Glaucoma cases were selected from the ophthalmic outpatient department of the University Medical Center Groningen (UMCG), using the VF database of the Groningen Longitudinal Glaucoma Study (GLGS).
17 Eight cases of other hospitals in the Netherlands were recruited via an advertisement and provided their medical history and most recent visual function assessment (visual acuity and at least 3 prior reliable VF assessments) for selection. We included cases who had a minimum of three consecutive reliable SAP assessments with the Glaucoma Hemifield Test reproducibly outside normal limits in at least one eye. The test pattern of these previous SAP assessments could be either the HFA 24-2 or 30-2 (depending on the test pattern used clinically in the concerning case. For both grids, the used thresholding strategy was SITA-Fast If the most recent SAP assessment was older than 6 months, the assessment was repeated, using the SAP 24-2 test pattern and SITA-Fast strategy (HFA; Carl Zeiss Meditec AG, Jena, Germany). Reliability criteria were defined as false positive responses ≤ 10% and fixation losses ≤ 20%. In the case of an increased number of fixation losses, fixation was considered acceptable if a well-defined blind spot was present and the technician had observed and reported a stable fixation.
17,18 One eye per case was selected based on the SAP mean deviation (MD) in decibels (dB) as a measure of severity and on the location of the VF defect — ensuring the presence of defects in both the superior and inferior hemifield in the study population — resulting in 3 subgroups of 12 cases each with early (MD > −6 dB), moderate (–12 dB < MD ≤ −6 dB), and severe (MD < −12 dB) glaucoma with diverse locations of VF defects within each group. Cases were allowed to have different types of glaucoma and concurrent other eye diseases, like myopia, as long as glaucoma was the presumed sole cause of VF loss and loss of visual acuity. Exclusion criteria were a best corrected visual acuity (BCVA) of worse than 0.3 logMAR and neurological disorders that could affect test performance, as assessed with a questionnaire (asking if the person is currently or was previously under the care of a neurologist, and, if yes, for what reason).
Controls were recruited via advertisement. Potential controls who responded to the advertisement were asked to fill out a questionnaire to screen for any known eye abnormalities, a positive family history of glaucoma, and neurological disorders that could affect the test performance. Hereafter, a short eye-health check was performed, which included an intraocular pressure (IOP) measurement (Ocular Response Analyzer G3 non-contact tonometer; Reichert Technologies, Inc., Depew, NY, USA), a refraction and BCVA measurement (Nidek ARK-1s. Nidek Co., Ltd., Gamagori, Japan), a frequency doubling technology visual field test (FDT; C20-1 screening mode; Carl Zeiss, Jena, Germany), and a measurement of the peripapillary retinal nerve fiber layer thickness as assessed by spectral domain optical coherence tomography (OCT; Copernicus, Optopol Technologies, Zawierci, Poland). Exclusion criteria were any known eye abnormality, a positive family history of glaucoma, any known neurological disorders that could affect test performance, a BCVA worse than 0.1 logMAR, a cornea-compensated IOP (IOPcc) above 22 millimeters of mercury (mm Hg), any reproducibly abnormal test location on the FDT test result, or any temporally located red clock hour abnormality in the peripapillary retinal nerve fiber layer on the OCT. One eye that met the eligibility criteria was included. During the recruitment process, we selected the cases and controls, per glaucoma severity subgroup (early, moderate, and severe), to make the groups age and sex similar, and we equalized the numbers of included right and left eyes.