efficacy and safety of continuous light-accelerated corneal cross-linking (CXL) in patients with progressive keratoconus.

METHODS:

This retrospective study analyzed 29 eyes of 29 consecutive patients with progressive keratoconus treated with epithelium-off riboflavin-ultraviolet induced accelerated CXL (30 mW/cm2–7.2 joules/cm2). Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, keratometry measurements at 3 and 6 mm (Kmax, Kmin, and Kmean), topographic astigmatism, central corneal thickness, anterior corneal aberrometric analysis (at 3 and 6 mm), endothelial cell density, and central foveal thickness were evaluated before and 24 and 60 months after surgery.

RESULTS:

UDVA significantly improved at 60 months postoperatively (P = .028). Kmax and Kmean at 3 mm significantly decreased at 24 (P = .009 and .006, respectively) and 60 (P = .017 and .034, respectively) months postoperatively, whereas Kmin significantly decreased only at 24 months postoperatively (P = .032). Kmax at 6 mm significantly decreased at 24 and 60 months postoperatively (P = .035 and .027, respectively). Cylinder error significantly decreased at 24 and 60 months postoperatively (P = .001 and .023, respectively). Wavefront aberration variables remained unchanged after surgery, except for spherical aberration at 6 mm that decreased at 24 and 60 months postoperatively (P = .038 and .031, respectively) and trefoil at 0° that significantly decreased at 24 months postoperatively (P < .005). Endothelial cell density and central foveal thickness showed no changes from baseline.

CONCLUSIONS:

Accelerated CXL was found to be effective in halting keratoconus progression and improving some of the visual, topographic, and wavefront aberration variables evaluated. High energy irradiance did not induce significant changes in corneal transparency, endothelial cell density, and central foveal thickness.

[J Refract Surg. 2020;36(11):724–730.]

Keratoconus is a multifactorial, progressive, ectatic disorder of the cornea characterized by corneal protrusion, irregular astigmatism, and loss of visual acuity,1 with a prevalence of approximately 54 in 100,000 in the general population.2 First described in 1998 by Spoerl et al,3 corneal cross-linking (CXL) currently represents the only treatment capable of slowing or halting progressive corneal steepening and thinning in patients with keratoconus. Standard CXL, using continuous irradiation of 3 mW/cm2 for 30 minutes, has been demonstrated to be safe and effective according to different clinical trials,4–6 despite being time-consuming (lasting 60 minutes overall) and often resulting in patient discomfort and slow surgical workflow. More recently, accelerated corneal CXL, which uses higher energy settings (up to continuous irradiation of 30 mW/cm2), has gained popularity owing to its shorter treatment duration (3 to 10 minutes). Preclinical studies in porcine corneas have revealed that accelerated CXL induces biomechanical changes equivalent to those produced by standard treatment.7,8 To date, few clinical studies have investigated the efficacy and safety of accelerated CXL with a total dose of 7.2 J/cm2, limited to a relatively short time of observation, with a lack of long-term studies.9–13

In this study, we report visual acuity, refractive, topography, and wavefront aberration results, as well as endothelial cell density and central foveal thickness measurements at 24 and 60 months after accelerated CXL, using a 30 mW/cm2 treatment protocol.

Patients and Methods

Study Group and Treatment Protocol

This study was conducted in accordance with the tenets of the Declaration of Helsinki and approved by the hospital ethics committee (protocol number 2017/0089448) of the Azienda USL–IRCCS of Reggio Emilia, Italy. Patients were informed about the potential risks and benefits of the procedure, and written informed consent was obtained from all patients before surgery.

We conducted a retrospective chart review of 35 eyes in 35 consecutive patients who underwent accelerated CXL from June 2013 through June 2018. To be included in the analysis, patients must have completed the 24- and 60-month follow-up visits. Treated eyes had mild-to-moderate progressive keratoconus (grades I to III according to Amsler-Krumeich classification).13 Progression of ectasia was defined as an increase in manifest refraction spherical equivalent of 0.50 diopters (D) or greater, Kmax increase of 1.00 D or greater, and corneal topographic refractive astigmatism increase of 1.00 D or greater, confirmed by two consecutive examinations over 9 to 12 months.13,14 Exclusion criteria were as follows: preoperative corneal thickness of less than 400 µm, maximum keratometry value (Kmax) of greater than 65.00 D, previous ocular surgery, corneal scars, history of herpetic keratitis, coexisting ocular pathology, connective tissue disease, pregnancy or nursing status, and systemic medications that would likely affect corneal wound healing.13 Patients were instructed to discontinue the use of hard contact lenses at least 2 weeks before examinations and treatment.

A complete ophthalmological examination, including uncorrected (UDVA) and corrected (CDVA) distance visual acuity, manifest refraction, slit-lamp biomicroscopy (two independent observers: AM and LF), dilated fundus examination, and optical coherence tomography (OCT), was performed at baseline and postoperatively at 24 and 60 months. Corneal topographic and corneal anterior wavefront aberration analyses were performed using a Scheimpflug photography–based topography system (Pentacam; Oculus Optikgerate GmbH). Only measurements with a good acquisition quality (QS: “OK”) were used for the analysis. Corneal topographic indices, including maximum (Kmax 3 and 6 mm) and minimum (Kmin 3 and 6 mm) keratometry, were analyzed before and after surgery. To investigate the effect of treatment in relation to cone location (Kmax), analyses were repeated in subgroups of keratoconus placed in the central 3 mm and peripheral keratoconus located outside 5 mm.

Corneal wavefront errors were analyzed at the 3- to 6-mm optical zone and decomposed into Zernike polynomials up to the sixth order. The parameters analyzed included total wavefront error, total higher and lower order aberrations, trefoil, coma, and spherical aberration. Visual acuity measurements included UDVA and CDVA and were assessed with the logMAR charts. Central foveal thickness was evaluated by OCT (3D-OCT 2000; Topcon Corporation). Endothelial cell density was measured with a non-contact endothelial specular microscope (CellCheck XL; Knonan Medical).

Efficacy measures of this study were UDVA, CDVA, keratometry measurements (Kmax, Kmin, and Kmean), topographic astigmatism, central corneal thickness, and corneal anterior wavefront aberration analyses. Safety measures were postoperative complications, corneal transparency, endothelial cell density, and central foveal thickness.

Surgical Technique

Accelerated CXL was performed under sterile conditions in the operating room, after applying topical anesthesia with 4% lidocaine and 0.2% oxybuprocaine hydrochloride drops (Table 1). Thirty minutes before treatment, 2% pilocarpine drops were instilled to reduce the amount of ultraviolet light reaching the posterior segment. The corneal epithelium was removed with a blunt spatula over a 9-mm surface diameter. Riboflavin (0.1% solution VibeX; Avedro, Inc) was instilled at the center of the cornea for 15 minutes (one drop every 2 minutes). The cornea was exposed to 365-nm ultraviolet-A light with a CXL system (Avedro, Inc) for 4 minutes at an irradiance level of 30 mW/cm2 with continuous light (total surface dose: 7.2 J/cm2). At the end, a soft therapeutic contact lens was applied until complete reepithelialization. Topical 0.3% netilmicin drops and 0.15% dexamethasone phosphate drops were given four times daily for 7 days, then three times daily for 7 days, and finally twice daily for 7 days. Sodium hyaluronate (0.15%) drops were administered six times daily for 3 months.

CXL Methods

Table 1:

CXL Methods

Statistical Analysis

Clinical and demographic data were expressed in terms of frequency and percentage for categorical variables and mean ± standard deviation for quantitative variables. Measurements at 24 and 60 months postoperatively were compared to baseline measurements by the paired t test. Comparisons were considered statistically significant if the P value was less than .05. Statistical analysis was performed using R for Windows (software release 3.5.1; The R Project for Statistical Computing).

Results

Of the 35 patients treated during the period covered by this study, 29 eyes of 29 patients (6 females and 23 males) with a mean age of 24.17 ± 5.86 years (range: 16 to 39 years) completed the scheduled visits and were included in the analysis. Six patients were lost during follow-up. Complete reepithelialization was achieved within 4 days in all cases. No postoperative complications such as corneal infections, infiltrates, or irreversible corneal opacities were observed at any time point during this study.

Preoperative and postoperative visual and refractive results are shown in Table 2. The mean UDVA was unvaried at 24 months (P = .078) but significantly improved at 60 months (P = .028) compared to the baseline value. There was no change in mean CDVA at 24 and 60 months (P = .16 and .30) postoperatively. At 24 months, 13 of 29 (44.8%) of the eyes gained at least one or two lines of UDVA, 11 of 29 (37.9%) showed no change, and 5 of 29 (17.3%) lost one or two lines. Similarly, 12 of 29 (41.4%) of the eyes gained at least one or two lines of CDVA, 13 of 29 (44.3%) showed no change, and 4 of 29 (14.3%) lost one line (Figure 1). Furthermore, at 60 months postoperatively, 14 of 29 (48.3%) of the eyes gained at least one or two lines of UDVA, 10 of 29 (34.5%) displayed no change, and 5 of 29 (17.2%) lost two lines. Moreover, 20 of 29 (69%) of the eyes gained at least one or two lines of CDVA, 8 of 29 (27.5%) showed no change, and 1 of 29 (3.5%) lost two lines (Figure 2).

Visual and Refractive Dataa

Table 2:

Visual and Refractive Data

Uncorrected (UDVA) and corrected (CDVA) distance visual acuity changes 24 months after accelerated corneal cross-linking. Percentage of patients showing variation in UDVA and CDVA from baseline are represented.

Figure 1.

Uncorrected (UDVA) and corrected (CDVA) distance visual acuity changes 24 months after accelerated corneal cross-linking. Percentage of patients showing variation in UDVA and CDVA from baseline are represented.

Uncorrected (UDVA) and corrected (CDVA) distance visual acuity changes 60 months after accelerated corneal cross-linking. Percentage of patients showing variation in UDVA and CDVA from baseline are represented.

Figure 2.

Uncorrected (UDVA) and corrected (CDVA) distance visual acuity changes 60 months after accelerated corneal cross-linking. Percentage of patients showing variation in UDVA and CDVA from baseline are represented.

Among the topographic measurements, anterior Kmax and Kmean at 3 mm significantly decreased at 24 (P = .009 and .006, respectively) and 60 (P = .017 and .034, respectively) months postoperatively, whereas Kmin significantly decreased only at 24 months postoperatively (P = .032). Anterior Kmax at 6 mm significantly decreased at 24 and 60 months postoperatively (P = .035 and .027, respectively). Anterior Kmean and Kmin at 6 mm remained unvaried at 24 or 60 months postoperatively (Table A, available in the online version of this article, Table 3, and Figure 3). Furthermore our results showed steepening of the Kmax of 1.00 D or greater in 21% of cases at 24 months postoperatively and 24% at 60 months postoperatively.

Anterior Corneal Aberrometric Analyses at 3 mma

Table A:

Anterior Corneal Aberrometric Analyses at 3 mm

Anterior Corneal Aberrometric Analyses at 6 mma

Table 3:

Anterior Corneal Aberrometric Analyses at 6 mm

Comparison of maximum, minimum, and mean keratometric values (Kmax, Kmin, Kmean) at 3 and 6 mm before and 24 and 60 months after accelerated corneal cross-linking. Data are represented as mean ± standard deviation.

Figure 3.

Comparison of maximum, minimum, and mean keratometric values (Kmax, Kmin, Kmean) at 3 and 6 mm before and 24 and 60 months after accelerated corneal cross-linking. Data are represented as mean ± standard deviation.

Topographic astigmatism decreased significantly at 24 and 60 months postoperatively (P = .001 and .023, respectively) (Table 2).

Central corneal thickness showed no significant changes at 24 and 60 months postoperatively (P = .087 and .751, respectively). Endothelial cell density and central foveal thickness remained unvaried after 24 and 60 months postoperatively (P = .101 and .167; P = .418 and .465, respectively).

Anterior corneal aberrometric analyses were conducted, including wavefront error, higher and lower order aberrations, spherical aberration, coma at 0°, coma at 90°, trefoil at 0°, and trefoil at 30° (Table A). Total wavefront error, total high order aberrations, total lower order aberrations, spherical aberration, coma at 0°, coma at 90°, and trefoil at 0° and at 30° values did not change at any postoperative time point.

Corneal wavefront aberration at 6 mm (Table 3) remained unvaried except for spherical aberration, which significantly decreased at 60 months (P = .031), and trefoil at 0°, which decreased significantly at 24 months (P = .037) postoperatively.

Discussion

Accelerated CXL was proposed to overcome the main disadvantage of conventional CXL (Dresden protocol), for both patients and surgeons (ie, the long duration of the procedure). To date, no accelerated CXL protocol has been validated with regard to long-term efficacy and safety.

The first result of this study is that our treatment protocol (30 mW/cm2 with a total dose of 7.2 J/cm2) was effective at halting the progression of keratoconus at 5 years postoperatively. None of the patients included in this study showed worsening of the corneal ectasia according to the refractive and topographic criteria used in this study to define keratoconus progression. Furthermore, none of the patients developed signs of corneal or macular damage after surgery, supporting the safety of the energy level used in this treatment.

Vounotrypidis et al9 reported the efficacy of accelerated CXL in a large cohort of patients over a period of 3 years. In their study, accelerated CXL showed similar results to conventional CXL preventing further reduction of the thinnest corneal thickness and the progression of the corneal ectasia. Moreover, in the subgroup analysis of eyes with mild to moderate keratoconus, accelerated CXL induced a significant reduction of Kmax and Kmean, improving the UDVA more than conventional CXL.

In a randomized clinical trial, Hashemi et al15 compared the 4-year results of accelerated (18 mW/cm2; 5 minutes) and standard (3 mW/cm2; 30 minutes) CXL. Their subgroup analysis by cone location showed that the topographic changes in Kmax at 3 and 8 mm were related to keratoconus pattern, and the efficacy of both treatment protocols was greater in central rather than peripheral cones. Likewise, in a 1-year follow-up study by Greenstein et al,16 the standard protocol showed better flattening in central than in peripheral keratoconus. In their study, thinning and endothelial cell loss were independent of cone localization.15,16 Our study confirms a greater flattening effect in patients with central cones.

Elbaz et al10 evaluated the 1-year results of accelerated CXL (irradiance of 9 mW/cm2; 10 minutes) in eyes affected by keratoconus. They found no statistically significant changes in CDVA, but reported a significant improvement in the mean UDVA at 12 months. Moreover, they did not observe statistically significant changes in keratometric measurements and refractive corneal astigmatism at any stage.

Furthermore, Sadoughi et al11 compared visual acuity and keratometry results of 10-minute accelerated CXL (irradiance of 9 mW/cm2; 10 minutes) to the standard CXL protocol. No significant improvement in UDVA and CDVA was observed at 1 year with both treatments. In contrast, Cummings et al12 found a significant improvement in CDVA after conventional and accelerated CXL at 1 year, whereas the UDVA improved only after accelerated CXL.

Toker et al17 compared standard CXL to three different irradiance-accelerated protocols at the 12-month follow-up visit, including a 9 mW/cm2 protocol (10 minutes), a 30 mW/cm2 protocol (4 minutes), and a 30 mW/cm2 protocol using pulsed-light 1 second on/1 second off (8 minutes). They concluded that both 9 mW/cm2 protocols and the 30 mW/cm2 protocol were less effective than standard CXL in terms of topographic, refractive, and visual acuity changes; however, all protocols were equally effective at halting disease progression.

In our study, CDVA remained unvaried after surgery, but UDVA showed a significant improvement at 60 months (Table 2).

Corneal higher order aberrations, especially coma, are important optical quality parameters and should be considered a tool for monitoring the efficacy of keratoconus treatments. Previous studies have shown the increased incidence of spherical and coma-like aberrations in eyes with keratoconus compared to normal controls.18,19 We found that trefoil at 0° decreased with a slight significance at 24 months compared to baseline. However, total wavefront error, trefoil, and spherical aberration values did not significantly change at any postoperative visit.

Ozgurhan et al20 found that the total higher order aberrations, coma, and secondary astigmatism values decreased significantly at 6, 12, and 24 months following treatment in pediatric patients with keratoconus. Ghanem et al21 and Caporossi et al7 reported a significant reduction in corneal higher order aberrations 24 months after performing standard CXL for progressive keratoconus.

The demarcation line could indicate the transition zone between the cross-linked anterior corneal stroma and the untreated posterior corneal stroma, which results from the difference in refractive indices or reflective properties of the cross-linked versus untreated corneal stroma. For this reason, the stromal demarcation line is commonly used as a measure of the extension and depth of CXL treatment within the stroma.22–24 In the current study, the demarcation line was not assessed as a result of being invisible beyond 6 months after surgery. In our recent study on patients treated with continuous and pulsed-light accelerated CXL, the demarcation line, measured at 1 month, was shallower after continuous than after pulsed light treatment.21 Despite the more superficial treatment, the current study results support the long-term efficacy of continuous light accelerated CXL 30 mW/cm2 on halting keratoconus progression at 5 years.

Kymionis et al25 compared the 30 mW/cm2 for 3 minutes protocol with an increased irradiance of 18 mW/cm2 for 7 minutes protocol (7.5 J/cm2) and found comparable outcomes in demarcation line depth and change in mean endothelial cell density. Our study showed no significant change in central corneal thickness at 24 and 60 months after treatment, in agreement with the results published by Bozkurt et al.26

One of the main concerns with accelerated CXL protocols, especially with increased irradiance, is the safety of the corneal endothelium given the greater amount of energy delivered to the cornea. Endothelial damage has been shown to occur when a threshold of 0.65 J/cm2 of energy reaches the endothelium.27 Considering a cornea with a minimum thickness of 400 µm, this translates to a total irradiance of 9.75 J/cm2 required to cause endothelial damage.28 Increasing the total irradiance from 5.4 J/cm2 to the 7.2 J/cm2 energy employed in this study, this value is still within the safety threshold. A possible validation of this hypothesis may come from this study, where endothelial cell density remained unchanged 5 years after surgery, confirming the safety of this energy level. Furthermore, no changes in central foveal thickness were observed at any time point during this study, suggesting that CXL, conducted at a maximum level of irradiance, is not a possible cause of damage to the retina.29

The limitations of this study are its retrospective nature, the absence of a control group, and the limited number of patients included. Strengths of this study are the long follow-up and the thorough examinations conducted at every time point interval. To the best of our knowledge, this is the first study to evaluate the long-term efficacy and safety of an accelerated irradiance protocol over 5 years.

In this study, 30 mW/cm2 for 4 minutes, 7.2 J/cm2 accelerated CXL was demonstrated to be a long-term effective and safe treatment capable of halting keratoconus progression and improving some visual and topographic parameters.

References

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  15. Hashemi H, Mohebbi M, Asgari S. Standard and accelerated corneal cross-linking long-term results: a randomized clinical trial. Eur J Ophthalmol. 2020;30(4):650–657. doi:10.1177/1120672119839927 [CrossRef]
  16. Greenstein SA, Fry KL, Hersh PS. Effect of topographic cone location on outcomes of corneal collagen cross-linking for keratoconus and corneal ectasia. J Refract Surg. 2012;28(6):397–405. doi:10.3928/1081597X-20120518-02 [CrossRef]
  17. Toker E, Çerman E, Özcan DÖ, Seferoglu ÖB. Efficacy of different accelerated corneal crosslinking protocols for progressive keratoconus. J Cataract Refract Surg. 2017;43(8):1089–1099. doi:10.1016/j.jcrs.2017.05.036 [CrossRef]
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  23. Mazzotta C, Paradiso AL, Baiocchi S. Qualitative investigation of corneal changes after accelerated corneal collagen cross-linking (A-CXL) by in vivo confocal microscopy and corneal OCT. J Clin Exp Ophthalmol. 2013;313(06):4–6. doi:10.4172/2155-9570.1000313 [CrossRef]
  24. Moramarco A, Iovieno A, Sartori A, Fontana L. Corneal stromal demarcation line after accelerated crosslinking using continuous and pulsed light. J Cataract Refract Surg. 2015;41(11):2546–2551. doi:10.1016/j.jcrs.2015.04.033 [CrossRef]
  25. Kymionis GD, Tsoulnaras KI, Liakopoulos DA, Skatharoudi CA, Grentzelos MA, Tsakalis NG. Corneal stromal demarcation line depth following standard and a modified high intensity corneal cross-linking protocol. J Refract Surg. 2016;32(4):218–222. doi:10.3928/1081597X-20160216-01 [CrossRef]
  26. Bozkurt E, Ozgurhan EB, Akcay BI, et al. Refractive, topographic, and aberrometric results at 2-year follow-up for accelerated corneal cross-link for progressive keratoconus. J Ophthalmol. 2017;2017:5714372. doi:10.1155/2017/5714372 [CrossRef]
  27. Lang PZ, Hafezi NL, Khandelwal SS, Torres-Netto EA, Hafezi F, Randleman JB. Comparative functional outcomes after corneal crosslinking using standard, accelerated, and accelerated with higher total fluence protocols. Cornea. 2019;38(4):433–441. doi:10.1097/ICO.0000000000001878 [CrossRef]
  28. Wollensak G, Spoerl E, Wilsch M, Seiler T. Endothelial cell damage after riboflavin-ultraviolet-A treatment in the rabbit. J Cataract Refract Surg. 2003;29(9):1786–1790. doi:10.1016/S0886-3350(03)00343-2 [CrossRef]
  29. Choi M, Kim J, Kim EK, Seo KY, Kim TI. Comparison of the conventional Dresden protocol and accelerated protocol with higher ultraviolet intensity in corneal collagen cross-linking for keratoconus. Cornea. 2017;36(5):523–529. doi:10.1097/ICO.0000000000001165 [CrossRef]

CXL Methods

ParameterVariable
Treatment targetEfficacy and safety of accelerated CXL
Fluence (total) (J/cm2)7.2
Soak time and interval (minutes)15
Intensity (mW/cm2)30
Treatment time (minutes)4
Epithelium statusEpithelium-off
ChromophoreRiblofavin, dextran
Chromophore carrierDisiodium hydrogen phosphate, sodium chloride
Chromophore concentrationRiboflavin 0.1%, dextran 20%
Light source365 nm
Irradiation mode (interval)Continuous
Protocol abbreviation in manuscriptCXL

Visual and Refractive Dataa

VariablePreoperativePostoperative 24 MonthsPbPostoperative 60 MonthsPc
logMAR UDVA (Snellen)0.61 ± 0.32 (20/81)0.52 ± 0.31 (20/66).0780.49 ± 0.32 (20/61).028d
logMAR CDVA (Snellen)0.17 ± 0.12 (20/29)0.15 ± 0.11 (20/28).1600.13 ± 0.18 (20/27).302
Cylinder error (D)3.00 ± 1.122.34 ± 1.18.001d2.54 ± 1.04.023d
Central corneal thickness (µm)496.72 ± 36.38501.90 ± 34.41.087495.03 ± 35.34.751
TP (µm)473.52 ± 34.54477.38 ± 33.98.148469.31 ± 30.56.430
ECD (cells/mm2)2,401.28 ± 231.422,466.03 ± 317.13.1012,459.03 ± 304.98.167
Central foveal thickness (µm)240.97 ± 20.31242.59 ± 20.96.418241.34 ± 20.25.465

Anterior Corneal Aberrometric Analyses at 6 mma

VariablePreoperativePostoperative 24 MonthsPbPostoperative 60 MonthsPc
Kmin (D)44.30 ± 1.5944.40 ± 1.74.86243.70 ± 1.05.143
Kmax (D)46.40 ± 2.0646.30 ± 1.99.035d45.70 ± 1.68.027d
Kmean (D)45.30 ± 1.6845.20 ± 1.61.05844.90 ± 1.25.066
WFE TOT (µm)10.23 ± 5.1010.04 ± 3.80.7289.84 ± 4.24.543
HOA (µm)2.54 ± 1.242.59 ± 0.93.7452.46 ± 1.01.615
LOA (µm)9.88 ± 4.989.69 ± 3.70.7189.52 ± 4.14.561
Spherical aberration (µm)−0.41 ± 0.78−0.24 ± 0.70.038d−0.30 ± 0.78.031d
Coma at 0° (µm)0.42 ± 0.940.53 ± 0.80.2450.35 ± 0.88.668
Coma at 90° (µm)−1.99 ± 1.18−2.12 ± 0.93.429−1.92 ± 1.00.693
Trefoil at 0° (µm)0.11 ± 0.32−0.01 ± 0.26.037d0.07 ± 0.46.580
Trefoil at 30° (µm)0.02 ± 0.20−0.01 ± 0.46.7100.11 ± 0.29.122

Anterior Corneal Aberrometric Analyses at 3 mma

VariablePreoperativePostoperative 24 MonthsPbPostoperative 60 MonthsPc
Kmin (D)44.5 ± 2.9444.30 ± 2.76.032d44.00 ± 2.33.113
Kmax (D)47.20 ± 3.0146.30 ± 2.91.009d46.30 ± 2.44.017d
Kmean (D)45.80 ± 2.9445.20 ± 3.01.006d45.1 ± 2.33.034d
WFE TOT (µm)1.93 ± 0.871.81 ± 0.68.0971.70 ± 0.71.061
HOA (µm)0.52 ± 0.270.50 ± 0.21.5010.46 ± 0.22.149
LOA (µm)1.86 ± 0.831.74 ± 0.65.0741.67 ± 0.62.083
Spherical aberration (µm)−0.01 ± 0.190.00 ± 0.15.752−0.04 ± 0.12.232
Coma at 0° (µm)0.10 ± 0.180.09 ± 0.15.7970.08 ± 0.18.736
Coma at 90° (µm)−0.44 ± 0.26−0.44 ± 0.21.913−0.38 ± 0.21.165
Trefoil at 0° (µm)−0.00 ± 0.17−0.01 ± 0.05.8590.01 ± 0.09.655
Trefoil at 30° (µm)0.01 ± 0.110.01 ± 0.08.8790.01 ± 0.06.829
Authors

From the Ophthalmology Unit (AM, VM, MGR, DI, LF) and Research and Statistics Infrastructure (LB), Azienda USL–IRCCS di Reggio Emilia, Reggio Emilia, Italy.

The authors have no financial or proprietary interest in the materials presented herein.

AUTHOR CONTRIBUTIONS

Study concept and design (AM, LF); data collection (VM, MGR, DI); analysis and interpretation of data (VM, LB); writing the manuscript (MGR); critical revision of the manuscript (AM, VM, DI, LB, LF); statistical expertise (LB); administrative, technical, or material support (VM, MGR, DI, LF)

Correspondence: Antonio Moramarco, MD, Ophthalmic Unit, Azienda USL–IRCCS di Reggio Emilia, Viale Risorgimento 80, 42010 Reggio Emilia, Italy. Email: moramarco.antonio@libero.it

Received: March 29, 2020
Accepted: August 13, 2020

10.3928/1081597X-20200819-01

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