Changes of matrix metalloproteinases in the stroma after corneal cross-linking in rabbits.

AIM: To observe changes in the content of matrix metalloproteinases (MMPs) in the corneal stroma after corneal cross-linking (CXL) in rabbits, and further explore the corneal pathophysiological process after CXL. METHODS: Forty-two rabbits (42 eyes) were randomly divided into seven groups. One group served as the control group, while the other six groups were treated with CXL. The concentrations of MMPs in corneal stroma were evaluated through parallel reaction monitoring at baseline and 3, 7, 15, 30, 90, and 180d after treatment. RESULTS: The levels of MMP-2 in the corneal stroma of rabbits were 0.76±0.07, 2.78±1.39, 4.12±0.69, 2.00±0.29, 2.00±0.30, 1.22±0.18, and 1.35±0.18 (10-9 mol/g) at baseline and 3, 7, 15, 30, 90, and 180d after treatment, respectively. The contents of tissue inhibitor of metalloproteinase-1 (TIMP-1) were 1.83±0.26, 7.94±0.58, 6.95±2.64, 3.81±0.48, 3.07±0.92, 1.72±0.19, and 1.69±0.74 (10-9 mol/g), respectively. The ratios of MMP-2/TIMP-1 were 0.42±0.33, 0.36±0.20, 0.62±0.10, 0.54±0.15, 0.68±0.13, 0.71±0.10, and 0.68±0.09, respectively. After CXL, the expression of MMP-2 and TIMP-1 in the rabbit corneal stroma was initially increased and subsequently decreased. The levels of MMP-2 remained higher than those recorded at baseline 180d after treatment, but it was not statistically significant. The levels of TIMP-1 returned to baseline levels at 90d after treatment. The ratio of MMP-2/TIMP-1 started to rise from 7d after CXL. It was significantly higher than that calculated at baseline 30-180d after CXL. The results for MMP-1, -3, -7, -9, -13, and TIMP-2 were negative. CONCLUSION: CXL can lead to changes in the content of MMP-2 and TIMP-1 in the rabbit corneal stroma. The ratio of MMP-2/TIMP-1 remains higher versus baseline, indicating that MMP-2 is involved in the corneal pathophysiological process after CXL.

Efficacy of iontophoresis-assisted epithelium-on corneal cross-linking for keratoconus.

Corneal cross-linking (CXL) is a noninvasive therapeutic procedure for keratoconus that is aimed at improving corneal biomechanical properties by induction of covalent cross-links between stromal proteins. It is accomplished by ultraviolet A (UVA) radiation of the cornea, which is first saturated with photosensitizing riboflavin. It has been shown that standard epithelium-off CXL (S-CXL) is efficacious, and it has been recommended as the standard of care procedure for keratoconus. However, epithelial removal leads to pain, transient vision loss, and a higher risk of corneal infection. To avoid these disadvantages, transepithelial CXL was developed. Recently, iontophoresis has been adopted to increase riboflavin penetration through the epithelium. Several clinical observations have demonstrated the safety and efficacy of iontophoresis-assisted epithelium-on CXL (I-CXL) for keratoconus. This review aimed to provide a comprehensive summary of the published studies regarding I-CXL and a comparison between I-CXL and S-CXL. All articles used in this review were mainly retrieved from the PubMed database. Original articles and reviews were selected if they were related to the I-CXL technique or related to the comparison between I-CXL and S-CXL.

Iontophoresis-assisted corneal crosslinking using 0.1% riboflavin for progressive keratoconus.

AIM: To report the clinical results of iontophoresis-assisted epithelium-on corneal crosslinking (I-CXL) using 0.1% riboflavin in distilled water for progressive keratoconus. METHODS: In this prospective clinical study, we examined 94 eyes of 75 patients with progressive keratoconus who were treated with I-CXL using 0.1% riboflavin in distilled water. Best correct visual acuity (BCVA), Scheimpflug tomography, corneal topography, anterior segment optical coherence tomography, intraocular pressure, and endothelial cell density were evaluated at baseline and 1, 3, 6, 12, and 24mo after I-CXL. RESULTS: After 24mo I-CXL, compared to the level at baseline, BCVA significantly improved 0.14±0.07 (P=0.010); mean keratometry signifi-cantly decreased 0.72±1.97 (P=0.021); maximum keratometry significantly reduced 2.30±5.01 (P=0.014); central keratoconus index significantly reduced 0.04±0.08 (P=0.007). The demarcation line was visible in 83.1% of eyes at 1mo after treatment, with a depth of 298.95±51.97 µm, and gradually indistinguishable. One eye had repeat treatment. Intraocular pressure and endothelial cell density did not change significantly. CONCLUSION: I-CXL using 0.1% riboflavin halts keratoconus progression within 24mo, resulting in a significant improvement in visual and topographic parameters. Moreover, the depth of the demarcation line is similar to that previously reported in standard epithelium-off CXL procedures.

Riboflavin concentration in corneal stroma after intracameral injection.

AIM: To evaluate the enrichment of riboflavin in the corneal stroma after intracameral injection to research the barrier ability of the corneal endothelium to riboflavin in vivo. METHODS: The right eyes of 30 New Zealand white rabbits were divided into three groups. Different concentrations riboflavin-balanced salt solutions (BSS) were injected into the anterior chamber (10 with 0.5%, 10 with 1%, and 10 with 2%). Eight corneal buttons of 8.5 mm in diameter from each group were dissected at 30min after injection and the riboflavin concentrations in the corneal stroma were determined using high-performance liquid chromatography (HPLC) after removing the epithelium and endothelium. The other two rabbits in every group were observed for 24h and sacrificed. As a comparison, the riboflavin concentrations from 16 corneal stromal samples were determined using HPLC after instillation of 0.1% riboflavin-BSS solution for 30min on the corneal surface (8 without epithelium and 8 with intact epithelium). RESULTS: The mean riboflavin concentrations were 11.19, 18.97, 25.08, 20.18, and 1.13 µg/g for 0.5%, 1%, 2%, de-epithelialzed samples, and the transepithelial groups, respectively. The color change of the corneal stroma and the HPLC results showed that enrichment with riboflavin similar to classical de-epithelialized corneal collagen crosslinking (CXL) could be achieved by intracameral 1% riboflavin-BSS solution after 30min; the effect appeared to be continuous for at least 30min. CONCLUSION: Riboflavin can effectively penetrate the corneal stroma through the endothelium after an intracameral injection in vivo, so it could be an enhancing method that could improve the corneal riboflavin concentration in transepithelial CXL.

Progress of corneal collagen cross-linking combined with refractive surgery.

As a photochemical reaction that can stiffen the cornea, corneal collagen cross-linking (CXL) is the only promising method of preventing the progress of keratectasia, such as keratoconus and secondary ectasia following refractive surgery. The aim of CXL is to stabilize the underlying condition, with a small chance of visual improvement. Combining CXL with refractive surgery targeting both stabilization and reshaping of the corneal tissue for visual function improvement is a good treatment option. This review aims to provide a comprehensive and unbiased summary of the published research regarding combined CXL and refractive surgery, including measures and results, to help elucidate the future direction of CXL.

[Corneal collagen cross-linking in the treatment of progressive keratoconus-preliminary results].

OBJECTIVE: To evaluate the efficacy and safety of riboflavin-ultraviolet-A (UV-A)-induced corneal collagen cross-linking (CXL) in the management of progressive keratoconus. METHODS: It was a retrospective case series study. Twenty-three eyes of 13 patients with progressive keratoconus were included. Corneal collagen crosslinking was performed under topical anesthesia including corneal de-epithelization (8 mm diameter) and instillation of 0.1% riboflavin (in 20% dextran T500 solution) every 3 minutes for a total of 30 minutes. The irradiation is performed for another 30 min using a solid-state UV-A illuminator at 370 nm and an irradiance of 3 mW/cm(2). Average follow-up was 15.23 ± 3.39 months (range: 12 to 22 months). Visual acuity, corneal topography, in vivo confocal microscopy, and endothelial cell count were evaluated at baseline and at 1, 3, 6, and 12 months follow-up. RESULTS: Mean uncorrected visual acuity(UCVA) and best spectacle-corrected visual acuity (BSCVA) increased 0.115 ± 0.158 LogMAR (t = 3.418, P = 0.0026) and 0.114 ± 0.218 LogMAR (t = 2.441, P = 0.0236) 12 months postoperatively respectively. Interim analysis of treated eyes showed a flattening of the steepest simulated keratometry value (K-max) and astigmatism by an average of (1.893 ± 3.713) diopters (D) (t = 2.391, P = 0.0262) and (0.117 ± 1.488) D (t = 0.370, P = 0.715) respectively at 12 months. Central corneal thickness decreased by (27.5 ± 26.8) µm (t = 4.812, P = 0.000) and (1.54 ± 19.4) µm ( t = 0.147, P = 0.885) at one month and 12 months postoperatively respectively.Intraocular pressure, endothelial cell count, lens and fundus didn't change significantly at 12 months follow-up. CONCLUSIONS: CXL stabilised and improved the UCVA and BSCVA as well as the maximum k-readings at 1 year postoperatively in our cohort. It seems to be a safe and promising procedure to stop the progression of keratoconus.

Clinical evaluation of pranoprofen combined with fluorometholone eye drops on postoperative reaction of corneal cross-linking.

PURPOSE: To evaluate the efficacy and safety of pranoprofen eye drops for reducing postoperative ocular pain and inflammation after corneal cross-linking (CXL). METHODS: Twenty-seven patients (38 eyes) with keratoconus undergoing CXL were examined and randomly divided into control (12 cases; 18 eyes) and experimental groups (15 cases; 20 eyes). The patients in the control group were given fluorometholone eye drops, and those in the experimental group were administered with fluorometholone combined with pranoprofen eye drops．Corneal irritation and haze were compared between the two groups at 1 month postoperatively． RESULTS: At 1 to 3 days after surgery, the corneal irritation in the experimental group was significantly reduced compared with that in the control group (P<0.05), but there was no significant difference on 5 to 7 days postoperatively (P>0.05)．The average degree of haze in the experimental group was significantly lower than that in the control group 1 month after surgery (P<0.05), but there was no significant difference in the best-corrected vision acuity and intraocular pressure between the two groups. There were 2 cases with P<20 mmHg intraocular pressure in the control group. CONCLUSION: The combined use of fluorometholone and pranoprofen can significantly reduce inflammatory response, alleviate corneal irritation at early stage after CXL, effectively prevent and control the average of haze, and reduce the incidence of steroid-induced ocular hypertension after surgery．

Corneal collagen crosslinking for corneal ectasia of post-LASIK: one-year results.

AIM: To evaluate the efficacy and safety of corneal collagen crosslinking (CXL) to prevent the progression of post-laser in situ keratomileusis (LASIK) corneal ectasia. METHODS: In a prospective, nonrandomized, single-centre study, CXL was performed in 20 eyes of 11 patients who had LASIK for myopic astigmatism and subsequently developed keratectasia.The procedure included instillation of 0.1% riboflavin-20% dextrane solution 30 minutes before UVA irradiation and every 5 minutes for an additional 30 minutes during irradiation. The eyes were evaluated preoperatively and at 1-, 3-, 6-, and 12-month intervals. The complete ophthalmologic examination comprised uncorrected visual acuity, best spectacle-corrected visual acuity, endothelial cell count, ultrasound pachymetry, corneal topography, and in vivo confocal microscopy. RESULTS: CXL appeared to stabilise or partially reverse the progression of post-LASIK corneal ectasia without apparent complication in our cohort. UCVA and BCVA improvements were statistically significant(P<0.05) beyond 12 months after surgery (improvement of 0.07 and 0.13 logMAR at 1 year, respectively). Mean baseline flattest meridian keratometry and mean steepest meridian keratometry reduction (improvement of 2.00 and 1.50 diopters(D), respectively) were statistically significant (P<0.05) at 12 months postoperatively. At 1 year after CXL, mean endothelial cell count did not deteriorate. Mean thinnest cornea pachymetry increased significantly. CONCLUSION: The results of the study showed a long-term stability of post-LASIK corneal ectasia after crosslinking without relevant side effects. It seems to be a safe and promising procedure to stop the progression of post-LASIK keratectasia, thereby avoiding or delaying keratoplasty.

Study on the surface properties of surface modified silicone intraocular lenses.

AIM: To prepare a new-type soft intraocular lens (IOL) that silicone intraocular lenses (IOLs) were modified by surface modification technique to assess IOLs biocompatibility. METHODS: With the technique of ion beam combined with low temperature and low pressure plasma, the surface characteristics of the IOLs including physical and optical properties were determined by the instruments of IOLs resolution, UV/VIS scanning spectrophotometer, contact angle measurement system, electron spectroscopy for chemical analysis (ESCA) and scanning electron microscope (SEM). RESULTS: The color of titanium (Ti) modified IOLs was light yellow and that of titanium nitride (TiN) modified IOLs was light brown. The absorptive degree of ultraviolet rays and the hydrophilicity of the surfaces of modified IOLs were increased, and appeared suitable chemical compositions. The resolution of unmodified and modified IOLs reached normal standard. The surfaces of unmodified and Ti-modified IOLs appeared uniform. The surfaces of TiN-modified IOLs presented fine porcelain structure. CONCLUSION: The optical properties of all IOLs and the surface morphology of the modified IOLs were not affected by modification processes. The surface properties of the modified IOLs were improved.