flavin-mononucleotide and Keratoconus

We were able to show a significant increase in corneal stiffness of rabbit and porcine eyes after combined riboflavin/UVA-induced collagen cross-linking. In this study,we tried to treat keratoconus patients with this method to stop the progression of corneal ectasia.. We treated 16 eyes of 15 patients with progressive keratoconus and mostly moderate keratectasia (48-56 dpt). After removal of the epithelium (7 mm X), riboflavin solution was applied on the cornea, which was irradiated with UVA (370 nm,3 mW/cm(2)) at a distance of 1 cm for 30 min.Post-operative follow-up controls were conducted every 3 months in the first year and then every 6 months, always including visual acuity testing, corneal topography and measurements of endothelial cell density. The follow-up time was between 1 and 3 years.. Progression of keratectasia was stopped in all patients. Best corrected visual acuity and the maximal keratometry values improved slightly in about 50% of the cases. In all patients corneal transparency, the degree of keratectasia registered by corneal topography and the density of endothelial cells remained unchanged within the follow-up time. No negative side-effects were observed.. Our results show that collagen cross linking might be a useful conservative treatment modality to stop the progression of keratoconus. By this means the need for keratoplasty might be significantly reduced. Given the simplicity of the technique and minimal costs of the treatment it might also be well suited for developing countries.Further studies are envisaged to exclude long-term side effects and to evaluate the long term durability of the mechanical stiffness effect.

Topics: Adolescent; Adult; Animals; Cell Count; Collagen; Corneal Topography; Cross-Linking Reagents; Endothelium, Corneal; Female; Flavin Mononucleotide; Follow-Up Studies; Humans; Keratoconus; Male; Middle Aged; Photochemotherapy; Swine; Visual Acuity

Microemulsions are widely studied as potential ocular drug delivery vehicles. In the present study we show the versatility of possible use microemulsions as ocular delivery vehicle. The ME is loaded with a hydrophilic drug, riboflavin phosphate (RFP) and a lipophilic, docosahexaenoic acid in triglyceride form (TG-DHA), each separately. These drugs treat keratoconus and dry eye syndrome, respectively. The advantage of using ME loaded with RFP is in overcoming eye epithelium debridement during collagen cross-linking therapy for treatment of keratoconus. ME loaded with lipophilic TG-DHA provides convenient dosage in liquid aqueous form of administration of highly lipophilic TG-DHA, which is known as a protective molecule in dry eye syndrome. The capability of RFP-loaded MEs was demonstrated in terms of improvement of biomechanical strength of the rabbit cornea, as a result of successful penetration of RFP through the intact epithelium. TG-DHA-loaded microemulsion applied topically onto an eye with induced dry eye syndrome showed the significant relief of the dry eye condition.

Topics: Animals; Biomechanical Phenomena; Collagen; Disease Models, Animal; Docosahexaenoic Acids; Drug Delivery Systems; Dry Eye Syndromes; Emulsions; Epithelium, Corneal; Flavin Mononucleotide; Humans; Hydrophobic and Hydrophilic Interactions; Keratoconus; Male; Permeability; Rabbits; Triglycerides; Ultraviolet Rays

Keratoconus is a progressive condition caused by the thinning of the cornea, which eventually deforms the front surface of the eye into a cone shape leading to ghosting, multiple images, glare, and several other vision problems. Currently, keratoconus is treated with UV-induced riboflavin (Rb)-mediated collagen cross-linking, which requires a physical removal of the corneal epithelium under topical anesthesia. This study reports the penetration of Rb and its more water-soluble form, riboflavin-5'-monophosphate (RbP), into the bovine cornea ex vivo. Using ex vivo bovine corneal tissues and 0.8 mg/mL drug solutions in phosphate buffer, it was established that RbP penetration into the cornea within 3 h of diffusion experiment was greater (17.3 ± 0.8 μg) compared with Rb (10.4 ± 4.2 μg). In the cornea, RbP was found to convert to Rb, which is mediated with enzymes present in this tissue. Several formulations including the conventional and propylene glycol-containing liposomes with encapsulated RbP have been developed, and their effect on the drug penetration into the bovine cornea was evaluated. Encapsulation of RbP into the liposomes did not provide any statistically significant improvement in the penetration of RbP into the cornea.

Topics: Animals; Cattle; Cornea; Cross-Linking Reagents; Epithelium, Corneal; Flavin Mononucleotide; Keratoconus; Liposomes; Ultraviolet Rays

Corneal collagen cross-linking (CXL) has been described as a promising therapy for keratoconus. According to standard CXL protocol, epithelium should be debrided before treatment to allow penetration of riboflavin into the corneal stroma. However, removal of the epithelium can increase procedure risks. In this study we aim to evaluate stromal penetration of a biocompatible riboflavin-based nanoemulsion system (riboflavin-5-phosphate and riboflavin-base) in rabbit corneas with intact epithelium. Two riboflavin nanoemulsions were developed. Transmittance and absorption coefficient were measured on corneas with intact epithelia after 30, 60, 120, 180, and 240 minutes following exposure to either the nanoemulsions or standard 0.1% or 1% riboflavin-dextran solutions. For the nanoemulsions, the epithelium was removed after measurements to assure that the riboflavin had passed through the hydrophobic epithelium and retained within the stroma. Results were compared to de-epithelialized corneas exposed to 0.1% riboflavin solution and to the same riboflavin nanoemulsions for 30 minutes (standard protocol). Mean transmittance and absorption measured in epithelialized corneas receiving the standard 0.1% riboflavin solution did not reach the levels found on the debrided corneas using the standard technique. Neither increasing the time of exposure nor the concentration of the riboflavin solution from 0.1% to 1% improved riboflavin penetration through the epithelium. When using riboflavin-5-phosphate nanoemulsion for 240 minutes, we found no difference between the mean absorption coefficients to the standard cross-linking protocol (p = 0.54). Riboflavin nanoemulsion was able to penetrate the corneal epithelium, achieving, after 240 minutes, greater stromal concentration when compared to debrided corneas with the standard protocol (p = 0.002). The riboflavin-5-phosphate nanoemulsion diffused better into the stroma than the riboflavin-base nanoemulsion.

Topics: Absorption; Animals; Collagen; Cornea; Drug Stability; Emulsions; Epithelium, Corneal; Flavin Mononucleotide; Keratoconus; Nanostructures; Rabbits; Riboflavin; Time Factors

This work shows a retrospective evaluation of the patients with progressive keratoconus, stadium I, II, III, to which corneal collagen cross-linking was performed to stop the evolution. The patients were monitored by refraction, visual acuity, keratometry, pachimetry and topography. In all cases it was noticed an improvement or the maintenance of the followed parameters.

Topics: Adolescent; Adult; Collagen; Corneal Topography; Cross-Linking Reagents; Endothelium, Corneal; Female; Flavin Mononucleotide; Follow-Up Studies; Humans; Keratoconus; Male; Photochemotherapy; Retrospective Studies; Visual Acuity; Vitamin B Complex

To evaluate the efficacy of transepithelial cross-linking (CXL) in keratoconic eyes after Intacs implantation.. Twenty-five eyes of 17 patients with bilateral keratoconus underwent Intacs implantation with subsequent cross-linking (CXL) treatment. Inclusion criteria were absence of corneal scarring, contact lens intolerance, corneal thickness higher than 400 mum, and endothelial cell density more than 3000 per square millimeter. Preoperative and 3-month-postoperative uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), manifest refractions, and mean and steepest keratometric (K) values were reviewed retrospectively. The results in Intacs group were compared with those obtained after CXL/Intacs.. There were 10 males and 5 females; mean age was 25.14 +/- 7.11 (range 16-39) years old. Mean time between implantation of Intacs and CXL was 3.98 months. CXL after Intacs resulted in an additional improvement in UCVA, BCVA, sphere, cylinder, and keratometry. Intacs resulted in an improvement of 1.9 Snellen lines (P < 0.05) of UCVA and 1.7 Snellen lines (P < 0.05) of BCVA. CXL performed after Intacs treatment yielded an additional 1.2 Snellen lines (P < 0.05) of UCVA and 0.36 Snellen lines (P < 0.05) of BCVA. The decrease in spherical, cylindrical, mean K, and steepest K values was 2.08 diopters (D) (P < 0.05), 0.47 D (P > 0.05), 2.22 D (P < 0.05), and 1.27 D (P < 0.05), respectively, after Intacs treatment with an additional 0.5 D (P < 0.05), 0.15 D (P > 0.05), 0.35 D (P > 0.05), and 0.76 D (P < 0.05) of improvement gained after CXL in each respective parameter.. Intacs implantation with transepithelial CXL is effective in eyes with keratoconus. Collagen cross-linking has an additive effect on Intacs implantation in these eyes and may be considered as an enhancement/stabilizing procedure.

Topics: Adolescent; Adult; Cell Count; Collagen; Corneal Stroma; Corneal Topography; Endothelium, Corneal; Epithelium, Corneal; Female; Flavin Mononucleotide; Humans; Keratoconus; Male; Photochemotherapy; Photosensitizing Agents; Prostheses and Implants; Prosthesis Implantation; Refraction, Ocular; Retreatment; Retrospective Studies; Treatment Outcome; Ultraviolet Rays; Visual Acuity; Young Adult

This work shows four cases with progressive keratoconus to which corneal collagen crosslinking was performed one year ago. It was followed the clinical, functional pachymetric and topographic evolution. It was observed an increased corneal thickness, the reduction of the maximum keratometric values. These aspects are better evidenced for the incipient stadium.

Topics: Adolescent; Adult; Collagen; Corneal Topography; Cross-Linking Reagents; Drug Therapy, Combination; Endothelium, Corneal; Female; Flavin Mononucleotide; Humans; Keratoconus; Male; Photochemotherapy; Treatment Outcome; Visual Acuity; Vitamin B Complex

To analyze anterior corneal elevation changes on Orbscan II following corneal collagen cross-linking (CXL) with riboflavin.. This retrospective study included 8 patients (14 eyes) with keratoconus who underwent CXL, with a mean follow-up of 7 months (range: 5 to 10 months). Pre- and postoperative (at last clinic attendance) anterior elevation difference maps were examined for overall patterns of change. On preoperative maps, distances from maximum anterior elevation to pupil center and to topographic geometric center were compared between the two patterns identified. Pre- and postoperative topography, best spectacle-corrected visual acuity (BSCVA), and refraction were also compared between the two patterns.. Two patterns of anterior elevation change were visually identified: (1) paracentral steepening, no change, or flattening centrally; and (2) central steepening. The preoperative maps of eyes that manifested pattern 1 had shorter mean distances for maximum anterior elevation to pupil center (1.70 vs. 2.27 mm) and maximum anterior elevation to geometric center (1.45 vs. 1.99 mm) than those that resulted in pattern 2. Mean maximum topographic simulated keratometry decreased (P = .004) and mean irregularity indices at 3 mm (P =.03) and 5 mm (P =.04) were reduced postoperatively in pattern 1 eyes; all increased in pattern 2 eyes. Mean BSCVA improved postoperatively for both patterns. Mean preoperative myopia decreased in pattern 1 eyes by 0.44 diopters (D), whereas it increased for pattern 2 eyes by 1.83 D.. Corneal shape change influenced by anisotropy of collagen distribution is a factor in the outcome of CXL treatment for keratoconus.

Topics: Adolescent; Adult; Collagen; Cornea; Corneal Stroma; Corneal Topography; Female; Flavin Mononucleotide; Humans; Keratoconus; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Refraction, Ocular; Retrospective Studies; Ultraviolet Rays; Visual Acuity; Young Adult

To determine whether corneal collagen cross-linking with riboflavin (C3-R) augments the effect of inferior-segment Intacs (Addition Technology) in the treatment of keratoconus.. Private practice, Beverly Hills, California, USA.. A retrospective nonrandomized comparative case series comprised 12 eyes of 9 patients who had inferior-segment Intacs placement without C3-R (Intacs-only group) and 13 eyes of 12 patients who had inferior-segment Intacs placement combined with C3-R (Intacs with C3-R group). The 2 groups were matched preoperatively. All patients had inferior-segment Intacs placed with the incision in the steep axis of manifest refraction. Corneal collagen cross-linking with riboflavin was performed after the Intacs segments were inserted. Outcome measures were topographic keratometry values and the lower-upper (L-U) ratio, which is a topographic measure of the degree of keratoconus. Preoperative data were compared to results 1 day postoperatively and measurements at the last postoperative visit.. The Intacs with C3-R group had a significantly greater reduction in cylinder than the Intacs-only group (P<.05). Steep and average keratometry were reduced significantly more in the Intacs with C3-R group (P<.05). There was a greater reduction in L-U ratio in the Intacs with C3-R group (P<.05).. The addition of C3-R to the Intacs procedure resulted in greater keratoconus improvements than Intacs insertion alone.

Topics: Adult; Collagen; Combined Modality Therapy; Corneal Stroma; Corneal Topography; Cross-Linking Reagents; Female; Flavin Mononucleotide; Humans; Keratoconus; Male; Polymethyl Methacrylate; Prostheses and Implants; Prosthesis Implantation; Retrospective Studies; Treatment Outcome; Ultraviolet Rays; Visual Acuity