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. 2023 Mar 7:17:757-767.
doi: 10.2147/OPTH.S398843. eCollection 2023.

Validation of a Modified National Eye Institute Grading Scale for Corneal Fluorescein Staining

Kenneth Sall  1 , Gary N Foulks  2 , Andrew D Pucker  1 , Karen L Ice  1 , Richard C Zink  1 , George Magrath  1
Affiliations

Validation of a Modified National Eye Institute Grading Scale for Corneal Fluorescein Staining

Kenneth Sall et al. Clin Ophthalmol. .

Abstract

Purpose: Validation of the novel Lexitas modified NEI scale for use in assessment of corneal fluorescein staining.

Patients and methods: A series of 18 illustrations and 14 clinical photographs depicting varying severity levels of corneal fluorescein staining were assessed by 3 independent examiners. Regions of the cornea were graded for staining severity based on 3 different grading scales: the original NEI staining scale (density-based scoring; 0-3 scale), a structured version of the NEI scale (dot-count scoring; 0-3 scale), and the Lexitas modified NEI staining scale (0-4 scale with half-point increments). Kappa statistics (simple and weighted) were computed to determine intra-examiner image grading repeatability for each examiner over 2 separate assessments. Inter-examiner assessment reliability utilized the scores from the first read of each examiner, and pairs of examiners to compute kappa statistics.

Results: Data was analyzed from the scores provided by the examiners from each gradable corneal region on 32 images (18 illustrations and 14 photographs) for a total of 154 corneal regions across the 3 grading scales for each validation run. The mean intra-examiner simple/weighted kappa values using the NEI density, NEI dot count, and the Lexitas modified NEI staining scales were 0.67/0.72, 0.91/0.94, 0.80/0.92 for the graded illustrations, and 0.83/0.88, 0.76/0.85, 0.77/0.88 for the graded photographs, respectively. The mean inter-examiner simple/weighted kappa values using the NEI density, NEI dot count, and the Lexitas modified NEI staining scales were 0.59/0.65, 0.86/0.90, and 0.78/0.91 for the graded illustrations, and 0.80/0.88, 0.84/0.89, 0.69/0.88 for the graded photographs, respectively.

Conclusion: The expanded scale of the Lexitas modified NEI staining scale demonstrated a high degree of reliability and repeatability of grading assessments within and across individual examiners, comparing favorably with the original NEI staining scale. A future investigation into the in-office utility of the Lexitas modified NEI staining scale is warranted.

Keywords: clinical trials; corneal sodium fluorescein staining; dry eye disease; repeatability; validation.

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Conflict of interest statement

AD Pucker, RC Zink, and G Magrath are employees of Lexitas Pharma Services, KL Ice is a co-founder and former employee of Lexitas Pharma Services. K Sall and GN Foulks are consultants to Lexitas Pharma Services. AD Pucker has received research or consulting support from Alcon, Art Optical, CopperVision, Euclid Systems, Kala, and Nevakar over the past three years, though this work is unrelated to the current project. K Sall has received consulting support from Allysta, Cloudbreak, Famy, Tarsier, Biorasi, Premark, Betaliq, Lexitas and Glaukos, although this work is unrelated to the current project. GN Foulks has received consulting support from Allysta, Aramis, Bristol Myers Squibb, Hanall, Nicox, Kala, and Tarsus, although this work is unrelated to the current project. AD Pucker reports grants from Alcon, non-financial support from Art Optical, personal fees from CopperVision, Euclid Systems, Kala, and Nevakar, outside the submitted work. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Corneal fluorescein staining scales used in the validation of the Lexitas modified NEI scale. Descriptions for each grade of the NEI scale (density), NEI scale (dot count) and the Lexitas modified NEI scale are presented. *Confluence defined as closely adjacent multiple dots, but not merging into a solid area of staining. **Coalescence defined as merging of dots into a solid area of staining.
Figure 2
Figure 2
Reference illustrations provided to the independent examiners as examples for each grade level of the (A) original NEI density, (B) structured NEI dot count, (C) Lexitas modified NEI (score range 0.0–2.0), and (D) Lexitas modified NEI (score 2.0–4.0) staining scales.
Figure 3
Figure 3
The average intra-examiner kappa statistics (across all regions of the cornea) are presented by examiner (A, B, C), staining scale (NEI density, NEI dot count, Lexitas modified NEI), and kappa statistic type (simple, weighted) for the corneal fluorescein staining images, with the kappa values being presented for the illustrations in (A), and the photographs in (B).
Figure 4
Figure 4
The intra-examiner kappa statistics for each region of the cornea are presented by examiner (A, B, C), staining scale (NEI density, NEI dot count, Lexitas modified NEI), and kappa statistic type (simple, weighted) for the corneal fluorescein staining images, with the kappa values being presented for the illustrations in (A), and the photographs in (B).
Figure 5
Figure 5
The average inter-examiner kappa statistics (across all regions of the cornea) are presented by paired examiners (A-B, A-C, B-C), staining scale (NEI density, NEI dot count, Lexitas modified NEI), and kappa statistic type (simple, weighted) for the corneal fluorescein staining images, with the kappa values being presented for the illustrations in (A), and the photographs in (B).
Figure 6
Figure 6
The inter-examiner kappa statistics for each region of the cornea are presented by paired examiners (A-B, A-C, B-C), staining scale (NEI density, NEI dot count, Lexitas modified NEI), and kappa statistic type (simple, weighted) for the corneal fluorescein staining images, with the kappa values being presented for the illustrations in (A), and the photographs in (B).
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