Issue: July 10, 2020
Disclosures: Hardten reports he is a consultant for Glaukos and has financial interest in ESI and proprietary interest in KeraFlow. Lindstrom reports he is a consultant for Glaukos and has proprietary interest in KeraFlow. Reeves reports he has proprietary interest in KeraFlow.
July 02, 2020
4 min read

KeraFlow system improves riboflavin loading for corneal cross-linking

The loading phase is faster with the system, which is also more comfortable for patients and technicians.

Issue: July 10, 2020
Disclosures: Hardten reports he is a consultant for Glaukos and has financial interest in ESI and proprietary interest in KeraFlow. Lindstrom reports he is a consultant for Glaukos and has proprietary interest in KeraFlow. Reeves reports he has proprietary interest in KeraFlow.
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Corneal collagen cross-linking is now FDA approved and is a mainstay of the U.S. and global armamentarium for patients with potentially progressive keratoconus.

A recent meta-analysis of the prevalence and risk factors for keratoconus suggested that patients with a history of eye rubbing, family history of keratoconus, allergies, asthma and eczema were at a higher risk for keratoconus than the general population. The researchers suggested a prevalence of 1.38 per 1,000 population. In studies that reported gender, the prevalence in men was 20.6 per 1,000 and 18.33 per 1,000 in women. Now that we have intervention strategies for reducing progression in patients with keratoconus, we are looking for ways to effectively find the patients who are at risk of progression and effectively and efficiently treat them with corneal collagen cross-linking.

David Hardten
David R. Hardten

At Minnesota Eye Consultants, we have participated in several clinical trials for cross-linking beginning in 2008. We are excited that there is an approved option now with the Avedro system, recently acquired by Glaukos. Every year we are doing more treatments, and we have as a goal to improve the ease of the procedure for the patients, physicians and staff.

Sherman Reeves
Sherman W. Reeves

One device that has been helpful to us in performing cross-linking procedures recently gained FDA approval. It is the KeraFlow corneal irrigation system (ESI), which enhances the ease and effectiveness of riboflavin corneal stromal loading. While the KeraFlow can be used to deliver solutions for irrigation in cases of chemical burn, antibiotics and other fluids, our main use of this device has been for the delivery of riboflavin during corneal collagen cross-linking procedures.

Richard L. Lindstrom
Richard L. Lindstrom

In the original clinical trials for cross-linking, the eye was held open with a lid speculum for the entire procedure. After the epithelium was removed, riboflavin was dropped onto the eye every 5 minutes to achieve loading of the cornea. We experienced significant corneal dehydration through this method. Even when we altered our technique and allowed the eyelids to close in between applications of the riboflavin solution, the cornea would at times desiccate, requiring hypotonic solutions to reestablish adequate corneal thickness for cross-linking.

We now use the KeraFlow device to obtain a continuous soaking of the cornea with the riboflavin solution. This allows the patient’s lids to stay closed and the cornea to remain hydrated during the entire loading session. The technician can simply push a minute amount of the riboflavin solution from the syringe every 20 to 30 seconds to replenish the concentration that has been diluted by the patient’s tears. We have experienced faster and better loading with this approach. It is also much easier on the patient.


Since the earliest clinical trials, we have used a slit lamp to evaluate for corneal loading, either through the appearance of flare with riboflavin color or more commonly with a color change to the cornea that is present full thickness. We now can load a full amount of Avedro riboflavin solution in most patients in 10 minutes after the epithelium has been removed. If the cornea is not fully loaded after inspection, we can reinsert the device and load for additional time. One caveat to be aware of is that in a patient with an extreme Bell’s reflex, care should be taken to ensure the KeraFlow maintains adequate contact with the superior cornea so that this area can be loaded adequately.

In a poster presented at the 2019 American Society of Cataract and Refractive Surgery meeting, we described the results of a trial using the KeraFlow for epithelium-on corneal cross-linking. Through using a solution with 0.6% riboflavin with benzalkonium chloride and proparacaine before application of Photrexa (riboflavin 5’-phosphate ophthalmic solution), there was adequate saturation through intact epithelium using a continuous soak with an average time of 20.5 minutes, a rate almost 10 minutes faster than the FDA-approved epithelium-off loading process.

Some pearls for use of the KeraFlow are important to understand. We first administer topical anesthetic to the eye and place some additional anesthetic on the sponge portion of the KeraFlow. There is a roller clamp on the tubing, and we adjust that roller clamp to the closed position. This prevents solution from entering the tubing before you are ready to control the flow. The syringe of Photrexa is attached securely to the tubing. Either the viscous or non-viscous solution can be delivered through the device. The roller clamp is then opened.

KeraFlow is inserted
Figure 1. The KeraFlow is inserted under the eyelids.

Source: David R. Hardten, MD, Sherman W. Reeves, MD, and Richard L. Lindstrom, MD

When the syringe is attached, there will not be flow unless the syringe plunger is depressed. We slowly depress the plunger to move the fluid to the end of the tubing and onto the sponge. We then hold the lids open with fingers and slide the domed shell under the upper lid first and then gently retropulse the globe while putting the lower section of the shell below the lower lid (Figure 1). The patient then gently closes the eyes over the device and should be looking straight ahead. Every 1 to 2 minutes, the technician advances the plunger a small amount, trying to deliver approximately 0.1 cc of fluid. There is 3 mL of Photrexa in the syringe, so care should be taken to plan on spacing most of the delivery over 15 to 20 minutes. There is approximately 1 cc in the tubing remaining when the plunger is fully depressed. The roller clamp is closed and the cornea examined with the slit lamp (Figure 2). We save the tubing solution for a secondary loading in case the physician examines the cornea and needs more solution; this can be delivered by placing the device on the cornea again, taking the syringe off, holding the tubing above the eye and slowly opening the roller clamp.

cornea is examined for adequate loading
Figure 2. The cornea is examined for adequate loading, with riboflavin fully saturating the cornea.

The cross-linking then progresses with the Avedro light source in the standard fashion.

In summary, we have found the KeraFlow riboflavin fluid delivery system to improve the loading of riboflavin for corneal collagen cross-linking. It is quicker than standard loading, and it is more comfortable for patients and technicians.