PHOTREXA® VISCOUS and PHOTREXA® are indicated for use in corneal collagen cross-linking in combination with the KXL™ System for the treatment of

Using topical anesthesia, debride the epithelium to a diameter of approximately 9 mm using standard aseptic technique. Post epithelial debridement, instill 1 drop of PHOTREXA VISCOUS topically on the eye every 2 minutes for 30 minutes.

At the end of the 30 minute soaking period, examine the eye under the slit lamp for the presence of a yellow flare in the anterior chamber. If the yellow flare is not detected, instill 1 drop of PHOTREXA VISCOUS every 2 minutes for an additional 2 to 3 drops and recheck for the presence of a yellow flare. This process can be repeated as necessary.

Once the yellow flare is observed, perform ultrasound pachymetry. If corneal thickness is less than 400 microns, instill 2 drops of PHOTREXA every 5 to 10 seconds until the corneal thickness increases to at least 400 microns. Irradiation should not be performed unless this 400 micron threshold is met and the yellow flare is seen.

Irradiate the eye for 30 continuous minutes at 3mW/cm2 at a wavelength of 365 nm, centered over the cornea, using the KXL System as per the instructions in the KXL manual. During irradiation, continue topical instillation of PHOTREXA VISCOUS onto the eye every 2 minutes for the 30 minute irradiation period.

For topical ophthalmic use. Do not inject.

Single use PHOTREXA VISCOUS and PHOTREXA only. Discard syringe(s) after use.

PHOTREXA VISCOUS and PHOTREXA are for use with the KXL System only.

PLEASE REFER TO THE KXL OPERATOR’S MANUAL FOR SPECIFIC DEVICE INSTRUCTIONS.

None.

Ulcerative keratitis can occur. Monitor for resolution of epithelial defects. [See Adverse Reactions (6)].

The following clinically significant adverse reactions are described elsewhere in the labeling:

Ulcerative keratitis [Warnings and Precautions (5)]

PHOTREXA VISCOUS (riboflavin 5’-phosphate in 20% dextran ophthalmic solution) 0.146% and PHOTREXA (riboflavin 5’-phosphate ophthalmic solution) 0.146% are intended for topical ophthalmic administration as part of corneal collagen cross-linking with the KXL System.

PHOTREXA VISCOUS and PHOTREXA are supplied as:

• PHOTREXA VISCOUS in a 3 mL glass syringe containing sterile 1.56 mg/mL riboflavin 5’-phosphate in 20% dextran ophthalmic solution for topical administration.
• PHOTREXA in a 3 mL glass syringe containing sterile 1.46 mg/mL riboflavin 5’-phosphate ophthalmic solution for topical administration.

PHOTREXA VISCOUS (riboflavin 5’-phosphate in 20% dextran ophthalmic solution) 0.146% is a yellow sterile buffered viscous solution containing 1.56 mg/mL riboflavin 5’-phosphate and 20% dextran 500. The pH of the solution is approximately 7.1 and the osmolality is 284-368 mOsm/kg. Each 1 mL of solution contains 1.64 mg of riboflavin 5’-phosphate sodium (equivalent to 1.284 mg riboflavin). Riboflavin 5’-phosphate sodium USP is a mixture of the sodium salts of riboflavin, riboflavin monophosphates, and riboflavin diphosphates. The inactive ingredients are dibasic sodium phosphate, dextran, monobasic sodium phosphate, sodium chloride, and water for injection.

PHOTREXA (riboflavin 5’-phosphate ophthalmic solution) 0.146% is a yellow sterile buffered solution containing 1.46 mg/mL riboflavin 5’-phosphate. The pH of the solution is approximately 7.1 and the osmolality is 157-181 mOsm/kg. Each 1 mL of solution contains 1.53 mg of riboflavin 5’-phosphate sodium (equivalent to 1.20 mg riboflavin). Riboflavin 5’-phosphate sodium USP is a mixture of the sodium salts of riboflavin, riboflavin monophosphates, and riboflavin diphosphates. The inactive ingredients are dibasic sodium phosphate, monobasic sodium phosphate, sodium chloride, and water for injection.

The chemical formula for riboflavin 5’-phosphate sodium (Vitamin B2) is C17H20N4NaO9P with a molecular mass of 478.33 g/mol.

Please refer to the KXL System Operator’s Manual for a specific device description and instructions.

Three prospective, randomized, parallel-group, open-label, sham-controlled trials were conducted to evaluate the safety and effectiveness of riboflavin ophthalmic solution/UVA irradiation for performing corneal collagen cross-linking. These trials were sham-controlled for the first 3 months and had a total duration of 12 months for safety and efficacy evaluations. Study 1 enrolled 58 patients with progressive keratoconus and 49 patients with corneal ectasia following refractive surgery. Study 2 enrolled 147 patients with progressive keratoconus, and Study 3 enrolled 130 patients with corneal ectasia following refractive surgery. In each study, patients had one eye designated as the study eye and were randomized to receive one of two study treatments (CXL or sham) in their study eye at the baseline visit. The patients were evaluated at Day 1, Week 1, and Months 1, 3, 6, and 12. At Month 3 or later, patients had the option of receiving CXL treatment in both the sham study eyes and non-study eyes and were followed-up for 12 months from the time of receiving CXL treatment.

Approximately 56% and 89% of the sham study eyes in patients with progressive keratoconus received CXL treatment by Month 3 and Month 6, respectively. The average age of keratoconus patients was 33 years. The average baseline Kmax value was 61 diopters. For corneal ectasia patients in Study 1 and Study 3, approximately 60% and 90% of the sham study eyes received CXL treatment by Month 3 and Month 6, respectively. The average age of corneal ectasia patients was 43 years and the average baseline Kmax was 55 diopters. A majority (93%) of the corneal ectasia patients had LASIK only, 5 (3%) patients had photorefractive keratectomy (PRK) only, and 8 (4%) patients had both LASIK and PRK.

In each study, the maximum corneal curvature (Kmax) was assessed at baseline, Months 1, 3, and 12. The CXL-treated eyes showed increasing improvement in Kmax from Month 3 through Month 12 (Figure 1). Progressive keratoconus patients had an average Kmax reduction of 1.4 diopters in Study 1 and 1.7 diopters in Study 2 at Month 12 in the CXL-treated eyes while the sham eyes had an average increase of 0.5 diopter in Study 1 and 0.6 diopter in Study 2 at Month 12; the difference (95% CI) between the CXL and sham groups in the mean change from baseline Kmax were -1.9 (-3.4, -0.3) diopters in Study 1 and -2.3 (-3.5, -1.0) diopters in Study 2.

For corneal ectasia patients, at Month 12, the CXL-treated eyes had an average Kmax reduction of 1.0 diopter in Study 1 and 0.5 diopter in Study 3 while the sham eyes had an average increase of 1.0 diopter in Study 1 and 0.5 diopter in Study 3; the treatment difference between the CXL and sham groups was: -2.0 (-3.0, -1.1) diopters in Study 1 and -1.1 (-1.9, -0.3) diopters in Study 3.

Figure 1: Mean (SD) (Diopter) Baseline Kmax and Change from Baseline Kmax

Post-baseline missing data were imputed using last available Kmax value. For the sham study eyes that received CXL treatment after baseline, the last Kmax measurement recorded prior to receiving CXL treatment was used in the analysis for later time points. In Study 3, four patients in the CXL group had missing baseline Kmax value and were excluded from the analysis.

Single-use foil pouches of PHOTREXA® VISCOUS and PHOTREXA® are provided in a kit of two (2): one (1) PHOTREXA® VISCOUS and one (1) PHOTREXA® (NDC- 25357-025-03).

Each foil pouch contains a 3 mL glass syringe of PHOTREXA® VISCOUS or PHOTREXA® contained within a Tyvek® pouch.

Kits should be stored at 2°-8°C (36°-46°F). Care should be taken to minimize exposure of the syringe to light once removed from its protective packaging. Discard syringe after use.

For topical ophthalmic use.

PHOTREXA® VISCOUS and PHOTREXA® should be used with the KXL System only.

• Patients should be advised not to rub their eyes for the first five days after their procedure.
• Patients may be sensitive to light and have a foreign body sensation. Patients should be advised that there may be discomfort in the treated eye and that sunglasses may help with light sensitivity.
• If patients experience severe pain in the eye or any sudden decrease in their vision, they should be advised to contact their physician immediately.
• If the bandage contact lens that was placed on the patient’s eye on the day of treatment falls out or becomes dislodged, the patient should be advised not to replace it and to contact their physician immediately.

PHOTREXA® VISCOUS (riboflavin 5’-phosphate in 20% dextran ophthalmic solution) 0.146%, PHOTREXA® (riboflavin 5’-phosphate ophthalmic solution) 0.146% and the KXL® System are marketed by: Avedro, a Glaukos company, 30 North Avenue, Burlington, MA 01803.

Version:
Issued October 2022

ML-00043 REV2