The Effect of Sodium Iodide on Stromal Loading, Distribution and Degradation of Riboflavin in a Rabbit Model of Transepithelial Corneal Crosslinking

Abstract

Purpose: To evaluate effects of sodium iodide (NaI) on riboflavin concentration in corneal stroma before and during ultraviolet A (UVA) light exposure using a novel transepithelial corneal collagen crosslinking (CXL) procedure (EpiSmart CXL system, CXL Ophthalmics, Encinitas CA). Methods: Riboflavin solutions with NaI (Ribostat, CXL Ophthalmics, Encinitas CA) and without NaI were used for CXL in rabbits using EpiSmart. A pilot study determined sufficient riboflavin loading time. Four rabbits were dosed and monitored. Riboflavin fluorescence intensity was assessed from masked slit-lamp photos. A 12 min loading time was selected. Sixteen additional rabbits received the two formulae in contralateral eyes for CXL. Riboflavin uptake was assessed at 0, 10, 15, 20, 25, and 30 min of UVA exposure using a scale for riboflavin fluorescence previously validated against stromal concentration. Post sacrifice, corneal stromal samples were analyzed for concentrations of riboflavin and riboflavin 5ʹ-phosphate. Results: Eyes dosed with NaI riboflavin had higher riboflavin grades compared to eyes dosed with the NaI-free riboflavin formulation immediately after riboflavin loading and persisting throughout UVA exposure, with significantly higher (P < 0.01 to < 0.05) riboflavin grades from 15 through 25 min of UVA exposure. Riboflavin grades decreased more slowly in eyes dosed with NaI riboflavin through 25 minutes of UVA exposure. Minor conjunctival irritation was noted with or without NaI. Conclusion:The addition of NaI to riboflavin solution is associated with increased riboflavin concentration in corneal stroma throughout a clinically relevant time course of UVA exposure. This effect may be a combination of enhanced epithelial penetration and reduced riboflavin photodegradation and should enhance intrastromal crosslinking.

Pachymetric Assessment After EpiSmart® Epithelium-on Cross-Linking for Keratoconus and Post-Surgical Ectasia

“… 22 It was also confirmed in vivo that the riboflavin solution containing iodide promotes persistence of riboflavin throughout UVA exposure. 21 A previous report of clinical application demonstrated significant improvements in visual acuity and corneal topography with a low rate of adverse events. 16 …”

“…The epithelium-on treatment protocol has been described in previous publications. 16 , 20 , 21 Corneal anesthesia was obtained with 2–3 drops of topical proparacaine (0.5%, Alcon Laboratories, Fort Worth TX). At the slit lamp, a proprietary, non-disruptive sponge wand (EpiPrep ® CXL Ophthalmics, Encinitas, CA) was used to modify surface lipids in the tear film.…”

“…The patient was then reclined, and a second proprietary round loading sponge (CXL Ophthalmics, Encinitas CA) was placed on the cornea to serve as a reservoir for the fixed drug combination Riboflavin and sodium iodide (RiboStat ® ; CXL Ophthalmics, Encinitas, CA). 16 , 20 , 21 …”

EpiSmart Crosslinking for Keratoconus: A Phase 2 Study

“…Subjects were treated with the EpiSmart system (CXL Ophthalmics, LLC), comprising ophthalmic sponges for the preparation of the cornea and drug delivery (EpiPrep; CXL Ophthalmics), 10 , 18 riboflavin 5′-phosphate and sodium iodide (0.5%/0.015%) ophthalmic solution (RiboStat; CXL Ophthalmics), 18 , 19 and an ultraviolet-A illuminator (CXL Ophthalmics) that delivers ultraviolet light (365 nm wavelength) in a 12-mm diameter circular pattern onto the corneas in 15-second on/15-second off cycles. 10 , 18 , 19 The technique was as previously described by Stulting et al 10 Proparacaine anesthetic was instilled in the eye(s) immediately before treatment. The sterile ophthalmic sponge wand was hydrated with proparacaine solution and used to remove lipids, mucus, and any other debris from the surface of the cornea without disruption of the epithelium.…”

“…[15][16][17] The EpiSmart epi-on crosslinking procedure (CXL Ophthalmics, Encinitas, CA) has been shown in animal models to obtain adequate stromal riboflavin levels across an intact epithelium 18 and to maintain a sustained riboflavin concentration without supplemental riboflavin drops throughout ultraviolet-A (UVA) exposure. 19 Stulting et al 10 reported on 308 patients with keratoconus treated with EpiSmart who showed improvements in vision and improvements in keratometric end points, each sustained over 24 months. This same report also demonstrated significant improvement in coma which can account for some of the significant visual improvements seen.…”