Clinical Observation of Transepithelial Corneal Collagen Cross-linking by Iontophoresis 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 m A current, and ultraviolet radiation(370 nm,.3 m W /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 to59.91, and the astigmatism declined from 3.86 to 3.19. Central corneal thickness decreased from 460.93 μm to 455.40μm,.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 mm Hg to 12.62 mm Hg. 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.

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.

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 >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.

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 β-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.

Variation in Central Corneal Thickness during Open- or Closed-Eye Riboflavin Instillation for Corneal Collagen Cross-linking

Purpose:To assess the effect of having an open or closed eye on the variation in central corneal thickness during riboflavin instillation for corneal collagen cross-linking (CXL).Methods:.Thirty eyes of 15 New Zealand White rabbits underwent an in vivo anterior segment optical coherence tomography (OCT) examination at 0,10,20,and 30 min after riboflavin instillation on the de-epithelialized corneal surface.Each eye of every rabbit was randomly placed into one of two different treatment groups(open-eye or closed-eye)during the instillation;.the examinations were performed one after the other.After instillation for 30 min,the changes in the corneal stroma and anterior chamber were observed by slit lamp.Results:.A significant decrease in the central corneal thickness(CCT).was demonstrated during riboflavin instillation;.the variations were smaller in the measurements performed with the eye closed than with the eye open.(81.36±15.13μm and129.20±12.05μm respectively)..Both methods turned the corneal stroma and anterior chamber yellow.Conclusion:Keeping the eye closed during riboflavin instillation reduced the decrease in the CCT..The same yellow change in the corneal stroma and anterior chamber occurred,but the exposure time of the ocular surface was shorter.Therefore,.keeping the eye closed was a more effective and safer method than keeping the eye open.

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 μm before and after epithelial removal, respectively. Mean CCT was 443±42 and 411±39 μm 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≥400 μm after UVA irradiation and II with CCT<400 μm 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.(Eye Science 2013; 28:15-19)

A histological examination of corneal epithelium after iontophoresis with different riboflavin solutions

To the Editor:Currently,from a pathological point of view,corneal collagen crosslinking(CXL)with riboflavin is the only new therapy for controlling keratoconus progression.Riboflavin,as a photosensitizer,can be activated after the ultraviolet radiation in the cornea and prevent it from damaging intraocular organizations.Therefore,the concentration of riboflavin in the corneal stroma must be maintained at a sufficient level during the treatment.[1]Riboflavin,a type of water-soluble macromolecule,is resistant to permeating the corneal epithelial barrier.Thus,de-epithelial eye-dripping was adopted conventionally with complications such as inevitable pain,long recovery time,potential risk of infection,and so on;transepithelial corneal CXL is increasingly becoming a research hotspot.It is thus critically important to improve the transepithelial penetration of riboflavin.Although iontophoresis was reported,it had a slightly higher effect with no clear mechanism analysis.[2,3,4]Corneal epithelium is lipophilic and hydrophobic,and hydrophilic drugs enter corneal stroma via intercellular pathways.In this study,permeability effects of riboflavin in different solvents into the cornea via iontophoresis were compared,and the changes of corneal epithelial cell layer organizations were analyzed to examine the solvent components that are most beneficial to iontophoresis and investigate the underlying mechanism of the penetration effect.