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Integrate SD-OCT into glaucoma diagnosis and management

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Dr Blair B Lonsberry
MS OD MEd FAAO

Glaucoma is defined as an optic neuropathy characterised by progressive damage to the optic nerve and surrounding retinal nerve fibre layer (RNFL).1 Traditionally, standard automated perimetry (SAP) is the most commonly used method for ‘diagnosing’, assessing the rate of visual function loss and estimating risk of impairment from glaucoma.2 A variety of clinical signs will make a patient a glaucoma suspect, including a positive family history of glaucoma, elevated IOP, enlarge optic nerve cupping and RNFL defects.3

Diagnosis of glaucoma typically involves finding a visual field defect (for example, nasal step) that corresponds with a defect located on the optic nerve or RNFL. A visual field examination is standard for measuring glaucoma progression and many clinical trials have evaluated glaucoma progression using a SAP visual field examination.4 However, some glaucomatous eyes show only structural changes, for example, in the RNFL and/or the optic nerve head (ONH), without changes in visual function. Complete assessment of glaucoma progression requires not only functional but also structural evaluation.2,4

Since the 1960s, it has been known that the size of the cup relative to the size of optic disc, or the cup-to-disc ratio (CDR), is a useful measure of glaucomatous damage.5 In glaucoma, there is a loss of retinal ganglion cells (RGCs) and their axons, resulting in a consequent thinning of the neuroretinal rim and progressive enlargement of CDR occurs. Loss of the neuroretinal rim tends to occur first in the superior and inferior poles, and consequently, the vertical CDR has become a more commonly used parameter in clinical practice.6

The ability to detect glaucoma based on CDR is limited due to the wide variability of CDRs in the normal population. This variability is partially explained by the relationship between the CDR and the size of the optic disc. Eyes with large optic discs tend to have large cups, whereas eyes with small discs tend to have small cups. Despite the large variation in ‘normal’ CDR, CDRs are still used extensively in clinical practice to document the optic disc and determine those patients suspected of having glaucoma.5,6 By documenting CDRs, clinicians hope to be able to better diagnose the disease and detect progressive structural damage.

However, relatively large interobserver variability has been reported for CDR measurements.7 Such variability would be most likely to allow only large changes in this parameter to be detected over time, such as CDR changes of at least 0.2.5 A study by Tatham and colleagues showed that assessment of CDR is an insensitive method for evaluation of progressive neural losses in glaucoma. Even relatively small changes in CDR may be associated with large losses of RGCs, especially in eyes with large CDRs. Subjective evaluation of photographs of the optic disc is often used for assessing glaucomatous structural change but this approach is qualitative rather than quantitative, and even expert opinions vary.6

RNFL evaluation also has an important role in the diagnosis and management of glaucomatous patients. At early stages of the disease, significant losses of RGCs have been found to correspond to relatively small changes in visual field measured by SAP.8 There is mounting evidence indicating that progressive CDR or RNFL changes can frequently be seen before the appearance of statistically significant defects on SAP.2 In fact, experimental studies have shown that as many as 25 per cent to 50 per cent of RGCs may need to be lost before the decrease in SAP threshold sensitivity values exceed normal variability and reaches statistical significance. Several studies have shown significant rates of structural damage in eyes with early glaucoma in the absence of apparent visual field deterioration.8,9

With the advent of optical coherence tomography (OCT) technology, diagnosis and management of glaucoma has been revolutionised. OCT technology was introduced in the early 1990s and gave clinicians their first opportunity to obtain repeatable and reliable objective assessment of the RNFL and to a more limited degree, optic nerve. With the introduction of spectral domain OCT (SD-OCT), there is the ability to obtain detailed 3-D imaging of the retina and optic nerve, allowing a much more accurate and repeatable evaluation.3,9,10,11

OCT technology uses a low-coherence infrared beam to cause interference patterns as they pass through the retina/optic nerve. Scans of the optic nerve and surrounding RNFL are analysed and compared to normative databases determined for the specific type of OCT being used.3

The normative databases vary depending on the manufacturer, for example, age, race, refractive error.3 The standard has been to use fundus photographs (stereo) to track progression changes in the optic nerve.4,5,9 With the introduction of the OCT, are optic nerve photographs still the standard?

A study by Sharma and colleagues compared the clinical assessment of optic nerve photos with the assessment using a Cirrus HD-OCT. The optic disc size designated by the SD-OCT is smaller than that designated by observers of colour fundus images, probably because the SD-OCT considers the optic disc margin to be the easily identified opening in Bruch’s membrane, whereas designation of the optic disc boundary during readings from photographs may be influenced by the contrast of reddish optic disc tissue with surrounding peripapillary tissues of darker colour, and the edge of Bruch’s membrane is not always evident.

They concluded the Cirrus HD-OCT algorithm for calculating optic disc, cup and rim size is qualitatively in keeping with a clinician’s traditional evaluation. What was found to be superior was the repeatability of the measurements in the HD-OCT images and this reduced variance should narrow the region of uncertainty between values found in normal eyes and the values found in glaucoma. High repeatability also is an important feature when monitoring for progressive change.5

Figure 1 shows a case of a patient with unilateral glaucoma in his right eye secondary to IOP spikes secondary to steroid injections. Note the superior and inferior nasal visual field defects in the right eye with an apparently normal visual field in the left eye.

977 Figure 1 OD - F 977 Figure 1 OS - F

Figure 1. Visual field from a 60-year-old white male with history of IOP spikes secondary to steroid injections for lower back stenosis. Asymmetry noted in CDR with vertical elongation noted in the right eye. Note the superior and inferior nasal defects (steps) in the right eye, and apparently normal visual field in the left eye.

Figure 2 is a print-out of a combined optic nerve and RNFL scan on the patient using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) and a print-out from the Spectralis OCT (Heidelberg Engineering, Carlsbad, CA). The Cirrus HD-OCT shows a corresponding thinning in the superior and inferior temporal RNFL quadrants as shown on the TSNIT graphs. Average NFL thickness is in the red or abnormal zone in the right eye compared to a normative database, with a ‘suspicious’ (yellow) thickness in the left eye. Average NFL thickness is used as it has been found to be the most clinically useful in separating out normal from ‘abnormal’ NFL thickness.3,10,11

Note the symmetry index is flagged as abnormal. Glaucoma is an asymmetrical disease and it is crucial to look at the symmetry index. It is possible that the average NFL thickness could be in the green (normal) range in both eyes, but if the symmetry index is abnormal it may suggest that patient is suspicious for glaucoma, which would be overlooked if the clinician is only looking at the ‘normal’ NFL thickness.

977 Figure 2a Cirrus HD-OCT - F 977 Figure 2b Spectralis OCT - F

Figure 2. Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) and Spectralis OCT (Heidelberg Engineering, Carlsbad, CA) for the 60-year-old white male with the visual field presented in Figure 1. Note the ‘red’ flagged average NFL thickness and symmetry index in the Cirrus OCT parameters and the flattened TSNIT curve (compared to the left eye curve), with additional red flagged superior and inferior sections of the pie graphs which corresponds with the inferior and superior nasal defects noted on the right visual field. Similarly, the Spectralis has the same flattened right TSNIT curve for the right eye and the similar red flagged superior and inferior RNFL thickness in the pie graph associated with the superior and inferior visual field defects noted on the visual field. Note that both the Cirrus HD-OCT and the Spectralis OCT have flagged the inferior NFL in the left eye as ‘suspicious’ or thinner than age expected norms with no apparent visual field defect noted in the left visual field, potentially picking up an early preperimetric thinning of the patient’s NFL that has not manifested as an observable visual field defect.

Looking at the pie graphs, the superior and inferior quadrants in the right eye are red indicating that the patient’s NFL is abnormally thin compared to age expected norms. Additionally, the optic nerve parameters are also represented, which shows a vertically elongation of the CDR and a thin neuroretinal rim. Also shown is a print-out from the Spectralis OCT, showing patterns similar to those noted with the Cirrus HD-OCT. The TSNIT graph shows a ‘normal’ left eye but a flattened line graph in the right eye with the line dipping into the abnormal thickness range in the superior and inferior temporal quadrants corresponding to the inferior/superior nasal visual field defects.

Interesting to note is that the visual field in the left eye appears to be normal with no significant visual field defects noted in the pattern standard deviation (PSD) plot. However, when looking at the Cirrus HD-OCT and the Spectralis print-out, you note that the inferior temporal NFL is flagged in yellow or suspicious. Is there a preperimetric thinning of the left NFL that is not showing as an observable visual field defect? Remember, it is estimated that 25-50 per cent NFL loss maybe needed to get an observable visual field defect.8 The use of SD-OCT technology may allow the clinician to pick up preperimetric visual field defects, allowing the clinician to more closely monitor that patient or potentially initiate therapy at an early stage in the disease process.

It is well known that the circa parapapillary NFL (cpNFL) and the optic nerve are critical in the diagnosis of glaucoma9-12 but evidence is accumulating that measurements of the inner retinal layers in the macular region may be additional parameters for glaucoma detection.12 The ganglion cell complex (GCC) consists of the RNFL, the ganglion cell layer and the inner plexiform layer. The GCC is becoming an increasingly important area to assess, particularly in patients with early glaucoma.

Studies have shown that GCC and cpRNFL thickness exhibit similar diagnostic performance for the detection of early glaucoma.9,10,11 Nakatani and colleagues demonstrated that macular parameters (GCC) in SD-OCT had comparably high discriminating power for early glaucoma and high reproducibility comparable with peripapillary RNFL parameters. SD-OCT increased the diagnostic value of macular parameters for early glaucoma.12 Akashi and colleagues demonstrated that the diagnostic performances of average cpRNFL thickness and average GCC thickness to identify early glaucoma and all-stage glaucoma were similar among Cirrus, RTVue and 3-D OCT measurements in our study population.10

Figure 3 shows a patient who presented with asymmetrical IOPs (24 OD, 20 OS) and asymmetrical CDR (0.75/0.75 OD, 0.6/0.6 OS). FDT visual field shows no apparent visual field defects in either eye; however, the GCC as measured by the Cirrus SD-OCT is normal in the left eye but abnormal in the right eye compared to age normative database. Note that the Cirrus SD-OCT measures the GCC by removing the NFL for the GCC and utilises only the ganglion cell layer and the inner plexiform layer combined thickness.

977 Figure 3a FDT Screening - F 977 Figure 3b GCC Analysis Print Out - F
Figure 3A. FDT screening visual field of a 66-year-old male patient who presented with asymmetrical IOP (24 OD, 20 OS) and asymmetrical CDR (0.75/0.75 OD, 0.6/0.6 OS). No glaucomatous visual field defects noted on the screening FDT visual field. Figure 3B. GCC analysis print-out from the Cirrus SD-OCT for this patient. Note the superior GCC thinning (flagged in red on the pie graph) and the normal GCC in the left eye.

This is compared to the Spectralis OCT, which utilises a posterior pole retinal thickness map where retinal thickness around the macula is measured and symmetry of retinal thickness is compared between corresponding ‘grids’ between right and left eyes, and additionally between the interior and superior corresponding quadrants in the same eye.

Is it appropriate to treat this patient who has asymmetrical and above ‘normal’ IOP, asymmetry in his CDR and an abnormal GCC but no observable visual field defect? To add to the clinical picture, Figure 4 depicts the RNFL and ONH scan performed on this patient and there is noticeable thinning in the NFL in the superior quadrant correlating with the abnormal GCC noted in Figure 3. Traditionally, patients are not ‘diagnosed’ with and begun treatment for glaucoma unless there is an observable and repeatable visual field defect. With the advent of SD-OCT, the paradigm of when to treat is shifting.

977 Figure 4 Cirrus HD-OCT - F

Figure 4. Print-out of a Cirrus SD-OCT ONH and RNFL from the patient depicted in Figure 3. Note the abnormal (red flagged) average NFL thickness and the superior quadrant on the pie graph representing a superior NFL thinning compared to age norms. ONH parameters in the right eye are also flagged in red with an average CDR of approximately 0.72 compared to 0.59 in the left eye and an abnormal neuroretinal rim area compared to age norms. The NFL thinning noted in the superior quadrant correlates with abnormal thinning noted on the GCC printout in Figure 3; however, no corresponding visual field defect was noted on the FDT screening.

Glaucoma is a progressive disease with no cure, but with early detection and treatment there is the hope of slowing progression and preventing significant vision loss. A subjective evaluation of the disc and the RNFL status is currently the reference standard for the assessment of glaucomatous structural change. This approach is qualitative rather than quantitative, and even expert opinions vary on what is considered progression.4,8,9,10 What is needed is an objective, qualitative and repeatable means to monitor progression in patients.

Progressive visual field loss has traditionally been the measure of functional loss with respect to glaucoma and is often the determining factor on whether treatment is modified.1,9 However, reliability is always a concern when performing visual field testing due to its reliance on the patient and their subjective assessment during the testing process.

Guided progression analysis (GPA) has been introduced to visual field testing in instruments such as the Humphrey Visual Field Analyzer (Carl Zeiss Meditec, Dublin, CA) attempting to take patient variability into consideration and determine if there is progressive loss in visual function over time. Similar to the guided progression analysis that is found in the Humphrey Visual Field, OCTs also have a form of GPA and is useful for progression detection in an objective and structural capacity (versus the subjective and functional with visual field testing) in glaucoma to complement other reference standard strategies.9

It also has to be remembered that as the disease progresses, testing and the emphasis placed on particular tests also has to change. For example, traditionally a 24-2 visual field is used in the diagnosis and early progression testing for glaucoma, but with more advanced visual field loss the clinician may have to change to a 10-2 visual field and potentially more emphasis being placed on changes in the visual field compared to imaging equipment dependent on the reliability of the scan that can be obtained. In addition, 10-2 visual field testing may also need to be considered in the early diagnosis of glaucoma as paracentral VF defects are thought to be an early visual field defect seen particularly in normal tension glaucoma,13 which may also correspond to the new GCC scans that we are obtaining. With the advances in technology, our ‘traditional’ approach to glaucoma diagnosis and management will also have to advance.

Summary

OCT technology has revolutionised how eye-care professionals diagnosis and manage their patients, in particular when it comes to glaucoma. OCT technology has developed into a reliable and repeatable quantitative assessment of retinal and optic nerve structure. The potential of this advanced technology is to identify those patients who present with glaucoma, even preperimetric glaucoma, without completely relying on a subjective and often unreliable visual field assessment. With the added advanced glaucoma tools like ganglion cell analysis and guided progression analysis, the OCT is becoming a mainstay in the diagnosis and management of patients.

 

1.         Harwerth RS, Wheat JL, Fredette MJ, Anderson DR. Linking structure and function in glaucoma. Prog Retinal Eye Research 2010; 29: 4: 249-271.

2.         Lisboa R, Leite MT, Zangwill LM, Tafreshi A, Weinreb RN, Medeiros FA. Diagnosing preperimetric glaucoma with spectral domain optical coherence tomography. Ophthalmology 2012; 119: 11: 2261-2269.

3.         Aref AA, Budenz DL. Spectral domain optical coherence tomography in the diagnosis and management of glaucoma. Ophthalmic Surgery, Lasers & Imaging : the Official Journal of the International Society for Imaging in the Eye 2010; 41: 6: S15-27.

4.         Medeiros FA, Zangwill LM, Bowd C, Mansouri K, Weinreb RN. The structure and function relationship in glaucoma: implications for detection of progression and measurement of rates of change. Invest Ophthalmol Vis Sci 2012; 53: 11: 6939-6946.

5.         Sharma A, Oakley JD, Schiffman JC, Budenz DL, Anderson DR. Comparison of automated analysis of Cirrus HD OCT spectral-domain optical coherence tomography with stereo photographs of the optic disc. Ophthalmology 2011; 118: 7: 1348-1357.

6.         Tatham AJ, Weinreb RN, Zangwill LM, Liebmann JM, Girkin CA, Medeiros FA. The relationship between cup-to-disc ratio and estimated number of retinal ganglion cells. Invest Ophthalmol Vis Sci 2013; 54: 5: 3205-3214.

7.         Lievens CW, Judd TA. Using the original Judd-Lievens C/D ratio grading card (JLC) to improve interobserver reliability. Optometric Education 2007; 32: 2: 57-62.

8.         Medeiros FA, Lisboa R, Weinreb RN, Liebmann JM, Girkin C, Zangwill LM. Retinal ganglion cell count estimates associated with early development of visual field defects in glaucoma. Ophthalmology 2013; 120: 4: 736-744.

9.         Na JH, Sung KR, Lee JR, Lee KS, Baek S, Kim HK, Sohn YH. Detection of glaucomatous progression by spectral-domain optical coherence tomography. Ophthalmology 2013; 120: 7: 1388-1395.

10.       Akashi A, Kanamori A, Nakamura M, Fujihara M, Yamada Y, Negi A. Comparative assessment for the ability of Cirrus, RTVue, and 3D-OCT to diagnose glaucoma. Invest Ophthalmol Vis Sci 2013; 54: 7: 4478-4484.

11.       Leite MT, Rao HL, Zangwill LM, Weinreb RN, Medeiros FA. Comparison of the diagnostic accuracies of the Spectralis, Cirrus, and RTVue optical coherence tomography devices in glaucoma. Ophthalmology 2011; 118: 7: 1334-1339.

12.       Nakatani Y, Higashide T, Ohkubo S, Takeda H, Sugiyama K. Evaluation of macular thickness and peripapillary retinal nerve fiber layer thickness for detection of early glaucoma using spectral domain optical coherence tomography. J Glaucoma 2011; 20: 4: 252-259.

13.       Seong M, Sung KR, Choi EH, Kang SY, Cho JW, Um TW, Kim YJ, Park SB, Hong HE, Kook MS. Macular and peripapillary retinal nerve fibre layer measurements by spectral domain optical coherence tomography in normal-tension glaucoma. Invest Ophthalmol Vis Sci 2010; 51: 3: 1446-1452.



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