Restricted Access

You must be logged in to view this content.

Glaucoma red-green disease

$currentPage/@nodeName

Dr Jack Phu
BOptom (Hons) BSc
School of Optometry and Vision Science, Centre for Eye Health, UNSW

Glaucomatous optic neuropathy is one of the leading causes of irreversible blindness in the Western world, with an increasing prevalence due to increasing and ageing population.1

Although glaucoma is classically described as ‘a bilateral but sometimes asymmetric optic neuropathy, with characteristic cupping, loss of the neuroretinal rim and nerve fibre layer, and corresponding visual field defect’, its actual diagnostic criteria are vague.

Although landmark studies in glaucoma have often given a set of diagnostic criteria for their patients with glaucoma, these still vary widely and show that there is no single test that is adequate for the diagnosis or determination of progression of glaucoma. The use of various instruments or clinical signs to define glaucoma are inconsistent.2 Even until the 1990s, there were studies that used intraocular pressure (IOP) as the criterion for the diagnosis of glaucoma, which we know may occur even in the presence of apparently ‘normal’ IOP.3

Another challenge in the diagnosis and management of glaucoma is pre-perimetric glaucoma. The classic glaucoma continuum described by Weinreb and colleagues begins at a stage when the eye is normal and progresses until total blindness.4

The pathological process in glaucoma is the acceleration of normal retinal ganglion cell apoptosis, and this progresses from an undetectable state to a state of apparent, clinical nerve fibre damage, before it is detected by perimetric testing, and then finally functional impairment and blindness.

The stage where clinically apparent structural loss of the neuroretinal rim or nerve fibre layer is known as pre-perimetric glaucoma. With this clinical entity, clinicians become more dependent on structural measurements for assessing glaucoma.

Imaging techniques such as scanning laser polarimetry (GDx), confocal scanning laser ophthalmoscopy (HRT), and optical coherence tomography (OCT) allow eye-care practitioners to objectively detect, diagnosis and monitor changes to the optic nerve head.

Despite the usefulness of these imaging modalities in clinical practice, especially in the case of clinically earlier glaucoma,5-7 the United States Federal Drug Administration (FDA) lists only visual functions as endpoints for studies on glaucoma, and these include visual fields, colour vision, visual acuity and contrast sensitivity.8

The FDA states that in order for structural endpoints to be included, they need to demonstrate clinical correlation to current or predicted future visual function, since it is argued that functional loss is a better representation of the real world.

Another limitation of imaging techniques is that they are affected by patient factors such as age, disease severity, disc size and axial length. This is compounded by the limited range of patients in each instrument’s normative database, which is used to compare a patient’s result to determine whether they are range, borderline or abnormal.

These problems may result in false positives or false negatives, and this has been referred to as ‘red’ and ‘green’ disease. Red disease occurs when an instrument flags a nerve fibre layer as being ‘red’—disease—but it is clinically normal, and green disease occurs when it is flagged as being ‘green’—normal—but clinical examination suggests that it is actually pathological.9

The following four cases illustrate the need for careful clinical examination in the diagnosis and management of glaucoma, rather than relying solely on the measurements from the instrument.

 

CASE REPORTS

 

Case 1

KK is a 24-year-old Asian male who presented for routine examination. Dilated fundus examination showed cup-disc ratios of 0.6 OD and 0.3 OS with a slightly thin inferior neuroretinal rim. Nerve fibre layer appeared intact on fundoscopic examination. Intraocular pressures were 16 mmHg OU. Central corneal thicknesses were 553 µm OD and 557 µm OS. Automated perimetry results were within normal limits. Baseline OCT testing showed inconsistent flagging of thin areas in right and left eyes in all three sector maps.

For example, the right eye 36 sector map flagged the 2 o’clock region as being borderline, while the four sector map flagged the inferior quadrant as being borderline. However, with a fundoscopically normal nerve fibre layer, as well an absence of wedge or focal defects with colour fundus photography, this patient was diagnosed with ‘red disease’ and was considered a glaucoma suspect. (Figure 1A)

103 Red -green Figure 1 - F

Figure 1. (Top to bottom) Colour fundus photos, colour thickness map from OCT, sector RNFL thicknesses

A: Case 1. Although the instrument flagged a superior sector and inferior quadrant in the right eye and inferior and superior sectors as outside normal limits, fundoscopic and photographic examination shows intact neuroretinal rim in the right eye (solid white arrows) and left eye (dashed white arrows)

B: Case 2. The instrument flagged the inferior sector of the right eye as being outside normal limits, but the neuroretinal rim appears intact and there is no apparent nerve fibre layer defect (solid black arrow)

Case 2

KP is a 30-year-old Asian female who presented for routine examination of high myopia and glaucoma suspect status. Dilated fundus examination showed cup-disc ratios of 0.7 OD and 0.6 OS with small and tilted discs OU due to high myopia of  7.00 D OU. The nerve fibre layer appeared intact in both eyes. Intraocular pressures were 16 mmHg OD and 17 mmHg OS. Central corneal thicknesses were 549 µm OD and 551 µm OS. Automated perimetry results were within normal limits. OCT imaging flagged the inferior sector as being outside normal limits in the right eye, with two adjacent sectors which were flagged as above normal limits. This was likely to have been due to a tilted disc configuration.

This patient was diagnosed with ‘red disease’ and continued to be monitored as a glaucoma suspect. (Figure 1B)

Case 3

FT is a 64-year-old Asian female who presented for routine eye examination. Anterior examination showed heavy pigment deposition on the corneal endothelium and also on the trabecular meshwork and Schwalbe’s line with gonioscopy. Dilated fundus examination showed cup-disc ratios of 0.3 OD and 0.5 OS. Neuroretinal rim was full and pink OD, and there was inferior pallor with associated nerve fibre loss OS. Intraocular pressures were 28 mmHg OD and 29 mmHg OS. Central corneal thicknesses were 573 µm OD and 549 µm OS. Automated perimetry results were within normal limits. OCT imaging showed all sectors to be within normal limits OU. However, fundoscopic examination and colour fundus photography showed clear inferior nerve fibre loss.

This patient was diagnosed with pigmentary glaucoma (green disease) and was commenced on timolol 0.5% mane to both eyes. (Figure 2A)

103 Red -green Figure 2 - F

Figure 2. (Top to bottom) Colour fundus photos, colour thickness map from OCT, sector RNFL thicknesses

A: Case 3. The instrument reported all sectors to be within normal limits or above normal limits; however, the fundus photo shows clear inferior wedge defect (solid white arrows) and thinning of the inferior rim (dashed white arrows)

B: Case 4. The instrument also reported sectors to be within normal limits, with only two sectors of the right eye being flagged as borderline; however, fundoscopic examination shows thinning of the neuroretinal rim in both eyes (dashed black arrows) and absent nerve fibre layers (solid black arrows)

Case 4

HK is a 71-year-old Asian female who presented for routine eye examination. Anterior examination showed grade 3+ mixed cataracts in both eyes. Dilated fundus examination showed cup-disc ratios of 0.9 OU with deep cupping, and inferior and superior notching of the neuroretinal rim with associated nerve fibre loss OU. Intraocular pressures were 23 mmHg OD and 22 mmHg OS. Central corneal thicknesses were 503 µm OD and 509 µm OS. Automated perimetry results were unreliable OU. OCT imaging labelled the nerve fibre layer to be within normal limits in all quadrants OU. Once again, fundoscopic examination and colour fundus photography, despite dense cataracts, showed severe thinning of the neuroretinal rim.

The patient was diagnosed with primary open-angle glaucoma (green disease) and was commenced on timolol 0.5% mane to both eyes. (Figure 2B)

Conclusion

These four cases demonstrate that along with the suite of technologies available to clinicians, glaucoma remains a clinical diagnosis. OCT imaging is an excellent technology that provides an objective measurement of structure in ocular disease and allows clinicians to have a quantitative tool to monitor structural changes over time. However, there are limitations to these devices.

Clinicians must be aware of red disease and green disease, especially in the context of pre-perimetric glaucoma, and be cognisant of the overall clinical findings to arrive at a diagnosis and formulate the most appropriate management plan for each individual patient.

  1. Cook C, Foster P. Epidemiology of glaucoma: what’s new? Canadian J Ophthalmol 2012; 47: 223-226.
  2. Bathija R, Gupta N, Zangwill L, Weinreb RN. Changing definition of glaucoma. J Glaucoma 1998; 7: 165-169.
  3. Kroese M, Burton H. Primary open angle glaucoma. The need for a consensus case definition. J Epidemiol Community Health 2003; 57: 752-754.
  4. Weinreb RN, Friedman DS, Fechtner RD, Cioffi GA, Coleman AL, Girkin CA, Liebmann JM et al. Risk assessment in the management of patients with ocular hypertension. Am J Ophthalmol 2004; 138: 458-467.
  5. Bowd C, Zangwill LM, Berry CC, Blumenthal EZ, Vasile C, Sanchez-Galeana C, Bosworth CF et al. Detecting early glaucoma by assessment of retinal nerve fiber layer thickness and visual function. Invest Ophthalmol Vis Sci 2001; 42: 1993-2003.
  6. Mardin CY, Horn FK, Jonas JB, Budde WM. Preperimetric glaucoma diagnosis by confocal scanning laser tomography of the optic disc. Brit J Ophthalmol 1999; 83: 299-304.
  7. Mardin CY, Jünemann AGM. The diagnostic value of optic nerve imaging in early glaucoma. Curr Opin Ophthalmol 2001; 12: 100-104.
  8. Weinreb RN, Kaufman PL. Glaucoma research community and FDA look to the future, II: NEI/FDA glaucoma clinical trial design and endpoints symposium: Measures of structural change and visual function. Invest Ophthalmol Vis Sci 2011; 52: 11: 7842-7851.
  9. Chong GT, Lee RK. Glaucoma versus red disease: imaging and glaucoma diagnosis. Curr Opin Ophthalmol 2012; 23: 79-88.


Like us on Facebook




Subscribe to our News RSS Feed

Latest Tweets




Recent Comments