CXL Group Research Articles

Comparison of Corneal Collagen Cross-Linking and Voriconazole Treatments in Experimental Fungal Keratitis for Aspergillus fumigatus.

AimsTo compare the antifungal efficacy of corneal cross-linking (CXL) and voriconazole in experimental Aspergillus keratitis models.MethodsThirty-nine New Zealand rabbits were divided into three groups: a control group, a voriconazole group (M group), and a voriconazole combined with CXL group (CXL-M group). The ulcer area was measured via slit lamp imaging, the corneal and corneal epithelial thickness, and ulcer depth was measured via anterior segment optical coherence tomography (AS-OCT). The existence time of the hyphae was observed via in vivo confocal microscopy (IVCM), and the cornea was taken for pathological examination after modeling and at the end of the study to determine the hyphae and corneal repair. The observation times were as follows: at successful modeling and at 1, 4, 7, 14, 21, and 28 days after intervention.ResultsIn the CXL-M group, ulcer area and depth decreased continuously from Day 4 to Day 28 after CXL (all P < 0.05). In the CXL-M group, ulcer area and depth were smaller than those in the other two groups from Day 4 to Day 21 after CXL (all P < 0.05, except ulcer area in the CXL-M vs. M group on Day 21). The duration of hyphae in the CXL-M group was significantly shorter than in the other two groups (P = 0.025). On Day 28, in CXL-M group, corneal thickness was thicker than baseline (P < 0.05). Meanwhile, in CXL-M group, corneal and corneal epithelial thickness were significantly thinner than in the other two groups (P < 0.001). The CXL-M group had no complications, such as corneal perforation, at the end of the study.ConclusionsVoriconazole combined with CXL is effective in treating Aspergillus-infected keratitis. Combined therapy could effectively inhibit Aspergillus, accelerate corneal repair, and shorten the course of the disease.

Crosslinking vs. Observation in Fellow Eyes of Keratoconus Patients.

Purpose To evaluate whether unilateral crosslinking (CXL) and conservative follow-up of the fellow eye is an acceptable management strategy in patients with keratoconus (KC). Methods Seventy-nine fellow eyes of KC subjects that initially underwent unilateral CXL were included. Thirty fellow eyes ultimately received CXL (group 1) whereas 49 fellow eyes were followed (group 2). Best spectacle corrected visual acuity (BSCVA) and corneal tomographic parameters were collected in all eyes preoperatively and at the last follow-up. Results Subjects who received CXL in the fellow eye (group 1) were younger than subjects who did not (group 2, p=0.026). Group 1 eyes had higher baseline K1 (p=0.026), K2 (p=0.006), Km (p=0.01), and Kmax (p=0.002) compared to group 2 eyes. Amongst the 49 naïve fellow eyes (group 2), 19 eyes showed evidence of progression. Progressing naïve eyes had higher baseline K1, K2, Km, and Kmax (p < 0.01); progressors also had thinner pachymetry at the pupil, apex, and thinnest point (p < 0.01). Baseline values of K1 ≥ 43.5 Diopter (D), K2 > 45.1D, Km > 44.3D, Kmax > 47.9D, astigmatism > 1.4D, pachymetry at the pupil <475 μm, and thinnest pachymetry <478 μm were tentative predictors of progression in the naïve fellow eye. Conclusions Unilateral CXL with vigilant follow up of the fellow eye may be an acceptable management strategy in a subset of KC eyes.

Scleral Cross-Linking in Form-Deprivation Myopic Guinea Pig Eyes Leads to Glaucomatous Changes.

PurposeTo investigate the potential glaucomatous changes caused by scleral cross-linking (CXL) in a guinea pig form-deprivation (FD) myopia model.MethodsEighty 4-week-old tricolor guinea pigs were divided into four groups: FD only, genipin CXL only, FD plus CXL, and control. Refractive error, axial length (AL), intraocular pressure (IOP), and structural and vasculature optic disc changes in optical coherence tomography (OCT) and OCT angiography (OCTA) were measured at baseline and day 21. CXL efficacy was evaluated by scleral rigidity Young's modulus values. Histological and molecular changes in the anterior chamber angle, retina, and sclera were assessed.ResultsBaseline parameters were similar among groups (P > 0.05). The FD plus CXL group at day 21 had the least increase of AL (0.14 ± 0.08 mm) and highest IOP elevation (31.5 ± 3.6 mmHg) compared with the FD-only group (AL: 0.68 ± 0.17 mm; IOP: 22.2 ± 2.6 mmHg) and the control group (AL: 0.24 ± 0.09 mm; IOP: 17.4 ± 1.8 mmHg) (all P < 0.001). OCT and OCTA parameters of the optic disc in the FD plus CXL group at day 21 showed glaucomatous changes and decreased blood flow signals. Sclera rigidity increased in the CXL and FD plus CXL groups. Advanced glycation end products deposited extensively in the retina, choroid, and sclera of FD plus CXL eyes.ConclusionsCXL causes increased IOP and subsequent optic disc, anterior segment, and scleral changes while inhibiting myopic progression and axial elongation in FD guinea pig eyes. Therefore, applying CXL to control myopia raises safety concerns.

Evaluation of the effectiveness of combined staged surgical treatment in patients with keratoconus.

This study performs comparative assessment of the results of different types of two-stage surgical treatment in patients with keratoconus, including combination of corneal collagen cross-linking with intrastromal corneal ring segments followed by topography-guided photorefractive keratectomy. Prospective review of 101 patients (101 eyes) with keratoconus was performed. Patients underwent corneal collagen cross-linking (32 patients), intrastromal corneal ring segments (48 patients), and a combination of these two procedures (21 patients). Transepithelial topography-guided photorefractive keratectomy was performed as the second stage of treatment in all patients with obtained stable refractive results at 8 months after first stage. Main outcome measures were visual acuity (uncorrected distance and corrected distance) and corneal topographic indices. Comparison of the studied parameters after first stage surgical treatment between non-combined CXL and combined groups demonstrated a statistically significant difference for uncorrected distance visual acuity, corrected distance visual acuity, and cylindrical refraction values (p<0.05). We observed significant improvement of visual acuity and key corneal topographic indices after topography-guided photorefractive keratectomy in all study groups (p<0.05). In 50 (49.5%) patients customized excimer laser ablation gave the possibility of full spherical and cylindrical corrections. Ten eyes (10%) had delayed epithelial healing, no corneal stromal opacities developed. This study shows that combined two-stage surgical treatment of keratoconus, consisting of intrastromal corneal ring segment implantation with corneal collagen cross-linking followed by topography-guided photorefractive keratectomy, is clinically more effective to prevent keratectasia progression and increase visual acuity than the use of non-combined two-stage techniques.

Repeatability and Agreement of a New Scheimpflug Device and a Hartmann-Shack Aberrometer With a Ray-Tracing Aberrometer in Normal, Keratoconus, and CXL Groups

To assess repeatability and agreement of a Scheimpflug topographer and a Hartmann-Shack aberrometer with a ray-tracing aberrometer in normal, keratoconus, and corneal cross-linking (CXL) groups. In this cross-sectional, observational study, normal, keratoconus, and CXL groups with 125 eyes in each of the three groups were included. All eyes underwent three sets of measurements, at a single visit, using the Pentacam AXL Wave (Oculus Optikgeräte GmbH) and iTrace (Tracey Technologies). Keratometry, pachymetry, objective refraction, and total ocular aberrations including root mean square (RMS) lower order aberrations (LOAs), RMS higher order aberrations (HOAs), RMS coma, and spherical aberrations (SA) were analyzed. Objective assessment of haze after CXL was done using the Pentacam AXL Wave. Repeatability was assessed using within-subject standard deviation (Sw), test-retest variability, within-subject coefficient of variation (COV), and intraclass correlation coefficient (ICC). Bland-Altman analysis assessed 95% limits of agreement and correlation coefficient (r) determined the strength of the relationship between measurements. The Pentacam AXL Wave had Sw for keratometry of 0.12 in the normal group and 0.15 in the keratoconus group and lower (poorer) Sw of 0.17 in the CXL group. For pachymetry, Sw was 9.18, 9.53, and 10.11 in the normal, keratoconus, and CXL groups, respectively. Total aberrations had ICCs ranging from 0.88 for RMS HOAs to 0.95 for SA in the normal group, 0.86 for RMS HOAs to 0.92 for SA in the keratoconus group, and 0.72 for RMS HOAs to 0.82 for SA (poorer) in the CXL group. In the normal group, mean differences between the two devices were nonsignificant for all parameters except SA (0.011 ± 0.038 μm, P < .01; limits of agreement = -0.09 to 0.07; r = 0.87). In the keratoconus group, mean differences were significant in all aberrations except RMS LOAs (-0.27 ± 0.85 μm, P = .10; limits of agreement = -3.3 to 3.8; r = 0.92). In the CXL group, all parameters varied significantly (P < .006). The Pentacam AXL Wave showed comparable repeatability in the normal and keratoconus groups, but was poorer in the CXL group, more so with increasing corneal haze. Both devices can be used interchangeably in normal eyes, except for SA, but not in eyes with keratoconus or CXL for aberration measurements. [J Refract Surg. 2022;38(3):201-208.].

Comparison of contact lens-assisted and transepithelial corneal crosslinking with standard epithelium-off crosslinking for progressive keratoconus: 24-month clinical results.

To compare the outcomes of contact lens-assisted corneal crosslinking (CACXL) and transepithelial CXL (TECXL) with standard epithelium-off (epi-off) CXL for progressive keratoconus. Advanced Eye Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Retrospective, comparative study. Patients with progressive keratoconus undergoing CXL with a minimum follow-up of 24 months were included. CACXL and TECXL were performed in patients with epithelium-on minimal pachymetry between 350 μm and 450 μm. The main outcome measures included change in maximum keratometry (Kmax), corrected distance visual acuity (CDVA), and efficacy in halting progression (increase in Kmax ≥1 diopter [D]). Standard epi-off CXL, CACXL, and TECXL were performed in 34, 14, and 10 eyes, respectively. Baseline Kmax and CDVA were comparable for all groups. Kmax reduced significantly by -2.83 ± 3.35 D, -3.18 ± 2.74 D, and -2.02 ± 1.66 D in the standard epi-off CXL (P < .01), CACXL (P = .001), and TECXL (P = .004) groups, respectively; the reduction was comparable for all groups (P = .63). CDVA improved by -0.14 ± 0.24, -0.04 ± 0.19, and -0.12 ± 0.17 logMAR in the standard epi-off CXL (P = .006), CACXL (P = .42), and TECXL (P = .05) groups, respectively; the reduction was comparable for all groups (P = .46). Progression was documented in 2 eyes (6%) in the standard epi-off CXL group and in 0 eyes of the CACXL and TECXL groups (P = .61). CACXL and TECXL were comparable with the standard epi-off CXL for progressive keratoconus.

Accelerated versus conventional corneal collagen crosslinking: Short-term clinical outcomes in stabilizing keratoconus.

PURPOSE:The purpose of the study is to compare the short-term outcomes of corneal collagen crosslinking (CXL) using the conventional (Dresden) protocol and an accelerated CXL (ACXL) protocol to stop keratoconus (KC) progression.METHODS:A chart review was performed for all the patients with KC who underwent CXL in the last 7 years. Data were compared at baseline and at all follow-up examinations for uncorrected visual acuity (UCVA), best spectacle corrected visual acuity (BCVA), keratometry (K), central corneal thickness, and complications of CXL. Pre- and post-intervention values were compared for each group. P < 0.05 was statistically significant.RESULTS:After the treatment, there was a statistically greater improvement in UCVA in the conventional CXL (CCXL) group (49%) compared to the ACXL group (34%) (P = 0.028). The improvement in BCVA was similar between the groups (P = 0.060). Gain of two lines of UCVA and stability were comparable between groups (P = 0.078 and P = 0.060, respectively). The average flat K and steep K values fluctuated remarkably across different follow-up assessments in both the groups. At 3 months of follow-up, there was a statistically significantly faster return to baseline levels of flat and steep Ks in the CCXL group (P = 0.028 and P = 0.002, respectively).CONCLUSION:The findings of the current study confirm the efficacy and safety of accelerated high-fluence CXL compared to CCXL. Both protocols were effective in stabilizing KC at 9th-month and the last follow-up visit. Larger prospective randomized controlled trials and longer follow-up are required to confirm our findings.

Study of corneal backscatter by Scheimpflug imaging in patients with keratoconus treated with corneal Cross‐linking

AbstractPurposeTo compare corneal densitometry obtained using Pentacam HR in the eyes of patients with keratoconus treated with corneal collagen cross‐linking (CXL) versus the eyes of healthy controls.MethodsAn observational case‐control study was carried out on 18 eyes of 15 patients with keratoconus treated with CXL (classical therapy), and 30 eyes of 15 healthy controls, in which ocular pathology had previously been ruled out. All patients underwent a Scheimpflug corneal tomography with Pentacam HR. For the analysis, the backscattering of light is measured in the anterior (120 µm) central and posterior (60 µm) corneal layers.ResultsThe group of patients treated with CXL therapy were 11 men and 4 women, the mean age was 28.06 years (range 17–44 years). In the CXL group the mean light scattering in the previous layer was 24.35 ± 1.074 (C: 21.6 ± 0.68 p &gt; 0.05); central layer 14.68 ± 0.53 (C: 14.48 ± 0.41 p &lt;0.05); posterior layer 10.75 ± 0.35 (C: 11.04 ± 0.36 p &lt; 0.05) and full thickness 16.6 ± 0.62 (C: 15.71 ± 0.44 p &lt; 0.05).ConclusionsThere are statistically significant differences in the densitometry values of the anterior layer of patients with keratoconus treated with CXL compared to healthy controls. We did not find statistically significant differences for the central, posterior and total variables.

Comparison of deep anterior lamellar keratoplasty and corneal cross-linking in patients with advanced keratoconus.

To compare outcomes of deep anterior lamellar keratoplasty (DALK) and corneal cross-linking (CXL) in patients with advanced keratoconus, with the primary aim of assessing CXL as a potential therapeutic alternative. Retrospective, multi-center, comparative study. Patients with advanced keratoconus (maximum keratometry reading (K-max) > 58D, best spectacle-corrected visual acuity worse than 0.52logMAR), undergoing either DALK or CXL treatment at four tertiary ophthalmic centers in Wenzhou, Hangzhou, Nanjing and Wuhan were included. Visual acuity, refractive error, corneal topography and complications were evaluated at baseline and at least 2 year postoperatively. 75 eyes of 72 patients were included, of which 37 eyes underwent DALK and 38 eyes, CXL. A larger reduction in Kmax was observed in the DALK group (-18.18 ± 9.44 D versus -1.10 ± 2.70D, p < 0.001). Seven eyes (18%) in the CXL group showed progression of keratoconus. No disease progression was observed in the DALK group. Greater improvements in best spectacle-corrected visual acuity (logMAR) were observed in the DALK group (-0.59 ± 0.25 versus -0.24 ± 0.44, p < 0.001). Compared to CXL, DALK leads to larger reductions in Kmax and better improvement in visual acuity in advanced keratoconus.

Epithelial Flap Corneal Cross-linking.

To compare standard epithelium-off corneal cross-linking (standard Epi-Off CXL) to corneal cross-linking with an epithelial flap (Epi-Flap CXL). Patients who had undergone sequential bilateral CXL for progressive keratoconus were included in this comparative interventional case series. One eye was treated with the Epi-Off CXL technique and the fellow eye with the Epi-Flap CXL technique. Postoperative pain was measured using the Verbal Rating Scale and corneal densitometry using a Scheimpflug camera. Sex, age, corrected distance visual acuity, keratometry, and corneal thickness were also recorded. Twenty-four eyes of 12 patients with keratoconus with a mean age of 27.15 ± 5.15 years were included. The Verbal Rating Scale scores were significantly lower in patients who had Epi-Flap CXL on the first (1.00 [interquartile range (IQR): 0.00 to 1.00] vs 3.00 [IQR: 3.00 to 3.75], P = .01) and third (0.00 [IQR: 0.00 to 1.00] vs 1.00 [IQR: 0.00 to 1.00], P = .01) postoperative day compared to the Epi-Off CXL group. No pain was observed in both groups after the third day. After 12 months, the Epi-Flap CXL group showed significantly less anterior corneal haze (measured as corneal densitometry) compared to the patients treated with Epi-Off CXL (P = .01). Both groups demonstrated stability of keratometry and corneal thickness at 12 months after CXL (P < .01). Epi-Flap CXL is associated with less postoperative pain and anterior stromal haze in patients undergoing CXL for progressive keratoconus with no loss of efficacy. [J Refract Surg. 2021;37(11):741-745.].

Comparative Analysis of Matrix-Regenerating Agent and Corneal Cross-Linking in an Experimental Alkali Burn Rabbit Model

Purpose This study aimed to investigate the clinical and histopathological effects of corneal cross-linking (CXL) and matrix-regenerating agent (RGTA) treatments after corneal alkali burn. Materials and Methods Twenty-four alkali-burned corneas from 24 rabbits were divided into three groups: control, CXL, and RGTA. All animals were investigated for epithelial healing, opacification, ulceration, and neovascularization at days 1, 7, 14, and 21 after the alkali burn. Corneas were excised and sent for histological examination on day 21. Results One animal each from the CXL and control groups exhibited moderate ulceration, while no ulceration was observed in the RGTA group. No significant difference was observed among the groups in corneal thickness or corneal opacity measurements at the final visit (p=0.058 and p=0.544, respectively). Both RGTA and CXL treatments were effective in terms of epithelial healing and neovascularization (p=0.023 and p=0.03, respectively). On histological examination, the CXL and RGTA groups were more effective in treating epithelial loss, stromal edema, corneal vascularization, and leukocytic infiltration than the control group (p<0.05). The immunohistochemical staining scores of the CXL and RGTA groups for caspase-3, vascular endothelial growth factor, and matrix metalloproteinase-9 in the epithelium and stroma were significantly lower than those in the control group (p<0.05). In the immunohistochemical examination for inducible nitric oxide synthase, epithelial staining scores were similar among the groups (p>0.05). In contrast, the stromal staining scores of the CXL and RGTA groups were lower than those of the control group (p<0.05). Conclusion Both CXL and RGTA therapies were effective in reducing anatomical and histopathological complications after corneal alkali burn. Further investigation is needed to determine the optimal timing, duration, and dosage of these treatments.

Safety of accelerated corneal collagen cross-linking in keratoconus patients on the basis of macular segmentation.

To investigate the safety of accelerated corneal collagen cross-linking (A-CXL) in patients with keratoconus on the basis of thickness analysis measurements of retinal layers and retinal morphology. This was a retrospective and comparative study. The study included 64 eyes of 32 patients with keratoconus disease. One eye of the patients underwent A-CXL for progressive keratoconus (CXL group) and the fellow eye was followed due to the absence of progression. Patients with at least 1-year follow-up after A-CXL were included. Keratometry, pachymetry and corrected-distance visual acuity (CDVA) levels of the patients were compared. The segmentation analysis of the individual retinal layers of the eyes with (CXL group) and without CXL (no CXL group) was compared with spectral domain-optical coherence tomography automatic segmentation program at baseline and at the last follow-up. The thickness of the retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer and retina pigment epithelium layer in the central 1-mm subfield defined by the ETDRS was analyzed. The mean age of keratoconus patients was 23.9 ± 5.4years, patients were more likely to be male (21/11, 65.6%), and the mean follow-up duration was 13.9 ± 1.5months. When keratometry, pachymetry and CDVA levels were compared, only a significant difference was found between CDVA at the last follow-up (0.21 vs. 0.11 LogMAR). No significant difference was observed in neither retinal morphology nor segmentation of individual retinal layers at baseline and at the final evaluation (P > 0.05). It has been observed that the A-CXL protocol did not cause a significant change in both retinal layer thickness and macular morphology.

COMPARATIVE STUDY OF CROSS LINKING VERSUS STROMAL PUNCTURE IN KERATOCONUS

Background: Keratoconus is a non-inflammatory condition where the cornea assumes a conical shape because of thinning and protrusion of the corneal stroma. The corneal thinning induces irregular astigmatism, myopia, and corneal protrusion, leading to mild to marked impairment in the quality of vision. Symptoms are highly variable and, in part, depend on the stage of progression of the disorder. Objective: To compare refractive and topographic outcomes between cross-linking (CXL) and corneal stromal puncture in stiffening the cornea and halt the progression of Keratoconus. Patients and Methods: This randomized controlled study included 19 patients (30 eyes) with keratoconus. They were not presenting with any eye disease and had never undergone eye surgery. The total number of subjects meeting the inclusion and exclusion criteria. They were divided into 2 groups, group (A) 9 patient: 15 eyes received cross-linking and group (B) 10 patient: 15 eyes received corneal puncture. All examination, investigation and the procedure were done at El Sayed Galal Hospital and Nour al Hyaa eye Hospital, Cairo. Results: The results showed significant improvement in postoperative value of UCVA, BCVA, than its preoperative value. In addition, a statistically significant decrease of postoperative K1 in both group than its preoperative value while there was a statistically significant increase of K2 postoperative value compared to preoperative value in puncture group, K2 showed significant decease postoperative in CXL group. There was significant increase in corneal thickness postoperatively compared to preoperative values in puncture group, corneal thickness showed significant decrease postoperatively in CXL group. Comparing both groups, there was significant improvement in postoperative UCVA, postoperative BCVA in puncture group than in CXL group. On the other hand, there was a significant decrease in mean of postoperative corneal thickness in CXL group than puncture group. Conclusion: Overall, the results of this study continue to support the efficacy of CXL in progressive keratoconus and explored new modality of its treatment by anterior stromal puncture (ASP), with an improvement in UCVA, and BCVA 3 months after operation.

Corneal collagen cross-linking (CXL) versus combined CXL and femtosecond laser-assisted intracorneal ring segment implantation for the treatment of keratoconus

Background The corneal cross-linking procedure has been proven to be an effective method to treat and stabilize keratoconus progression, but early vision rehabilitation is still needed in patients. Aim The aim was to compare the results of the combined CXL and intrastromal corneal ring segment implantation procedure to that of the cross-linking-alone procedure in terms of visual acuity, refraction, and some corneal topographic parameters in keratoconic patients. Design This was a prospective, comparative, and interventional study. Patients and methods This study was carried out on 44 keratoconic patients (60 eyes) of both sexes who ranged from 18 to 36 years. Thirty eyes were subjected to the CXL-alone procedure and 30 eyes were subjected to the combined procedure. Measurements were performed in all patients preoperatively and at 3, 6 months, and 1 year postoperatively including unaided visual acuity, best-corrected visual acuity, refractive, and topographic outcomes. Results Through the entire study period, both procedures were safe and effective in treating and stabilizing keratoconus progression. Furthermore, the combined group showed additional improvements over the CXL group for the following: UDVA at 3 months (P=0.0028), best-corrected visual acuity at 1 year (P=0.011), refractive and keratometric astigmatism at all follow-up visits and corneal asphericity at 3 months (P=0.013) and 6 months (P=0.0221) of follow-up. No severe intraoperative or postoperative complications were observed during the entire study period in either group. Conclusions The combined procedure is safe and effective for earlier improvement of visual and refractive outcomes in addition to the corneal stabilizing effect.

Repeatability of corneal and epithelial thickness measurements with anterior segment optical coherence tomography in keratoconus.

PurposeTo investigate the repeatability in corneal thickness (CT) and epithelial thickness (ET) measurements using spectral domain anterior segment optical coherence tomography (AS-OCT, REVO NX, Optopol) in keratoconus, and examine the effect of corneal crosslinking (CXL) on repeatability.MethodsA cross-sectional study of 259 eyes of 212 patients with keratoconus attending the corneal disease clinic at a university hospital tertiary referral center were enrolled. Two groups were analysed: eyes with no prior history of CXL (Group A) and eyes with prior CXL (Group B). Repeatability of measurements was assessed using the intraclass correlation coefficient (ICC) and coefficient of variation (CV).ResultsIn Group A, central corneal thickness (CCT) was 472.18 ± 45.41μm, and the ET was found to be the thinnest in the inferior-temporal aspect at 51.79 ± 5.97μm and thickest at the superior-nasal aspect at 56.07 ± 5.70μm. In Group B, CCT was 465.11± 42.28μm, and the ET was the thinnest at the inferior-temporal aspect at 50.63 ± 5.52μm and thickest at the superior aspect at 56.80 ± 6.39μm. When evaluating CT measurements, ICC was above 0.86 and 0.83 for Group A and Group B respectively. When evaluating ET measurements, ICC was above 0.82 for both groups. CXL had no statistically significant impact on the repeatability of measurements.ConclusionsAS-OCT provides repeatable CT and ET measurements in the central and peripheral cornea in patients with keratoconus. Repeatability is not affected by a history of CXL.

Comparison of modified corneal cross-linking with intrastromal voriconazole for the treatment of fungal corneal ulcer.

The present study aimed to evaluate the efficacy of modified corneal cross-linking (CXL) for the treatment of fungal corneal ulcers compared with that following intrastromal voriconazole injection. In total, 31 patients with fungal corneal ulcers treated at The General Hospital of Northern Theater Command between October 2017 and October 2019 were enrolled. Among them, 10 eyes were treated with ultraviolet A (UV-A)/riboflavin CXL (CXL group), whilst 21 eyes were treated with debridement combined with intrastromal voriconazole (stromal injection group). Preoperative microbiological examination was performed in both groups, and evaluated using Fisher's exact test. Postoperatively, infection control and total efficacy rates, localized lesion, ulcer healing rate 1 week after surgery, visual acuity and complications were evaluated using Fisher's exact test, however visual acuity was analyzed by mixed-model ANOVA. The results showed that the pre-operative species distribution between the CXL and stromal injection groups did not significantly differ. The infection control rate in the CXL group was notably higher compared with that in the stromal injection group (P=0.04). Furthermore, the total efficacy rate in the CXL group was also markedly higher compared with that in the stromal injection group, though no statistically significant differences were observed. Localized lesions were observed in nine eyes (90.0%) in the CXL group and nine eyes (42.9%) in the stromal injection group (P=0.02). However, the rate of ulcer healing at 1 week postoperatively and the logarithm of the minimum angle of resolution (logMAR) of visual acuity were not found to be significantly different between the two groups. In terms of complications, with the exception of one patient in the CXL group exhibiting loss of corneal transparency and one patient in the stromal injection group presenting with partial corneal thinning, no other forms of complications were observed. In conclusion, the present study suggested that CXL could have a beneficial impact for treating fungal corneal ulcers in the aspects of infection control, localized lesions and accelerated epithelialization. In addition, except the loss of corneal transparency, this treatment approach could be applied with reduced risks of adverse events.

Effect of Corneal Cross-linking versus Standard Care on Keratoconus Progression in Young Patients: The KERALINK Randomized Controlled Trial

To examine the efficacy and safety of corneal cross-linking (CXL) for stabilization of progressive keratoconus. Observer-masked, randomized, controlled, parallel-group superiority trial. Sixty participants 10 to 16 years of age with progressive keratoconus, one eye of each deemed the study eye. The study eye was randomized to either CXL plus standard care or standard care alone, with spectacle or contact lens correction as necessary for vision. The primary outcome was steep keratometry (K2) in the study eye as a measure of the steepness of the cornea at 18 months. Secondary outcomes included keratoconus progression defined as a 1.5-diopter (D) increase in K2, visual acuity, keratoconus apex corneal thickness, and quality of life. Of 60 participants, 30 were randomized to CXL and standard care groups. Of these, 30 patients in the CXL group and 28 patients in the standard care group were analyzed. Mean K2 in the study eye 18 months after randomization was 49.7 D (standard deviation [SD], 3.8 D) in the CXL group and 53.4 D (SD, 5.8 D) in the standard care group. The adjusted mean difference in K2 in the study eye was -3.0 D (95% confidence interval [CI], -4.9 to -1.1 D; P= 0.002), favoring CXL. Adjusted differences between groups in uncorrected and corrected vision favored eyes receiving CXL: -0.31 logarithm of the minimum angle of resolution (logMAR; 95% CI, -0.50 to -0.11 logMAR; P= 0.002) and -0.51 logMAR (95% CI, -1.37 to 0.35 logMAR; P= 0.002). Keratoconus progression in the study eye occurred in 2 patients (7%) randomized to CXL compared with 12 patients (43%) randomized to standard care. The unadjusted odds ratio suggests that on average, patients in the CXL arm had 90% (odds ratio, 0.1; 95% CI, 0.02-0.48; P= 0.004) lower odds of experiencing progression compared with those receiving standard care. CXL arrests progression of keratoconus in the majority of young patients. CXL should be considered as a first-line treatment in progressive disease. If the arrest of keratoconus progression induced by CXL is sustained in longer follow-up, particular benefit may be derived from avoiding a later requirement for contact lens wear or corneal transplantation.

Depth- and direction-dependent changes in solute transport following cross-linking with riboflavin and UVA light in ex vivo porcine cornea

Diffusion is an important mechanism of transport for nutrients and drugs throughout the avascular corneal stroma. The purpose of this study was to investigate the depth- and direction-dependent changes in stromal transport properties and their relationship to changes in collagen structure following ultraviolet A (UVA)-riboflavin induced corneal collagen cross-linking (CXL). After cross-linking in ex vivo porcine eyes, fluorescence recovery after photobleaching (FRAP) was performed to measure fluorescein diffusion in the nasal-temporal (NT) and anterior-posterior (AP) directions at corneal depths of 100, 200, and 300 μm. Second harmonic generation (SHG) imaging was also performed at these three corneal depths to quantify fiber alignment. For additional confirmation, an electrical conductivity method was employed to quantify ion permeability in the AP direction in corneal buttons and immunohistochemistry (IHC) was used to image collagen structure. Cross-linked corneas were compared to a control treatment that received the riboflavin solution without UVA light (SHAM). The results of FRAP revealed that fluorescein diffusivity decreased from 23.39 ± 11.60 μm2/s in the SHAM group to 19.87 ± 10.10 μm2/s in the CXL group. This change was dependent on depth and direction: the decrease was more pronounced in the 100 μm depth (P = 0.0005) and AP direction (P = 0.001) when compared to the effect in deeper locations and in the NT direction, respectively. Conductivity experiments confirmed a decrease in solute transport in the AP direction (P < 0.0001). FRAP also detected diffusional anisotropy in the porcine cornea: the fluorescein diffusivity in the NT direction was higher than the diffusivity in the AP direction. This anisotropy was increased following CXL treatment. Both SHG and IHC revealed a qualitative decrease in collagen crimping following CXL. Analysis of SHG images revealed an increase in coherency in the anterior 200 μm of CXL treated corneas when compared to SHAM treated corneas (P < 0.01). In conclusion, CXL results in a decrease in stromal solute transport, and this decrease is concentrated in the most anterior region and AP direction. Solute transport in the porcine cornea is anisotropic, and an increase in anisotropy with CXL may be explained by a decrease in collagen crimping.

Corneal cross-linking versus conventional management for keratoconus: a lifetime economic model

Aims To assess the cost-effectiveness of corneal collagen cross-linking (CXL) versus no CXL for keratoconus in the United States (US). Methods A discrete-event microsimulation was developed to assess the cost-effectiveness of corneal cross-linking (CXL, Photrexa + KXL combination product) versus no CXL for patients with keratoconus. The lifetime model was conducted from a US payor perspective. The source for CXL efficacy and safety data was a 12-month randomized, open-label, sham-controlled, multi-center, pivotal trial comparing CXL versus no CXL. Other inputs were sourced from the literature. The primary outcome was the incremental cost per quality-adjusted life year gained. Costs (2019 USD) and effects were discounted 3% annually. The impacts of underlying uncertainty were evaluated by scenario, univariate, and probabilistic analyses. Results Starting at a mean baseline age of 31 years and considering a mixed population consisting of 80% slow-progressors and 20% fast-progressors, the CXL group was 25.9% less likely to undergo penetrating keratoplasty (PK) and spent 27.9 fewer years in advanced disease stages. CXL was dominant with lower total direct medical costs (-$8,677; $30,994 versus $39,671) and more QALYs (1.88; 21.80 versus 19.93) compared to no CXL. Considering the impact of reduced productivity loss in an exploratory scenario, CXL was associated with a lifetime cost-savings of $43,759 per patient. CXL was cost-effective within 2 years and cost-saving within 4.5 years. Limitations Limitations include those that are common to similar pharmacoeconomic models that rely on disparate sources for inputs and extrapolation on short-term outcomes to a long-term analytical horizon. Conclusions Keratoconus is a progressive and life-altering disease with substantial clinical, economic, and humanistic consequences. The economic value of cross-linking is maximized when applied earlier in the disease process and/or younger age, and extends to improved work productivity, out-of-pocket costs, and quality of life.

The ABCD Keratoconus Grading System-A Useful Tool to Estimate Keratoconus Progression in the Pediatric Population.

To evaluate the ABCD grading system in pediatric keratoconus. A retrospective cohort analysis of all children with keratoconus followed up at the Shamir medical center between 2010 and 2017. A recommendation by the treating physician to undergo corneal crosslinking (CXL) was used as an estimate for clinically significant disease progression. The ABCD grading was not available to the treating physician and was computed post hoc. The ABCD grading was compared between patients who required CXL with those who did not. A single eye of each patient was included. Fifty eyes of 50 children were analyzed. The mean age at presentation was 15.56 ± 1.36 years. In 23 eyes, progression of keratoconus was recorded and CXL was performed (CXL-group). On presentation, the stable and CXL groups did not differ significantly in their clinical parameters. In the CXL-group, a statistically significant increase was seen in the ABCD staging (P < 0.001). In the stable group, the ABCD staging did not change significantly in parallel visits (P = 0.87). An increase of 1 point in the sum of the ABCD staging showed a 5-fold risk for undergoing CXL (odds ratio = 5.28; 95% CI, 1.82-15.34). There was no significant change in the Amsler-Krumeich classification in the CXL group. Among a cohort of pediatric patients with keratoconus, worsening in the ABCD grading was associated with disease progression, whereas no significant change was demonstrated in the Amsler-Krumeich classification The ABCD grading system is a useful tool for initial assessment of disease progression in the pediatric population, in which early recognition is of paramount importance.