Slit Lamp Examination

Each participant underwent a complete ophthalmological examination at baseline, which included relevant medical history, blood pressure measurement, best-corrected visual acuity, slitlamp biomicroscopy, gonioscopy, Goldmann applanation tonometry, central corneal thickness measurement, dilated funduscopy, stereoscopic ophthalmoscopy of the optic disc with a 78-diopter lens, and simultaneous stereoscopic disc photography. In addition to photography, the structure of the optic disc and nerve fiber layer was measured with a variety of imaging devices, including the Heidelberg Retina Tomograph (Heidelberg Engineering, Heidelberg, Germany), GDx (Carl Zeiss Meditec, Dublin, California), and optical coherence tomography (Stratus OCT; Carl Zeiss Meditec). Tests of visual function included SAP, short-wavelength automated perimetry, and frequency doubling technology perimetry. See Table 2 for details of the examinations and tests completed at each visit. We tracked all systemic and ocular procedures and medications and any concurrent conditions that might affect vision.
This examination protocol is repeated annually for patients with glaucoma, ocular hypertension, and suspected glaucoma, who receive treatment and glaucoma medications at no cost at the discretion of their glaucoma specialist. Transportation is provided when needed.
All color simultaneous stereophotographs were taken using a Nidek Stereo Camera Model 3-DX (Nidek Inc, Palo Alto, California) after maximal pupil dilation. All photograph evaluations were performed using a simultaneous stereoscopic viewer (Asahi Pentax Stereo Viewer II; Pentax, Tokyo, Japan) with a standard fluorescent light bulb. Certified photograph graders evaluated all photographs. To be certified, individuals were trained and then tested on separate standardized sets of stereophotographs depicting (1) glaucomatous and healthy eyes and (2) progressing and nonprogressing eyes. Recent evidence from the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study indicated that reproducibility of stereophotograph assessment is good when graders have been trained using this type of formal protocol.16 (link),17 (link)
Each photograph was graded by 2 independent graders according to a standard protocol using the standard photographs as reference. Each grader was masked to the participant’s identity, diagnostic status, study, race, and other results. In cases of disagreement, a third senior grader adjudicated. All photographs were graded for quality and evidence of glaucoma damage. To assess between-grader reproducibility, 80 randomly chosen stereophotographs graded by IDEA (Imaging Data Evaluation and Analysis) Center personnel were evaluated for consensus between 2 graders; 73 of 80 (91%) were assigned the same diagnostic classification of glaucoma or healthy both times. Among the same 80 photographs, IDEA Center graders agreed on a vertical cup-disc ratio within 0.2 mm 70 of 80 times (87%). Adjudication of baseline photos was required in 31% of African descent and 28% of European descent eyes.

Participants were excluded if they had a history of intraocular surgery (except for uncomplicated cataract surgery), as were participants with diseases affecting the visual field (eg, pituitary lesions, demyelinating diseases, human immunodeficiency virus seropositivity, AIDS, or diabetes mellitus), those using medications known to affect visual field sensitivity, or those with problems affecting color vision other than glaucoma. Each participant underwent a complete ophthalmological examination to rule out the presence of other ocular diseases. This examination included slitlamp biomicroscopy, IOP measurement, and dilated stereoscopic fundus examination.
All DIGS and ADAGES participants were familiar with perimetry or were given practice tests before the baseline data collection. Eyes included in this analysis had 2 reliable SAP test results. The only exception was the inclusion of 50 eyes (22 AD and 28 ED eyes) with only 1 SAP test when the result of that test was normal. These eyes belonged to 35 participants (17 AD and 18 ED). In addition, most participants had 22 short-wavelength automated perimetry (SWAP) and FDT tests on each eye. All tests were performed within a 3-month period, and the order of the tests was randomized across participants. Stereoscopic photographs were taken within 6 months of the visual field tests.
Color simultaneous stereoscopic photographs of the optic disc were obtained using the commercially available Nidek Stereo Camera Model 3-DX (Nidek Inc, Palo Alto, California) after maximal pupillary dilation. Photographs were independently assessed by 2 trained graders who were masked to the identity and diagnosis of the participant, to the evaluation of the other grader, and to the ancestry of the participants. In cases where the 2 graders disagreed, a third experienced grader served as an adjudicator. Stereoscopic photographs were evaluated using a stereoscopic viewer (Asahi Pentax Stereo Viewer II; Asahi Optical Co, Tokyo, Japan) illuminated with color-corrected fluorescent lighting. Glaucomatous optic neuropathy was defined by evidence of any of the following: excavation, neuroretinal rim thinning or notching, nerve fiber layer defects, or an asymmetry of the vertical cup-disc ratio of at least 0.2 between the 2 eyes.

The methods for ADAGES have been described in the baseline study design article.7 (link) The methods relevant to this particular study are reviewed in this section.
Baseline data from participants in the National Eye Institute–funded Diagnostic Innovations in Glaucoma Study (DIGS) and ADAGES who did not have ocular disease were used for all the analyses in the present study. The methods followed in DIGS and ADAGES are identical. All participants gave written informed consent. The institutional review boards at all 3 sites approved the study methods. Methods adhere to the tenets of the Declaration of Helsinki and to the Health Insurance Portability and Accountability Act. Healthy control subjects for ADAGES and DIGS were recruited to join the present study by advertisement, from family members of patients, and from primary eye care clinics.
Each healthy control underwent a complete ophthalmological examination that included medical history, measurement of Snellen best-corrected visual acuity, Early Treatment Diabetic Retinopathy Study visual acuity, color vision, central corneal thickness, axial length, slitlamp biomicroscopy, gonioscopy, applanation tonometry, lens opacity estimation with version III of the Lens Opacities Classification System grading system, keratometry, dilated funduscopy, stereoscopic ophthalmoscopy of the optic disc with a 78-diopter (D) lens, and simultaneous stereoscopic fundus photography. Standard and visual function–specific perimetry tests were performed. However, only standard automated perimetry was used to define normality for inclusion in this study. Information regarding systemic conditions, medications, and several risk factors associated with glaucoma were also obtained, including blood pressure measurement, family history, highest known intraocular pressure (IOP), age, and history of diabetes mellitus, heart disease, and vascular disease. In addition to photography, the structure of the optic disc, RNFL, and macula were quantified using HRT and OCT.