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Safety and efficacy of riboflavin-assisted collagen cross-linking of cornea in progressive keratoconus patients: A prospective study in North East India.
Bhattacharyya, A, Sarma, P, Das, K, Agarwal, B, Medhi, J, Das Mohapatra, SS
Indian journal of pharmacology. 2019;(3):157-167
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Abstract
INTRODUCTION Riboflavin- and ultraviolet (UV)-A-mediated collagen cross-linking of the cornea is a frequently used therapeutic measure for the treatment of progressive keratoconus (PK). First, riboflavin increases cross-linking and second, it serves as a protective shield to other deep ocular structures. However, pharmacogenomic variation in riboflavin efficacy is reported. As the Northeast Indian population represents a genetically diverse group of population compared to mainstream India, we have assessed the efficacy of the procedure in a northeastern population with PK. METHODS In this study, 78 eyes with PK were included (n = 39 in the treatment arm and n = 39 in the control arm). The primary objective was to evaluate the effect of corneal collagen cross-linking using riboflavin (C3R) (epithelium off) on maximum keratometry. The secondary objectives were evaluation of change in corneal topography parameters, i.e., minimum keratometry (Kmin), simulated keratometry (Sim K), subjective refraction (cylinder power, spherical power, and spherical equivalent [SE]), uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), and contrast sensitivity (CS) and safety (intraocular pressure, endothelial cell density, and percentage hexagonality) at 1, 3, and 6 months following C3R procedure. RESULTS Statistically significant improvement was noted in Kmin (6 months), Sim K (3 and 6 months), cylinder power (3 and 6 months), spherical power (3 and 6 months), SE (3 and 6 months), BCVA (6 months), and UCVA (1, 6 months) in the C3R group (n = 39) when compared to the control group (n = 39). The mean CS decreased at 1 month and gradually improved to achieve statistically significant value at 6 months in the C3R group (P < 0.05). CONCLUSION Riboflavin-assisted C3R treatment showed promising efficacy in the treatment of PK patients in our population. As the collagen turnover rate of cornea is 2-3 years and the progression of PK is highly variable, we need long-term studies to evaluate the efficacy of C3R over time, requirement of repeat therapy, and safety of repeat cross-linking.
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Morphological and functional correlations in riboflavin UV A corneal collagen cross-linking for keratoconus.
Mazzotta, C, Caporossi, T, Denaro, R, Bovone, C, Sparano, C, Paradiso, A, Baiocchi, S, Caporossi, A
Acta ophthalmologica. 2012;(3):259-65
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PURPOSE To investigate the correlations between corneal structural modifications assessed by in vivo corneal confocal microscopy with visual function [uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA)] and morphological data (corneal topography, pachymetry, elevation analysis) after riboflavin UV A corneal collagen cross-linking (CXL) for the stabilization of progressive keratoconus. METHODS Forty-four eyes with progressive keratoconus were enrolled in the Siena Eye Cross Study (prospective nonrandomized phase II open trial). All eyes underwent Riboflavin UV A CXL. Preoperative and postoperative evaluation comprised: UCVA, BSCVA, optical pachymetry (Visante OCT, Zeiss, Germany), corneal topography (CSO, Florence, Italy) and tomography (Orbscan IIz; B&L, Rochester, NY, USA) and in vivo confocal microscopy (Heidelberg Retina Tomograph II; Rostock, Heidelberg Gmbh, Germany). Examinations were performed preoperatively 6 months and one day before treatment and at 1, 3, 6 and 12 months of follow-up. RESULTS In vivo corneal confocal microscopy showed time-dependent postoperative epithelial and stromal modifications after cross-linking. Epithelial thinning associated with stromal oedema and keratocytes apoptosis explained initial tendency towards slightly reduced VA and more glare one month postoperatively in 70% of eyes. Furthermore, a statistically not significant early worsening of topographic mean K values was observed. Orbscan II analysis significantly underestimated pachymetric values after treatment. Pachymetric underestimation was rectified by high-resolution optical pachymetry provided by the Visante OCT system. After the third post-CXL month, epithelial thickening, disappearance of oedema and new collagen compaction recorded by in vivo corneal confocal microscopy explained the improvements in visual performance during the follow-up. Changes in stromal reflectivity and collagen compaction observed by in vivo confocal microscopy were associated with corneal flattening and reduction in anterior elevation values recorded by differential topographic analysis. CONCLUSION Corneal structural changes assessed by in vivo corneal confocal microscopy demonstrated significant correlations with visual function (UCVA and BSCVA) and morphological (corneal topography, pachymetry, elevation analysis) findings recorded after riboflavin-UV A-induced CXL.
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Clinical and corneal biomechanical changes after collagen cross-linking with riboflavin and UV irradiation in patients with progressive keratoconus: results after 2 years of follow-up.
Goldich, Y, Marcovich, AL, Barkana, Y, Mandel, Y, Hirsh, A, Morad, Y, Avni, I, Zadok, D
Cornea. 2012;(6):609-14
Abstract
PURPOSE To assess the biomechanical and keratometric effects and the safety of treatment of progressive keratoconus with UV-riboflavin collagen cross-linking (CXL). METHODS This is a prospective clinical controlled study. Fourteen eyes of 14 patients with progressive keratoconus were treated with CXL after corneal deepithelization. Patients were assessed preoperatively, at week 1 and at months 1, 3, 6, 9, 12, and 24 after treatment. We measured uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA) (logarithm of the minimum angle of resolution), refraction, biomicroscopy and fundus examination, intraocular pressure, axial length, endothelial cell density, corneal topography, minimal corneal thickness, macular optical coherence tomography, and corneal biomechanics with the ocular response analyzer. RESULTS Comparing the preoperative results with 24-month postoperative results, we observed significant improvement in BCVA (0.21 ± 0.1 to 0.14 ± 0.1, P = 0.002) and stability in UCVA (0.62 ± 0.5 and 0.81 ± 0.49, P = 0.475). We observed a significant decrease in steepest-meridian keratometry (diopters) (53.9 ± 5.9 to 51.5 ± 5.4, P = 0.001) and in mean cylinder (diopters) (10.2 ± 4.1 to 8.1 ± 3.4, P = 0.001). Significant elongation of the eyes was observed, from 24.39 ± 1.7 mm to 24.71 ± 1.9 mm (P = 0.007). No significant change was observed in mean simulated keratometry, minimal corneal thickness, endothelial cell density, corneal hysteresis, and corneal resistance factor or foveal thickness. CONCLUSIONS Two years after CXL, the observation of stable UCVA, improved BCVA, and reduced keratometry suggests stabilization in progression of keratoconus. Unchanged corneal thickness, endothelial cell density, and foveal thickness suggest the long-term safety of this procedure. The observed increase in axial length and stability in corneal biomechanical parameters measured with the ocular response analyzer require further study for verification and explanation.
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Effect of riboflavin status on the homocysteine-lowering effect of folate in relation to the MTHFR (C677T) genotype.
Moat, SJ, Ashfield-Watt, PA, Powers, HJ, Newcombe, RG, McDowell, IF
Clinical chemistry. 2003;(2):295-302
Abstract
BACKGROUND Riboflavin (vitamin B(2)) is the precursor for FAD, the cofactor for methylenetetrahydrofolate reductase (MTHFR). MTHFR catalyzes the formation of 5-methyltetrahydrofolate, which acts as a methyl donor for homocysteine remethylation. Individuals with the MTHFR 677C-->T mutation have increased plasma total homocysteine (tHcy) concentrations, particularly in association with low folate status. It has been proposed that riboflavin may act together with folate to lower plasma tHcy, particularly in individuals with the thermolabile MTHFR T variant. METHODS We measured B-vitamin status and plasma tHcy in 126 healthy individuals 20-63 years of age (42 CC, 42 CT, and 42 TT MTHFR genotypes) at baseline and after three interventions (4 months): placebo plus natural diet; daily 400 microg folic acid supplement plus natural diet; and increased dietary folate to 400 microg/day. RESULTS At baseline and after nutritional intervention, lower riboflavin status was associated with increased plasma tHcy concentrations. Plasma tHcy was 2.6 micromol/L higher in the lowest plasma riboflavin quartile compared with the highest (P <0.02) and was 4.2 micromol/L higher in the highest erythrocyte glutathione reductase activation coefficient (EGRAC) quartile compared with the lowest (P <0.001). This effect was not restricted to those with the T allele. Folic acid given as a 400 microg/day supplement appeared to exacerbate a tendency toward riboflavin deficiency, as suggested by an increase in the proportion of individuals with EGRAC > or =1.4 from 52% to 65% after supplementation (P <0.05). CONCLUSIONS Folate and riboflavin interact to lower plasma tHcy, possibly by maximizing the catalytic activity of MTHFR. The effect may be unrelated to MTHFR genotype.