Transcatheter arterial chemoembolization using CalliSpheres beads loaded with arsenic trioxide for unresectable large or huge hepatocellular carcinoma: a prospective study.

OBJECTIVES: To determine the safety and efficacy of transcatheter arterial chemoembolization with CalliSpheres® beads loaded with arsenic trioxide (CBATO-TACE) in the first-line treatment of patients with large (5 cm ≤ maximum diameter < 10 cm) or huge (maximum diameter ≥ 10 cm) hepatocellular carcinoma (HCC). METHODS: Patients were randomly allocated to the CBATO-TACE group and the conventional transcatheter arterial chemoembolization (cTACE) group. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall survival (OS), treatment response, and treatment-related adverse events (TRAEs). The extrahepatic collateral arteries, liver function, and liver fibrosis after the first TACE were also evaluated. RESULTS: From September 2018 to September 2020, a total of 207 patients who underwent TACE were consecutively enrolled in this study. The median PFS was 9.5 months (range: 8.0 - 11.0) in the CBATO group, which was significantly longer than that in the cTACE group (6.0 months, range: 4.0-6.0) (p < 0.0001). Patients in the CBATO group had a median OS of 22 months (range: 20.0 - 27.0) compared with 16 months (range: 15.0 - 20.0) in the cTACE group (p = 0.0084). The most common TRAEs were fever (p = 0.043), and nausea and vomiting (p = 0.002), which were more observed in the cTACE group. In addition, the progressive disease time, pulmonary metastasis rate (p = 0.01), the mean number of extrahepatic collateral arteries (p = 0.01), and average number of TACE sessions (p = 0.025) were significantly decreased in the CBATO group. CONCLUSIONS: CBATO-TACE achieved better therapeutic outcomes and similar safety profile compared to cTACE in large or huge HCC patients. Furthermore, CBATO-TACE was able to reduce extrahepatic collateral arteries production and extrahepatic lung metastasis. CLINICAL RELEVANCE STATEMENT: Our study showed that CalliSpheres® beads loaded with arsenic trioxide (CBATO-TACE) were effective and safe for the treatment of large and giant HCC. In addition, CBATO-TACE can reduce lateral hepatic branch artery formation and extrahepatic pulmonary metastasis, which provides a new treatment approach for unresectable HCC. KEY POINTS: • We compare long-term efficacy and safety of transcatheter arterial chemoembolization with CalliSpheres® beads loaded with arsenic trioxide (CBATO-TACE) and conventional transcatheter arterial chemoembolization (cTACE) in patients with large (5 cm ≤ maximum diameter < 10 cm) or huge HCC (maximum diameter ≥ 10 cm). • Compared with cTACE, CBATO-TACE significantly improved therapeutic outcomes, overall survival, and progression-free survival in patients with large or huge HCC. The safety assessment suggested that CBATO-TACE is a safe treatment that improves the quality of life and has good treatment adherence.

Analysis of the effect of calcium ions on promoting the penetrability of riboflavin into the corneal stroma by iontophoresis.

PURPOSE: To investigate the effect of calcium ions on promoting the penetrability of riboflavin into the corneal stroma by iontophoresis and to analyse the possible mechanism. METHODS: Forty rabbits were divided into five groups randomly: 0.1% riboflavin-balanced salt solution (BSS) by iontophoresis group, 0.1% riboflavin-saline solution by iontophoresis group, 0.1% riboflavin-zinc gluconate solution by iontophoresis group, 0.1% riboflavin-calcium gluconate solution by iontophoresis group and classical riboflavin instillation after corneal de-epithelialization as the control group. The riboflavin concentrations in corneal stroma were determined and compared by high-performance liquid chromatography (HPLC) after removing epithelium and endothelium. RESULTS: Iontophoretic delivery of a 0.1% riboflavin-calcium gluconate solution was the closest to the effect of classical de-epithelialization. The other solvents were unsufficient at enhancing the permeability of the riboflavin. CONCLUSION: Calcium ions can promote the penetrability of riboflavin into the corneal stroma by iontophoresis.

[Progress on iron metabolism and ferroptosis in macrophages].

Macrophages play vital roles in iron metabolism and are also modulated by iron. Macrophages are crucial to the recycling of iron and systemic iron homeostasis, and the functional heterogeneity of macrophages contributes to the different effects on iron metabolism. Conversely, iron can affect the development, function, and polarization of macrophages. Macrophages can initiate ferroptosis through a series of signaling pathways when overloaded with intracellular iron. Macrophages ferroptosis can aggravate local inflammatory reactions and promote the progression of various diseases such as metabolism, infection, and inflammation, so inhibiting macrophages ferroptosis may be an important therapeutic target. In addition, inhibiting M1-like macrophages ferroptosis and promoting M2-like macrophages ferroptosis are important in inhibiting the progression of malignant tumors.

Interference of MDM2 attenuates vascular endothelial dysfunction in hypertension partly through blocking Notch1/NLRP3 inflammasome pathway.

BACKGROUND: Hypertension is a life-threatening disease mainly featured as vascular endothelial dysfunction. This study aims to explore the regulatory role of murine double minute 2 (MDM2) in hypertension and vascular damage. METHODS: Mice were infused with angiotensin II (AngII) to establish a hypertension mouse model in vivo and AngII-stimulated HUVECs were constructed to simulate the damage of vascular endothelial cells in hypertension in vitro. The plasmids targeting to MDM2 was injected to mice or transfected to HUVECs. qRT-PCR and western blot were performed to detect corresponding gene expression in mice aorta. Blood pressure was measured. H&E and Masson staining were conducted to evaluate histological changes of aorta. Responses to the acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in aorta. ZO-1 expression and cell apoptosis were detected by immunofluorescence and TUNEL, respectively. Network formation ability was determined employing a tube formation. RESULTS: MDM2 was upregulated in hypertensive mice. Knockdown of MDM2 inhibited AngII-induced high BP, histological damage, vascular relaxation to Ach, and promoted the levels of p-eNOS and ZO-1 in the aorta in hypertensive mice. MDM2 knockdown inactivated Notch1 signaling and NLRP3 inflammasome, while the inhibitory effect of MDM2 knockdown on NLRP3 inflammasome activation was partly restored by the activation of Notch1. Furthermore, knockdown of MDM2 relieved AngII-induced endothelial dysfunction in HUVECs, as well as suppressing AngII-promoted cell apoptosis. Whereas, the impacts generated by MDM2 knockdown were partly weakened by the activation of Notch1 signaling or NLRP3 inflammasome. CONCLUSION: In summary, knockdown of MDM2 can attenuate vascular endothelial dysfunction in hypertension, which may be achieved through inhibiting the activation of Notch1 and NLRP3 inflammasome.

[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 observation on high intensity focused ultrasound combined with transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma].

OBJECTIVE: To study on the efficacy, prognosis and security of high-intensity focused ultrasound (HIFU) combined with transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). METHODS: Totally 72 HCC patients treated by HIFU from December 2009 to January 2011 were divided into two groups according to treatment methods: 40 cases in HIFU group, 32 cases in TACE + HIFU treatment group (combined group). Then set up a control group include 40 cases treated by only TACE in the same period (TACE group). The improvement of clinical symptoms, AFP, reduce rate of tumor volume, survival rate of 1 year after operation and postoperative complications in front and behind the treatment were analyzed. RESULTS: There was no significant statistical difference on the improvement of clinical symptoms in all these three groups (P > 0.05) after treatment for HCC. There is no significant statistical difference also on reduce rate of tumor volume and decrease rate of AFP in both HIFU group (35.0%, 41.4%) and TACE group (37.5%, 41.9%) (χ² = 0.054, P = 0.816; χ² = 0.002, P = 0.965). Both reduce rate of tumor volume (62.5%) and decrease rate of AFP (72.0%) in combined group were better than HIFU group (χ² = 5.394, P = 0.020; χ² = 5.098, P = 0.024) and TACE group (37.5%, 41.9%) (χ² = 4.448, P = 0.035; χ² = 5.062, P = 0.024). Kaplan-Meier survival curve showed that there was no significant statistical difference on short-term survival rate in the 3 groups. But the long-term survival rate of combined group was better than TACE group and HIFU group. CONCLUSION: TACE combined with HIFU is a effective, safe and noninvasive treatment method to HCC.

[Expression of liver-intestine cadherin and its significance in hepatocellular carcinoma].

OBJECTIVE: To explore the expression and clinical significance of LI (liver-intestine)-cadherin mRNA and protein expression level in hepatocellular carcinoma. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical techniques were used to detect the expression of the LI-cadherin mRNA and protein in 56 cases of hepatocellular carcinoma, 44 cases of corresponding paracancerous tissues and 9 cases of normal liver tissues. The relationships with its clinicopathological characteristics were analyzed. RESULTS: The mRNA of LI-cadherin was expressed in 56 cases of hepatocellular carcinoma tissues and 44 cases of corresponding paracancerous tissues. But its expression was not detected in normal tissues. Semiquantitative analysis showed that the mRNA expression level of LI-caherin was greater in hepatocellular carcinoma tissues than that in corresponding paracancerous tissues (0.653 ± 0.147 vs 0.534 ± 0.138). The differences were statistically significant (P < 0.01). The positive rates of LI-cadherin protein were 64.29% (36/56) in hepatocellular carcinoma tissues, 22.73% (10/44) in paracancerous tissues and 0% (0/9) in normal tissues. CONCLUSION: The expression of LI-cadherin is up-regulated significantly in HCC. The over-expression of LI-cadherin protein is correlated with the lymph node metastasis and tumor thrombi in portal vein. It indicates that LI-cadherin may play an important role in the progression and metastasis of HCC.

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.

[Expression of estrogen receptor and progesterone receptor in hilar cholangiocarcinoma and their clinical significances].

OBJECTIVE: To investigate the relationship between the expression of estrogen receptor (ER) and progesterone receptor (PgR) and histological type, pathological grading and clinical staging in hilar cholangiocarcinoma (HCCA). To evaluate their roles in the development of it. METHODS: ER and PgR were assessed in 42 specimens of HCCA by immunohistochemical assay. RESULTS: The positive rate of ER and PgR was 66.7% and 64.3%. The expression of ER and PgR was significantly different between poor and well tumor differentiation, as well as between papillary and sclerosing variant. CONCLUSION: The positive rate of ER and PgR was detected significantly in HCCA. They might be an important biological marker to evaluate the malignancy and prognosis of it.

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.

Combined cancer testis antigens enhanced prediction accuracy for prognosis of patients with hepatocellular carcinoma.

Cancer testis antigens (CTAs) are selectively expressed in malignant cells and can serve as ideal targets for immunotherapy. We investigated the expressions of MAGE-A3, MAGE-A4, MAGE-C2 and NY-ESO-1 to determine if combinatorial expressions of CTAs might be as potential prognostic markers for patients with hepatocellular carcinoma (HCC). In tumor tissues of 142 HCC patients, the mRNA expressions of MAGE-A3, MAGE-A4, MAGE-C2 and NY-ESO-1 were 78.9%, 33.8%, 74.6% and 14.1% respectively. Furthermore, the expressions of MAGE-A3, MAGE-A4 and combination of MAGE-A3, MAGE-A4 and NY-ESO-1 (CTAs-A3/A4/NY) showed positive correlations with serum AFP, tumor stages and Ki-67 (P < 0.05). In addition, mRNA expressions of CTAs were significantly consistent with protein expressions of CTAs by immunohistochemistry (P > 0.05). Receiver operating characteristic curves (ROC) analysis showed that CTAs-A3/A4/NY had larger areas under ROC curve (0.768), specificity (99.1%), Youden's index (44.6), positive predictive value (90.9%) and negative predictive value (89.9%) for predicting HCC recurrence than other CTAs. Moreover, the combinatorial expression of CTAs-A3/A4/NY was significantly associated with HCC recurrence by Kaplan-Meier analysis (HR = 69.36, P < 0.01) and multivariate Cox analysis (RR = 17.11, P < 0.01). The combinatorial expression of CTAs-A3/A4/NY mRNA promotes the predictive accuracy of HCC recurrence and itself may be a potential target for immunotherapy of HCC as well.

Research progress in corneal cross-linking agents.

Corneal collagen cross-linking with UVA-riboflavin is currently the only method for preventing the progression of keratoconus from the pathological perspective. Topical application of a direct cross-linking agent is now attracting widespread attention in clinical settings. This article reviews the research progress in the application of indirect or direct cross-linking agents (e.g., riboflavin, glucose, ribose, glutaraldehyde, formaldehyde, glyceraldehyde, short chain aliphatic ß-nitro alcohol, and genipin) in the treatment of corneal diseases and analyzes the cross-linking efficacy, toxicity, and merits and disadvantages of each cross-linking agent, providing clinical information for further studies.

Corneal refractive surgery and phakic intraocular lens for treatment of amblyopia caused by high myopia or anisometropia in children.

OBJECTIVE: A systematic review of literature was performed to compare various visual function parameters including the final visual acuity outcome and/or adverse events between corneal refractive surgery (CLRS) and phakic intraocular lens implantation (p-IOLi) in the treatment of refractive amblyopic children. DATA SOURCES: Two reviewers independently searched the PubMed, EMBASE, and Controlled Trials Register databases for publications from 1991 to 2013. STUDY SELECTION: There were 25 articles, including 597 patients and 682 eyes, was included in CLRS group. Among them, 21 articles reported the use of CLRS in the treatment of myopic anisometropia for 318 patients (13 photorefractive keratectomy or laser epithelial keratomileusis and eight laser in situ keratomileusis). And 11 articles had the results of CLRS in treating hyperopic anisometropic amblyopia children. Eleven articles reported the effect of p-IOLi for treating high myopia or anisometropic amblyopia, including 61 patients (75 eyes). Age, pre- and postoperation best-corrected vision acuity (BCVA), and spherical equivalent (SE) were compared in CLRS and p-IOLi groups. RESULTS: The average age of CLRS group and p-IOLi group has no statistically significant difference. The SE in CLRS group for myopic anisometropia amblyopia patients was (-10.13 ± 2.73) diopters (D) and for hyperopic anisometropia amblyopia patients was (5.58 ± 1.28) D. In p-IOLi group the SE was (-14.01 ± 1.93) D. BCVA was improved significantly in both groups, and even better in p-IOLi group. Refractive errors were corrected in both groups, but there was no clinically significant difference in final SE between each group. More than one-half of the children had improved binocular fusion and stereopsis function in both groups. CONCLUSIONS: Both CLRS group and p-IOLi group showed their advantage in treating refractive amblyopia in children. In comparing p-IOLi with CLRS for treatment of refractive amblyopia, no statistically significant difference in final BCVA was observed.

Iontophoretic delivery of riboflavin into the rabbit cornea: a primary study.

PURPOSE: To determine the penetrability of riboflavin into the corneal stroma by iontophoresis and to compare the permeability effects of different solvents. METHODS: Twenty rabbits were randomly divided into four groups: a group that received 0.1% riboflavin-balanced salt solution (BSS) by iontophoresis, a group that received 0.1% riboflavin-saline solution by iontophoresis, a group that received 0.1% riboflavin-distilled water solution by iontophoresis, and a control group that received classical riboflavin instillation after corneal de-epithelialization. The degree of yellowing of the de-epithelialized corneal stromal button from each rabbit was compared. RESULTS: The yellow color scores for the corneal stromal buttons in the three iontophoresis groups were compared with those of control group. Iontophoretic delivery of a 0.1% riboflavin-distilled water solution yielded similar yellow changes in the corneal stromal button when compared with classical riboflavin instillation after de-epithelialization. However, the other two solvents did not sufficiently enhance the permeability of riboflavin. CONCLUSION: Riboflavin can effectively penetrate into the corneal stroma to saturation levels by iontophoresis. Using distilled water as the solvent can promote penetrability.

Corneal collagen fibril changes after ultraviolet a/riboflavin corneal crosslinking.

PURPOSE: The aim was to investigate the changes in collagen type 1 and type 3 in rabbit corneas undergoing corneal crosslinking with ultraviolet A and riboflavin and to analyze the possible mechanisms of corneal haze formation. METHODS: After removal of the central epithelium, the right corneas of 60 New Zealand rabbits were crosslinked with riboflavin and ultraviolet A, and 10 additional rabbits were used as the control group. The animals were killed 3, 7, 15, 30, 90, and 180 days postoperatively. Collagen type 1 and type 3 were analyzed using picrosirius red stain by means of polarized light microscopy. The biochemical changes in collagen type 3 at the time points indicated above were determined by Western blot analyses. RESULTS: Collagen type 3 was significantly increased 30 days after corneal crosslinking compared with that in the control cornea, gradually increased until reaching its maximum value 90 days after riboflavin and ultraviolet A crosslinking, and then decreased until it returned to the normal state 180 days after crosslinking. There were no significant changes in collagen type 1 over time after corneal crosslinking. In agreement with the picrosirius red staining results, the western blot analyses showed that collagen type 3 was detected 15 days after the crosslinking treatment and continued to be present. However, 180 days after the crosslinking treatment, collagen type 3 could not be found in the crosslinked corneas. CONCLUSIONS: These findings suggest that ultraviolet A/riboflavin crosslinking results in collagen type 3 synthesis and degradation, which may offer at least a partial explanation for the formation of corneal haze.

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.

Clinical observation of transepithelial corneal collagen cross-linking by lontophoresis of riboflavin in treatment of keratoconus.

PURPOSE: To evaluate the efficacy and safety of transepithelial collagen cross-linking by iontophoretic delivery of riboflavin in treatment of progressive keratoconus. METHODS: Eleven patients (15 eyes) with progressive keratoconus were enrolled. After 0.1% riboflavin-distilled water solution was deliveried via transepithelial iontophpresis for 5 min with 1 mA current, and ultraviolet radiation (370 nm, 3 mW/cm2) was performed at a 1.5 cm distance for 30 min. The follow up were 6 months in all eyes. The uncorrected visual acuity, corrected visual acuity, endothelial cell counting, corneal thickness, intraocular pressure, corneal curvature, corneal topography, OCT and corneal opacity before and 6-month after surgery were analyzed. RESULTS: At 6 month postoperatively, mean uncorrected visual acuity and corrected visual acuity changed from 0.36 to 0.30 and from 0.42 to 0.57 without statistical significance. The mean value of each index of corneal curvature declined without statistical significance.Kmax value dereased from 60.91 to 59.91, and the astigmatism declined from 3.86 to 3.19. Central corneal thickness decreased from 460.93 µm to 455.40 µm, and thinnest corneal thickness declined from 450.87 µm to 440.60 µm with no statistical significance. Intraocular pressure was significantly elevated from 10.85 mmHg to 12.62 mmHg. Endothelial cell count did not change significantly. No corneal haze occurred. Mean depth of corneal demarcation line was 288.46 µm at 1 month postoperatively. CONCLUSION: Transepithelial corneal collagen cross-linking by iontophoresis is effective and safe in the treatment of progressive keratoconus, and yields stable clinical outcomes during 6-month follow up. However, long-term follow up is urgently required.

New techniques to improve classical corneal collagen cross-linking treatment.

OBJECTIVE: The aim of this review is to comprehensively and unbiasedly summarize the improvements in the techniques for classical corneal collagen cross-linking (CXL) by covering the reasons for this improvement, measure, and effect to approach the future direction of the CXL. DATA SOURCES: All articles used in this review were mainly retrieved from the PubMed database. STUDY SELECTION: Original articles and reviews were selected if they were related to the improvement in the technique of classical CXL. Data were mainly extracted from 94 articles, which are listed in the reference section of this review. RESULTS: This innovative research involves every step such as instrument preparation, epithelial management, riboflavin instillation, and UVA irradiation. These clinical and experimental results seem promising. CONCLUSIONS: CXL treatment is the only recent promising method for preventing the progress of keratoconus. The limitations and potential complications that accompany classical CXL such as corneal thickness limitations, ultraviolet-A (UVA) light injury, and the impact of de-epithelialization encourage people to research new improvements in techniques. While this research needs to be further investigated, we hope our review can help related researchers and patients.

Comparison of central corneal thickness using ultrasound pachymetry during corneal collagen cross-linking.

PURPOSE: To study variation in central corneal thickness (CCT) during corneal collagen cross-linking(CXL) using ultrasound pachymetry. METHODS: Twenty patients (26 eyes) with progressing keratoconus undergoing riboflavin-UVA-induced CXL were involved in this study. Intraoperative CCT measurement using ultrasonic pachymetry was performed during the procedure. Measurements were obtained before operation, after epithelial removal, after riboflavin drop instillation, and after UVA irradiation. RESULTS: Mean CCT was 495 +/- 56 and 450 +/- 52 microm before and after epithelial removal, respectively. Mean CCT was 443 +/- 42 and 411 +/- 39 microm after riboflavin drop instillation and after UVA irradiation, respectively. Statistically significant decreases in CCT occurred between the preoperative period and after epithelial removal, after riboflavin drop instillation and after UVA irradiation. Twenty-six eyes from 20 patients undergoing CXL were divided into 2 groups (I with CCT > or = 400 microm after UVA irradiation and II with CCT < 400 microm after UVA irradiation). No statistically significant difference was noted between I and II in preoperative endothelial cell count, but a statistically greater postoperative endothelial cell count was noted in I compared to II. A statistically significant difference was evident between preoperative and postoperative endothelial cell counts in Group II (P < 0.05). CONCLUSION: Performing CXL with the use of riboflavin and UVA irradiation resulted in a statistically significant decrease in CCT, to a level where the corneal endothelium may be damaged.