Slit Lamp-Based Ocular Scoring Systems: Commentary

In the recent December 2017 issue, Eaton et al.^1,2 present 2 articles on slit lamp-based ocular scoring systems: the first reviews established techniques and the second presents a novel method. In the first, they note the invention of the slit lamp by Gullstrand over a century ago. This instrument, also known as a biomicroscope, together with the phoropter, the tonometer, and the visual acuity chart, is the sine qua non of the ophthalmologist's office. Used by a trained clinician, the globe can be evaluated from tear film posterior to the vitreous for clarity of the media, and a host of diseases diagnosed (or ruled out). With respect to preclinical development of technologies, assessment of the effect of local ocular therapy on the anterior segment and the vitreous is key to evaluating the potential for a novel therapeutic to be evaluated in humans.

In the first article, ¹ the authors review published methods. These include the well-known Draize method that is performed without magnification or use of stains. ³ The Organisation for Economic Co-operation and Development method for assessment of acute ocular irritation, typically used for exposure to chemicals in the workplace, is generally similar to the Draize method. [However, the current version of this guidance specifies that “fluorescein staining should be routinely used and a slit lamp biomicroscope used when considered appropriate (e.g., assessing depth of injury when corneal ulceration is present) as an aid in the detection and measurement of ocular damage….”]* The authors also review the reports from Hackett, McDonald, and Shadduck using the slit lamp.^4,5As noted in the Eaton review, there is a very large body of normative data as well as experience with novel therapeutics, many of which have gone on to clinical evaluation. Some of these evaluations have been published (e.g.,^6–8 ), whereas others are referenced in the preclinical summary of approved drugs (www.accessdata.fda.gov/scripts/cder/daf).

However, the authors note that these were originally developed for use in albino rabbit eyes, whereas nonclinical testing of ophthalmic products typically requires 2 species, and, frequently, pigmented eyes. Each of these methods has its benefits (ease of use and long history of use) and deficits (the semiquantitative aspects of the measurements, the rarely evaluated within- and between-investigator reproducibility, and no measures of aqueous and anterior vitreous cells, for example). It is clearly time for an updated method for use in preclinical research.

In the second article, the authors present such a method. It is very logically organized and well thought out. It was developed with awareness of human evaluation methods (e.g., the SUN), specifically developed to score human uveitis. ⁹ However, as a new method, by definition it has several as yet untested aspects, some of which are much the same as the authors indicate for the older methods; it is still semiquantitative. First, could observers other than the researchers who developed it get the same results? Second, has it been “benchmarked” with products that are known to be safe in humans, and those known to be irritating? How does it compare for molecules and formulations as evaluated in the McDonald–Shadduck method? Third, how do the concentration–response and frequency–response seen in this preclinical method compare with human clinical experience? For example, as used in the most frequently used species, rabbits, would the concentration at which no adverse events observed be similar to, more potent, or less potent than in humans?

In its favor, the new methodology proposed by Eaton et al. attempts to address some of the standardization issues by suggesting specific settings for slit lamp observations. It includes a much wider range of observations to include anterior chamber and vitreous cells, includes measures targeting the posterior segment (important in the evaluation of intravitreal drugs and devices), and ties the SUN scoring method to nonclinical evaluations.

In summary, we applaud the work of Eaton et al. in reviewing and developing a new method in any area that needs innovation. We look forward to reading reports demonstrating additional experience using this new method to evaluate novel therapeutics.