Corneal Collagen Cross-linking For Keratoconus Research Articles

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis.

Keratoconus is a bilateral and progressive corneal ectasia. In order to slow down its progression, corneal collagen cross-linking (CXL) has recently been introduced as an efficient treatment option. In biological and chemical sciences, crosslinking refers to new chemical bonds formed between reactive molecules. Hence, the aim of corneal collagen CXL is to synthetically increase the formation of crosslinks between collagen fibrils in the corneal stroma. Despite the fact that the efficiency of the conventional CXL (C-CXL) protocol has already been shown in several clinical studies, it might benefit from improvements in duration of the procedure and removal of corneal epithelium. Hence, in order to provide a coherent evaluation of two new and optimized CXL protocols, we studied keratoconus patients who had undergone one of the three CXL treatments: iontophoresis (I-CXL), accelerated CXL (A-CXL), and conventional CXL (C-CXL). A-CXL is a 6 time faster CXL procedure using a ten time higher UVA irradiance but still including an epithelium removal. Iontophoresis is a transepithelial non-invasive technique in which a small electric current is applied to improve riboflavin penetration throughout the cornea. Using anterior segment optical coherence tomography (AS OCT) and in vivo confocal microscopy (IVCM), we conclude that regarding the depth of treatment penetration, conventional CXL protocol remains the standard for treating progressive keratoconus. Accelerated CXL seems to be a quick, effective and safe alternative to treat thin corneas. The use of iontophoresis is still being investigated and should be considered with greater caution.

Corneal collagen cross-linking for keratoconus: Results of 3-year follow-up in Pakistani population

ObjectiveTo assess the effectiveness and safety of corneal collagen cross-linking with riboflavin and ultraviolet A (UV-A) light in arresting the progression of keratoconus. DesignProspective, nonrandomized experimental study. ParticipantsSeventy-one eyes of 66 patients with progressive keratoconus. MethodsCorneal cross-linking was carried out with riboflavin and UV-A light in patients with progressive keratoconus at Al-Shifa Trust Eye Hospital, Pakistan. Standard protocol of cross-linking comprising epithelial debridement, instillation of isotonic riboflavin (0.1%) for 30 minutes, followed by application of UV-A light for 30 minutes with riboflavin was followed. Variables of interest were uncorrected and best corrected visual acuity (BCVA) with spectacles, spherical equivalent refraction, maximum keratometric reading, and central corneal thickness. Three-year results of these variables after cross-linking were analyzed. ResultsMean age of patients was 19.79 ± 3.71 years; 75.8% were male and 24.2% were female. After 3 years, uncorrected visual acuity improved in 31.0% by mean 2.0 ± 1.06 Snellen lines, remained same in 64.8%, and deteriorated in 4.2% by mean 1.33 ± 0.57 lines. BCVA improved in 56.3% by mean 2.37 ± 1.10 Snellen lines, remained the same in 40.8%, and deteriorated in 2.8% by mean 1.50 ± 0.70 lines. Spherical equivalent refraction decreased in 33.8% by mean 2.29 ± 1.48 D, remained stable in 60.6%, and increased in 5.6% by mean 1.43 ± 0.42 D. Maximum keratometric reading showed mean regression of 2.64 ± 1.42 D in 60.6%, stabilization in 35.2%, and mean progression of 2.0 ± 0.17 D in 4.2%. In 95.8% of cases, progression of keratoconus halted. Central corneal thickness was decreased by mean 10.32 ± 21.19 µm. ConclusionsCross-linking is an effective and safe treatment option in halting the progression of keratoconus.

Corneal collagen cross-linking in keratoconus – long-term prospective study

To determine the refractometric, keratometric and functional results 3 years after cross-linking therapy in patients with keratoconus. Eighty-one patients in various stages of keratoconus were studied, all meeting eligibility criteria for the cross-linking technique. The results showed a decrease both in the K-values, of about 1.5 D, and in the refraction. Visual acuity improved by 1, 2 or 3 Snellen lines in 70% of the cases. The cross-linking technique is a modern method for stopping the progression of keratoconus.

Results of Corneal Collagen Cross-Linking for Keratoconus

Results of Corneal Collagen Cross-Linking for Keratoconus

One-Year Results of Simultaneous Topography-Guided Photorefractive Keratectomy and Corneal Collagen Cross-Linking in Keratoconus Utilizing a Modern Ablation Software.

Purpose. To evaluate effectiveness of simultaneous topography-guided photorefractive keratectomy and corneal collagen cross-linking in mild and moderate keratoconus. Methods. Prospective nonrandomized interventional study including 20 eyes of 14 patients with grade 1-2 keratoconus that underwent topography-guided PRK using a Custom Ablation Transition Zone (CATz) profile with 0.02% MMC application immediately followed by standard 3 mw/cm2 UVA collagen cross-linking. Maximum ablation depth did not exceed 58 μm. Follow-up period: 12 months. Results. Progressive statistically significant improvement of UCVA from 0.83 ± 0.37 logMAR preoperative, reaching 0.25 ± 0.26 logMAR at 12 months (P < 0.001). Preoperative BCVA (0.27 ± 0.31 logMAR) showed a progressive improvement reaching 0.08 ± 0.12 logMAR at 12 months (P = 0.02). Mean Kmax reduced from 48.9 ± 2.8 to 45.4 ± 3.1 D at 12 months (P < 0.001), mean Kmin reduced from 45.9 ± 2.8 D to 44.1 ± 3.2 D at 12 months (P < 0.003), mean keratometric asymmetry reduced from 3.01 ± 2.03 D to 1.25 ± 1.2 D at 12 months (P < 0.001). The safety index was 1.39 at 12 months and efficacy index 0.97 at 12 months. Conclusion. Combined topography-guided PRK and corneal collagen cross-linking are a safe and effective option in the management of mild and moderate keratoconus. Precis. To our knowledge, this is the first published study on the use of the CATz ablation system on the Nidek Quest excimer laser platform combined with conventional cross-linking in the management of mild keratoconus.

Safety and Visual Outcome of Visian Toric ICL Implantation after Corneal Collagen Cross-Linking in Keratoconus: Up to 2 Years of Follow-Up.

Purpose. To evaluate the long-term safety and clinical outcome of phakic Visian toric implantable collamer lens (ICL) insertion after corneal collagen cross-linking (CXL) in progressive keratoconus. Methods. This was a retrospective study of 30 eyes (19 patients), with progressive keratoconus, who underwent sequential CXL followed by Visian toric ICL implantation after 6 months. Results. At baseline, 6 eyes had stage I, 14 eyes stage II, and 10 eyes stage III keratoconus graded by Amsler-Krumeich classification. At 6 months after CXL, only K (steep) and K (max) decreased significantly from baseline, with no change in visual acuity or refraction. Flattening in keratometric readings was stable thereafter. There was significant improvement in mean uncorrected distance visual acuity (1.57 ± 0.56 to 0.17 ± 0.06 logMAR, P < 0.001) and mean corrected distance visual acuity (0.17 ± 0.08 to 0.11 ± 0.05 logMAR, P < 0.001) at 12 months after ICL implantation that was maintained at the 2-year follow-up. Mean cylinder power and mean spherical equivalent (SE) also decreased significantly after ICL implantation. A small hyperopic shift in SE (+0.25 D) was observed at 2 years that did not alter visual outcomes. Conclusions. Visian toric ICL implantation following CXL is an effective option for improving visual acuity in patients with keratoconus up to 2 years.

Safety and efficacy of epithelium removal and transepithelial corneal collagen crosslinking for keratoconus.

This review aims to assess the efficacy and safety of epithelial removal (ER) and transepithelial (TE) corneal collagen crosslinking (CXL) for the treatment of keratoconus. We used MEDLINE to identify all ER and TE CXL studies on keratoconic eyes (n≥20, follow-up ≥12 months). Ex vivo and studies for non-keratoconus indications or in conjunction with other procedures were excluded. Data on uncorrected (UDVA) and corrected (CDVA) distance visual acuity, refractive cylinder, maximum keratometry (Kmax), and adverse events were collected at the latest follow-up and 1 year. Only one randomised controlled trial (RCT) qualified inclusion. Forty-four ER and five TE studies were included. For logMAR UDVA, CDVA, mean spherical equivalent, refractive cylinder and Kmax, at latest follow-up 81, 85, 93, 62, and 93% ER studies vs 66.7, 80, 75, 33, and 40% TE studies reported improvement, respectively. Whereas at 1 year, 90, 59, and 91% ER studies vs 80, 50, and 25% TE studies reported improvement, respectively. The majority of studies showed reduced pachymetry in both groups. Treatment failure, retreatment rates, and conversion to transplantation were reported to be up to 33, 8.6, and 6.25%, respectively, in ER studies only. Stromal oedema, haze, keratitis, and scarring were only reported in ER studies, whereas endothelial cell counts remained variable in both groups. Both ER and TE studies showed improvement in visual acuity, refractive cylinder but Kmax worsened in most TE studies. Adverse events were reported more with ER studies. This review calls for more high quality ER and TE studies with comparable parameters for further assessment of safety and efficacy.

Additive Effect of Repeated Corneal Collagen Cross-linking in Keratoconus

To report the long-term clinical outcome in a patient diagnosed as having bilateral progressive keratoconus who received a single corneal collagen cross-linking (CXL) treatment in the right eye and repeated CXL in the left eye. Observational case report. Topographical changes were assessed by high-resolution Scheimpflug imaging. The right eye underwent a standard epithelium-off CXL procedure in February 2008, followed by the left eye 4 weeks later. In 2012, the left eye was treated with CXL for a second time. Irradiation was performed in all cases at a fluence of 5.4 J/cm². Energy settings were 30 minutes @ 3 mW/cm² for the CXL procedures performed in 2008, and 10 minutes @ 9 mW/cm² for the second CXL procedure of the left eye that was performed in 2012. The right eye that underwent a single CXL procedure showed a flattening of keratometry values between 2008 and 2012, followed by stabilization. The left eye showed a similar flattening effect between 2008 and 2012, followed by another flattening effect after the second CXL procedure and accompanied by a distinct increase in corrected distance visual acuity. Following repeated CXL, the corneal stroma and endothelium remained inconspicuous, and postoperative haze and visibility of the stromal demarcation line was similar to what is usually observed after a single CXL procedure. Whether the additive flattening effect of the anterior surface observed in this single case goes along with an additive increase in biomechanical stiffness remains to be seen.

Long-term results of combined transepithelial phototherapeutic keratectomy and corneal collagen crosslinking for keratoconus: Cretan protocol

To present the long-term results of combined transepithelial phototherapeutic keratectomy (PTK) and corneal collagen crosslinking (CXL) for keratoconus. Vardinoyiannion Eye Institute of Crete, University of Crete, Heraklion, Crete, Greece. Prospective case series. Patients with progressive keratoconus had combined transepithelial PTK and CXL (Cretan protocol). Visual and refractive outcomes and the endothelial cell density (ECD) were evaluated preoperatively and postoperatively. Twenty patients (23 eyes) were enrolled; postoperatively 23 eyes were evaluated at 1 and 2 years, 11 at 3 years, and 7 at 4 years. The mean follow-up was 33.83 months±10.82 (SD) (range 24 to 56 months). No intraoperative or postoperative complications occurred. The mean uncorrected distance visual acuity improved significantly from 0.99±0.57 logMAR preoperatively to 0.61±0.36 logMAR at the last follow-up (P<.001) and the mean corrected distance visual acuity, from 0.27±0.24 logMAR to 0.17±0.14 logMAR (P=.018), respectively. The mean steep and mean flat keratometry readings decreased significantly from 53.39±7.14 diopters (D) and 47.17±4.87 D, respectively, preoperatively to 49.99±4.36 D (P<.001) and 45.47±2.95 D (P=.002), respectively, at the last follow-up. The mean corneal astigmatism improved significantly from -6.27±4.19 D preoperatively to -4.52±2.80 D (P<.001) at the last follow-up. No significant ECD alterations occurred (P>.05). Combined transepithelial PTK and CXL was effective and safe in keratoconic patients over a long-term follow-up. No author has a financial or proprietary interest in any material or method mentioned.

Corneal collagen cross-linking in keratoconus: a systematic review and meta-analysis.

The aim of this study was to determine the effectiveness of corneal collagen cross-linking (CXL) for the treatment of progressive keratoconus (KC). Some of the published literature, including a few small, randomized controlled trials (RCTs), demonstrated good results after CXL, but large RCTs with long-term follow-up to establish a cause-effect relationship are lacking. Using PubMed, EMBASE, and the Cochrane Library database, we searched for relevant studies published between October 2007 and March 2014. A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify the effectiveness of CXL for treating KC. The primary outcome parameters included uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), refraction, corneal topography, and corneal thickness at baseline and at 1, 3, 6, 12, and 18 months after CXL. A total of 1171 participants (1557 eyes) were enrolled in this meta-analysis. CXL may be effective in halting the progress of KC for at least 12 months under certain conditions. However, further research from randomized trials is needed to confirm our findings.

Is accelerated corneal collagen cross-linking for keratoconus the way forward? Yes.

Is accelerated corneal collagen cross-linking for keratoconus the way forward? Yes.

Is accelerated corneal collagen cross-linking for keratoconus the way forward? No.

Collagen cross-linking (CXL) was introduced in the late nineties and was later adopted as a treatment option for keratoconus, pellucid marginal degeneration, and post-LASIK ectasia in 2003.1, 2, 3 CXL is the only treatment modality for these conditions that addresses the underlying stromal weakening and thus halts disease progression. Recently, accelerated CXL was proposed as an alternative technique, whereby corneal stiffening can be achieved with higher fluence and reduced overall exposure time.

Comparison of clinical results of two pharmaceutical products of riboflavin in corneal collagen cross-linking for keratoconus

BackgroundTo compare the 6-month results of two formulations of Riboflavin provided by Sina Darou, Iran, and Uznach, Switzerland, in corneal collagen cross-linking (CXL) for keratoconus patients.FindingsConsidering the results of the previous study about the similarity of the formulations and the active ingredients of the two types of Riboflavin, they were used in the CXL procedure of 60 keratoconic eyes (30 eyes in each group). After 6 months, the mean improvement of UCVA (0.239), BCVA (0.707), and MRSE (0.513) did not differ significantly between the two groups. The mean decrease in max- K (0.731), mean- K (0.264), central corneal thickness (0.759), and Q-value (0.669) did not show any significant difference between the two groups. The two groups had no significant difference in endothelial cell count decrease (0.229). The Sina Darou formulation decreased corneal hysteresis more than the Swiss formulation (P = 0.057) but there were no significant differences in the mean decrease of corneal resistance factor between the two groups (P = 0.117).ConclusionsBased on the early results, the results of visual acuity, refraction, and corneal topography using Sina Darou and Uznach formulations of Riboflavin showed that both were effective in CXL. However, considering the relatively significant difference in corneal hysteresis changes between the two groups, this study will continue to report the long-term results.

Corneal and lens densitometry after corneal collagen cross-linking for keratoconus

PurposeThe study aimed at investigating retrospectively the values of corneal and lens densitometry using the Pentacam Scheimpflug system after corneal cross-linking (CXL).Materials and methodsThis study included 50 eyes of 50 patients who had undergone CXL for keratoconus. The Pentacam Scheimpflug system was used before the procedure to measure objectively the corneal and lens densitometry values. The same measurements were recorded during the follow-up visits at 1, 3, 6, and 12 months using the Scheimpflug image taken at the same axis as at the baseline visit. During the same preoperative and follow-up visits, slit-lamp examination was performed by the same examiner to grade the corneal haze on a scale from 1 to 4.ResultsThe mean Scheimpflug corneal densitometry at baseline was 16.30 ± 1.90 (measured on a scale of 100). At 1 month postoperatively, the corneal densitometry increased to 28.81 ± 4.33. Between 6 and 12 months postoperatively, there was a decrease in the corneal densitometry values by 4.78, which was statistically significant (P < 0.001). At 12 months postoperatively, the corneal densitometry did not return to baseline levels. At baseline, the mean preoperative clinical haze at slit-lamp was 0.31 ± 0.70 (grading from 0 to 4). At 1 month, there was a statistically significant increase in the clinical haze by 1.40 (P < 0.001). Regarding Scheimpflug lens densitometry values, it was 7.91 ± 2.51 at baseline and 7.93 ± 2.61 at 12 months postoperatively.ConclusionScheimpflug corneal densitometry and the clinical corneal haze peaked at 1 month, followed by a gradual decline. They reached near baseline levels at 12 months, but at significantly higher values. Lens densitometry was not affected by CXL.

Characteristics influencing outcomes of corneal collagen crosslinking for keratoconus and ectasia: Implications for patient selection

To determine preoperative patient characteristics that may predict topography and visual acuity outcomes of corneal collagen crosslinking (CXL). Cornea and refractive surgery practice. Cohort study. Crosslinking was performed in eyes with keratoconus or corneal ectasia. Multiple regression and odds ratio analyses were performed to determine independent predictors of changes in topography-derived maximum keratometry (K) and corrected distance visual acuity (CDVA) 1 year postoperatively. Preoperative characteristics included sex, age, uncorrected distance visual acuity (UDVA), CDVA, maximum keratometry (K), corneal thickness, corneal haze, disease group, and cone location. Postoperative improvement in maximum K was defined as flattening of 2.0 diopters (D) or more and worsening as steepening of 1.0 D or more. Improvement in CDVA was defined as a gain of 2 lines or more and worsening as a loss of 1 line or more. The study comprised 104 eyes (66 keratoconus; 38 corneal ectasia). Eyes with a preoperative CDVA of 20/40 or worse were 5.9 times (95% confidence interval [CI], 2.2-6.4) more likely to improve 2 Snellen lines or more. Eyes with a maximum K of 55.0 D or more were 5.4 times (95% CI, 2.1-14.0) more likely to have topographic flattening of 2.0 D or more. No preoperative characteristics significantly predicted worsening of visual acuity or corneal topography. Patients with worse preoperative CDVA and higher K values, particularly with a CDVA of 20/40 or worse or a maximum K of 55.0 D or more, were most likely to have improvement after CXL. No preoperative characteristics were predictive of CXL failure.

Safety and Visual Outcome of Visian Toric ICL Implantation After Corneal Collagen Cross-linking in Keratoconus

To evaluate the safety and clinical outcome of phakic Visian toric implantable collamer lens (ICL) (STAAR Surgical, Monrovia, CA) insertion after corneal collagen cross-linking (CXL) in progressive keratoconus. A retrospective study examined the results of the two-step CXL and Visian toric ICL implantation in 16 eyes of 10 patients with keratoconus. The two procedures were done at an interval of 6 months. Data were collected preoperatively, at the 6-month follow-up visit after CXL, and at the 6-month follow-up visit after ICL implantation. CXL induced a statistically significant decrease in steep keratometry (50.02 ± 4.07 at baseline to 48.74 ± 4.05 at 6 months after CXL, P = .001) without any significant change in visual acuity or refraction. At 6-month follow-up after ICL implantation, mean K (max) was 50.49 ± 4.07 versus 52.29 ± 4.79 D at baseline (P = .001). Mean uncorrected distance visual acuity improved from 1.67 ± 0.49 to 0.17 ± 0.06 logMAR (P = .001) and mean corrected distance visual acuity improved from 0.15 ± 0.06 to 0.12 ± 0.04 logMAR (P = .023). Mean spherical equivalent decreased from -7.24 ± 3.53 to -0.89 ± 0.76 D (P = .001) and mean cylinder decreased from 2.64 ± 1.28 to 1.16 ± 0.64 D (P = .001). The safety and efficacy indices were 1.08 ± 0.13 and 0.97 ± 0.08, respectively. No intraoperative or postoperative complications occurred. Implantation of the Visian toric ICL following CXL is an effective option for improving visual acuity in patients with keratoconus.

Outcomes of Corneal Collagen Cross-linking for Keratoconus the Effect of Cone Location

ABSTRACT Aim One-year outcome of corneal collagen cross-linking (CXL) for keratoconus with reference to topographic cone location. Materials and methods Clinical audit of the results of CXL were used. Three hundred and seventy-eight eyes of 225 patients with preoperative and 12-month completed follow-up were included. Cone location was defined by cone location magnitude index (CLMI) using the Keratron scout topography system. The eyes were divided into two groups–central with cone location within 3 mm zone of the topography map and paracentral with cone location between the 3 and 5 mm zones. Results The overall group showed a mean flattening of the CLMI of 1.67 D [preoperative 53.35 ± 5.63 D, 12 months 51.69 ± 4.67 (p = 0.095)]. The flattening in central cone group was 2.67 D [preoperative 54.01 ± 5.3819, at 12 months to 51.341 ± 4.588 (p = 0.016)]. In paracentral cone group the flattening was lesser at 1.73 D [preoperative apex K 52.805 ± 6.382, at 12 months 51.03 ± 4.82 (p = 0.006)]. The difference between groups was statistically significant (p &lt; 0.001). The central cone group showed no significant shift in cone position [preoperative 1.0059 ± 0.24, at 12 months 0.986 ± 0.206 (p = 0.45)]. The paracentral cone group showed a significant mean shift of 1.05 mm in cone location [preoperative 2.224 ± 0.440, at 12 months 1.196 ± 0.529 (p = 0.001)]. Conclusion Cone location has an impact on the results of corneal cross-linking. The paracentral cones show a significant shift toward the center of the cornea and the central cones show a larger flattening. How to cite this article Agrawal V. Outcomes of Corneal Collagen Cross-linking for Keratoconus the Effect of Cone Location. Int J Kerat Ect Cor Dis 2013;2(1):16-19.

Sterile keratitis after corneal collagen crosslinking in a child

Corneal collagen crosslinking (CXL) is a non invasive technique used in halting the progression of keratoconus. Complications with this modality are rare. We report a case of an 8-year-old child who developed sterile infiltrates in the immediate postoperative period after uneventful corneal collagen crosslinking for keratoconus. The infiltrates resolved with topical steroid therapy. There was also present coexisting vernal keratoconjunctivitis (VKC) which was controlled with topical 2% cyclosporine A eye drops prior to crosslinking treatment. This case highlights importance of controlling VKC prior to CXL in keratoconus as it adds to the risk of developing post operative sterile keratitis.

Phototherapeutic keratectomy versus mechanical epithelial removal followed by corneal collagen crosslinking for keratoconus

ObjectiveTo compare the visual outcomes of patients with keratoconus treated with either phototherapeutic keratectomy (PTK) or mechanical epithelial removal prior to corneal collagen crosslinking (CXL). DesignComparative study. ParticipantsThe records of 34 patients (34 eyes) who had PTK (17 eyes) or mechanical (17 eyes) epithelial removal prior to CXL for keratoconus were reviewed retrospectively. MethodsCXL was performed by 1 of 3 surgeons (G.M., W.B.J., or K.B.). Of the eyes, 17 had undergone mechanical epithelial removal prior to CXL and were consecutively selected, after matching with the 17 eyes in the PTK group, for the variables of procedure date, average keratometry, and pachymetry. All eyes had central cones. Manifest refraction spherical equivalent, sphere, cylinder, best-corrected distance visual acuity, and pachymetry were measured and compared preoperatively and in follow-up. ResultsThe mean change between the pre- and postoperative manifest refraction spherical equivalent for the PTK and mechanical groups was 1.68 ± 0.80 and 0.26 ± 0.90, respectively (p < 0.05). The mean change between pre- and postoperative cylinder for the PTK and mechanical groups was 0.53 ± 0.28 and 0 ± 0.18, respectively (p < 0.05). The mean number of lines of improvement in the PTK and mechanical groups were 0.33 ± 0.82 and −0.58 ± 0.45 lines, respectively (p > 0.05). ConclusionsEarly results suggest that CXL with laser epithelial removal is superior to CXL with mechanical epithelial removal because it reduces refractive error in qualified patients. Although not statistically significant, there was also a trend for PTK CXL patients to have better visual outcomes.