New Objective criteria to effectively define Glaucomatous Optic Neuropathy: BJO

Iyer JV, Boland MV, Jefferys J, et al. held an investigation that generated a large, internationally representative dataset to identify objective criteria from OCT and perimetry that denote a useful, specific definition of GON in eyes with OAG for comparisons among glaucoma research studies.

A cross-sectional study of adult patients with glaucoma from nine centres on five continents evaluated de-identified physician diagnosis, OCT and perimetry results for 2580 eyes (1531 patients) in an online database. Each eye was graded by their glaucoma specialist as either definite, probable or not GON. Objective measures from OCT and perimetry, derived from an online consensus panel comprising 176 glaucoma specialists globally, were compared against the three diagnostic levels.

Data were included for patients older than 21 years, for whom at least 2 reliable OCT scans and visual field tests were available, the most recent of each within 12 months, and all tests performed within a 2-year period. Eyes were excluded that had any secondary cause for GON, such as uveitic or neovascular disease.

Structural data that was documented per eye included: OCT analyses from two tests per eye, instrument type, signal strength/quality, average retinal nerve fibre layer (NFL) thickness, rim area, disc area, vertical cup/disc ratio, retinal NFL quadrant statistical grading provided by instrument software (abnormal, borderline, normal), superior temporal two clock hour NFL statistical grading, inferior temporal two clock hour NFL statistical grading and macular OCT ganglion cell/inner plexiform thickness with number of zones superior and inferior statistically abnormal.

Functional data documented included perimetric data from two 24-2 or 30-2 tests per eye with test dates, false positive %, quality grading (acceptable or not acceptable, as determined by clinician), Glaucoma Hemifield Test (GHT) result, GHT abnormal region (upper, lower, both, undetermined—as assessed by at least 3 test points abnormal at p<5% on the pattern deviation plot), mean deviation (MD) and probability, pattern SD (PSD) and probability, number of abnormal (p><5%) non-edge points in the upper and/or lower field of the pattern deviation plot, and similar perimetric data from two 10-2 field tests, if performed. Eyes without OCT NFL and HVF 24-2 or 30-2 data were excluded. Refractive error data was not collected.><5% the pattern deviation plot), mean deviation (MD) and probability, pattern SD (PSD) and probability, number of abnormal (p<5%) non-edge points in the upper and/or lower field of the pattern deviation plot, and similar perimetric data from two 10-2 field tests, if performed. Eyes without OCT NFL and HVF 24-2 or 30-2 data were excluded. Refractive error data was not collected><5%) non-edge points in the upper and/or lower field of the pattern deviation plot, and similar perimetric data from two 10-2 field tests, if performed.

Sensitivity for a set of criteria was estimated as the percent of eyes with 'definite GON' who met those criteria. Specificity for a set of criteria was estimated as percent of eyes with 'no GON' who did not meet those criteria.

Diagnoses were 54% 'definite', 22% 'probable' and 24% 'not GON'. Using only OCT data or only field data had inadequate specificity (<90%). The best definitional choice for data from either the most recent or the preceding OCT/field pair had 77% sensitivity at 98% specificity and consisted of abnormal OCT superior or inferior nerve fibre layer quadrant with matching, opposite, abnormal Glaucoma Hemifield Test.><90%) The best definitional choice for data from either the most recent or the preceding OCT/field pair had 77% sensitivity at 98% specificity and consisted of abnormal OCT superior or inferior nerve fibre layer quadrant with matching, opposite, abnormal Glaucoma Hemifield Test.

OCT NFL features

Data for OCT NFL thickness abnormality by clock hour was evaluated as number of abnormal (red) zones in two superior temporal clock hours (11, 12 o'clock, right eyes; 12, 1 o'clock, left eyes) and in two inferior temporal clock hours (6, 7 o'clock, right eyes; 5, 6 o'clock, left eyes; table 2). Among 'definite GON' eyes, inferior NFL had 2 clock hours abnormal 3 times more often than superiorly (39% vs 11%; 497 vs 143 eyes). The 'not GON' eyes had at least one clock hour abnormal superior or inferior in 10% (58 eyes), while 81% (1025) of definite eyes met this criterion. One percent of 'not GON' eyes had 2 clock hours abnormal, so this criterion had good specificity, but its sensitivity for definite GON was only 44%.

Perimetry features

In the more recent visual field test provided, 85% of 'definite GON' eyes had GHT 'outside normal limits' with 3 points abnormal (p<5%) in the abnormal hemifield (our standard criterion), but 15% of 'not GON' also had that abnormal GHT outcome (specificity=85%; table 3). 'Definite GON' eyes with either upper or lower GHT abnormality had nearly twice the rate of defect in the upper field (29%) as in the lower field (17%), matching the corresponding greater OCT inferior defect rate. In the number of visual field test points abnormal (p><5%), 95% of 'definite GON' eyes (1457) had ≥3 abnormal points in either upper or lower field, but so did 49% of 'not GON' eyes ><5%) in the abnormal hemifield ( standard criterion), but 15% of 'not GON' also had that abnormal GHT outcome (specificity=85%;). 'Definite GON' eyes with either upper or lower GHT abnormality had nearly twice the rate of defect in the upper field (29%) as in the lower field (17%), matching the corresponding greater OCT inferior defect rate. In the number of visual field test points abnormal (p<5%), 95% of 'definite GON' eyes (1457) had ≥3 abnormal points in either upper or lower field, but so did 49% of 'not GON' eyes><5%), 95% of 'definite GON' eyes (1457) had ≥3 abnormal points in either upper or lower field, but so did 49% of 'not GON' eyes.

OCT NFL and perimetry combination criteria in defining GON

Criterion 1: When either the most recent or the preceding pair of tests had an abnormal OCT quadrant with matching superior/inferior GHT abnormality, the sensitivity was 77% or specificity was 98%.

Criterion 2: It was tested allowing either abnormal GHT or, when GHT was normal, PSD probability ≤2% with OCT quadrant defect in either the most recent or the preceding pair of tests. Its sensitivity was 75%, specificity 98%.

Criterion 3 was defined as having matching abnormal OCT quadrant and GHT abnormalities at the most recent test pair: sensitivity =73%, specificity =98%. Criterion 1 was significantly more sensitive than criteria 2 (p=0.001) and 3 (p<0.0001). Only 6% (96/1539) of definite GON had normal OCT quadrants and normal GHT. Criterion 4 was an abnormal OCT quadrant with matching GHT abnormality on both the most recent pair and preceding pair of tests: sensitivity =65% (997/1539; 95% CI 62, 67%), specificity =99% (674/681: 9%% CI 98, 100%).>< 0.0001). Only 6% (96/1539) of definite GON had normal OCT quadrants and normal GHT.

Criterion 4 was an abnormal OCT quadrant with matching GHT abnormality on both the most recent pair and preceding pair of tests: sensitivity =65%, specificity =99%.

The authors identified criteria from OCT and visual field test results that can define GON objectively, facilitating standardisation of outcome comparisons across clinical glaucoma research studies. The large number of eyes studied and their worldwide distribution support the validity and generalisability of the findings.

The authors concluded, "In summary, this large international database provides useful, objective criteria that identify three-fourth of those identified as GON by experts across a range of derivation groups, while effectively excluding those without GON. In ongoing research,23 multiple experts will grade each eye as GON on a 0–100 likelihood scale, after reviewing colour fundus photographs, NFL and macular OCT, and standard and central visual field testing. These approaches will help to determine objective data that can provide standards that would be available to compare research outcomes among glaucoma investigations."

Source: Iyer JV, Boland MV, Jefferys J, et al. Br J Ophthalmol 2021;105:789–793

doi:10.1136/bjophthalmol-2020-316237