dry eye dx and tx

The Controversy Over Corneal Staining

BY KELLY K. NICHOLS, OD, MPH, PHD

Not very often do cross-cutting issues emerge and simultaneously take stage like corneal staining has over the past year. The assessment of corneal staining, including the significance of staining to patients and the impact of staining on clinical care, are of major concern to clinicians and researchers alike.

What's the Fuss?

I can't recall a clinical issue that has received as much media and impassioned podium time as corneal staining, all for something seemingly as benign, yet as important, as the assessment of ocular surface integrity. Some say, why all the fuss? Fortunately, the fuss has shed light on the challenges of evaluating, documenting and interpreting corneal staining. From a research perspective, this controversy has been a reminder of the importance of clinical equipoise and the difficulties of clinical research.

Clinical Equipoise

Equipoise is the state of being balanced or in equilibrium. In clinical research, it generally indicates that all involved will accept study outcomes, without bias, in an area where there's uncertainty. Data are data, regardless of the research sponsor, and no clinical study is without flaw.

Over the years I've come to realize that the "ideal" study can't exist, most likely because it isn't feasible or is too expensive. As a researcher and clinician, assessing study design, methods and results requires equipoise, as well as hope that the best study was performed given all of the critical factors (such as time and money).

Figure 1. The computer-generated red dots correspond to areas of staining with fluorescein. Image courtesy of D. Wu, J. Nichols, and J. Barr, The Ohio State University, 2007.

Corneal Staining

This brings us to the topic of corneal staining. Anyone who follows dry eye has chronicled the FDA trials (and tribulations) of Inspire Pharmaceutical's Prolacria (aka diquafosol). Previous phase III trials with diquafosol have demonstrated a consistent reduction in average corneal staining, although the endpoint of corneal staining clearance (staining to no staining) wasn't significant in the last trial. This has resulted in continued talks with the FDA regarding approval. What does that mean? Generally speaking, staining is important, hard to document and the significance of staining to a patient and clinician is still worth a debate. It's a poorly understood topic.

Staining Grid

I've heard extreme responses to this work (staininggrid.com). In my opinion, the systematic method of the staining grid protocol is worth comment. In the ever-changing world of ocular surface research, a definition and grading scheme for staining were selected and, more importantly, maintained throughout this series of small studies. If you understand what each category label on the graph indicates, trends emerge that warrant further investigation and careful thought by clinicians using these products.

We're Working on It

Several researchers and groups are attempting to create accepted staining scales to allow for easier interpretation and extrapolation of study data. Biomedical image analysis techniques are being developed to quantify staining (Figure 1) and to eliminate some controversy in the future. CLS

Dr. Nichols is an associate professor at The Ohio State University College of Optometry in the area of dry eye research.