01. The Optic Nerve

Here are the slides that I used for a discussion with the UBC residents on 19Feb2010 on the optic nerve as it relates to glaucoma. The comments on each slide are a mix of the speaker notes I had prepared prior to our session along with a reflective discussion of what we ended up talking about.

02. Outline

The residents were asked to read a few references in advance of the teaching session, including the section on the optic nerve in the American Academy of Ophthalmology Basic and Clinical Science Course, two articles on glaucomatous optic neuropathy classification, and a book chapter on the Heidelberg Retinal Tomogram for detecting progression.

The plan was, with that basic background, to have a meaningful discussion on glaucomatous optic neuropathy, its clinical evaluation, quantitative measurement and how to record optic nerve findings.

03. Optic disk appearance in POAG

We started by discussing the key points in this article that two glaucoma fellows wrote under Dr Drance’s guidance in which the optic disk appearances in primary open angle glaucoma were described in 1999. It is important to appreciate these anatomic differences that we see in glaucoma so that we know what it is that we are looking for when we are assessing the optic nerve.

04. Agreement among clinicians patterns disk damage

Two years following the initial article describing the disk appearance, an study was published based on these clinical appearances to look at how well clinicians can agree on the findings. Although the study describes their agreement as good, the residents and I in our discussion were not as impressed with their being great clinical agreement.

05. Glaucomatous optic disk classificationi

The 4 different glaucomatous optic disc changes as described in these articles are focal, myopic, senile sclerotic, and generalized. A fifth category of unclassifiable was reserved for discs showing more than one of these features.

06. Clinical evaluation

What are the different ways of examining the optic nerve in the clinical setting? 

[Wait for audience to mention the different methods then discuss advantages & disadvantages of each…eg stereo vs mono; magnification low vs high]

Direct: higher mag but no stereo

Indirect: young kids or uncooperative folks

Lens with slit lamp: appreciate subtle contour differences with narrow beam

- normal disc 1.5-2.2 mm diameter

- mag factors 60D is 1

- 78D multiply reading by 1.1

- 90D multiply reading by 1.3

Lastly, after looking at the nerve, how do you document the appearance in the patient’s medical record?

Most important: make some sort of note even if c/d; better, draw including sloping marks, notches, convex forward. We spent some time discussing techniques of drawing the disc appearance in some form in the chart and the surprising statistic from Paul Lee’s study of how rarely clinicians following patients for glaucoma actually documented the optic disc appearance. So, if we draw something, we are doing better than most others.

Reference is http://irserver.ucd.ie/dspace/handle/10197/276 

Fremont AM, Lee PP, Mangione CM, Kapur K, Adams JL, Wickstrom SL, Escarce JJ.

Patterns of care for open-angle glaucoma in managed care. Arch Ophthalmol. 2003 Jun;121(6):777-83.

07. Intro - quantitative measurement

Let’s discuss the different imaging modalities of the optic nerve. But, first, what is it that we are really measuring? Where is the damage in glaucoma? It is actually the ganglion cell layer of the retina. These tests measure the ganglion cells as reflected by the nerve fibre layer and their axons that form the optic nerve.

As the strength of these tests lies in their detection of progression, we’ll spend more time discussing how to look for progression with the HRT. 

08. Different quantitative devices & their principles

Who can name the different ways we document the structure of the optic nerve?

- Stereo disc photos: the so called gold-standard. Important role in baseline documentation that can stand the test of time as technologies change

- GDX (nfl): scanning laser polarimetry, variation of CSLO but polarizer and modulator detect birifringent properties of nerve fibre layer relative (not absolute) thickness

- OCT (nfl): optical coherence tomography, using interferometry & low coherence light for hi-res cross section

- HRT (nerve head): confocal scanning laser ophthalmoscopy, series of optical tomographic slices

A favourite here at UBC since 1994 when the first generation introduced and used for the ‘Baker/CNIB’ study of risk factors

All these ways of documenting the optic nerve structure just give some objective data to what we see with proper clinical assessment. In fact, none of these modalities are any better than a trained clinician in determining whether someone has glaucoma. The strength lies in tests that can be used to look for progression over time.

The newest technology is Spectral Domain OCT; yet again incompatible with all prior OCT technologies but the first OCT technology that has promise to actually be able to detect change and the highest resolution devices to date. Heidelberg’s latest machine even combines both the HRT and Spectral Domain OCT. We did not discuss this technology in any detail during this session.

09. Intro - more details on HRT

Much of the rest of our session was devoted to a further understanding of how to detect progression using the HRT3 version of the HRT CSLO device with the goal of deciding whether a change is enough to lead to altering how a given patient would be treated. It should be pointed out that we have been using the HRT since 1994 and the FSM value for glaucoma detection, the Topographic Change Analysis for progression and the Glaucoma Probability Score for mathematical modelling/classification were developed by Drs Mikelberg, Swindale and Chauhan respectively (two current faculty and one former fellow.) Therefore, there is likely some bias toward speaking highly about this technology.

10. What is progression - stereo & topographic

There are two types of parameters that are looked at for change - stereometric and topograhic. The stereometric parameters are the different two dimensional values that are documented with each scan and are basically different ways of looking at different pieces of the pie if you cut the optic nerve into slices. Despite the categorization as Superior, Inferior, Supratemporal (ST), Infratemporal (IT), Upper and Lower might make you think that the disc is divided into 6 different distinct slices of pie, the Superior and Inferior actually refer to the supratemporal & infratemporal 2/3, Upper and Lower refer to upper and lower 1/2 and ST and IT are the only ones that are intuitively as described. These values are very much dependent on how the contour line is drawn on the initial visit. However, if viewing the results with the viewing software in the examining room as I do, I can always adjust the contour line based on clinical examination if I don’t think it was drawn correctly on the initial attempt.

The big strength in terms of sensitivity with this technology is the Topographic Change Analysis to look at small regions of the optic nerve for changes in area and volume of their excavation over time.

11. What is progression - topographic

The pixels are grouped into 4x4 clusters of ‘super-pixels’ to look for progression. At least 3 sets of scans are required before there is any meaningful data: the initial visit and at least two follow-ups. If a super-pixel changes over three visits, it is marked as red if it is further away and green if it is closer…adopting the doppler colour scheme.

12. What is progression - topographic

It gets somewhat confusing looking at all the different thumbnails that are produced with each exam. The black & white reflectance, the colourized Topography (made to simulate the clinical appearance,) the Probability Map containing only the red and green colours, and the Significance Map which is the one I tend to spend the most time on…which looks like the black and white Reflectance with the red & green probability superimposed.

We also discussed some of the hidden features of the HRT viewing software that are accessible from this screen but saved exploring these in greater depth for our regular glaucoma rounds discussion every 3 weeks. However, a key feature worth mentioning is that if you click on the B & W reflectance map thumbnail in the lower left, this unlocks some features that appear in the top right of the screen to view a series of all the reflectance images for the patient over time in a time-lapse photo mode which can help show if a nerve is just wobbling back and forth in its alignment or truly showing progressive excavation.

13. What is progression - topographic

This is the window that appears when selecting the Topographic Change Analysis for a patient. It shows those different thumbnails that were just discussed. A bit confusing is that the thumbnails in the middle row, labeled as Reflectance are actually the Significance images…ie the reflectance B & W images with the red & green significance super-pixels superimposed. The red gets darker from one scan to the next if the significance increases over time.

14. What is progression - topographic

This is just more details on how Bal Chauhan et al developed the cluster analysis as published in the ARVO journal IOVS in 2000.

15. What is progression - topographic

More from that original 2000 pub on the probability values.

16. What is progression - topographic

A bit challenging to understand when we tried to discuss this was the idea of the temporal filtering involved in generating the data such that overlapping series of each successive 3 probability maps are compared to filter out how much is changing between tests instead of just compared to the baseline. This is illustrated on this slide.

17. What is progression - topographic

Based on this temporal filtering for change on these super-pixels, we are left with the modern-day version of the HRT 3 software since in use since 2006. Most importantly, even those scans we have been doing as far back as 1994 with the first generation of the machine, although they only looked at 10 degrees around each optic nerve instead of 15, are all still valid to use for analysis for progression. Compare this to the OCT in which each new generation made all prior scans unusable, and we have a powerful instrument to document change over time - key to following patients with glaucoma.

18. What is progression - topographic

These next two slides are meant to show that in order to statistically prove progression, it is important that the data shows little variability. In other words, we need to keep the Standard Deviation of the measurement at each visit as small as possible in order to discern significant progression. In this case, although a follow-up visit is showing a much lower value, because the error in measurement is so large, we cannot prove that this change in value is significant.

19. What is progression - topographic

However, by keeping the variability very low, it this same change can reach statistical significance. The HRT nerve scan shows no significant variability if the test is repeated in the patient on the same day, whereas other tests, such as the OCT, can show large variations. The reason for this on the OCT is the much longer scan time lead to the normal micro-saccadic eye movements leading to the scan actually not even measuring the same area around the optic nerve from the time the scan starts until it is completed. Since each scan in the HRT is shorter than the duration of the micro-saccadic eye movement, it is not subject to this variability.

20. What is progression - topographic

Until 2006, this was the limit of how we analyzed for topographic change, click on different areas to read off the error probability.

21. What is progression - TCA

With the advent of the HRT3 software, we can now easily map out the area and volume of any significant cluster of super-pixels to document change graphically.

22. What is progression - TCA

This HRT3 software also showed those areas in which the change was becoming more significant as darker red.

23. What is progression - TCA

This just shows double-clicking on any red area to reveal the area and volume of that cluster over time.

24. What is progression - TCA

25. TCA progression case 1

And just another example showing this progression as it appears on the Topographic Change Analysis on the HRT.

26. TCA progression case 1

27. TCA progression case 1

28. What is progression - normalized parameters

We started this section on HRT progression by discussing Topographic Change and Stereometric Change. Let’s now look more at the stereometric normalized parameters to see how these can also be used to look for changes in the optic nerve from glaucoma.

29. What is progression - normalized parameters

The standard follow-up report shows 14 of the stereometric parameters including disk area, cup area, rim area, etc and how much these have changed since baseline. No indication of significance is provided and each parameter has a different unit as some are area, others volume and some even depth. Many of these parameters are important to follow for signs of progression but there needs to be any easier way than trying to figure out if a given change is significant.

30. Normalized parameters

This is where the idea of normalized parameters comes into play. The residents and I discussed what they thought normalized parameters were and there was some grasp of the concept. Contrary to what some people may have thought, these are not related to age-matched controls. Here, normalized data is a relative value compared to the baseline that gets assigned a value of 0. Since each parameter is being divided by its baseline value, the units cancel each other out so the normalized parameters have NO units. Values indicated glaucomatous progression approach -1 and those improving approach +1 so all the parameters have a value between +1 and -1. These values usually are not improving except from fluctuation in measurement between visits or if there is a sudden drop in pressure before disc damage could be permanent in which case the nerve can improve in its structure and the normalize parameters can move in the + direction.

31. Normalized parameters

As all the values are now between +1 and -1, they can all be compared on the same scale and plotted out over time. This makes it easier to see trends of change in the stereometric parameters.

32. Normalized parameters

Here is a graph of 10 of the normalized parameters for one patient over time and these parameters can all just be lumped together as an average which is show by the red squares joined by red lines.

33. Normalized parameters

In a patient that is showing progressive glaucomatous damage, you can see many of the individual parameters heading toward -1 over time for the first 4 tests and then levelling out; this is also nicely reflected in the average.

34. Normalized parameters

On the HRT, we see these normalized stereometric parameters get plotted as the average of those 10 normalized parameters as measured in 6 different regions. These regions, Temporal Superior (TS), Temporal Inferior (TI), Superior (S), Inferior (I), Upper (U), and Lower (L) are plotted with two per graph compared with the “Global” average of these averages (ie averaging the TS, TI, S, I, U, and L averaged values) so that you can see if these particular regions of the optic nerve are progressing and how their progression might compare to the general health of the whole nerve. OK, that’s alot to think about!

35. Normalized parameters

The rule of thumb is that a change in these average normalized parameters -0.05 is likely more than just fluctuation. Two consecutive changes is suspiscious and three confirmatory of progression. I would add that a single change of -0.20 is significant and also remember that this is still just an ancillary test that is meant to complement the clinical picture and other ancillary tests so should not be taken in isolation. If there is a single change of 0.05 and the Visual Field has also progressed or the intraocular pressure is definitely higher, then there is likely enough confirmatory evidence from these to confirm progression worth changing or initiating therapy.

36. Quantitative measurement - summary

To summarize, detection of glaucomatous progression is based on changes in normalized stereometric parameters or topographical changes in area and volume of excavation of the optic nerve. 

37. What are we going to do about progression?

Changes should be confirmed with two subsequent follow-up visits and correlated with the clinical picture. Discuss the findings with your patient and consider initiating treatment if none has been provided as yet, or changing the treatment if they are already being treated. Aside from the correlation with introacular pressure and visual field, other factors that can influence the decision to treat include numerous family members having glaucoma or at least one close family member having lost significant vision from glaucoma. You may also elect to change the management even if nothing else changes if there is a very large change on the HRT scan that convinces you of a high risk that significant visual loss is inevitable.

38. New features HRT 3

Here are three bonus slides I had tacked on to the end of the talk; this first one was hidden when we had this discussion with the residents as I already had covered it during the course of the talk. However, for completeness, here it is. This just lists the improvements that were introduced with the HRT3 software update in 2006 as they are quite significant in the day to day function of this device.

39. New features HRT 3

One of the major improvements is the improved alignment strategy with prior scans taking into account different ways that the tests might be mis-aligned.

40. Advantages of interacting with the HRT software

This bonus slide covers another area that we had also managed to work into the afternoon’s discussion, namely the advantages of using the viewing software in the examination room while also performing slit lamp biomicroscopic examination using the 66D lens. If the contour does not seem correct after examining the patient, it is easy to just redraw it so that the normalized stereometric data can be recalculated. Also, if a cluster of super-pixels looks like it is getting bigger or darker red, on the viewing software you can just double click on that region to see a graph of the area and volume over time; this can’t be done with paper unless the technician who performed the scan also looked over the Topographic Change Analysis, noticed significant clusters than double clicked and printed out graphs for every cluster they thought might have changed. By combining the HRT workstation with the clinical examination, I have changed how I see the optic nerve. Each modality helps improve the other in better understanding the optic nerve changes in glaucoma.

41. Summary of HRT portion of discussion

To summarize the HRT portion of the discussion, we looked at topographic and stereometric changes, discussed clinical correlation, altering therapy and how the HRT3 was improved for more accurate progression analysis.

42. The End

And thus concludes the session of glaucomatous optic neuropathy.