Validation of a photographic vitreous haze grading technique for clinical trials in uveitis

Abstract

Purpose: To validate a photographic vitreous haze grading technique using a 9-step logarithmic scale in patients enrolled in a randomized, controlled clinical trial in uveitis.

Design: Retrospective study of clinical trials methodology.

Setting: University-based department of ophthalmology.

Study population: Baseline fundus photographs of patients with intermediate uveitis, posterior uveitis, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment (MUST) trial.

Observational procedure: Grading of vitreous haze using a previously described photographic scale. Regrading of a subset of photographs to assess intraobserver agreement.

Main outcome measures: Interobserver and intraobserver intraclass correlation for photographic haze grading, and correlation between photographic and clinical vitreous haze scores, assessment of the clinical findings that significantly affect the photographic haze score.

Results: Vitreous haze was graded in 271 eyes (142 patients) by 3 postgraduate ophthalmologists. The interobserver and intraobserver intraclass correlations were excellent, with correlation coefficients between 0.84 and 0.93. There was moderately strong correlation between the photographic and clinical vitreous haze scores (r=0.51; P<.001), with significant differences among the mean and median photographic haze scores for the 3 lowest clinical grades of haze, 0, 1+, and 2+. Other parameters that correlated with photographic vitreous haze score included visual acuity of 20/50 or worse (P=.003), degrees of posterior synechiae (P<.001), lens abnormality (P=.023) or posterior capsule obscuration (P=.001), and amount of anterior vitreous cell (P=.002).

Conclusions: Photographic grading of vitreous haze with a 9-step logarithmic scale is a highly reproducible methodology that may be adaptable to use in future clinical trials.

Trial registration: ClinicalTrials.gov NCT00132691.

Copyright © 2011 Elsevier Inc. All rights reserved.

Figures

FIGURE 1

Bar graph showing the distribution of clinical vitreous haze ranks at baseline for 133 right eyes of 142 patients enrolled in the Multicenter Uveitis Steroid Treatment (MUST) trial. Eighty-four percent of right eyes were graded 0 or 1+, or 2 clinical grade steps.

FIGURE 2

Bar graph showing the distribution of clinical vitreous haze grades at baseline for the 132 fellow left eyes of these patients. Eighty-one percent of left eyes were graded 0 or 1+, or 2 clinical grade steps.

FIGURE 3

Bar graph showing the distribution of the photographic vitreous haze grade at baseline for 133 right eyes of 142 patients enrolled in the Multicenter Uveitis Steroid Treatment (MUST) trial. Eighty percent of right eyes were graded 0 to 5.0, a total of 6 photographic grade steps.

FIGURE 4

Bar graph showing the distribution of the clinical vitreous haze grades at baseline for the 132 fellow left eyes of these patients. Seventy-nine percent of left eyes were graded 0 to 6.0, a total of 7 photographic grade steps.

FIGURE 5

Bar graph showing the distribution of the mean photographic vitreous haze grades for the 65 right eyes with a clinical vitreous haze rank of 1+ on the Nussenblatt scale. The number of eyes with each score is shown on the vertical axis. The horizontal axis displays mean photographic vitreous haze scores of 3 readings clustered around whole numbers and including scores 0.33 higher and lower than each whole digit, except at the lowest and highest grades.

FIGURE 6

Comparison of the photographic vitreous haze grader standards to Multicenter Uveitis Steroid Treatment (MUST) trial baseline photographs that were clinically graded as having 1+ vitreous haze rank on the Nussenblatt scale. The left column displays the photographic vitreous haze grader standards 1, 2, 3, and 4; grades 0, 5, 6, 7, and 8 are not shown.5 The 3 columns on the right contain MUST trial baseline photographs of right eyes that were assigned a clinical vitreous haze rank of 1+. Each row contains 3 photographs that had a mean photographic haze score in the range of the standard image in the first column. The first 3 rows contain 9 of the15 vitreous haze rank 1+ right eyes from clinic 20 and demonstrate the ability of photographic grading to subdivide the clinical rank 1+ from that clinic into 3 separate grades. The bottom row contains 3 of 4 eyes that clinically were ranked as having 1+ vitreous haze by clinic 6. They are aligned with the photographic haze grader standard image 4, but in reality were graded as (Left) 4.0, (Middle) 5.0, and (Right) 6.0. The fourth right eye from this clinic (not shown) that was ranked 1+ clinically had a photographic haze score of 5.33, demonstrating a systematic difference in clinical haze ranking between clinic 20 and clinic 6.