Laboratory Studies
Patients suspected of having normal-tension glaucoma may need workup to rule out other causes for optic neuropathy, including, but not limited to, CBC, erythrocyte sedimentation rate (ESR), serology for syphilis (micro-hemagglutination-Treponema pallidum [MHA-TP], not Venereal Disease Research Laboratory [VDRL] test), and if suggested by the pattern of visual field loss, neuroimaging.
Progressive visual field loss in a patient with glaucoma is shown in the image below.
Example of progressive visual field loss over time (from top to bottom) in a patient with glaucoma. Notice the early appearance of an inferior nasal step and arcuate loss, with progressive enlargement and increasing density of the scotomata over time. Courtesy of M. Bruce Shields, MD.
Some researchers have suggested an autoimmune etiology for some glaucomatous optic neuropathies and have identified monoclonal gammopathies. Serum protein electrophoresis can identify these rare individuals.
Imaging Studies
Fundus photography provides a permanent record of the appearance of the optic disc. Photographs taken over a period of time may be compared to track the progression of glaucoma.
The retinal nerve fiber layer sometimes can be imaged on high-contrast black and white film using red-free techniques. This can allow identification of nerve fiber layer defects that are characteristic of glaucomatous damage.
New techniques that use optical analysis of different physical properties of light can document the status of the optic nerve and the thickness of the nerve fiber layer, and they can be used to detect changes over time. The value of these technologies for diagnosing and following glaucoma over time continues to be an active topic of discussion and investigation. Modalities of the various technologies continue to be upgraded and enhanced, hopefully increasing the accuracy and likelihood of detecting glaucomatous damage.
Confocal scanning laser ophthalmoscopy (eg, HRT III) can examine the optic disc and peripapillary retina in 3 dimensions and provides quantitative information about the cup, neuroretinal rim, and contour of the nerve fiber layer. Increased resolution and software enhancements continue to improve this technology.
Scanning laser polarimetry (eg, GDX) measures the change in the polarization state of an incident laser light passing through the naturally birefringent nerve fiber layer to provide indirect estimates of peripapillary nerve fiber layer thickness. Improvements in neutralizing corneal light polarization (as opposed to that of the nerve fiber layer) have helped to decrease artifact in data obtained by this methodology.
Optical coherence tomography (eg, Stratus OCT) uses reflected light in a manner analogous to the use of sound waves in ultrasonography to create computerized cross-sectional images of the retina and optic disc, and it also gives quantitative information about the peripapillary retinal nerve fiber layer thickness. Newer increased resolution and three-dimensional spectral analysis hardware and software are also helping to propel this technology. Retinal nerve fiber layer (RNFL) thickness maps generated by spectral-domain OCT can help detect the progression of RNFL in glaucoma patients. [12]
For these technologies, continuing studies show good reproducibility over time for the same instrument. However, significant variability and fluctuating correlation between instruments is still noted, especially when compared with visual field testing results and other clinical examination findings. Therefore, testing results for each modality should be clinically confirmed by examination findings and other testing and not just singly used for clinical decision-making. [13]
The combination of structural and functional measurements with standard automated perimetry and optical coherence tomography performs better in estimating the rate of retinal ganglion cell loss in glaucoma patients than either measure alone. [14]
Fluorescein angiography, ocular blood flow analysis via laser Doppler flowmetry, color vision measurements, contrast sensitivity testing, and electrophysiological tests (eg, pattern electroretinograms) are used currently as research tools in the evaluation and management of patients with POAG. Routine clinical use is not advocated at this time.
Ultrasound biomicroscopy (UBM) may prove to be helpful in the future for obtaining a better view of the angle, iris, and ciliary body structures to rule out anatomical pathology and secondary causes of elevated IOP.
Other Tests
Other tonometric methods
Goldmann applanation tonometry is considered the criterion standard. However, Goldmann applanation is dependent on corneal rigidity, curvature, thickness (measured by pachymetry), and other biomechanical properties, so there is much room for error in patients with atypical corneas or other eye conditions. Particularly, with the advent of refractive corneal procedures, and the subsequent exponential increase of postsurgical eyes, the issue of tonometric accuracy is becoming more and more paramount.
Studies now strongly suggest that applanation pressures vary significantly depending on corneal thickness, as follows:
-
Some patients diagnosed with OHT actually may be normotensive when corrected for increased corneal thickness.
-
Some supposed glaucoma suspects or patients with apparent low-tension glaucoma (with normal range IOPs on applanation) can have abnormally thin corneas on pachymetry (central corneal thickness measurements); therefore, their IOP measurements are underestimated by applanation.
-
Corneal thickness plays a role in the development of glaucoma in those with OHT (see Mortality/Morbidity and image below).
Ocular hypertension study (OHTS). Percentage of patients who developed glaucoma during this study, stratified by baseline intraocular pressure (IOP) and central corneal thickness (CCT).
Previously used correction algorithms for adjusting IOP based on corneal thickness are not recommended, since viscoelastic properties of the cornea also play a role and there is no linear relationship between corneal thickness and IOP.
Other technology
Other technologies for measuring intraocular pressure continue to be studied to determine if they are more accurate than Goldmann tonometry. To date, none have been able to surpass it in accuracy for all patients; however, in the future, they may be useful for those who have abnormal pachymetry or other corneal properties. Their role is yet to be finalized. [15, 16, 17, 18] Two examples of new technology are described below.
The Ocular Response Analyzer (ORA)® from Reichert [19] uses a rapid air impulse and an electro-optical system to record two applanation pressure measurements; one measurement is while the cornea is moving inward, and the other measurement is as the cornea returns. Because of its biomechanical properties, the cornea resists the dynamic air puff, thereby causing delays in the inward and outward applanation events and resulting in two different pressure values. See the image below.
Intraocular pressure measurements. Adapted from Reichert Ophthalmic Instruments, Ocular Response Analyzer, How does it work Web page.
The average of these two pressure values provides a repeatable, Goldmann-correlated IOP measurement. The difference between these two values is referred to as corneal hysteresis, which is a measurement of the corneal tissue properties that is a result of viscous damping in the corneal tissue. Low corneal hysteresis demonstrates that the cornea is less capable of absorbing (damping) the energy of the air pulse. There is good evidence that glaucoma progresses at a faster rate in patients who have low corneal hysteresis.
Some experts hypothesize that this is not primarily a function of corneal thinning, but rather a result of weakening of the tissue structure related to creation of the flap. Decreased corneal hysteresis may also play a role in indicating the presence or onset of other corneal tissue disorders.
The PASCAL Dynamic Contour Tonometer is a digital contact tonometer that directly measures IOP continuously based on a numeric output of IOP and ocular pulse amplitude (OPA). Unlike applanation tonometry, which is influenced by corneal thickness and other characteristics of the cornea, the PASCAL Dynamic Contour Tonometer provides a direct measurement of IOP, independent of interindividual variations in corneal properties and biomechanics, and also measures pulsatile pressure fluctuations caused by the change in ocular blood flow during systole versus diastole. [1, 19]
In cases of increased corneal or scleral rigidity (ie, S/P keratoplasty, scleral buckle), the newer methods, as described above, as well as other alternatives, such as pneumotonometry or Tono-Pen, may also be more accurate than applanation methods.
Other tests
Other tests of historical and research interest include the following:
-
Tonography, which has been used to help determine trabecular outflow facility, is primarily a research tool used in testing pharmacologic agents.
-
Provocative testing (eg, water-drinking test) was used in the past to try to differentiate who would develop early open-angle glaucoma. This test was of no aid in distinguishing those patients who would develop visual field defects from those who would not develop them.
Patients whose visual field defects seem to progress in a manner uncharacteristic of glaucoma should have a workup for other causes of visual loss.
-
Advanced glaucomatous damage with increased cupping and substantial pallor of the optic nerve head. Courtesy of M. Bruce Shields, MD.
-
Flowchart for evaluation of a patient with suspected glaucoma. Used by permission of the American Academy of Ophthalmology.
-
Diagram of intraocular pressure distribution, with a visible skew to the right (somewhat exaggerated compared to the actual distribution). Note that, while uncommon, field loss among individuals with pressures in the upper teens can occur. Also, note that the average pressure among those with glaucomas is in the low 20s, even though most individuals with pressures in the low 20s do not have glaucoma. Used by permission from Survey of Ophthalmology.
-
Diagram showing the relative proportion of people in the general population who have elevated pressure (horizontally shaded lines) and/or damage from glaucoma (vertically shaded lines). Notice that most have elevated pressure but no sign of damage (ie, ocular hypertensives), but there are also those with normal pressures who still have damage from glaucoma (ie, normal tension glaucoma). Courtesy of M. Bruce Shields, MD.OHT = horizontal lines only NTG = vertical lines only POAG and other glaucomas with both elevated intraocular pressure and damage = overlapping horizontal and vertical lines
-
Humphrey visual field, right eye, showing patient with advanced glaucomatous field loss. Notice both the arcuate extension from the blind spot (Bjerrum scotoma) and the loss nasally (nasal step), which often occurs early in the disease process. Courtesy of M. Bruce Shields, MD.
-
Illustration of progressive optic nerve damage. Notice the deepening (saucerization) along the neural rim, along with notching and increased excavation/sloping of the optic nerve and circumlinear vessel inferiorly. Courtesy of M. Bruce Shields, MD.
-
Example of progressive visual field loss over time (from top to bottom) in a patient with glaucoma. Notice the early appearance of an inferior nasal step and arcuate loss, with progressive enlargement and increasing density of the scotomata over time. Courtesy of M. Bruce Shields, MD.
-
Optic nerve asymmetry in a patient with glaucomatous damage, left eye, showing optic nerve excavation inferiorly (similar to Image 5). Courtesy of M. Bruce Shields, MD.
-
Glaucomatous optic nerve damage, with sloping and nerve fiber layer rim hemorrhage at the 7-o'clock position. Hemorrhage is indicative of progressive damage, usually due to inadequate pressure control. Further notching and pallor corresponding to the area of hemorrhage usually is seen several weeks after resorption of the blood. Courtesy of M. Bruce Shields, MD.
-
Correction values according to corneal thickness.
-
Ocular hypertension study (OHTS). Percentage of patients who developed glaucoma during this study, stratified by baseline intraocular pressure (IOP) and central corneal thickness (CCT).
-
Intraocular pressure measurements. Adapted from Reichert Ophthalmic Instruments, Ocular Response Analyzer, How does it work Web page.
