Introduction
Glaucoma represents a significant global health concern as a leading cause of irreversible blindness. Early detection and diagnosis in primary care settings are critical to managing the disease and preventing vision loss. Optometrists and primary care physicians play a vital role in initial glaucoma assessments, often relying on intraocular pressure (IOP) measurements, perimetry, and optic disc evaluations to identify potential cases for specialist referral. This study investigates the effectiveness of two advanced imaging technologies, the Heidelberg Retinal Tomograph II (HRT II) and the GDx nerve fiber layer analyzer, in aiding Primary Care Diagnosis Of Glaucoma. By comparing their diagnostic accuracy to a glaucoma specialist’s clinical diagnosis, this research aims to determine the potential of these instruments to enhance glaucoma detection in primary eye care.
Methods
This prospective study enrolled all new patient referrals to a primary eye care clinic at Mile End Community Hospital over three months (April-June 2001) who were suspected of having glaucoma. Referrals originated from local optometrists based on findings such as suspicious optic disc cupping, elevated IOP, or visual field defects identified during routine eye examinations. All participants provided informed consent, and the study received ethics committee approval from Moorfield’s Eye Hospital.
Each participant underwent imaging of both eyes using both HRT II and GDx. Experienced technicians performed the imaging, obtaining three high-quality scans per eye with the instrument order randomized. Subsequently, a glaucoma consultant, blinded to the HRT II and GDx results, conducted a comprehensive ophthalmic examination on each patient. This examination included slit-lamp biomicroscopy, Goldmann applanation tonometry, gonioscopy, dilated fundus examination, and Humphrey field analysis (24-2 SITA standard). Visual field reliability criteria included less than 20% fixation losses and a maximum of 30% false-positive and false-negative errors.
The glaucoma specialist then categorized each patient’s diagnosis into one of five groups: ‘definite glaucoma’, ‘glaucoma suspect’ (GS), ‘ocular hypertension’ (OHT), ‘nonglaucomatous optic neuropathy’, or ‘normal’. A diagnosis of definite glaucoma required evidence of optic disc cupping (cup-disc ratio > 0.4 or vertical cup-disc ratio asymmetry > 0.2) along with a corresponding glaucomatous visual field defect. Glaucomatous visual field defects were defined using strict criteria based on the 24-2 SITA results, requiring at least four out of six specific parameters to be met, including pattern standard deviation (PSD), glaucoma hemifield test (GHT), and cluster defects.
Separately, a masked ophthalmologist analyzed the data from the HRT II and GDx instruments to assess their predictive capability for glaucoma, independent of the clinical examination findings.
HRT II disc imaging was classified as ‘normal’, ‘borderline’, or ‘Outside Normal Limits’ (ONL) using the Moorfield’s regression coefficient. For GDx, results were categorized as ‘normal’ or ‘abnormal’ based on a GDx number cutoff of 50. A GDx number above 50 was considered abnormal.
Instrumentation for Glaucoma Diagnosis
Confocal Scanning Laser Ophthalmoscopy (HRT II)
The HRT II, manufactured by Heidelberg Engineering, utilizes diode laser technology to create detailed topographical measurements of the optic disc. It captures 32 optical sections at varying focal depths to construct a three-dimensional image. For each eye, three 15° field-of-view scans of acceptable quality were acquired, and the HRT software (version 1.11) generated a mean topographic image. A trained technician then manually outlined the optic disc margin on this mean image, guided by stereoscopic optic disc photographs. The Moorfield’s regression classification, which uses a 99% prediction interval based on the relationship between optic disc area and neuroretinal rim area, provided a categorical assessment of the optic disc, classifying it as ONL, Within Normal Limits (WNL), or borderline (B). In this study, an ‘ONL’ classification by HRT II was considered indicative of glaucoma.
Scanning Laser Polarimetry (GDx)
The GDx nerve fiber layer analyzer, from Laser Diagnostic Technologies, employs scanning laser polarimetry to assess the retinal nerve fiber layer (RNFL). It uses polarized laser light to measure retardation in the peripapillary retina, which is influenced by the birefringent properties of the RNFL. This retardation data is used to create an image where each pixel corresponds to a retardation value. The GDx software (version 2.0.09) calculates a ‘GDx number’, a neural network-derived parameter reflecting glaucoma likelihood. GDx numbers range from 0 to 100, with higher values suggesting a greater likelihood of glaucoma. According to the GDx manual, scores below 30 are typically normal, scores between 30 and 80 suggest glaucoma suspicion, and scores above 80 are highly suggestive of glaucoma. Similar to HRT II, three acceptable quality scans were obtained per eye, and a mean retardation map was generated. A technician outlined the optic disc margin based on this mean retardation image. Notably, a corneal compensator was not used in this study due to software limitations at the time of data collection.
Statistical Analysis and Results
For statistical analysis, the study defined ‘glaucomatous’ as only those patients diagnosed with definite glaucoma by the specialist. All other diagnostic categories, including glaucoma suspect and ocular hypertension, were classified as ‘nonglaucomatous’. For HRT II, ‘ONL’ results were considered ‘abnormal’, while ‘B’ and ‘WNL’ were ‘normal’.
Receiver Operating Characteristic (ROC) curves were used to determine the optimal GDx number cutoff for differentiating between ‘normal’ and ‘abnormal’. Table 1 displays the sensitivity, specificity, and area under the ROC curve (AUC) for various GDx number cutoffs, compared to the clinician’s diagnosis. A GDx number of 50 was chosen as the optimal cutoff due to its highest AUC.
Table 1: Sensitivity, Specificity, and Area Under the ROC Curve for GDx Number in Agreement with Clinician’s Diagnosis
| GDx Number Cutoff | Sensitivity (%) | Specificity (%) | AUC |
|---|---|---|---|
| (Values from original article’s Table 1 would be inserted here) |
Note: Actual values from the original Table 1 should be inserted here to complete the table.
Sensitivity and specificity tables were then generated to compare the diagnostic agreement of HRT II and GDx with the glaucoma specialist’s clinical diagnosis (considered the gold standard). Paired t-tests were employed to compare GDx numbers between glaucoma and non-glaucoma groups, while χ2 tests were used for categorical HRT data. Linear regression analysis was conducted to assess the influence of age on GDx number. Kappa statistics were used to quantify the level of agreement between each imaging device and the clinician’s diagnosis. SPSS Version 10 was used for all statistical analyses.
